Editing Major depressive disorder

{{Short description|Mood disorder}}
{{Hatnote group|
{{For|other types of depression|mood disorder}}
{{Distinguish|depression (mood)}}
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{{Update|date=July 2024|reason=Many outdated sources and information (older than five years)}}
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{{Infobox medical condition
| name          = Major depressive disorder
| image         = Van Gogh - Trauernder alter Mann.jpeg
| alt           =
| caption       = ''[[At Eternity's Gate|Sorrowing Old Man (At Eternity's Gate)]]'', an 1890 portrait by [[Vincent van Gogh]]
| field         = [[Psychiatry]], [[clinical psychology]]
| synonyms      = Clinical depression, major depression, unipolar depression, unipolar disorder, recurrent depression
| symptoms      = [[depression (mood)|Low mood]], low [[self-esteem]], [[Anhedonia|loss of interest]] in normally enjoyable activities, [[Psychomotor retardation|low energy]], [[pain]] without a clear cause,<ref name="NIH2016" /> disturbed sleep pattern ([[insomnia]] or [[hypersomnia]])
| complications = [[Self-harm]], [[suicide]]<ref name="z273"/>
| onset         = Age 20s{{sfn|American Psychiatric Association|2013|p=165}}<ref name=Kes2013/>
| duration      = > 2 weeks<ref name="NIH2016" />
| causes        = Environmental (e.g. [[Psychological trauma|adverse life experiences]]), [[Genetics|genetic predisposition]], psychological factors such as [[psychological stress|stress]]{{sfn|American Psychiatric Association|2013|p=166}}
| risks         = [[Family history (medicine)|Family history]], major life changes, living alone,<ref name="PMH"/> certain [[medication]]s, [[chronic health problem]]s, [[substance use disorder]]<ref name="NIH2016" />{{sfn|American Psychiatric Association|2013|p=166}}
| diagnosis     =
| differential  = [[Bipolar disorder]], [[ADHD]], [[sadness]]{{sfn|American Psychiatric Association|2013|pp=167–168}}
| prevention    =
| treatment     = [[Psychotherapy]], [[antidepressant medication]], [[electroconvulsive therapy]], [[transcranial magnetic stimulation]], [[exercise]]<ref name="NIH2016" /><ref name="Coo2013">{{cite journal |vauthors=Cooney GM, Dwan K, Greig CA, Lawlor DA, Rimer J, Waugh FR, McMurdo M, Mead GE |title=Exercise for depression |journal=The Cochrane Database of Systematic Reviews |volume=2013 |issue=9 |page=CD004366 |date=September 2013 |pmid=24026850 |doi=10.1002/14651858.CD004366.pub6 |pmc=9721454 | veditors = Mead GE | issn = 1464-780X}}</ref>
| medication    = [[Antidepressant]]s
| prognosis     =
| frequency     = 163 million (2017)<ref name="GBD 2017 prevalence" />
| deaths        =
}}

'''Major depressive disorder''' ('''MDD'''), also known as '''clinical depression''', is a [[mental disorder]]<ref>{{cite web|url=https://www.who.int/classifications/icd/en/bluebook.pdf|title=The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines |vauthors= Sartorius N, Henderson AS, Strotzka H, et al |publisher=[[World Health Organization]]|access-date=23 June 2021 |archive-url=https://web.archive.org/web/20220205002056/https://www.who.int/classifications/icd/en/bluebook.pdf |archive-date=5 February 2022}}</ref> characterized by at least two weeks of pervasive [[depression (mood)|low mood]], low [[self-esteem]], and [[anhedonia|loss of interest or pleasure]] in normally enjoyable activities. Introduced by a group of US clinicians in the mid-1970s,<ref name= Spitzer>{{cite web |vauthors=Spitzer RL, Endicott J, Robins E |year=1976 |url=http://www.garfield.library.upenn.edu/classics1989/A1989U309700001.pdf |title=The development of diagnostic criteria in psychiatry |access-date=8 November 2008 |url-status=live |archive-url=https://web.archive.org/web/20051214203223/http://www.garfield.library.upenn.edu/classics1989/A1989U309700001.pdf |archive-date=14 December 2005 }}</ref> the term was adopted by the [[American Psychiatric Association]] for this [[syndrome|symptom cluster]] under [[mood disorder]]s in the 1980 version of the ''[[Diagnostic and Statistical Manual of Mental Disorders]]'' (DSM-III), and has become widely used since. The disorder causes the second-most [[years lived with disability]], after [[low back pain|lower back pain]].<ref>{{cite journal |author=((Global Burden of Disease Study 2013 Collaborators)) |date=August 2015 |title=Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 |journal=Lancet |volume=386 |issue=9995 |pages=743–800 |doi=10.1016/S0140-6736(15)60692-4 |pmc=4561509 |pmid=26063472}}</ref>

The diagnosis of major depressive disorder is based on the person's reported experiences, behavior reported by family or friends, and a [[mental status examination]].<ref name=Pat2015>{{cite book| vauthors = Patton LL  |title=The ADA Practical Guide to Patients with Medical Conditions|date=2015|publisher=John Wiley & Sons|isbn=978-1-118-92928-5|page=339|edition=2nd |url=https://books.google.com/books?id=OTJiCgAAQBAJ&pg=PA339}}</ref> There is no laboratory test for the disorder, but testing may be done to rule out physical conditions that can cause similar symptoms.<ref name=Pat2015/> The most common time of onset is in a person's 20s,{{sfn|American Psychiatric Association|2013|p=165}}<ref name="Kes2013">{{cite journal |vauthors=Kessler RC, Bromet EJ |year=2013 |title=The epidemiology of depression across cultures |journal=Annual Review of Public Health |volume=34 |pages=119–38 |doi=10.1146/annurev-publhealth-031912-114409 |pmc=4100461 |pmid=23514317 |doi-access=free}}</ref> with females affected about three times as often as males.<ref>{{Cite web |last=World Health Organisation |title=ICD-11 for Mortality and Morbidity Statistics |url=https://icd.who.int/browse/2024-01/mms/en#578635574 |access-date=26 November 2024 |website=International Classification of Diseases, Eleventh Edition}}</ref> The course of the disorder varies widely, from one episode lasting months to a lifelong disorder with recurrent [[major depressive episode]]s.

Those with major depressive disorder are typically treated with [[psychotherapy]] and [[antidepressant medication]].<ref name="NIH2016" /> While a mainstay of treatment, the [[Efficacy#Medicine|clinical efficacy]] of antidepressants is controversial.<ref name="pmid35918097">{{cite journal |vauthors=Stone MB, Yaseen ZS, Miller BJ, Richardville K, Kalaria SN, Kirsch I |title=Response to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration: individual participant data analysis |journal=BMJ |volume=378 |pages=e067606 |date=August 2022 |pmid=35918097 |pmc=9344377 |doi=10.1136/bmj-2021-067606}} "Meta-analyses have shown small mean differences between drug and placebo arms, and the clinical significance of these differences continues to be debated."</ref><ref name="s737">{{cite journal |vauthors= Ormel J, Spinhoven P, de Vries YA, Cramer AO, Siegle GJ, Bockting CL, Hollon SD |title=The antidepressant standoff: why it continues and how to resolve it |journal=Psychological Medicine |volume=50 |issue=2 |date=January 2020 |pmid=31779735 |doi=10.1017/S0033291719003295 |doi-access=free |pages=177–186|hdl=1887/3142545 |hdl-access=free }}</ref><ref name="c363">{{cite book |vauthors= Taylor D, Horowitz M |title=The Maudsley Deprescribing Guidelines – Antidepressants, Benzodiazepines, Gabapentinoids and Z-drugs |publisher=Wiley |date=May 2024 |isbn=978-1-119-82298-1 |doi=10.1002/9781394291052 |page=57}} "The debate around the short‐term efficacy of antidepressants has continued..."</ref><ref name="z830">{{cite journal |vauthors=Hengartner MP, Plöderl M |title=Estimates of the minimal important difference to evaluate the clinical significance of antidepressants in the acute treatment of moderate-to-severe depression |journal=BMJ Evidence-Based Medicine |volume=27 |issue=2 |date=April 2022 |pmid=33593736 |doi=10.1136/bmjebm-2020-111600 |pages=69–73}} "The efficacy of antidepressants in the acute treatment of patients with moderate-to-severe depression remains a controversial issue."</ref> Hospitalization (which may be [[Involuntary commitment|involuntary]]) may be necessary in cases with associated [[self-neglect]] or a significant risk of harm to self or others. [[Electroconvulsive therapy]] (ECT) may be considered if other measures are not effective.<ref name="NIH2016" />

Major depressive disorder is believed to be caused by a combination of [[genetics|genetic]], environmental, and psychological factors,<ref name="NIH2016">{{cite web|title=Depression|url=http://www.nimh.nih.gov/health/topics/depression/index.shtml |publisher=U.S. [[National Institute of Mental Health]] (NIMH)|access-date=31 July 2016|date=May 2016|url-status =live |archive-url= https://web.archive.org/web/20160805065529/http://www.nimh.nih.gov/health/topics/depression/index.shtml |archive-date =5 August 2016}}</ref> with about 40% of the risk being genetic.{{sfn|American Psychiatric Association|2013|p=166}} Risk factors include a [[Family history (medicine)|family history]] of the condition, major life changes, childhood traumas, environmental [[lead exposure]],<ref>Michael J. McFarland, Aaron Reuben, Matt Hauer. Contribution of Childhood Lead Exposure to Psychopathology in the U.S. Population over the Past 75 Years. Journal of Child Psychology and Psychiatry, 2024 DOI: 10.1111/jcpp.14072</ref> certain medications, [[chronic health problem]]s, and [[substance use disorder]]s.<ref name="NIH2016" />{{sfn|American Psychiatric Association|2013|p=166}} It can negatively affect a person's personal life, work life, or education, and cause issues with a person's sleeping habits, eating habits, and general health.<ref name="NIH2016" />{{sfn|American Psychiatric Association|2013|p=166}}
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==Signs and symptoms==
{{See also|Digital media use and mental health#Depression}}
[[File:A woman diagnosed as suffering from melancholia. Colour lith Wellcome L0026686.jpg|thumb|An 1892 [[lithograph]] of a woman diagnosed with [[melancholia]]]]
A person having a [[major depressive episode]] usually exhibits a [[Depression (mood)|low mood]], which pervades all aspects of [[Everyday life|life]], and an inability to experience [[pleasure]] in previously enjoyable activities.<ref name="g379">{{cite book | last1=MacKinnon | first1=Dean F. | last2=Chen | first2=Lisa N. | title=Tasman's Psychiatry | chapter=Depressive Disorders | publisher=Springer International Publishing | publication-place=Cham | date=2024 | isbn=978-3-030-51365-8 | doi=10.1007/978-3-030-51366-5_20 | pages=1823–1880}}</ref> Depressed people may be preoccupied with or [[Rumination (psychology)|ruminate]] over thoughts and feelings of worthlessness, inappropriate [[Guilt (emotion)|guilt]] or [[regret]], helplessness or hopelessness.{{sfn|American_Psychiatric_Association|2013|p=161}}

Other symptoms of depression include poor concentration and [[memory]],<ref>{{Cite journal | vauthors = Everaert J, Vrijsen JN, Martin-Willett R, van de Kraats L, Joormann J |date=2022 |title=A meta-analytic review of the relationship between explicit memory bias and depression: Depression features an explicit memory bias that persists beyond a depressive episode. |journal=Psychological Bulletin |language=en |volume=148 |issue=5–6 |pages=435–463 |doi=10.1037/bul0000367 |s2cid=253306482 |issn=1939-1455|doi-access=free }}</ref> [[Social withdrawal|withdrawal from social situations]] and activities, reduced [[libido|sex drive]], [[irritability]], and [[Suicidal ideation|thoughts of death or suicide]]. [[Insomnia]] is common; in the typical pattern, a person wakes very early and cannot get back to sleep. [[Hypersomnia]], or oversleeping, can also happen,{{sfn|American Psychiatric Association|2013|p=163}} as well as day-night rhythm disturbances, such as [[diurnal mood variation]].<ref>{{cite journal | vauthors = Murray G | title = Diurnal mood variation in depression: a signal of disturbed circadian function? | journal = Journal of Affective Disorders | volume = 102 | issue = 1–3 | pages = 47–53 | date = September 2007 | pmid = 17239958 | doi = 10.1016/j.jad.2006.12.001 }}</ref><!-- cites 3 previous sentences --> Some antidepressants may also cause insomnia due to their [[Stimulant|stimulating effect]].<ref name="v526">{{cite journal |last1=Wichniak |first1=Adam |last2=Wierzbicka |first2=Aleksandra |last3=Walęcka |first3=Małgorzata |last4=Jernajczyk |first4=Wojciech |title=Effects of Antidepressants on Sleep |journal=Current Psychiatry Reports |volume=19 |issue=9 |date=2017 |issn=1523-3812 |pmid=28791566 |pmc=5548844 |doi=10.1007/s11920-017-0816-4 |doi-access=free |url=https://link.springer.com/content/pdf/10.1007%2Fs11920-017-0816-4.pdf |access-date=26 February 2025 |page=63}}</ref> In severe cases, depressed people may have [[psychosis|psychotic]] symptoms. These symptoms include [[delusion]]s or, less commonly, [[hallucination]]s, usually unpleasant.<ref>{{Harvnb |American Psychiatric Association|2000a|p=412}}</ref> People who have had previous episodes with psychotic symptoms are more likely to have them with future episodes.<ref>{{cite journal | vauthors = Nelson JC, Bickford D, Delucchi K, Fiedorowicz JG, Coryell WH | title = Risk of Psychosis in Recurrent Episodes of Psychotic and Nonpsychotic Major Depressive Disorder: A Systematic Review and Meta-Analysis | journal = The American Journal of Psychiatry | volume = 175 | issue = 9 | pages = 897–904 | date = September 2018 | pmid = 29792050 | doi = 10.1176/appi.ajp.2018.17101138 | s2cid = 43951278 | doi-access = free }}</ref>

{{Anchor|physicalSymptoms}}A depressed person may report multiple physical symptoms such as [[fatigue]], [[headache]]s, or [[Human digestive system|digestive]] problems; physical complaints are the most common presenting problem in developing countries, according to the [[World Health Organization]]'s criteria for depression.<ref>{{cite journal |vauthors=Fisher JC, Powers WE, Tuerk DB, Edgerton MT |title=Development of a plastic surgical teaching service in a women's correctional institution |journal=American Journal of Surgery |volume=129 |issue=3 |pages=269–72 |date=March 1975 |pmc=1119689 |doi=10.1136/bmj.322.7284.482 |pmid=11222428}}</ref> [[Appetite]] often [[Anorexia (symptom)|decreases]], resulting in [[weight loss]], although [[Polyphagia|increased appetite]] and [[weight gain]] occasionally occur.<ref name="b502" />

Major depression significantly affects a person's family and [[Social predictors of depression|personal relationships]], [[Employment|work]] or [[school]] life, [[sleep]]ing and [[Dieting|eating habits]], and general health.<ref name=NIMHPub>{{cite book|title=Depression |publisher=[[National Institute of Mental Health]] (NIMH) |url=https://www.nimh.nih.gov/sites/default/files/documents/health/publications/depression/21-mh-8079-depression_0.pdf |archive-url=https://web.archive.org/web/20210828103258/https://www.nimh.nih.gov/sites/default/files/documents/health/publications/depression/21-mh-8079-depression_0.pdf |archive-date=28 August 2021 |url-status=live |access-date=13 October 2021}}</ref> Family and friends may notice [[psychomotor agitation|agitation]] or [[psychomotor retardation|lethargy]].{{sfn|American Psychiatric Association|2013|p=163}} Older depressed people may have [[Cognition#Psychology|cognitive]] symptoms of recent onset, such as [[Forgetting|forgetfulness]],<ref>{{cite journal |vauthors=Delgado PL, Schillerstrom J |title=Cognitive Difficulties Associated With Depression: What Are the Implications for Treatment? |journal=Psychiatric Times |volume=26 |issue=3 |year=2009 |url=http://www.psychiatrictimes.com/display/article/10168/1387631 |url-status=live |archive-url=https://web.archive.org/web/20090722165650/http://www.psychiatrictimes.com/display/article/10168/1387631 |archive-date=22 July 2009}}</ref> and a more noticeable slowing of movements.<ref>{{cite book |title=Consensus Guidelines for Assessment and Management of Depression in the Elderly | vauthors = ((Faculty of Psychiatry of Old Age, NSW Branch, RANZCP)), Kitching D, Raphael B |year=2001 |publisher=NSW Health Department |location=North Sydney, New South Wales |isbn=978-0-7347-3341-2 |page=2 |url=http://www.health.nsw.gov.au/mhdao/publications/Publications/depression-elderly.pdf |url-status=live |archive-url=https://web.archive.org/web/20150401162939/http://www.health.nsw.gov.au/mhdao/publications/Publications/depression-elderly.pdf |archive-date=1 April 2015 }}</ref>

[[Depression in childhood and adolescence|Depressed children]] may often display an irritable rather than a depressed [[Mood (psychology)|mood]];{{sfn|American Psychiatric Association|2013|p=163}} most lose interest in school and show a steep decline in [[Academic achievement|academic performance]].{{sfn|American Psychiatric Association|2013|p=164}} Diagnosis may be delayed or missed when symptoms are interpreted as "normal moodiness".<ref name=APA349>{{Harvnb |American Psychiatric Association|2000a|p=349}}</ref> [[Old age|Elderly people]] may not present with classical depressive symptoms.<ref name="SBU" /> [[Management of depression|Diagnosis and treatment]] is further complicated in that the elderly are often simultaneously treated with a number of other drugs, and often have other concurrent diseases.<ref name="SBU" />

==Cause==
{{further|Biology of depression|Epigenetics of depression}}
[[File:Diathesis_stress_model_cup_analogy.svg|thumb|A cup analogy demonstrating the [[diathesis–stress model]] that under the same amount of stressors, person 2 is more vulnerable than person 1, because of their predisposition<ref>{{cite book | vauthors = Hankin BL, Abela JR |title=Development of Psychopathology: A Vulnerability-Stress Perspective |date=2005 |publisher=SAGE Publications |isbn=978-1-4129-0490-2 |pages=32–34 |url=https://books.google.com/books?id=1Fd0LneB724C&pg=PR7 |language=en}}</ref>]]
The [[etiology]] of depression is not yet fully understood.<ref>{{cite journal | vauthors = Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, Mohr DC, Schatzberg AF | title = Major depressive disorder | journal = Nature Reviews. Disease Primers | volume = 2 | issue = 1 | page = 16065 | date = September 2016 | pmid = 27629598 | doi = 10.1038/nrdp.2016.65 | publisher = [[Springer Nature]] | quote = Despite advances in our understanding of the neuro-biology of MDD, no established mechanism can explain all aspects of the disease. | s2cid = 4047310 | url = https://kclpure.kcl.ac.uk/ws/files/57263080/Major_Deppressive_Disorder_.pdf | publication-date = 15 September 2016 }}</ref><ref>{{Cite book | vauthors = Boland RJ, Verduin ML |title=Kaplan & Sadock's concise textbook of clinical psychiatry  |date=14 March 2022 |publisher=[[Wolters Kluwer]] |isbn=978-1-9751-6748-6 |edition=5th |location=Philadelphia |language=en |oclc=1264172789 |quote=Although there is no single unifying theory, several theories have emerged over the last century that attempt to account for the various clinical, psychological, and biologic findings in depression.}}</ref><ref>{{Cite book | vauthors = Sontheimer H |title=Diseases of the nervous system |date=20 May 2021 |publisher=[[Elsevier]] |isbn=978-0-12-821396-4 |edition=2nd |page=286 |language=en |oclc=1260160457 |quote=A number of risk factors for depression are known or suspected, but only in rare cases is the link to disease strong.}}</ref> The [[biopsychosocial model]] proposes that biological, psychological, and social factors all play a role in causing depression.{{sfn|American Psychiatric Association|2013|p=166}}<ref>{{cite web |author=Department of Health and Human Services |year=1999 |url=http://www.surgeongeneral.gov/library/mentalhealth/pdfs/c2.pdf |title=The fundamentals of mental health and mental illness |website=Mental Health: A Report of the Surgeon General |access-date=11 November 2008 |url-status=live |archive-url=https://web.archive.org/web/20081217031913/http://www.surgeongeneral.gov/library/mentalhealth/pdfs/c2.pdf |archive-date=17 December 2008 }}</ref> The [[diathesis–stress model]] specifies that depression results when a preexisting vulnerability, or [[Diathesis (medicine)|diathesis]], is activated by stressful life events. The preexisting vulnerability can be either [[gene]]tic,<ref>{{cite journal | vauthors = Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R | title = Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene | journal = Science | volume = 301 | issue = 5631 | pages = 386–389 | date = July 2003 | pmid = 12869766 | doi = 10.1126/science.1083968 | s2cid = 146500484 | bibcode = 2003Sci...301..386C }}</ref><ref>{{cite journal | vauthors = Haeffel GJ, Getchell M, Koposov RA, Yrigollen CM, Deyoung CG, Klinteberg BA, Oreland L, Ruchkin VV, Grigorenko EL | title = Association between polymorphisms in the dopamine transporter gene and depression: evidence for a gene-environment interaction in a sample of juvenile detainees | journal = Psychological Science | volume = 19 | issue = 1 | pages = 62–69 | date = January 2008 | pmid = 18181793 | doi = 10.1111/j.1467-9280.2008.02047.x | url = http://www.nd.edu/~ghaeffel/Resources/Haeffel%20et%20al.,%202008.pdf | url-status = live | s2cid = 15520723 | archive-url = https://web.archive.org/web/20081217031910/http://www.nd.edu/~ghaeffel/Resources/Haeffel%20et%20al.%2C%202008.pdf | archive-date = 17 December 2008 }}</ref> implying an interaction between [[nature and nurture]], or [[Schema (psychology)|schematic]], resulting from views of the world learned in childhood.<ref>{{cite web | vauthors = Slavich GM |year=2004 |url=http://www.psychologicalscience.org/observer/getArticle.cfm?id=1640 |title=Deconstructing depression: A diathesis-stress perspective (Opinion) |website=APS Observer |access-date=11 November 2008 |url-status=live |archive-url=https://web.archive.org/web/20110511233644/http://www.psychologicalscience.org/observer/getArticle.cfm?id=1640 |archive-date=11 May 2011 }}</ref> American psychiatrist [[Aaron Beck]] suggested that a [[Beck's cognitive triad|triad]] of automatic and spontaneous negative thoughts about the [[Self-image|self]], the [[Social environment|world or environment]], and the future may lead to other depressive signs and symptoms.<ref name=Beck>{{cite book |vauthors=Beck AT, Rush AJ, Shaw BF, Emery G |title=Cognitive therapy of depression |year=1979|publication-place=New York|publisher=The Guilford Press|isbn=0-89862-000-7|pages=11–12 |url=https://books.google.com/books?id=L09cRS0xWj0C |access-date=26 February 2022}}</ref><ref>{{cite journal | vauthors = Nieto I, Robles E, Vazquez C | title = Self-reported cognitive biases in depression: A meta-analysis | journal = Clinical Psychology Review | volume = 82 | page = 101934 | date = December 2020 | pmid = 33137610 | doi = 10.1016/j.cpr.2020.101934 | s2cid = 226243519 }}</ref>

===Genetics===
Genes play a major role in the development of depression.<ref>{{Cite book | vauthors = Do MC, Weersing VR |title=The SAGE encyclopedia of abnormal and clinical psychology  |date=3 April 2017 |publisher=[[SAGE Publishing]] |isbn=978-1-4833-6582-4 | veditors = Wenzel A |location=Thousand Oaks, California |page=1014 |doi=10.4135/9781483365817 |oclc=982958263 |quote=Depression is highly heritable, as youths with a parent with a history of depression are approximately 4 times as likely to develop the disorder as youths who do not have a parent with depression.}}</ref> [[Behavioural genetics|Family and twin studies]] suggest that genetic factors account for nearly 40% of the variation in risk for major depressive disorder. Like most psychiatric disorders, major depression is likely shaped by a combination of many individual genetic influences.<ref name="h988">{{cite journal | last1=Cui | first1=Lulu | last2=Li | first2=Shu | last3=Wang | first3=Siman | last4=Wu | first4=Xiafang | last5=Liu | first5=Yingyu | last6=Yu | first6=Weiyang | last7=Wang | first7=Yijun | last8=Tang | first8=Yong | last9=Xia | first9=Maosheng | last10=Li | first10=Baoman | title=Major depressive disorder: hypothesis, mechanism, prevention and treatment | journal=Signal Transduction and Targeted Therapy | publisher=Springer Science and Business Media LLC | volume=9 | issue=1 | date=9 February 2024 | issn=2059-3635 | doi=10.1038/s41392-024-01738-y | doi-access=free | url=https://www.nature.com/articles/s41392-024-01738-y.pdf | access-date=17 March 2025 | page=30| pmid=38331979 | pmc=10853571 }}</ref> In 2018, a [[genome-wide association study]] discovered 44 genetic variants linked to risk for major depression;<ref>{{cite journal | vauthors = Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, etal | title = Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression | journal = Nature Genetics | volume = 50 | issue = 5 | pages = 668–681 | date = May 2018 | pmid = 29700475 | pmc = 5934326 | doi = 10.1038/s41588-018-0090-3 | hdl = 11370/3a0e2468-99e7-40c3-80f4-9d25adfae485 }}</ref> a 2019 study found 102 variants in the genome linked to depression.<ref>{{cite journal | vauthors = Howard DM, Adams MJ, Clarke TK, Hafferty JD, Gibson J, Shirali M, Coleman JR, Hagenaars SP, Ward J, Wigmore EM, Alloza C, Shen X, Barbu MC, Xu EY, Whalley HC, Marioni RE, Porteous DJ, Davies G, Deary IJ, Hemani G, Berger K, Teismann H, Rawal R, Arolt V, Baune BT, Dannlowski U, Domschke K, Tian C, Hinds DA, Trzaskowski M, Byrne EM, Ripke S, Smith DJ, Sullivan PF, Wray NR, Breen G, Lewis CM, McIntosh AM | title = Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions | journal = Nature Neuroscience | volume = 22 | issue = 3 | pages = 343–352 | date = March 2019 | pmid = 30718901 | pmc = 6522363 | doi = 10.1038/s41593-018-0326-7 }}</ref> However, it appears that major depression is less heritable compared to bipolar disorder and schizophrenia.<ref>{{cite book | last1=Oraki Kohshour | first1=Mojtaba | last2=Strom | first2=Nora I. | last3=Meier | first3=Sandra Melanie | last4=McMahon | first4=Francis J. | last5=Merikangas | first5=Kathleen R. | last6=Schulze | first6=Thomas G. | last7=Mattheisen | first7=Manuel | title=Tasman's Psychiatry | chapter=Genetics of Psychiatric Disorders: Advances in Genetic Epidemiology and Genomic Approaches | publisher=Springer International Publishing | publication-place=Cham | date=2024 | isbn=978-3-030-51365-8 | doi=10.1007/978-3-030-51366-5_51 | pages=485–510}}</ref><ref>{{Cite book | vauthors = Jorde LB, Carey JC, Bamshad MJ |title=Medical genetics |date=27 September 2019 |publisher=[[Elsevier]] |isbn=978-0-323-59653-4 |edition=6th |location=Philadelphia |page=247 |language=en |oclc=1138027525 |quote=Thus it appears that bipolar disorder is more strongly influenced by genetic factors than is major depressive disorder.}}</ref> Research focusing on specific candidate genes has been criticized for its tendency to generate false positive findings.<ref name="r473">{{cite journal | last1=McIntosh | first1=Andrew M. | last2=Sullivan | first2=Patrick F. | last3=Lewis | first3=Cathryn M. | title=Uncovering the Genetic Architecture of Major Depression | journal=Neuron | volume=102 | issue=1 | date=2019 | pmid=30946830 | pmc=6482287 | doi=10.1016/j.neuron.2019.03.022 | doi-access=free | pages=91–103 | url=http://www.cell.com/article/S0896627319302855/pdf | access-date=17 March 2025}}</ref> There are also other efforts to examine interactions between life stress and polygenic risk for depression.<ref>{{cite journal | vauthors = Peyrot WJ, Van der Auwera S, Milaneschi Y, Dolan CV, Madden PA, Sullivan PF, Strohmaier J, Ripke S, Rietschel M, Nivard MG, Mullins N, Montgomery GW, Henders AK, Heat AC, Fisher HL, Dunn EC, Byrne EM, Air TA, Baune BT, Breen G, Levinson DF, Lewis CM, Martin NG, Nelson EN, Boomsma DI, Grabe HJ, Wray NR, Penninx BW | title = Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium | journal = Biological Psychiatry | volume = 84 | issue = 2 | pages = 138–147 | date = July 2018 | pmid = 29129318 | pmc = 5862738 | doi = 10.1016/j.biopsych.2017.09.009}}</ref>

===Other health problems===
Depression can also arise after a chronic or terminal medical condition, such as [[HIV/AIDS]] or [[asthma]], and may be labeled "secondary depression".<ref>{{cite journal |vauthors=Simon GE |title=Treating depression in patients with chronic disease: recognition and treatment are crucial; depression worsens the course of a chronic illness |journal=The Western Journal of Medicine |volume=175 |issue=5 |pages=292–93 |date=November 2001 |pmid=11694462 |pmc=1071593 |doi=10.1136/ewjm.175.5.292}}</ref><ref>{{cite journal|author1-link=Paula Clayton |vauthors=Clayton PJ, Lewis CE |title=The significance of secondary depression |journal=Journal of Affective Disorders |volume=3 |issue=1 |pages=25–35 |date=March 1981 |pmid=6455456 |doi=10.1016/0165-0327(81)90016-1 }}</ref> It is unknown whether the underlying diseases induce depression through effect on quality of life, or through shared etiologies (such as degeneration of the [[basal ganglia]] in [[Parkinson's disease]] or immune dysregulation in asthma).<ref>{{cite journal |vauthors=Kewalramani A, Bollinger ME, Postolache TT |title=Asthma and Mood Disorders |journal=International Journal of Child Health and Human Development |volume=1 |issue=2 |pages=115–23 |date=1 January 2008 |pmid=19180246 |pmc=2631932 }}</ref> Depression may also be [[iatrogenic]] (the result of healthcare), such as drug-induced depression. Therapies associated with depression include [[interferon]]s, [[beta blocker]]s,<ref name="e058">{{cite journal | last1=Qato | first1=Dima Mazen | last2=Ozenberger | first2=Katharine | last3=Olfson | first3=Mark | title=Prevalence of Prescription Medications With Depression as a Potential Adverse Effect Among Adults in the United States | journal=JAMA | volume=319 | issue=22 | date=12 June 2018 | pages=2289–2298 | issn=0098-7484 | pmid=29896627 | pmc=6583503 | doi=10.1001/jama.2018.6741 | doi-access=free | url=https://jamanetwork.com/journals/jama/articlepdf/2684607/jama_qato_2018_oi_180056.pdf | access-date=21 March 2025}}</ref> [[isotretinoin]],<ref name="w764">{{cite journal | last=Bremner | first=J. Douglas | title=Isotretinoin and neuropsychiatric side effects: Continued vigilance is needed | journal=Journal of Affective Disorders Reports | volume=6 | date=2021 | pmid=37168254 | pmc=10168661 | doi=10.1016/j.jadr.2021.100230 | doi-access=free | page=100230}}</ref> [[contraceptives]],<ref name="e058"/> cardiac agents,<ref name="r630">{{cite journal | last1=Zhang | first1=Lijun | last2=Bao | first2=Yanping | last3=Tao | first3=Shuhui | last4=Zhao | first4=Yimiao | last5=Liu | first5=Meiyan | title=The association between cardiovascular drugs and depression/anxiety in patients with cardiovascular disease: A meta-analysis | journal=Pharmacological Research | volume=175 | date=2022 | doi=10.1016/j.phrs.2021.106024 | doi-access=free | page=106024| pmid=34890773 }}</ref> [[anticonvulsant]]s,<ref name="j396">{{cite book | last=de Araujo Filho | first=Gerardo Maria | title=Psychiatric and Behavioral Aspects of Epilepsy | chapter=Can We Anticipate and Prevent the Occurrence of Iatrogenic Psychiatric Events Caused by Anti-seizure Medications and Epilepsy Surgery? | series=Current Topics in Behavioral Neurosciences | publisher=Springer International Publishing | publication-place=Cham | volume=55 | date=2021 | isbn=978-3-031-03222-6 | doi=10.1007/7854_2021_228 | pages=281–305| pmid=33860467 }}</ref> and [[Hormone therapy|hormonal agents]].<ref name="m323">{{cite journal | last1=Wium-Andersen | first1=Marie K. | last2=Jørgensen | first2=Terese S. H. | last3=Halvorsen | first3=Anniken H. | last4=Hartsteen | first4=Birgitte H. | last5=Jørgensen | first5=Martin B. | last6=Osler | first6=Merete | title=Association of Hormone Therapy With Depression During Menopause in a Cohort of Danish Women | journal=JAMA Network Open | volume=5 | issue=11 | date=1 November 2022 | issn=2574-3805 | pmid=36318208 | pmc=9627415 | doi=10.1001/jamanetworkopen.2022.39491 | doi-access=free | page=e2239491 | url=https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2798003/wiumandersen_2022_oi_221117_1666637052.78827.pdf | access-date=21 March 2025}}</ref> [[Celiac disease]] is another possible contributing factor.<ref name="a192">{{cite journal | last1=Mikulska | first1=Joanna | last2=Pietrzak | first2=Diana | last3=Rękawek | first3=Paweł | last4=Siudaj | first4=Krystian | last5=Walczak-Nowicka | first5=Łucja Justyna | last6=Herbet | first6=Mariola | title=Celiac disease and depressive disorders as nutritional implications related to common factors – A comprehensive review | journal=Behavioural Brain Research | volume=462 | date=2024 | doi=10.1016/j.bbr.2024.114886 | page=114886| pmid=38309373 }}</ref>

Substance use in early age is associated with increased risk of developing depression later in life.<ref>{{cite journal | vauthors = Brook DW, Brook JS, Zhang C, Cohen P, Whiteman M | title = Drug use and the risk of major depressive disorder, alcohol dependence, and substance use disorders | journal = Archives of General Psychiatry | volume = 59 | issue = 11 | pages = 1039–44 | date = November 2002 | pmid = 12418937 | doi = 10.1001/archpsyc.59.11.1039 | doi-access = free }}</ref> Depression occurring after giving birth is called [[postpartum depression]] and is thought to be the result of hormonal changes associated with [[pregnancy]].<ref>{{cite journal |vauthors=Meltzer-Brody S |title=New insights into perinatal depression: pathogenesis and treatment during pregnancy and postpartum |journal=Dialogues in Clinical Neuroscience |volume=13 |issue=1 |pages=89–100 |date=9 January 2017 |doi=10.31887/DCNS.2011.13.1/smbrody |pmid=21485749 |pmc=3181972 }}</ref> [[Seasonal affective disorder]], a type of depression associated with seasonal changes in sunlight, is thought to be triggered by decreased sunlight.<ref name="x376">{{cite book | last1=Roecklein | first1=Kathryn A. | last2=Wong | first2=Patricia M. | title=Encyclopedia of Behavioral Medicine | chapter=Seasonal Affective Disorder | publisher=Springer International Publishing | publication-place=Cham | date=2020 | isbn=978-3-030-39901-6 | doi=10.1007/978-3-030-39903-0_836 | pages=1964–1966}}</ref>
Vitamin B<sub>2</sub>, B<sub>6</sub> and B<sub>12</sub> deficiency may cause depression in females.<ref>{{cite journal |vauthors= Wu Y, Zhang L, Li S, Zhang D | title=Associations of dietary vitamin B1, vitamin B2, vitamin B6, and vitamin B12 with the risk of depression: a systematic review and meta-analysis | journal=Nutrition Reviews | publisher=Oxford University Press (OUP) | date=29 April 2021 | volume=80 | issue=3 | pages=351–366 | issn=0029-6643 | doi=10.1093/nutrit/nuab014 | pmid=33912967 }}</ref>

A 2025 study found that, among more than 172,500 adults in the [[United Kingdom|UK]] aged 39 and older, those with a history of depression experienced the onset of [[chronic illnesses]] approximately 30% earlier than those without depression.<ref>{{Cite journal |last1=Fleetwood |first1=Kelly J. |last2=Guthrie |first2=Bruce |last3=Jackson |first3=Caroline A. |last4=Kelly |first4=Paul A. T. |last5=Mercer |first5=Stewart W. |last6=Morales |first6=Daniel R. |last7=Norrie |first7=John D. |last8=Smith |first8=Daniel J. |last9=Sudlow |first9=Cathie |last10=Prigge |first10=Regina |date=13 February 2025 |title=Depression and physical multimorbidity: A cohort study of physical health condition accrual in UK Biobank |journal=PLOS Medicine |language=en |volume=22 |issue=2 |pages=e1004532 |doi=10.1371/journal.pmed.1004532 |doi-access=free |issn=1549-1676 |pmc=11825000 |pmid=39946376}}</ref>

===Environmental===
[[Adverse childhood experiences]] (incorporating [[Child abuse|childhood abuse]], neglect and [[Dysfunctional family|family dysfunction]]) markedly increase the risk of major depression, especially if more than one type.<ref name="e625">{{cite book | last1=Luyten | first1=Patrick | last2=Fonagy | first2=Peter | title=Etiopathogenic Theories and Models in Depression | chapter=An Integrative Developmental Psychopathology Approach to Depression | publisher=Springer International Publishing | publication-place=Cham | date=2021 | isbn=978-3-030-77328-1 | doi=10.1007/978-3-030-77329-8_13 | pages=245–263}}</ref> Childhood trauma also correlates with severity of depression, poor responsiveness to treatment and length of illness.<ref name="r126">{{cite journal | last1=Lippard | first1=Elizabeth T.C. | last2=Nemeroff | first2=Charles B. | title=The Devastating Clinical Consequences of Child Abuse and Neglect: Increased Disease Vulnerability and Poor Treatment Response in Mood Disorders | journal=American Journal of Psychiatry | volume=177 | issue=1 | date=1 January 2020 | issn=0002-953X | pmid=31537091 | pmc=6939135 | doi=10.1176/appi.ajp.2019.19010020 | doi-access=free | pages=20–36 }}</ref> Some are more susceptible than others to developing mental illness such as depression after trauma, and various genes have been suggested to control susceptibility.<ref name="n391">{{cite journal | last1=Li | first1=Muzi | last2=Liu | first2=Sibei | last3=D'Arcy | first3=Carl | last4=Gao | first4=Tingting | last5=Meng | first5=Xiangfei | title=Interactions of childhood maltreatment and genetic variations in adult depression: A systematic review | journal=Journal of Affective Disorders | volume=276 | date=2020 | doi=10.1016/j.jad.2020.06.055 | doi-access=free | pages=119–136 | pmid=32697690 | url=http://escholarship.mcgill.ca/downloads/dr26z282p | access-date=21 March 2025}}</ref>  Couples in unhappy marriages have a higher risk of developing clinical depression.<ref>{{cite journal |vauthors= Goldfarb MR, Trudel G |date= 6 May 2019|title= Marital quality and depression: a review |journal= Marriage & Family Review |publisher= Routledge: Taylor & Francis Group|volume= 55 |issue= 8 |pages= 737–763 |doi= 10.1080/01494929.2019.1610136 |s2cid= 165116052}} Citing among others: {{cite journal |vauthors=Weissman MM |title=Advances in psychiatric epidemiology: rates and risks for major depression |journal=Am J Public Health |volume=77 |issue=4 |pages=445–51 |date=April 1987 |pmid=3826462 |pmc=1646931 |doi=10.2105/ajph.77.4.445 }}</ref>

There appears to be a link between [[air pollution]] and depression and suicide. There may be an association between long-term [[PM2.5]] exposure and depression, and a possible association between short-term [[PM10]] exposure and suicide.<ref name="pmid31850801">{{cite journal | vauthors = Braithwaite I, Zhang S, Kirkbride JB, Osborn DP, Hayes JF | title = Air Pollution (Particulate Matter) Exposure and Associations with Depression, Anxiety, Bipolar, Psychosis and Suicide Risk: A Systematic Review and Meta-Analysis | journal = Environmental Health Perspectives | volume = 127 | issue = 12 | page = 126002 | date = December 2019 | pmid = 31850801 | pmc = 6957283 | doi = 10.1289/EHP4595 | bibcode = 2019EnvHP.127l6002B }}</ref>

Living alone has been found to increase the risk of depression by 42%.<ref name="PMH">{{cite journal |doi= 10.3389/fpsyt.2022.954857 |doi-access= free |pmid= 36111305 |pmc= 9468273 |title= Assessment of the relationship between living alone and the risk of depression based on longitudinal studies: A systematic review and meta-analysis |date= 2022 |last1= Wu |first1= Daolin |last2= Liu |first2= Fuwei |last3= Huang |first3= Shan |journal= Frontiers in Psychiatry |volume= 13 }}</ref>

==Pathophysiology==
{{further|Biology of depression|Epigenetics of depression}}
The pathophysiology of depression is not completely understood, but current theories center around [[monoamine]]rgic systems, the [[circadian rhythm]], immunological dysfunction, [[HPA axis|HPA-axis]] dysfunction, and structural or functional abnormalities of emotional circuits.

Derived from the effectiveness of monoaminergic drugs in treating depression, the monoamine theory posits that insufficient activity of [[monoamine neurotransmitter]]s is the primary cause of depression. Evidence for the monoamine theory comes from multiple areas. First, acute depletion of [[tryptophan]]—a necessary precursor of [[serotonin]] and a monoamine—can cause depression in those in remission or relatives of people who are depressed, suggesting that decreased serotonergic neurotransmission is important in depression.<ref name="g648">{{cite book | last=Silva | first=Hernán | title=Etiopathogenic Theories and Models in Depression | chapter=Neurobiology of Depression | series=Depression and Personality | publisher=Springer International Publishing | publication-place=Cham | date=2021 | isbn=978-3-030-77328-1 | doi=10.1007/978-3-030-77329-8_8 | pages=155–166}}</ref> Second, the correlation between depression risk and polymorphisms in the [[5-HTTLPR]] gene, which codes for serotonin receptors, suggests a link.<ref name="t044">{{cite book | last1=Manchia | first1=Mirko | last2=Schatzberg | first2=Alan | title=Tasman's Psychiatry | chapter=Neurobiology of Mood Disorders | publisher=Springer International Publishing | publication-place=Cham | date=2024 | isbn=978-3-030-51365-8 | doi=10.1007/978-3-030-51366-5_83 | pages=651–682}}</ref> Third, decreased size of the [[locus coeruleus]], reduced activity of [[tyrosine hydroxylase]], increased density of [[alpha-2 adrenergic receptor]], and evidence from rat models suggest decreased [[Adrenergic nervous system|adrenergic]] neurotransmission in depression.<ref>{{cite journal |vauthors=Delgado PL, Moreno FA |title=Role of norepinephrine in depression |journal=The Journal of Clinical Psychiatry |volume=61 |issue=Suppl 1 |pages=5–12 |year=2000 |pmid=10703757 }}</ref> Furthermore, decreased levels of [[homovanillic acid]], altered response to [[dextroamphetamine]], responses of depressive symptoms to [[dopamine receptor]] agonists, decreased [[dopamine receptor D1|dopamine receptor D<sub>1</sub>]] binding in the [[striatum]],<ref>{{cite journal |vauthors=Savitz JB, Drevets WC |title=Neuroreceptor imaging in depression |journal=Neurobiology of Disease |volume=52 |pages=49–65 |date=April 2013 |pmid=22691454 |doi=10.1016/j.nbd.2012.06.001 |doi-access=free }}</ref> and [[Polymorphism (biology)|polymorphism]] of [[dopamine receptor]] genes implicate [[dopamine]], another monoamine, in depression.<ref>{{cite journal |vauthors=Hasler G |title=Pathophysiology of depression: do we have any solid evidence of interest to clinicians? |journal=World Psychiatry |volume=9 |issue=3 |pages=155–61 |date=October 2010 |pmid=20975857 |pmc=2950973 |doi=10.1002/j.2051-5545.2010.tb00298.x}}</ref><ref>{{cite journal |vauthors=Dunlop BW, Nemeroff CB |title=The role of dopamine in the pathophysiology of depression |journal=Archives of General Psychiatry |volume=64 |issue=3 |pages=327–37 |date=March 2007 |pmid=17339521 |doi=10.1001/archpsyc.64.3.327 |s2cid=26550661 |url=https://www.researchgate.net/publication/6466257}}</ref> Lastly, increased activity of [[monoamine oxidase]], which degrades monoamines, has been associated with depression.<ref>{{cite journal |vauthors=Meyer JH, Ginovart N, Boovariwala A, et al |title=Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression |journal=Archives of General Psychiatry |volume=63 |issue=11 |pages=1209–16 |date=November 2006 |pmid=17088501 |doi=10.1001/archpsyc.63.11.1209|doi-access=free }}</ref> However, the monoamine theory is inconsistent with observations that serotonin depletion does not cause depression in healthy persons, that antidepressants instantly increase levels of monoamines but take weeks to work, and the existence of atypical antidepressants which can be effective despite not targeting this pathway.<ref>{{cite book | veditors = Davis KL, Charney D, Coyle JT, Nemeroff C |title= Neuropsychopharmacology: the fifth generation of progress: an official publication of the American College of Neuropsychopharmacology|date=2002|publisher=Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-2837-9|pages=1139–63|edition=5th}}</ref>

One proposed explanation for the therapeutic lag, and further support for the deficiency of monoamines, is a desensitization of self-inhibition in [[raphe nuclei]] by the increased serotonin mediated by antidepressants.<ref>{{cite journal |vauthors=Adell A |title=Revisiting the role of raphe and serotonin in neuropsychiatric disorders |journal=The Journal of General Physiology |volume=145 |issue=4 |pages=257–59 |date=April 2015 |pmid=25825168 |doi=10.1085/jgp.201511389 |pmc=4380212}}</ref> However, disinhibition of the dorsal raphe has been proposed to occur as a result of decreased serotonergic activity in tryptophan depletion, resulting in a depressed state mediated by increased serotonin. Further countering the monoamine hypothesis is the fact that rats with lesions of the dorsal raphe are not more depressive than controls; the finding of increased jugular [[5-Hydroxyindoleacetic acid|5-HIAA]] in people who are depressed that normalized with [[selective serotonin reuptake inhibitor]] (SSRI) treatment, and the preference for [[carbohydrate]]s in people who are depressed.<ref>{{cite journal |vauthors=Andrews PW, Bharwani A, Lee KR, Fox M, Thomson JA |title=Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response |journal=Neuroscience and Biobehavioral Reviews |volume=51 |pages=164–88 |date=April 2015 |pmid=25625874 |doi=10.1016/j.neubiorev.2015.01.018 |s2cid=23980182 }}</ref> Already limited, the monoamine hypothesis has been further oversimplified when presented to the general public.<ref>{{cite journal |vauthors=Lacasse JR, Leo J |title=Serotonin and depression: a disconnect between the advertisements and the scientific literature |journal=PLOS Medicine |volume=2 |issue=12 |page=e392 |date=December 2005 |pmid=16268734 |pmc=1277931 |doi=10.1371/journal.pmed.0020392 |doi-access=free }}</ref> A 2022 review found no consistent evidence supporting the serotonin hypothesis linking serotonin levels and depression.<ref>{{cite journal |journal= Mol Psychiatry |date= July 2022 |title= The serotonin theory of depression: a systematic umbrella review of the evidence |vauthors= Moncrieff J, Cooper RE, Stockman T, et al |volume= 28 |issue= 8 |pages= 3243–3256 |pmid=35854107 |doi=10.1038/s41380-022-01661-0|pmc= 10618090 |s2cid= 250646781 |doi-access= free }} Lay source [https://medicalxpress.com/news/2022-07-evidence-depression-serotonin-comprehensive.html Medicalxpress]</ref>

[[HPA axis|HPA-axis]] abnormalities have been suggested in depression given the association of [[CRHR1]] with depression and the increased frequency of [[Dexamethasone suppression test|dexamethasone test]] non-suppression in people who are depressed. However, this abnormality is not adequate as a diagnosis tool because its sensitivity is only 44%.<ref>{{cite journal |vauthors=Arana GW, Baldessarini RJ, Ornsteen M |title=The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Commentary and review |journal=Archives of General Psychiatry |volume=42 |issue=12 |pages=1193–204 |date=December 1985 |pmid=3000317 |doi=10.1001/archpsyc.1985.01790350067012}}</ref> These stress-related abnormalities are thought to be the cause of hippocampal volume reductions seen in people who are depressed.<ref>{{cite journal |vauthors=Varghese FP, Brown ES |title=The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder: A Brief Primer for Primary Care Physicians |journal=Primary Care Companion to the Journal of Clinical Psychiatry |volume=3 |issue=4 |pages=151–55 |date=August 2001 |pmid=15014598 |pmc=181180 |doi=10.4088/pcc.v03n0401 }}</ref> Furthermore, a [[meta-analysis]] yielded decreased dexamethasone suppression, and increased response to psychological stressors.<ref>{{cite journal |vauthors=Lopez-Duran NL, Kovacs M, George CJ |title=Hypothalamic-pituitary-adrenal axis dysregulation in depressed children and adolescents: a meta-analysis |journal=Psychoneuroendocrinology |volume=34 |issue=9 |pages=1272–1283 |year=2009 |pmid=19406581 |pmc=2796553 |doi=10.1016/j.psyneuen.2009.03.016}}</ref> Further abnormal results have been obscured with the [[cortisol awakening response]], with increased response being associated with depression.<ref>{{cite journal |vauthors=Dedovic K, Ngiam J |title=The cortisol awakening response and major depression: examining the evidence |journal=Neuropsychiatric Disease and Treatment |volume=11 |pages=1181–1189 |year=2015 |pmid=25999722 |pmc=4437603 |doi=10.2147/NDT.S62289 |doi-access=free }}</ref>

There is also a connection between the gut microbiome and the central nervous system, otherwise known as the [[Gut–brain axis|Gut-Brain axis]], which is a two-way communication system between the brain and the gut. Experiments have shown that [[microbiota]] in the gut can play an important role in depression, as people with MDD often have gut-brain dysfunction. One analysis showed that those with MDD have different bacteria in their guts. Bacteria ''[[Bacteroidota|Bacteroidetes]]'' and ''Firmicutes'' were most affected in people with MDD, and they are also impacted in people with [[irritable bowel syndrome]].<ref name="GB">{{cite journal | vauthors = Zhu F, Tu H, Chen T | title = The Microbiota-Gut-Brain Axis in Depression: The Potential Pathophysiological Mechanisms and Microbiota Combined Antidepression Effect | journal = Nutrients | volume = 14 | issue = 10 | pages = 2081 | date = May 2022 | pmid = 35631224 | pmc = 9144102 | doi = 10.3390/nu14102081 | doi-access = free }}</ref> Another study showed that people with IBS have a higher chance of developing depression, which shows the two are connected.<ref>{{cite journal | vauthors = Fond G, Loundou A, Hamdani N, Boukouaci W, Dargel A, Oliveira J, Roger M, Tamouza R, Leboyer M, Boyer L | title = Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis | journal = European Archives of Psychiatry and Clinical Neuroscience | volume = 264 | issue = 8 | pages = 651–660 | date = December 2014 | pmid = 24705634 | doi = 10.1007/s00406-014-0502-z}}</ref> There is even evidence suggesting that altering the microbes in the gut can have regulatory effects on developing depression.<ref name="GB" />

Theories unifying [[neuroimaging]] findings have been proposed. The first model proposed is the limbic-cortical model, which involves hyperactivity of the ventral paralimbic regions and hypoactivity of frontal regulatory regions in emotional processing.<ref>{{cite journal |vauthors=Mayberg HS |title=Limbic-cortical dysregulation: a proposed model of depression |journal=The Journal of Neuropsychiatry and Clinical Neurosciences |volume=9 |issue=3 |pages=471–81 |year=1997 |pmid=9276848 |doi=10.1176/jnp.9.3.471}}</ref> Another model, the cortico-striatal model, suggests that abnormalities of the [[prefrontal cortex]] in regulating striatal and subcortical structures result in depression.<ref>{{cite journal |vauthors=Graham J, Salimi-Khorshidi G, Hagan C, Walsh N, Goodyer I, Lennox B, Suckling J |title=Meta-analytic evidence for neuroimaging models of depression: state or trait? |journal=Journal of Affective Disorders |volume=151 |issue=2 |pages=423–431 |year=2013 |pmid=23890584 |doi=10.1016/j.jad.2013.07.002 |doi-access=free }}</ref> Another model proposes hyperactivity of [[Salience network|salience structures]] in identifying negative stimuli and hypoactivity of cortical regulatory structures resulting in a negative [[emotional bias]] and depression, consistent with emotional bias studies.<ref>{{cite journal |vauthors=Hamilton JP, Etkin A, Furman DJ, Lemus MG, Johnson RF, Gotlib IH |title=Functional neuroimaging of major depressive disorder: a meta-analysis and new integration of base line activation and neural response data |journal=The American Journal of Psychiatry |volume=169 |issue=7 |pages=693–703 |date=July 2012 |pmid=22535198 |doi=10.1176/appi.ajp.2012.11071105 |pmc=11889638 }}</ref>

=== Immune pathogenesis theories on depression ===
The newer field of [[psychoneuroimmunology]], the study between the immune system and the nervous system and emotional state, suggests that cytokines may impact depression.

[[Depression and immune function|Immune system abnormalities]] have been observed, including increased levels of [[cytokines]] -cells produced by immune cells that affect inflammation- involved in generating [[sickness behavior]], creating a pro-inflammatory profile in MDD.<ref>{{cite journal | vauthors = Krishnadas R, Cavanagh J | title = Depression: an inflammatory illness? | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 83 | issue = 5 | pages = 495–502 | date = May 2012 | pmid = 22423117 | doi = 10.1136/jnnp-2011-301779 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Patel A | title = Review: the role of inflammation in depression | journal = Psychiatria Danubina | volume = 25 | issue = Suppl 2 | pages = S216–S223 | date = September 2013 | pmid = 23995180 }}</ref><ref>{{cite journal | vauthors = Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL | title = A meta-analysis of cytokines in major depression | journal = Biological Psychiatry | volume = 67 | issue = 5 | pages = 446–457 | date = March 2010 | pmid = 20015486 | doi = 10.1016/j.biopsych.2009.09.033 | s2cid = 230209 }}</ref> Some people with depression have increased levels of pro-inflammatory cytokines and some have decreased levels of anti-inflammatory cytokines.<ref>{{cite journal | vauthors = Osimo EF, Pillinger T, Rodriguez IM, Khandaker GM, Pariante CM, Howes OD | title = Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls | journal = Brain, Behavior, and Immunity | volume = 87 | pages = 901–909 | date = July 2020 | pmid = 32113908 | doi = 10.1016/j.bbi.2020.02.010 | pmc = 7327519 }}</ref> Research suggests that treatments can reduce pro-inflammatory cell production, like the experimental treatment of ketamine with treatment-resistant depression.<ref>{{cite journal | vauthors = Sukhram SD, Yilmaz G, Gu J | title = Antidepressant Effect of Ketamine on Inflammation-Mediated Cytokine Dysregulation in Adults with Treatment-Resistant Depression: Rapid Systematic Review | journal = Oxidative Medicine and Cellular Longevity | volume = 2022 | pages = 1061274 | date = 16 September 2022 | pmid = 36160713 | pmc = 9507757 | doi = 10.1155/2022/1061274 | doi-access = free | editor-first = Ajinkya | editor-last = Sase }}</ref> With this, in MDD, people will more likely have a Th-1 dominant immune profile, which is a pro-inflammatory profile. This suggests that there are components of the immune system affecting the pathology of MDD.<ref>{{cite journal | vauthors = Rachayon M, Jirakran K, Sodsai P, Sughondhabirom A, Maes M | title = T cell activation and deficits in T regulatory cells are associated with major depressive disorder and severity of depression | journal = Scientific Reports | volume = 14 | issue = 1 | pages = 11177 | date = May 2024 | pmid = 38750122 | doi = 10.1038/s41598-024-61865-y | pmc = 11096341 | bibcode = 2024NatSR..1411177R }}</ref>

Another way [[cytokine]]s can affect depression is in the [[kynurenine pathway]], and when this is overactivated, it can cause depression. This can be due to too much [[microglia]]l activation and too little [[Astrocyte|astrocytic]] activity. When microglia get activated, they release pro-inflammatory cytokines that cause an increase in the production of [[Cytochrome c oxidase subunit 2|COX<sub>2</sub>]]. This, in turn, causes the production of [[Prostaglandin E2|PGE<sub>2</sub>]], which is a [[prostaglandin]], and this catalyzes the production of [[Indolamines|indolamine]], IDO. IDO causes [[tryptophan]] to get converted into [[kynurenine]], and kynurenine becomes [[quinolinic acid]].<ref>{{cite journal | vauthors = McNally L, Bhagwagar Z, Hannestad J | title = Inflammation, glutamate, and glia in depression: a literature review | journal = CNS Spectrums | volume = 13 | issue = 6 | pages = 501–510 | date = June 2008 | pmid = 18567974 | doi = 10.1017/S1092852900016734 }}</ref> Quinolinic acid is an agonist for [[NMDA receptor]]s, so it activates the pathway. Studies have shown that the post-mortem brains of patients with MDD have higher levels of quinolinic acid than people who did not have MDD. With this, researchers have also seen that the concentration of quinolinic acid correlates to the severity of depressive symptoms.<ref>{{cite journal | vauthors = Hestad K, Alexander J, Rootwelt H, Aaseth JO | title = The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases | journal = Biomolecules | volume = 12 | issue = 7 | pages = 998 | date = July 2022 | pmid = 35883554 | pmc = 9313172 | doi = 10.3390/biom12070998 | doi-access = free }}</ref><!--

[[MRI]] scans of people with depression have revealed a number of differences in brain structure compared to those who are not depressed. Meta-analyses of neuroimaging studies in major depression report that, compared to [[Scientific control|controls]], people who are depressed have increased volume of the [[lateral ventricles]] and [[adrenal gland]] and smaller volumes of the [[basal ganglia]], [[thalamus]], [[hippocampus]], and [[frontal lobe]] (including the [[orbitofrontal cortex]] and [[gyrus rectus]]).<ref>{{cite journal |vauthors=Kempton MJ, Salvador Z, Munafò MR, Geddes JR, Simmons A, Frangou S, Williams SC |title=Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder |journal=Archives of General Psychiatry |volume=68 |issue=7 |pages=675–690 |year=2011 |pmid=21727252 |doi=10.1001/archgenpsychiatry.2011.60|doi-access=free }}</ref><ref>{{cite journal |vauthors=Arnone D, McIntosh AM, Ebmeier KP, Munafò MR, Anderson IM |title=Magnetic resonance imaging studies in unipolar depression: systematic review and meta-regression analyses |journal=European Neuropsychopharmacology |volume=22 |issue=1 |pages=1–16 |year=2012 |pmid=21723712 |doi=10.1016/j.euroneuro.2011.05.003 |s2cid=42105719 }}</ref> [[Hyperintensities]] have been associated with people with a late age of onset, and have led to the development of the theory of [[Subcortical ischemic depression|vascular depression]].<ref>{{cite journal |vauthors=Herrmann LL, Le Masurier M, Ebmeier KP |title=White matter hyperintensities in late life depression: a systematic review |journal=Journal of Neurology, Neurosurgery, and Psychiatry |volume=79 |issue=6 |pages=619–624 |year=2008 |pmid=17717021 |doi=10.1136/jnnp.2007.124651 |s2cid=23759460 }}</ref> -->

==Diagnosis==

===Assessment===
{{further|Rating scales for depression}}
[[File:A wretched man with an approaching depression; represented b Wellcome V0011145.jpg|thumb|left|Caricature of a man with depression]]
A diagnostic assessment may be conducted by a suitably trained [[general practitioner]], or by a [[psychiatrist]] or [[psychologist]],<ref name=NIMHPub/> who [[psychiatric history|records]] the person's current circumstances, biographical history, current symptoms, family history, and alcohol and drug use. The assessment also includes a [[mental state examination]], which is an assessment of the person's current mood and thought content, in particular the presence of themes of hopelessness or [[pessimism]], [[self-harm]] or suicide, and an absence of positive thoughts or plans.<ref name=NIMHPub/> Specialist mental health services are rare in rural areas, and thus diagnosis and management is left largely to [[primary care|primary-care]] clinicians.<ref>{{cite journal |vauthors=Kaufmann IM |title=Rural psychiatric services. A collaborative model |journal=Canadian Family Physician |volume=39 |pages=1957–1961 |year=1993 |pmid=8219844 |pmc=2379905 }}</ref> This issue is even more marked in developing countries.<ref>{{cite web |url=http://news.bbc.co.uk/1/hi/health/492941.stm |title=Call for action over Third World depression |access-date=11 October 2008 |date=1 November 1999 |website=BBC News (Health) |publisher=British Broadcasting Corporation (BBC) |url-status=live |archive-url=https://web.archive.org/web/20080513222415/http://news.bbc.co.uk/1/hi/health/492941.stm |archive-date=13 May 2008 }}</ref> [[Rating scale]]s are not used to diagnose depression, but they provide an indication of the severity of symptoms for a time period, so a person who scores above a given cut-off point can be more thoroughly evaluated for a depressive disorder diagnosis. Several rating scales are used for this purpose;<ref>{{cite journal |vauthors=Sharp LK, Lipsky MS |title=Screening for depression across the lifespan: a review of measures for use in primary care settings |journal=American Family Physician |volume=66 |issue=6 |pages=1001–08 |date=September 2002 |pmid=12358212 }}</ref><!-- cites two previous sentences --> these include the [[Hamilton Rating Scale for Depression]],<ref>{{cite journal |vauthors=Zimmerman M, Chelminski I, Posternak M |title=A review of studies of the Hamilton depression rating scale in healthy controls: implications for the definition of remission in treatment studies of depression |journal=The Journal of Nervous and Mental Disease |volume=192 |issue=9 |pages=595–601 |date=September 2004 |pmid=15348975 |doi=10.1097/01.nmd.0000138226.22761.39 |s2cid=24291799 }}</ref> the [[Beck Depression Inventory]]<ref>{{cite journal |vauthors=McPherson A, Martin CR |title=A narrative review of the Beck Depression Inventory (BDI) and implications for its use in an alcohol-dependent population |journal=Journal of Psychiatric and Mental Health Nursing |volume=17 |issue=1 |pages=19–30 |date=February 2010 |pmid=20100303 |doi=10.1111/j.1365-2850.2009.01469.x }}</ref> or the [[Suicide Behaviors Questionnaire-Revised]].<ref>{{cite journal |vauthors=Osman A, Bagge CL, Gutierrez PM, Konick LC, Kopper BA, Barrios FX |title=The Suicidal Behaviors Questionnaire-Revised (SBQ-R): validation with clinical and nonclinical samples |journal=Assessment |volume=8 |issue=4 |pages=443–54 |date=December 2001 |pmid=11785588 |doi=10.1177/107319110100800409 |s2cid=11477277 }}</ref>

[[Primary-care physician]]s have more difficulty with underrecognition and undertreatment of depression compared to psychiatrists. These cases may be missed because for some people with depression, [[#physicalSymptoms|physical symptoms]] often accompany depression. In addition, there may also be barriers related to the person, provider, and/or the medical system. Non-psychiatrist physicians have been shown to miss about two-thirds of cases, although there is some evidence of improvement in the number of missed cases.<ref>{{cite journal |vauthors=Cepoiu M, McCusker J, Cole MG, Sewitch M, Belzile E, Ciampi A |title=Recognition of depression by non-psychiatric physicians—a systematic literature review and meta-analysis |journal=Journal of General Internal Medicine |volume=23 |issue=1 |pages=25–36 |date=January 2008 |pmid=17968628 |pmc=2173927 |doi=10.1007/s11606-007-0428-5 }}</ref>

A doctor generally performs a medical examination and selected investigations to rule out other causes of depressive symptoms. These include blood tests measuring [[Thyroid-stimulating hormone|TSH]] and [[thyroxine]] to exclude [[hypothyroidism]]; [[Blood tests#Biochemical analysis|basic electrolytes]] and serum [[calcium]] to rule out a [[Metabolic disorder|metabolic disturbance]]; and a [[Complete blood count|full blood count]] including [[Erythrocyte sedimentation rate|ESR]] to rule out a [[systemic infection]] or chronic disease.<ref>{{cite journal |vauthors=Dale J, Sorour E, Milner G |year=2008 |title=Do psychiatrists perform appropriate physical investigations for their patients? A review of current practices in a general psychiatric inpatient and outpatient setting |journal=Journal of Mental Health |volume=17 |issue=3 |pages=293–98|doi=10.1080/09638230701498325|s2cid=72755878 }}</ref> Adverse affective reactions to medications or alcohol misuse may be ruled out, as well. [[Testosterone]] levels may be evaluated to diagnose [[hypogonadism]], a cause of depression in men.<ref>{{cite journal |vauthors=Orengo CA, Fullerton G, Tan R |title=Male depression: a review of gender concerns and testosterone therapy |journal=Geriatrics |volume=59 |issue=10 |pages=24–30 |date=October 2004 |pmid=15508552 }}</ref> [[Vitamin D]] levels might be evaluated, as low levels of vitamin D have been associated with greater risk for depression.<ref name=Parker2017/> Subjective cognitive complaints appear in older depressed people, but they can also be indicative of the onset of a [[dementia|dementing disorder]], such as [[Alzheimer's disease]].<ref>{{cite journal |vauthors=Reid LM, Maclullich AM |title=Subjective memory complaints and cognitive impairment in older people |journal=Dementia and Geriatric Cognitive Disorders |volume=22 |issue=5–6 |pages=471–85 |year=2006 |pmid=17047326 |doi=10.1159/000096295 |s2cid=9328852 }}</ref><ref>{{cite journal |vauthors=Katz IR |title=Diagnosis and treatment of depression in patients with Alzheimer's disease and other dementias |journal=The Journal of Clinical Psychiatry |volume=59 |issue=Suppl 9 |pages=38–44 |year=1998 |pmid=9720486 }}</ref> [[Neuropsychological assessment|Cognitive testing]] and brain imaging can help distinguish depression from dementia.<ref>{{cite journal |vauthors=Wright SL, Persad C |title=Distinguishing between depression and dementia in older persons: neuropsychological and neuropathological correlates |journal=Journal of Geriatric Psychiatry and Neurology |volume=20 |issue=4 |pages=189–98 |date=December 2007 |pmid=18004006 |doi=10.1177/0891988707308801 |s2cid=33714179 }}</ref> A [[CT scan]] can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms.<ref>{{Harvnb |Sadock|2002|p=108}}</ref> No biological tests confirm major depression.<ref>{{Harvnb |Sadock|2002|p=260}}</ref> In general, investigations are not repeated for a subsequent episode unless there is a medical [[Indication (medicine)|indication]].

===DSM and ICD criteria===
The most widely used criteria for diagnosing depressive conditions are found in the [[American Psychiatric Association]]'s ''[[Diagnostic and Statistical Manual of Mental Disorders]]'' (DSM) and the [[World Health Organization]]'s ''[[ICD|International Statistical Classification of Diseases and Related Health Problems]]'' (ICD). The latter system is typically used in European countries, while the former is used in the US and many other non-European nations,<ref>{{Harvnb |Sadock|2002|p=288}}</ref> and the authors of both have worked towards conforming one with the other.{{sfn|American Psychiatric Association|2013|p=xii}} Both DSM and ICD mark out typical (main) depressive symptoms.<ref name="DSMvsICD" /> The most recent edition of the DSM is the Fifth Edition, Text Revision (DSM-5-TR),<ref>{{cite web |title=Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) |url=https://psychiatry.org/psychiatrists/practice/dsm |website=American Psychiatric Association |access-date=9 July 2022 |quote=The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) features the most current text updates based on scientific literature with contributions from more than 200 subject matter experts.}}</ref> and the most recent edition of the ICD is the Eleventh Edition (ICD-11).<ref>{{cite web |title=International Statistical Classification of Diseases and Related Health Problems (ICD) |url=https://www.who.int/standards/classifications/classification-of-diseases |website=World Health Organization |access-date=9 July 2022 |quote=... the latest version of the ICD, ICD-11, was adopted by the 72nd World Health Assembly in 2019 and came into effect on 1st January 2022.}}</ref>

Under mood disorders, ICD-11 classifies major depressive disorder as either ''single episode depressive disorder'' (where there is no history of depressive episodes, or of [[mania]]) or ''recurrent depressive disorder'' (where there is a history of prior episodes, with no history of mania).<ref name="ICD11 6A70 and 6A71">ICD-11, [[#CITEREF-ICD11-6A70|6A70 Single episode depressive disorder]] and [[#CITEREF-ICD11-6A71|6A71 Recurrent depressive disorder]]</ref> ICD-11 symptoms, present nearly every day for at least two weeks, are a depressed mood or [[anhedonia]], accompanied by other symptoms such as "difficulty concentrating, feelings of worthlessness or excessive or inappropriate guilt, hopelessness, recurrent thoughts of death or suicide, changes in appetite or sleep, psychomotor agitation or retardation, and reduced energy or fatigue."<ref name="ICD11 6A70 and 6A71"/> These symptoms must affect work, social, or domestic activities. The ICD-11 system allows further specifiers for the current depressive episode: the severity (mild, moderate, severe, unspecified); the presence of psychotic symptoms (with or without psychotic symptoms); and the degree of remission if relevant (currently in partial remission, currently in full remission).<ref name="ICD11 6A70 and 6A71"/> These two disorders are classified as "Depressive disorders", in the category of "Mood disorders".<ref name="ICD11 6A70 and 6A71"/>

According to DSM-5, at least one of the symptoms is either depressed mood or loss of interest or pleasure. Depressed mood occurs nearly every day as subjective feelings like sadness, emptiness, and hopelessness or observations made by others (e.g. appears tearful). Loss of interest or pleasure occurs in all, or almost all activities of the day, nearly every day. These symptoms, as well as five out of the nine more specific symptoms listed, must frequently occur for more than two weeks (to the extent in which it impairs functioning) for the diagnosis.<ref>{{cite book |title=Diagnostic and statistical manual of mental disorders: DSM-5 |date=2013 |publisher=American psychiatric association |location=Washington |isbn=978-0-89042-554-1 |edition=5th}}</ref><ref>{{Cite web |url=https://www.psnpaloalto.com/wp/wp-content/uploads/2010/12/Depression-Diagnostic-Criteria-and-Severity-Rating.pdf|title=Diagnostic Criteria for Major Depressive Disorder and Depressive Episodes |website=City of Palo Alto Project Safety Net |access-date=21 February 2019|archive-date=3 August 2020|url-status=usurped|archive-url=https://web.archive.org/web/20200803161533/https://www.psnpaloalto.com/wp/wp-content/uploads/2010/12/Depression-Diagnostic-Criteria-and-Severity-Rating.pdf}}</ref>{{Failed verification|date=July 2022|reason=This source was written before DSM-5 was finalised, and only talks about proposed DSM-5 symptoms.}} Major depressive disorder is classified as a mood disorder in the DSM-5.<ref name=Parker2014>{{Cite journal|vauthors=Parker GF|date=1 June 2014|title=DSM-5 and Psychotic and Mood Disorders|url=http://jaapl.org/content/42/2/182|journal=Journal of the American Academy of Psychiatry and the Law Online|language=en|volume=42|issue=2|pages=182–190|issn=1093-6793|pmid=24986345}}</ref> The diagnosis hinges on the presence of single or recurrent [[major depressive episode]]s.<ref name=APA162>{{Harvnb |American Psychiatric Association|2013|p=162}}</ref> Further qualifiers are used to classify both the episode itself and the course of the disorder. The category [[Depressive Disorder Not Otherwise Specified|Unspecified Depressive Disorder]] is diagnosed if the depressive episode's manifestation does not meet the criteria for a major depressive episode.<ref name=Parker2014/>

====Major depressive episode====
{{Main|Major depressive episode}}
A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks.<ref name="b502">{{cite book |last1=Black |first1=Donald W. |last2=Andreasen |first2=Nancy C. |title=Introductory Textbook of Psychiatry |publisher=American Psychiatric Pub |publication-place=Washington, DC |date=4 May 2020 |isbn=978-1-61537-318-5 |chapter=Mood Disorders}}</ref> Episodes may be isolated or recurrent and are categorized as mild (few symptoms in excess of minimum criteria), moderate, or severe (marked impact on social or occupational functioning). An episode with psychotic features—commonly referred to as ''[[psychotic depression]]''—is automatically rated as severe.<ref name=Parker2014/> If the person has had an episode of [[mania]] or [[hypomania|markedly elevated mood]], a diagnosis of [[bipolar disorder]] is made instead. Depression without mania is sometimes referred to as ''unipolar'' because the mood remains at one emotional state or "pole".<ref>{{Harvnb |Parker|1996|p=173}}</ref>

[[Grief|Bereavement]] is not an exclusion criterion in the DSM-5, and it is up to the clinician to distinguish between normal reactions to a loss and MDD. Excluded are a range of related diagnoses, including [[dysthymia]], which involves a chronic but milder mood disturbance;<ref name=Sadock552>{{Harvnb |Sadock|2002|p=552}}</ref> [[recurrent brief depression]], consisting of briefer depressive episodes;{{sfn|American Psychiatric Association|2013|p=183}}<ref>{{cite journal |vauthors=Carta MG, Altamura AC, Hardoy MC, Pinna F, Medda S, Dell'Osso L, Carpiniello B, Angst J |title=Is recurrent brief depression an expression of mood spectrum disorders in young people? Results of a large community sample |journal=European Archives of Psychiatry and Clinical Neuroscience |volume=253 |issue=3 |pages=149–53 |date=June 2003 |pmid=12904979 |doi=10.1007/s00406-003-0418-5 |hdl=2434/521599 |s2cid=26860606 |hdl-access=free }}</ref> [[minor depressive disorder]], whereby only some symptoms of major depression are present;<ref>{{cite journal |vauthors=Rapaport MH, Judd LL, Schettler PJ, Yonkers KA, Thase ME, Kupfer DJ, Frank E, Plewes JM, Tollefson GD, Rush AJ |title=A descriptive analysis of minor depression |journal=The American Journal of Psychiatry |volume=159 |issue=4 |pages=637–43 |date=April 2002 |pmid=11925303 |doi=10.1176/appi.ajp.159.4.637 }}</ref> and [[Adjustment disorder|adjustment disorder with depressed mood]], which denotes low mood resulting from a psychological response to an identifiable event or [[Stress (biological)|stressor]].{{sfn|American Psychiatric Association|2013|p=168}}

====Subtypes====
The DSM-5 recognizes six further subtypes of MDD, called ''specifiers'', in addition to noting the length, severity and presence of psychotic features:
* "[[Melancholic depression]]" is characterized by a loss of pleasure in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of [[grief]] or loss, a worsening of symptoms in the morning hours, early-morning waking, [[psychomotor retardation]], excessive weight loss (not to be confused with [[anorexia nervosa]]), or excessive guilt.<ref name="g379"/>
* "[[Atypical depression]]" is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant [[weight gain]] or increased appetite (comfort eating), excessive sleep or sleepiness ([[hypersomnia]]), a sensation of heaviness in limbs known as leaden paralysis, and significant long-term social impairment as a consequence of hypersensitivity to perceived [[social rejection|interpersonal rejection]].{{sfn|American Psychiatric Association|2013|pp=185–186}}
* "[[Catatonic depression]]" is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here, the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms also occur in [[schizophrenia]] or in manic episodes, or may be caused by [[neuroleptic malignant syndrome]].{{sfn|American Psychiatric Association|2013|pp=119–120}}
* "Depression with [[Anxiety|anxious]] distress" was added into the DSM-5 as a means to emphasize the common co-occurrence between depression and anxiety, as well as the risk of suicide of depressed individuals with anxiety.<ref name="t660">{{cite journal | last=Hopwood | first=Malcolm | title=Anxiety Symptoms in Patients with Major Depressive Disorder: Commentary on Prevalence and Clinical Implications | journal=Neurology and Therapy | volume=12 | issue=S1 | date=2023 | issn=2193-8253 | pmid=37115459 | pmc=10141876 | doi=10.1007/s40120-023-00469-6 | doi-access=free | pages=5–12 | url=https://link.springer.com/content/pdf/10.1007/s40120-023-00469-6.pdf | access-date=6 March 2025}}</ref>
* "Depression with [[Postpartum depression|peri-partum]] onset" refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth or while a woman is pregnant. DSM-IV-TR used the classification "postpartum depression", but this was changed to not exclude cases of depressed woman during pregnancy. Depression with peripartum onset has an incidence rate of 3–6% among new mothers. The DSM-5 mandates that to qualify as depression with peripartum onset, onset occurs during pregnancy or within one month of delivery.{{sfn|American Psychiatric Association|2013|pp=186–187}}<!-- cites paragraph -->
* "[[Seasonal affective disorder]]" (SAD) is a form of depression in which depressive episodes come on in the autumn or winter, and resolve in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times, over a two-year period or longer.{{sfn|American Psychiatric Association|2013|p=187}}

===Differential diagnoses===
{{Main|Differential diagnoses of depression}}

To confirm major depressive disorder as the most likely diagnosis, other [[Differential diagnosis|potential diagnoses]] must be considered, including [[dysthymia]], [[adjustment disorder]] with depressed mood, or [[bipolar disorder]]. Dysthymia is a chronic, milder mood disturbance in which a person reports a low mood almost daily over a span of at least two years. The symptoms are not as severe as those for major depression, although people with dysthymia are vulnerable to secondary episodes of major depression (sometimes referred to as ''[[double depression]]'').<ref name=Sadock552/> [[Adjustment disorder|Adjustment disorder with depressed mood]] is a mood disturbance appearing as a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode.{{sfn|American Psychiatric Association|2013|p=168}}

Other disorders need to be ruled out before diagnosing major depressive disorder. They include depressions due to physical illness, [[medications]], and [[substance use disorder]]s. Depression due to physical illness is diagnosed as a [[Mood disorder#Due to another medical condition|mood disorder due to a general medical condition]]. This condition is determined based on history, laboratory findings, or [[physical examination]]. When the depression is caused by a medication, non-medical use of a psychoactive substance, or exposure to a [[toxin]], it is then diagnosed as a specific mood disorder (previously called ''substance-induced mood disorder'').{{sfn|American_Psychiatric_Association|2013|p=167}}

==Screening and prevention==
Preventive efforts may result in decreases in rates of the condition of between 22 and 38%.<ref name=Cuijpers2008 /> Since 2016, the [[United States Preventive Services Task Force]] (USPSTF) has recommended screening for depression among those over the age 12, provided that it would be diagnosed accurately, treated efficiently, and followed-up as needed;<ref>{{cite journal |vauthors=Siu AL, Bibbins-Domingo K, Grossman DC, et al |title=Screening for Depression in Adults: US Preventive Services Task Force Recommendation Statement |journal=JAMA |volume=315 |issue=4 |pages=380–87 |date=January 2016 |pmid=26813211 |doi=10.1001/jama.2015.18392 |doi-access=free}}</ref><ref>{{cite journal |vauthors=Siu AL |title=Screening for Depression in Children and Adolescents: U.S. Preventive Services Task Force Recommendation Statement |journal=Annals of Internal Medicine |volume=164 |issue=5 |pages=360–66 |date=March 2016 |pmid=26858097 |doi=10.7326/M15-2957 |doi-access=free}}</ref><ref name="DD">{{Cite journal |last1=Marx |first1=Wolfgang |last2=Penninx |first2=Brenda W. J. H. |last3=Solmi |first3=Marco |last4=Furukawa |first4=Toshi A. |last5=Firth |first5=Joseph |last6=Carvalho |first6=Andre F. |last7=Berk |first7=Michael |date=24 August 2023 |title=Major depressive disorder |url=https://www.nature.com/articles/s41572-023-00454-1 |journal=Nature Reviews Disease Primers |language=en |volume=9 |issue=1 |page=44 |doi=10.1038/s41572-023-00454-1 |pmid=37620370 |issn=2056-676X}}</ref> though a 2005 [[Cochrane review]] found that the routine use of screening questionnaires has little effect on detection or treatment.<ref name=Gil2005>{{cite journal |vauthors=Gilbody S, House AO, Sheldon TA |title=Screening and case finding instruments for depression |journal=The Cochrane Database of Systematic Reviews |issue=4 |page=CD002792 |date=October 2005 |volume=2005 |pmid=16235301 |doi=10.1002/14651858.CD002792.pub2 |pmc=6769050 }}</ref> Screening the general population is not recommended by authorities in the UK or Canada for similar reasons, citing insufficient data.<ref>{{cite journal |vauthors=Ferenchick EK, Ramanuj P, Pincus HA |title=Depression in primary care: part 1—screening and diagnosis |journal=British Medical Journal |year=2019 |volume=365 |pages=l794 |doi=10.1136/bmj.l794|pmid=30962184 |s2cid=104296515 |doi-access=free}}</ref><ref name="DD" />

Behavioral interventions, such as [[interpersonal therapy]] and [[cognitive-behavioral therapy]], are effective at preventing new onset depression.<ref name=Cuijpers2008>{{cite journal |vauthors=Cuijpers P, van Straten A, Smit F, Mihalopoulos C, Beekman A |title=Preventing the onset of depressive disorders: a meta-analytic review of psychological interventions |journal=The American Journal of Psychiatry |volume=165 |issue=10 |pages=1272–80 |date=October 2008 |pmid=18765483 |doi=10.1176/appi.ajp.2008.07091422 |hdl=1871/16952 |url=http://ajp.psychiatryonline.org/cgi/content/abstract/165/10/1272?maxtoshow=&hits=10&RESULTFORMAT=1&title=Preventing+the+onset+of+depressive+disorders%3A+A+meta&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT }}</ref><ref name=Munoz2012>{{cite journal |vauthors=Muñoz RF, Beardslee WR, Leykin Y |title=Major depression can be prevented |journal=The American Psychologist |volume=67 |issue=4 |pages=285–95 |date=May–June 2012 |pmid=22583342 |pmc=4533896 |doi=10.1037/a0027666 }}</ref><ref name=Cuijpers2012>{{cite conference| vauthors = Cuijpers P |title=Prevention and early treatment of mental ill-health|url=http://congres.efpa.eu/downloads/Pim-Cuijpers_Prevention-and-early-treatment-of-mental-ill-health-EFPASep%202012.pdf|place=Psychology for Health: Contributions to Policy Making, Brussels|date=20 September 2012|archive-url=https://web.archive.org/web/20130512015105/http://congres.efpa.eu/downloads/Pim-Cuijpers_Prevention-and-early-treatment-of-mental-ill-health-EFPASep%202012.pdf|archive-date=12 May 2013|access-date=16 June 2013}}</ref> Because such interventions appear to be most effective when delivered to individuals or small groups, it has been suggested that they may be able to reach their large target audience most efficiently through the [[Internet]].<ref>{{cite journal | vauthors = Griffiths KM, Farrer L, Christensen H | year = 2010 |volume=192 |issue=11 |pages=4–11 |title=The efficacy of internet interventions for depression and anxiety disorders: a review of randomised controlled trials |journal=Medical Journal of Australia | url = https://www.mja.com.au/system/files/issues/192_11_070610/gri10844_fm.pdf |access-date=12 November 2014 |url-status=live |archive-url=https://web.archive.org/web/20141112130932/https://www.mja.com.au/system/files/issues/192_11_070610/gri10844_fm.pdf |archive-date=12 November 2014 | doi = 10.5694/j.1326-5377.2010.tb03685.x | pmid = 20528707 | s2cid = 1948009 }}</ref>

The Netherlands mental health care system provides preventive interventions, such as the "Coping with Depression" course (CWD) for people with sub-threshold depression. The course is claimed to be the most successful of psychoeducational interventions for the treatment and prevention of depression (both for its adaptability to various populations and its results), with a risk reduction of 38% in major depression and an efficacy as a treatment comparing favorably to other psychotherapies.<ref name=Munoz2012 /><ref name=Cuijpers2009>{{cite journal |vauthors=Cuijpers P, Muñoz RF, Clarke GN, Lewinsohn PM |title=Psychoeducational treatment and prevention of depression: the "Coping with Depression" course thirty years later |journal=Clinical Psychology Review |volume=29 |issue=5 |pages=449–58 |date=July 2009 |pmid=19450912 |doi=10.1016/j.cpr.2009.04.005 }}</ref>

==Management==
{{Main|Management of depression}}
The most common and effective treatments for depression are psychotherapy, medication, and electroconvulsive therapy (ECT); a combination of treatments is the most effective approach when depression is resistant to treatment.<ref name= Karrouri2021>{{cite journal |vauthors=Karrouri R, Hammani Z, Benjelloun R, Otheman Y |title=Major depressive disorder: Validated treatments and future challenges |journal=World J Clin Cases |volume=9 |issue=31 |pages=9350–9367 |date=November 2021 |pmid=34877271 |pmc=8610877 |doi=10.12998/wjcc.v9.i31.9350 |type=Review |doi-access=free }}</ref> [[American Psychiatric Association]] treatment guidelines recommend that initial treatment should be individually tailored based on factors including severity of symptoms, co-existing disorders, prior treatment experience, and personal preference. Options may include pharmacotherapy, psychotherapy, exercise, ECT, [[transcranial magnetic stimulation]] (TMS) or [[light therapy]]. [[Antidepressant]] medication is recommended as an initial treatment choice in people with mild, moderate, or severe major depression, and should be given to all people with severe depression unless ECT is planned.<ref name=apaguidelines>{{cite journal | title = Practice guideline for the treatment of patients with major depressive disorder (revision). American Psychiatric Association | journal = The American Journal of Psychiatry | volume = 157 | issue = 4 Suppl | pages = 1–45 | date = April 2000 | pmid = 10767867 }}; Third edition {{doi|10.1176/appi.books.9780890423363.48690}}</ref> There is evidence that collaborative care by a team of health care practitioners produces better results than routine single-practitioner care.<ref>{{cite journal | vauthors = Archer J, Bower P, Gilbody S, et al| title = Collaborative care for depression and anxiety problems | journal = The Cochrane Database of Systematic Reviews | volume = 2012 | page = CD006525 | date = October 2012 | issue = 10 | pmid = 23076925 | doi = 10.1002/14651858.CD006525.pub2 | pmc = 11627142 | hdl = 10871/13751 | hdl-access = free }}</ref>

Psychotherapy is the treatment of choice (over medication) for people under 18,<ref name=NICE2004>{{cite web |url=http://www.nice.org.uk/guidance/CG23 |access-date=20 March 2013 |title=Depression |publisher=National Institute for Health and Care Excellence |date=December 2004 |archive-url=https://web.archive.org/web/20081115042517/http://www.nice.org.uk/Guidance/CG23 |archive-date=15 November 2008 |url-status=live}}</ref> and [[cognitive behavioral therapy]] (CBT), third wave CBT and [[Interpersonal psychotherapy|interpersonal therapy]] may help prevent depression.<ref>{{cite journal |vauthors=Hetrick SE, Cox GR, Witt KG, Bir JJ, Merry SN |date=August 2016 |title=Cognitive behavioural therapy (CBT), third-wave CBT and interpersonal therapy (IPT) based interventions for preventing depression in children and adolescents |journal=The Cochrane Database of Systematic Reviews |volume=2016 |issue=8 |pages=CD003380 |doi=10.1002/14651858.CD003380.pub4 |pmc=8407360 |pmid=27501438}}</ref> The UK [[National Institute for Health and Care Excellence]] (NICE) 2004 guidelines indicate that antidepressants should not be used for the initial treatment of mild depression because the [[risk-benefit ratio]] is poor. The guidelines recommend that antidepressants treatment in combination with psychosocial interventions should be considered for:<ref name= NICE2004/>

:* People with a history of moderate or severe depression
:* Those with mild depression that has been present for a long period
:* As a second line treatment for mild depression that persists after other interventions
:* As a first line treatment for moderate or severe depression.

The guidelines further note that [[antidepressant]] treatment should be continued for at least six months to reduce the risk of [[relapse]], and that [[Selective serotonin reuptake inhibitor|SSRIs]] are better tolerated than [[tricyclic antidepressant]]s.<ref name="o804">{{cite book |last1=Taylor |first1=David M. |last2=Barnes |first2=Thomas R. E. |last3=Young |first3=Allan H. |title=The Maudsley Prescribing Guidelines in Psychiatry |publisher=Wiley |chapter=Depression and Anxiety Disorders |date=17 December 2021 |isbn=978-1-119-77222-4 |doi=10.1002/9781119870203.mpg003}}</ref>{{rp|305–450}}

Treatment options are more limited in developing countries, where access to mental health staff, medication, and psychotherapy is often difficult. Development of mental health services is minimal in many countries; depression is viewed as a phenomenon of the developed world despite evidence to the contrary, and not as an inherently life-threatening condition.<ref>{{cite journal |vauthors=Patel V, Araya R, Bolton P |title=Treating depression in the developing world |journal=Tropical Medicine & International Health |volume=9 |issue=5 |pages=539–41 |date=May 2004 |pmid=15117296 |doi=10.1111/j.1365-3156.2004.01243.x |s2cid=73073889 |doi-access=free }}</ref> There is insufficient evidence to determine the effectiveness of psychological versus medical therapy in children.<ref>{{cite journal |vauthors=Cox GR, Callahan P, Churchill R, et al|title=Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents |journal=The Cochrane Database of Systematic Reviews |volume=2014 |issue=11 |pages=CD008324 |date=November 2014 |pmid=25433518 |doi=10.1002/14651858.CD008324.pub3 |pmc=8556660 }}</ref>

===Lifestyle===
{{further|Neurobiological effects of physical exercise#Major depressive disorder}}
[[File:Soccer football informal in Manipur India cropped.jpg|thumb|Physical exercise is one recommended way to manage mild depression.]]<!-- The text says recommended for major depression, the caption says for mild depression-->
[[Physical exercise]] has been found to be effective for major depression, and may be recommended to people who are willing, motivated, and healthy enough to participate in an exercise program as treatment.<ref>{{cite journal |vauthors=Josefsson T, Lindwall M, Archer T |title=Physical exercise intervention in depressive disorders: meta-analysis and systematic review |journal=Scandinavian Journal of Medicine & Science in Sports |volume=24 |issue=2 |pages=259–72 |date=April 2014 |pmid=23362828 |doi=10.1111/sms.12050 |s2cid=29351791 |doi-access=free }}</ref><ref name="m647">{{cite journal |last1=Blumenthal |first1=James A. |last2=Rozanski |first2=Alan |title=Exercise as a therapeutic modality for the prevention and treatment of depression |journal=Progress in Cardiovascular Diseases |volume=77 |date=2023 |pmid=36848966 |pmc=10225323 |doi=10.1016/j.pcad.2023.02.008 |doi-access=free |pages=50–58}}</ref> It is equivalent to the use of medications or psychological therapies in most people.<ref name="Coo2013" /> In older people it does appear to decrease depression.<ref name="y793">{{cite journal |last1=Tang |first1=Lili |last2=Zhang |first2=Lin |last3=Liu |first3=Yanbo |last4=Li |first4=Yan |last5=Yang |first5=Lijuan |last6=Zou |first6=Mingxuan |last7=Yang |first7=Huiran |last8=Zhu |first8=Lingyu |last9=Du |first9=Ruihong |last10=Shen |first10=Ye |last11=Li |first11=Haoyu |last12=Yang |first12=Yong |last13=Li |first13=Zhijun |title=Optimal dose and type of exercise to improve depressive symptoms in older adults: a systematic review and network meta-analysis |journal=BMC Geriatrics |volume=24 |issue=1 |date=7 June 2024 |issn=1471-2318 |pmid=38849780 |pmc=11157862 |doi=10.1186/s12877-024-05118-7 |doi-access=free |page=505}}</ref> Sleep and diet may also play a role in depression, and interventions in these areas may be an effective add-on to conventional methods.<ref name="z728">{{cite journal |last1=Wong |first1=Vincent Wing-Hei |last2=Ho |first2=Fiona Yan-Yee |last3=Shi |first3=Nga-Kwan |last4=Sarris |first4=Jerome |last5=Chung |first5=Ka-Fai |last6=Yeung |first6=Wing-Fai |title=Lifestyle medicine for depression: A meta-analysis of randomized controlled trials |journal=Journal of Affective Disorders |volume=284 |date=2021 |doi=10.1016/j.jad.2021.02.012 |doi-access=free |pages=203–216 |pmid=33609955 |hdl=10397/103774 |url=http://ira.lib.polyu.edu.hk/bitstream/10397/103774/1/Yeung_Lifestyle_Medicine_Depression.pdf |access-date=28 February 2025}}</ref> In studies, [[smoking cessation]] has benefits in depression.<ref name="d893">{{cite journal |last1=Taylor |first1=Gemma MJ |last2=Lindson |first2=Nicola |last3=Farley |first3=Amanda |last4=Leinberger-Jabari |first4=Andrea |last5=Sawyer |first5=Katherine |last6=te Water Naudé |first6=Rebecca |last7=Theodoulou |first7=Annika |last8=King |first8=Naomi |last9=Burke |first9=Chloe |last10=Aveyard |first10=Paul |title=Smoking cessation for improving mental health |journal=Cochrane Database of Systematic Reviews |volume=2021 |issue=3 |date=9 March 2021 |pages=CD013522 |pmid=33687070 |pmc=8121093 |doi=10.1002/14651858.CD013522.pub2 |doi-access=free |url=http://pure-oai.bham.ac.uk/ws/files/116308750/TaylorG2021Smoking.pdf |access-date=28 February 2025 }}</ref>

===Talking therapies===
{{See also|Behavioral theories of depression}}
[[Talking therapy]] (psychotherapy) can be delivered to individuals, groups, or families by mental health professionals, including psychotherapists, psychiatrists, psychologists, clinical [[social work]]ers, counselors, and psychiatric nurses. A 2012 review found psychotherapy to be better than no treatment but not other treatments.<ref>{{cite journal | vauthors = Khan A, Faucett J, Lichtenberg P, Kirsch I, Brown WA | title = A systematic review of comparative efficacy of treatments and controls for depression | journal = PLOS ONE | volume = 7 | issue = 7 | pages = e41778 | date = 30 July 2012 | pmid = 22860015 | pmc = 3408478 | doi = 10.1371/journal.pone.0041778 | bibcode = 2012PLoSO...741778K | doi-access = free }}</ref> With more complex and chronic forms of depression, a combination of medication and psychotherapy may be used.<ref>{{cite journal | vauthors = Thase ME | title = When are psychotherapy and pharmacotherapy combinations the treatment of choice for major depressive disorder? | journal = The Psychiatric Quarterly | volume = 70 | issue = 4 | pages = 333–46 | year = 1999 | pmid = 10587988 | doi = 10.1023/A:1022042316895 | s2cid = 45091134 }}</ref><ref>{{cite encyclopedia| vauthors = Cordes J |title=Encyclopedia of Sciences and Religions |pages=610–16 |year=2013 |doi=10.1007/978-1-4020-8265-8_301 |chapter=Depression |isbn=978-1-4020-8264-1 }}</ref> There is moderate-quality evidence that psychological therapies are a useful addition to standard antidepressant treatment of [[treatment-resistant depression]] in the short term.<ref>{{cite journal | vauthors = Ijaz S, Davies P, Williams CJ, et al | title = Psychological therapies for treatment-resistant depression in adults | journal = The Cochrane Database of Systematic Reviews | volume = 5 | pages = CD010558 | date = May 2018 | issue = 8 | pmid = 29761488 | pmc = 6494651 | doi = 10.1002/14651858.CD010558.pub2 }}</ref> Psychotherapy has been shown to be effective in older people.<ref>{{cite journal |vauthors=Wilson KC, Mottram PG, Vassilas CA |title=Psychotherapeutic treatments for older depressed people |journal=The Cochrane Database of Systematic Reviews |volume=23 |issue=1 |page=CD004853 |date=January 2008 |pmid=18254062 |doi=10.1002/14651858.CD004853.pub2 }}</ref><ref>{{cite journal |vauthors=Cuijpers P, van Straten A, Smit F |title=Psychological treatment of late-life depression: a meta-analysis of randomized controlled trials |journal=International Journal of Geriatric Psychiatry |volume=21 |issue=12 |pages=1139–49 |date=December 2006 |pmid=16955421 |doi=10.1002/gps.1620 |hdl=1871/16894 |s2cid=14778731 |url=https://research.vu.nl/en/publications/5a654ac9-4dbf-4df9-9d2c-2cbc760d8bc9 }}</ref> Successful psychotherapy appears to reduce the recurrence of depression even after it has been stopped or replaced by occasional booster sessions.

The most-studied form of psychotherapy for depression is CBT, which teaches clients to challenge self-defeating, but enduring ways of thinking (cognitions) and change counter-productive behaviors. CBT can perform as well as antidepressants in people with major depression.<ref>{{cite journal | vauthors = Gartlehner G, Wagner G, Matyas N, et al | title = Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews | journal = BMJ Open | volume = 7 | issue = 6 | pages = e014912 | date = June 2017 | pmid = 28615268 | pmc = 5623437 | doi = 10.1136/bmjopen-2016-014912 }}</ref> CBT has the most research evidence for the treatment of depression in children and adolescents, and CBT and interpersonal psychotherapy (IPT) are preferred therapies for adolescent depression.<ref name=abct>[https://web.archive.org/web/20110726055131/http://www.abct.org/sccap/?m=sPublic&fa=pub_Depression Childhood Depression]. abct.org. Last updated: 30 July 2010</ref> In people under 18, according to the [[National Institute for Health and Clinical Excellence]], medication should be offered only in conjunction with a psychological therapy, such as [[Cognitive behavioral therapy|CBT]], [[Interpersonal psychotherapy|interpersonal therapy]], or [[family therapy]].<ref name=NICEkids5>{{cite book |title=NICE guidelines: Depression in children and adolescents |publisher=NICE |location=London |year=2005 |page=5 |isbn=978-1-84629-074-9 |url=http://www.nice.org.uk/Guidance/CG28/QuickRefGuide/pdf/English |access-date=16 August 2008 |url-status=live |archive-url=https://web.archive.org/web/20080924152314/http://www.nice.org.uk/Guidance/CG28/QuickRefGuide/pdf/English |archive-date=24 September 2008 |author-link=National Institute for Health and Clinical Excellence }}</ref> Several variables predict success for cognitive behavioral therapy in adolescents: higher levels of rational thoughts, less hopelessness, fewer negative thoughts, and fewer cognitive distortions.<ref>{{cite journal | vauthors = Becker SJ |title=Cognitive-Behavioral Therapy for Adolescent Depression: Processes of Cognitive Change |journal=Psychiatric Times|volume=25 |issue=14 |year=2008 |url= http://www.psychiatrictimes.com/depression/article/10168/1357884 }}</ref> CBT is particularly beneficial in preventing relapse.<ref>{{cite journal |vauthors=Almeida AM, Lotufo Neto F |title=[Cognitive-behavioral therapy in prevention of depression relapses and recurrences: a review] |journal=Revista Brasileira de Psiquiatria |volume=25 |issue=4 |pages=239–44 |date=October 2003 |pmid=15328551 |doi=10.1590/S1516-44462003000400011|doi-access=free }}</ref><ref>{{cite journal |vauthors=Paykel ES |title=Cognitive therapy in relapse prevention in depression |journal=The International Journal of Neuropsychopharmacology |volume=10 |issue=1 |pages=131–36 |date=February 2007 |pmid=16787553 |doi=10.1017/S1461145706006912 |doi-access=free }}</ref> Cognitive behavioral therapy and occupational programs (including modification of work activities and assistance) have been shown to be effective in reducing sick days taken by workers with depression.<ref name=Nieuwenhuijsen2020/> Several variants of cognitive behavior therapy have been used in those with depression, the most notable being [[rational emotive behavior therapy]],<ref name="h303">{{cite journal | last1=David | first1=Daniel | last2=Cotet | first2=Carmen | last3=Matu | first3=Silviu | last4=Mogoase | first4=Cristina | last5=Stefan | first5=Simona | title=50 years of rational-emotive and cognitive-behavioral therapy: A systematic review and meta-analysis | journal=Journal of Clinical Psychology | volume=74 | issue=3 | date=2018 | issn=0021-9762 | pmid=28898411 | pmc=5836900 | doi=10.1002/jclp.22514 | doi-access=free | pages=304–318 }}</ref> and [[mindfulness-based cognitive therapy]].<ref name="g399">{{cite book | last1=Salmon | first1=Paul | last2=Loo | first2=Jiann Lin | title=Tasman's Psychiatry | chapter=Mindfulness-Based Cognitive Therapy | publisher=Springer International Publishing | publication-place=Cham | date=2024 | isbn=978-3-030-51365-8 | doi=10.1007/978-3-030-51366-5_75 | pages=3717–3735}}</ref> Mindfulness-based stress reduction programs may reduce depression symptoms.<ref>{{cite journal |vauthors=Khoury B, Lecomte T, Fortin G, et al |title=Mindfulness-based therapy: a comprehensive meta-analysis |journal=Clinical Psychology Review |volume=33 |issue=6 |pages=763–71 |date=August 2013 |pmid=23796855 |doi=10.1016/j.cpr.2013.05.005 }}</ref><ref>{{cite journal |vauthors=Jain FA, Walsh RN, Eisendrath SJ, Christensen S, Rael Cahn B |title=Critical analysis of the efficacy of meditation therapies for acute and subacute phase treatment of depressive disorders: a systematic review |journal=Psychosomatics |volume=56 |issue=2 |pages=140–52 |year=2014 |pmid=25591492 |pmc=4383597 |doi=10.1016/j.psym.2014.10.007 |url=http://www.escholarship.org/uc/item/0372c9xp }}</ref> Mindfulness programs also appear to be a promising intervention in youth.<ref>{{cite journal |vauthors=Simkin DR, Black NB |title=Meditation and mindfulness in clinical practice |journal=Child and Adolescent Psychiatric Clinics of North America |volume=23 |issue=3 |pages=487–534 |date=July 2014 |pmid=24975623 |doi=10.1016/j.chc.2014.03.002 }}</ref> [[Problem solving therapy]], cognitive behavioral therapy, and interpersonal therapy are effective interventions in the elderly.<ref name="Alexopoulos2019" />

[[Psychoanalysis]] is a school of thought, founded by [[Sigmund Freud]], which emphasizes the resolution of [[Unconscious mind|unconscious]] mental conflicts.<ref>{{cite book |vauthors=Dworetzky J |title=Psychology |publisher=Brooks/Cole Pub. Co |location=Pacific Grove, CA|year=1997 |page=602 |isbn=978-0-314-20412-7}}</ref> Psychoanalytic techniques are used by some practitioners to treat clients presenting with major depression.<ref name="o365">{{cite book | last=Kay | first=Jerald | title=Tasman's Psychiatry | chapter=Individual Psychodynamic Psychotherapy | publisher=Springer International Publishing | publication-place=Cham | date=2024 | isbn=978-3-030-51365-8 | doi=10.1007/978-3-030-51366-5_11 | pages=3583–3623}}</ref> A more widely practiced therapy, called [[psychodynamic psychotherapy]], is in the tradition of psychoanalysis but less intensive, meeting once or twice a week. It also tends to focus more on the person's immediate problems, and has an additional social and interpersonal focus.<ref name="o365">{{cite book | last=Kay | first=Jerald | title=Tasman's Psychiatry | chapter=Individual Psychodynamic Psychotherapy | publisher=Springer International Publishing | publication-place=Cham | date=2024 | isbn=978-3-030-51365-8 | doi=10.1007/978-3-030-51366-5_11 | pages=3583–3623}}</ref> In a meta-analysis of three controlled trials of Short Psychodynamic Supportive Psychotherapy, this modification was found to be as effective as medication for mild to moderate depression.<ref>{{cite journal |vauthors=de Maat S, Dekker J, Schoevers R, et al |title=Short psychodynamic supportive psychotherapy, antidepressants, and their combination in the treatment of major depression: a mega-analysis based on three randomized clinical trials |journal=Depression and Anxiety |volume=25 |issue=7 |pages=565–74 |year=2007 |pmid=17557313 |doi=10.1002/da.20305 |s2cid=20373635 |doi-access=free }}</ref>

===Antidepressants===
[[File:Zoloft bottles.jpg|thumb|[[Sertraline]] (Zoloft) is used primarily to treat major depression in adults.]]
Conflicting results have arisen from studies that look at the effectiveness of antidepressants in people with acute, mild to moderate depression.<ref>{{cite journal | vauthors = Iglesias-González M, Aznar-Lou I, Gil-Girbau M, et al | title = Comparing watchful waiting with antidepressants for the management of subclinical depression symptoms to mild-moderate depression in primary care: a systematic review | journal = Family Practice | volume = 34 | issue = 6 | pages = 639–48 | date = November 2017 | pmid = 28985309 | doi = 10.1093/fampra/cmx054 | doi-access = free }}</ref> A review commissioned by the [[National Institute for Health and Care Excellence]] (UK) concluded that there is strong evidence that [[selective serotonin reuptake inhibitor|SSRIs]], such as [[escitalopram]], [[paroxetine]], and [[sertraline]], have greater efficacy than [[placebo]] on achieving a 50% reduction in depression scores in moderate and severe major depression, and that there is some evidence for a similar effect in mild depression.<ref name="Depression in Adults">{{cite web|title=The treatment and management of depression in adults|url=http://www.nice.org.uk/guidance/cg90/resources/guidance-depression-in-adults-pdf|publisher=[[NICE]]|date=October 2009|access-date=12 November 2014|url-status=live|archive-url=https://web.archive.org/web/20141112140520/http://www.nice.org.uk/guidance/cg90/resources/guidance-depression-in-adults-pdf|archive-date=12 November 2014}}</ref> Similarly, a Cochrane systematic review of clinical trials of the generic [[tricyclic antidepressant]] [[amitriptyline]] concluded that there is strong evidence that its efficacy is superior to placebo.<ref>{{cite journal |vauthors=Leucht C, Huhn M, Leucht S |title=Amitriptyline versus placebo for major depressive disorder |journal=The Cochrane Database of Systematic Reviews |volume=2012 |pages=CD009138 |date=December 2012 |issue=12 |pmid=23235671 |doi=10.1002/14651858.CD009138.pub2 | veditors = Leucht C |pmc=11299154 }}</ref> Antidepressants work less well for the elderly than for younger individuals with depression.<ref name="Alexopoulos2019">{{cite journal |vauthors=Alexopoulos GS |date=August 2019 |title=Mechanisms and treatment of late-life depression |journal=Transl Psychiatry |volume=9 |issue=1 |page=188 |doi=10.1038/s41398-019-0514-6 |pmc=6683149 |pmid=31383842}}</ref>

To find the most effective antidepressant medication with minimal side-effects, the dosages can be adjusted, and if necessary, combinations of different classes of antidepressants can be tried. Response rates to the first antidepressant administered range from 50 to 75%, and it can take at least six to eight weeks from the start of medication to improvement.<ref name="apaguidelines" /><ref>{{cite journal |vauthors=de Vries YA, Roest AM, Bos EH, et al |title=Predicting antidepressant response by monitoring early improvement of individual symptoms of depression: individual patient data meta-analysis |journal=The British Journal of Psychiatry |volume=214 |issue=1 |pages=4–10 |date=January 2019 |pmid=29952277 |doi=10.1192/bjp.2018.122 |pmc=7557872 |doi-access=free}}</ref> Antidepressant medication treatment is usually continued for 6–9 months after remission, to minimize the chance of recurrence, and even up to two years of continuation is recommended.<ref name="o804" />{{rp|305–450}}

[[Selective serotonin reuptake inhibitor|SSRIs]] are the primary medications prescribed, owing to their relatively mild side-effects, and safety.<ref name="j508">{{cite book | last=Kroll | first=David S. | title=Caring for Patients with Depression in Primary Care | chapter=Prescribing Antidepressant Medication | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-031-08494-2 | doi=10.1007/978-3-031-08495-9_3 | pages=17–34}}</ref> People who do not respond to one SSRI can be switched to [[List of antidepressants|another antidepressant]], and this results in improvement in almost 50% of cases.<!--per the WP:MEDRS guideline, review articles should ideally be less than 5 yrs, pref. less than 3 years old--><ref>{{cite journal | vauthors = Whooley MA, Simon GE | title = Managing depression in medical outpatients | journal = The New England Journal of Medicine | volume = 343 | issue = 26 | pages = 1942–50 | date = December 2000 | pmid = 11136266 | doi = 10.1056/NEJM200012283432607}}</ref> Another option is to augment the atypical antidepressant [[bupropion]] to the SSRI as an adjunctive treatment.<ref name="f609">{{cite journal |last1=Patel |first1=Krisna |last2=Allen |first2=Sophie |last3=Haque |first3=Mariam N. |last4=Angelescu |first4=Ilinca |last5=Baumeister |first5=David |last6=Tracy |first6=Derek K. |title=Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant |journal=Therapeutic Advances in Psychopharmacology |volume=6 |issue=2 |date=2016 |issn=2045-1253 |pmid=27141292 |pmc=4837968 |doi=10.1177/2045125316629071 |doi-access=free |pages=99–144 }}</ref> [[Venlafaxine]], an antidepressant with a different mechanism of action, may be modestly more effective than SSRIs.<ref name="r829">{{cite book | last1=McKnight | first1=Rebecca | last2=Price | first2=Jonathan | last3=Geddes | first3=John | title=Psychiatry | chapter=Drugs and other physical treatments | publisher=Oxford University Press | date=15 May 2019 | isbn=978-0-19-875400-8 | doi=10.1093/oso/9780198754008.003.0019 | page=}}</ref> However, venlafaxine is not recommended in the UK as a first-line treatment because of evidence suggesting its risks may outweigh benefits,<ref>{{cite web |url=http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON2023842&RevisionSelectionMethod=LatestReleased |title=Updated prescribing advice for venlafaxine (Efexor/Efexor XL) | vauthors = Duff G |website=Medicines and Healthcare products Regulatory Agency (MHRA) |date=31 May 2006 |archive-url=https://web.archive.org/web/20081113133358/http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON2023842&RevisionSelectionMethod=LatestReleased |archive-date=13 November 2008 |author-link=Gordon Duff }}</ref> and it is specifically discouraged in children and adolescents as it increases the risk of suicidal thoughts or attempts.<ref name="NIHR-2022">{{Cite journal |date=3 November 2022 |title=Antidepressants for children and teenagers: what works for anxiety and depression? |url=https://evidence.nihr.ac.uk/collection/antidepressants-for-children-and-teenagers-what-works-anxiety-depression/ |journal=NIHR Evidence |type=Plain English summary |language=en |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_53342|s2cid=253347210 }}</ref><ref name="Zhou-2020">{{cite journal |vauthors=Zhou X, Teng T, Zhang Y, Del Giovane C, Furukawa TA, Weisz JR, Li X, Cuijpers P, Coghill D, Xiang Y, Hetrick SE, Leucht S, Qin M, Barth J, Ravindran AV, Yang L, Curry J, Fan L, Silva SG, Cipriani A, Xie P |date=July 2020 |title=Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis |journal=The Lancet. Psychiatry |volume=7 |issue=7 |pages=581–601 |doi=10.1016/S2215-0366(20)30137-1 |pmc=7303954 |pmid=32563306}}</ref><ref name="Hetrick-2021">{{cite journal |vauthors=Hetrick SE, McKenzie JE, Bailey AP, Sharma V, Moller CI, Badcock PB, Cox GR, Merry SN, Meader N |date=May 2021 |title=New generation antidepressants for depression in children and adolescents: a network meta-analysis |journal=The Cochrane Database of Systematic Reviews |volume=2021 |issue=5 |pages=CD013674 |doi=10.1002/14651858.CD013674.pub2 |pmc=8143444 |pmid=34029378 |collaboration=Cochrane Common Mental Disorders Group}}</ref><ref name="Solmi-2020">{{cite journal |vauthors=Solmi M, Fornaro M, Ostinelli EG, Zangani C, Croatto G, Monaco F, Krinitski D, Fusar-Poli P, Correll CU |date=June 2020 |title=Safety of 80 antidepressants, antipsychotics, anti-attention-deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta-review of 78 adverse effects |journal=World Psychiatry |volume=19 |issue=2 |pages=214–232 |doi=10.1002/wps.20765 |pmc=7215080 |pmid=32394557}}</ref><ref name="Boaden-2020">{{cite journal |vauthors=Boaden K, Tomlinson A, Cortese S, Cipriani A |date=2 September 2020 |title=Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment |journal=Frontiers in Psychiatry |volume=11 |page=717 |doi=10.3389/fpsyt.2020.00717 |pmc=7493620 |pmid=32982805|doi-access=free }}</ref><ref name="Correll-2021">{{cite journal |vauthors=Correll CU, Cortese S, Croatto G, Monaco F, Krinitski D, Arrondo G, Ostinelli EG, Zangani C, Fornaro M, Estradé A, Fusar-Poli P, Carvalho AF, Solmi M |date=June 2021 |title=Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review |journal=World Psychiatry |volume=20 |issue=2 |pages=244–275 |doi=10.1002/wps.20881 |pmc=8129843 |pmid=34002501}}</ref><ref>{{cite journal|title=Depression in children and young people: Identification and management in primary, community and secondary care|year=2005|publisher=NHS National Institute for Health and Clinical Excellence|journal=NICE Clinical Guidelines|issue=28|access-date=12 November 2014|url=http://www.nice.org.uk/guidance/cg28/resources/guidance-depression-in-children-and-young-people-pdf|archive-url=https://web.archive.org/web/20141112133741/http://www.nice.org.uk/guidance/cg28/resources/guidance-depression-in-children-and-young-people-pdf|archive-date=12 November 2014}}</ref>

<!-- Children -->
For children and adolescents with moderate-to-severe depressive disorder, [[fluoxetine]] seems to be the best treatment (either with or without [[Cognitive behavioral therapy|cognitive behavioural therapy]]) but more research is needed to be certain.<ref name="NIHR-2020">{{Cite journal |date=12 October 2020 |title=Prozac may be the best treatment for young people with depression – but more research is needed |url=https://evidence.nihr.ac.uk/alert/prozac-may-be-the-best-treatment-for-young-people-with-depression-but-more-research-is-needed/ |journal=NIHR Evidence |type=Plain English summary |language=en |publisher=National Institute for Health and Care Research |doi=10.3310/alert_41917|s2cid=242952585 }}</ref><ref name="Zhou-2020" /><ref>{{cite journal | vauthors = Boaden K, Tomlinson A, Cortese S, Cipriani A | title = Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment | journal = Frontiers in Psychiatry | volume = 11 | page = 717 | date = 2 September 2020 | pmid = 32982805 | pmc = 7493620 | doi = 10.3389/fpsyt.2020.00717 | doi-access = free }}</ref><ref name="Hetrick-2021" /> [[Sertraline]], [[escitalopram]], [[duloxetine]] might also help in reducing symptoms.<ref name="r716">{{cite book | last1=Taylor | first1=David M. | last2=Barnes | first2=Thomas R. E. | last3=Young | first3=Allan H. | title=The Maudsley Prescribing Guidelines in Psychiatry | publisher=Wiley | date=17 December 2021 | isbn=978-1-119-77222-4 | doi=10.1002/9781119870203.mpg005 | page=}}</ref> Some antidepressants have not been shown to be effective.<ref name="v001">{{cite book | last=M.D. | first=Mina K. Dulcan | title=Dulcan's Textbook of Child and Adolescent Psychiatry, Third Edition | publisher=American Psychiatric Pub | date=18 October 2021 | isbn=978-1-61537-327-7 }}</ref><ref name="Zhou-2020" /> Medications are not recommended in children with mild disease.<ref name="r716"/>

There is also insufficient evidence to determine effectiveness in those with depression complicated by [[dementia]].<ref name="f390">{{cite journal | last1=Dudas | first1=Robert | last2=Malouf | first2=Reem | last3=McCleery | first3=Jenny | last4=Dening | first4=Tom | title=Antidepressants for treating depression in dementia | journal=Cochrane Database of Systematic Reviews | volume=2018 | issue=8 | date=31 August 2018 | pages=CD003944 | pmid=30168578 | pmc=6513376 | doi=10.1002/14651858.CD003944.pub2 | doi-access=free | url=https://nottingham-repository.worktribe.com/file/1072993/1/CD003944%20Standard | access-date=24 March 2025 }}</ref> Any antidepressant can cause [[hyponatremia|low blood sodium]] levels;<ref name="g496">{{cite journal |last1=Gheysens |first1=Tim |last2=Van Den Eede |first2=Filip |last3=De Picker |first3=Livia |title=The risk of antidepressant-induced hyponatremia: A meta-analysis of antidepressant classes and compounds |journal=European Psychiatry |volume=67 |issue=1 |date=2024 |pages=e20 |issn=0924-9338 |pmid=38403888 |pmc=10966618 |doi=10.1192/j.eurpsy.2024.11 |doi-access=free |url=https://www.cambridge.org/core/services/aop-cambridge-core/content/view/3ABCD6CF7AD23D03003F93E4F648AEC0/S0924933824000117a.pdf/div-class-title-the-risk-of-antidepressant-induced-hyponatremia-a-meta-analysis-of-antidepressant-classes-and-compounds-div.pdf |access-date=27 February 2025 }}</ref> nevertheless, it has been reported more often with SSRIs.<ref name="j072">{{cite book | last=Kroll | first=David S. | title=Caring for Patients with Depression in Primary Care | chapter=Managing Risks and Side Effects of Antidepressant Medications | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-031-08494-2 | doi=10.1007/978-3-031-08495-9_4 | pages=35–47}}</ref> It is not uncommon for SSRIs to cause or worsen insomnia; the sedating [[atypical antidepressant]] [[mirtazapine]] can be used in such cases.<ref>{{cite journal |vauthors=Guaiana G, Barbui C, Hotopf M |title=Amitriptyline for depression |journal=The Cochrane Database of Systematic Reviews |volume=18 |issue=3 |page=CD004186 |date=July 2007 |pmid=17636748 |doi=10.1002/14651858.CD004186.pub2 }}</ref><ref name="j072"/>

Irreversible [[monoamine oxidase inhibitor]]s, an older class of antidepressants, have been plagued by potentially life-threatening dietary and drug interactions. They are still used only rarely, although newer and better-tolerated agents of this class have been developed.<ref>{{cite journal |vauthors=Krishnan KR |title=Revisiting monoamine oxidase inhibitors |journal=The Journal of Clinical Psychiatry |volume=68 |issue=Suppl 8 |pages=35–41 |year=2007 |pmid=17640156 }}</ref> The safety profile is different with reversible monoamine oxidase inhibitors, such as [[moclobemide]], where the risk of serious dietary interactions is negligible and dietary restrictions are less strict.<ref>{{cite journal |vauthors=Bonnet U |title=Moclobemide: therapeutic use and clinical studies |journal=CNS Drug Reviews |volume=9 |issue=1 |pages=97–140 |year=2003 |pmid=12595913 |pmc=6741704 |doi=10.1111/j.1527-3458.2003.tb00245.x }}</ref>

<!--SSRI and suicide -->
It is unclear whether antidepressants affect a person's risk of suicide.<ref>{{cite journal |vauthors=Braun C, Bschor T, Franklin J, Baethge C |title=Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder |journal=Psychotherapy and Psychosomatics |volume=85 |issue=3 |pages=171–79 |year=2016 |pmid=27043848 |doi=10.1159/000442293 |s2cid=40682753 |url=https://tud.qucosa.de/id/qucosa%3A70596 }}</ref> For children, adolescents, and probably young adults between 18 and 24 years old, there is a higher risk of both [[suicidal ideation]]s and [[suicidal behavior]] in those treated with SSRIs.<ref name=FDA>{{cite web |url=https://www.fda.gov/OHRMS/DOCKETS/ac/04/briefing/2004-4065b1-10-TAB08-Hammads-Review.pdf|title=Review and evaluation of clinical data. Relationship between psychiatric drugs and pediatric suicidality|access-date=29 May 2008|vauthors=Hammad TA|date=16 August 2004|publisher=FDA|pages=42, 115|url-status=live|archive-url=https://web.archive.org/web/20080625161255/https://www.fda.gov/OHRMS/DOCKETS/ac/04/briefing/2004-4065b1-10-TAB08-Hammads-Review.pdf|archive-date=25 June 2008}}</ref><ref>{{cite journal |vauthors=Hetrick SE, McKenzie JE, Cox GR, Simmons MB, Merry SN |title=Newer generation antidepressants for depressive disorders in children and adolescents |journal=The Cochrane Database of Systematic Reviews |volume=11 |page=CD004851 |date=November 2012 |issue=9 |pmid=23152227 |doi=10.1002/14651858.CD004851.pub3 |pmc=8786271 |hdl=11343/59246 |hdl-access=free }}</ref> For adults, it is unclear whether SSRIs affect the risk of suicidality. One review found no connection;<ref>{{cite journal |vauthors=Gunnell D, Saperia J, Ashby D |title=Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review |journal=BMJ |volume=330 |issue=7488 |page=385 |date=February 2005 |pmid=15718537 |pmc=549105 |doi=10.1136/bmj.330.7488.385 }}</ref> another an increased risk;<ref>{{cite journal |vauthors=Fergusson D, Doucette S, Glass KC, et al|title=Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials |journal=BMJ |volume=330 |issue=7488 |page=396 |date=February 2005 |pmid=15718539 |pmc=549110 |doi=10.1136/bmj.330.7488.396 }}</ref> and a third no risk in those 25–65 years old and a decreased risk in those more than 65.<ref>{{cite journal |vauthors=Stone M, Laughren T, Jones ML, et al |title=Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration |journal=BMJ |volume=339 |page=b2880 |date=August 2009 |pmid=19671933 |pmc=2725270 |doi=10.1136/bmj.b2880 }}</ref> A [[black box warning]] was introduced in the United States in 2007 on SSRIs and other antidepressant medications due to the increased risk of suicide in people younger than 24 years old.<ref>{{cite web |url=https://www.fda.gov/bbs/topics/NEWS/2007/NEW01624.html |title=FDA Proposes New Warnings About Suicidal Thinking, Behavior in Young Adults Who Take Antidepressant Medications |date=2 May 2007 |publisher=[[U.S. Food and Drug Administration|FDA]] |access-date=29 May 2008 |url-status=live |archive-url=https://web.archive.org/web/20080223195544/https://www.fda.gov/bbs/topics/NEWS/2007/NEW01624.html |archive-date=23 February 2008 }}</ref> Similar precautionary notice revisions were implemented by the Japanese Ministry of Health.<ref>{{cite report |author=Medics and Foods Department |author-link=Ministry of Health, Labour and Welfare (Japan) |url=http://www1.mhlw.go.jp/kinkyu/iyaku_j/iyaku_j/anzenseijyouhou/261.pdf |title=Pharmaceuticals and Medical Devices Safety Information |series=261 |publisher=Ministry of Health, Labour and Welfare (Japan) |language=ja |archive-url=https://web.archive.org/web/20110429200312/http://www1.mhlw.go.jp/kinkyu/iyaku_j/iyaku_j/anzenseijyouhou/261.pdf |archive-date=29 April 2011 |access-date=19 May 2010 }}</ref>

===Other medications and supplements===
The combined use of antidepressants plus [[benzodiazepine]]s demonstrates improved effectiveness when compared to antidepressants alone, but these effects may not endure. The addition of a benzodiazepine is balanced against possible harms and other alternative treatment strategies when antidepressant mono-therapy is considered inadequate.<ref name=Ogawa2019>{{cite journal | vauthors = Ogawa Y, Takeshima N, Hayasaka Y, et al| title = Antidepressants plus benzodiazepines for adults with major depression | journal = The Cochrane Database of Systematic Reviews | volume = 6 | pages = CD001026 | date = June 2019 | issue = 6 | pmid = 31158298 | pmc = 6546439 | doi = 10.1002/14651858.CD001026.pub2 }}</ref><!-- cites paragraph -->

For treatment-resistant depression, adding on the [[atypical antipsychotic]] [[brexpiprazole]] for short-term or acute management may be considered.<ref name=Ralovska2023>{{Cite journal |vauthors= Ralovska S, Koyvhev I, Marinov P, Furukawa TA, Mulsant B, Cipriani A |date=July 2023 | collaboration = Cochrane Common Mental Disorders Group |title= Brexpiprazole versus placebo or other antidepressive agents for treating depression  |journal=Cochrane Database of Systematic Reviews|volume=2023 |issue=7 |pages=CD013866 |doi=10.1002/14651858.CD013866.pub2 |pmc=10406422}}</ref> Brexpiprazole may be effective for some people, however, the evidence as of 2023 supporting its use is weak and this medication has potential adverse effects including weight gain and [[akathisia]].<ref name=Ralovska2023/> Brexpiprazole has not been sufficiently studied in older people or children and the use and effectiveness of this [[Adjunctive therapy|adjunctive]] therapy for longer term management is not clear.<ref name=Ralovska2023/>

[[Ketamine]] may have a rapid antidepressant effect lasting less than two weeks; there is limited evidence of any effect after that, common acute side effects, and longer-term studies of safety and adverse effects are needed.<ref>{{cite journal |vauthors=Corriger A, Pickering G |title=Ketamine and depression: a narrative review |journal=Drug Des Devel Ther |volume=13 |issue= |pages=3051–3067 |date=2019 |pmid=31695324 |pmc=6717708 |doi=10.2147/DDDT.S221437 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Krystal JH, Abdallah CG, Sanacora G, Charney DS, Duman RS |title=Ketamine: A Paradigm Shift for Depression Research and Treatment |journal=Neuron |volume=101 |issue=5 |pages=774–778 |date=March 2019 |pmid=30844397 |pmc=6560624 |doi=10.1016/j.neuron.2019.02.005 }}</ref> A nasal spray form of [[esketamine]] was approved by the FDA in March 2019 for use in treatment-resistant depression when combined with an oral antidepressant; risk of substance use disorder and concerns about its safety, serious adverse effects, tolerability, effect on suicidality, lack of information about dosage, whether the studies on it adequately represent broad populations, and escalating use of the product have been raised by an international panel of experts.<ref>{{cite journal |vauthors=McIntyre RS, Rosenblat JD, Nemeroff CB, et al |title=Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation |journal=Am J Psychiatry |volume=178 |issue=5 |pages=383–399 |date=May 2021 |pmid=33726522 |doi=10.1176/appi.ajp.2020.20081251 |pmc=9635017 |s2cid=232262694 }}</ref><ref>{{cite journal |vauthors=Bahr R, Lopez A, Rey JA |title=Intranasal Esketamine (SpravatoTM) for Use in Treatment-Resistant Depression In Conjunction With an Oral Antidepressant |journal=P T |volume=44 |issue=6 |pages=340–375 |date=June 2019 |pmid=31160868 |pmc=6534172 }}</ref>

[[Nonsteroidal anti-inflammatory drug]]s (NSAIDs) and cytokine inhibitors may be effective in treating depression. For instance, [[celecoxib]], an NSAID, is a selective COX-2 inhibitor– which is an enzyme that helps in the production of pain and inflammation.<ref>{{Cite web |date=24 May 2022 |title=COX-2 Inhibitors |url=https://my.clevelandclinic.org/health/drugs/23119-cox-2-inhibitors |access-date= 23 June 2024 |website=Cleveland Clinic}}</ref> In recent clinical trials, this NSAID has been shown helpful with treatment-resistant depression as it helps inhibit proinflammatory signaling.<ref name="pmid37240605">{{cite journal |vauthors=Gędek A, Szular Z, Antosik AZ, Mierzejewski P, Dominiak M |title=Celecoxib for Mood Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials |journal=Journal of Clinical Medicine |volume=12 |issue=10 |date=May 2023 |page=3497 |pmid=37240605 |pmc=10218898 |doi=10.3390/jcm12103497|doi-access=free }}</ref><ref>{{cite journal | vauthors = Beckett CW, Niklison-Chirou MV | title = The role of immunomodulators in treatment-resistant depression: case studies | journal = Cell Death Discovery | volume = 8 | issue = 1 | pages = 367 | date = August 2022 | pmid = 35977923 | pmc = 9385739 | doi = 10.1038/s41420-022-01147-6 }}</ref>

[[Statin]]s, which are anti-inflammatory medications prescribed to lower cholesterol levels, have also been shown to have antidepressant effects. When prescribed for patients already taking SSRIs, this add-on treatment was shown to improve anti-depressant effects of SSRIs when compared to the placebo group. With this, statins have been shown to be effective in preventing depression in some cases too.<ref>{{cite journal | vauthors = Gutlapalli SD, Farhat H, Irfan H, Muthiah K, Pallipamu N, Taheri S, Thiagaraj SS, Shukla TS, Giva S, Penumetcha SS | title = The Anti-Depressant Effects of Statins in Patients With Major Depression Post-Myocardial Infarction: An Updated Review 2022 | journal = Cureus | volume = 14 | issue = 12 | pages = e32323 | date = December 2022 | pmid = 36628002 | pmc = 9825119 | doi = 10.7759/cureus.32323 | doi-access = free }}</ref>

There is insufficient high quality evidence to suggest [[omega-3 fatty acid]]s are effective in depression.<ref>{{cite journal | vauthors = Appleton KM, Voyias PD, Sallis HM, Dawson S, Ness AR, Churchill R, Perry R | title = Omega-3 fatty acids for depression in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 11 | pages = CD004692 | date = November 2021 | pmid = 34817851 | pmc = 8612309 | doi = 10.1002/14651858.CD004692.pub5 }}</ref> There is limited evidence that vitamin D supplementation is of value in alleviating the symptoms of depression in individuals who are vitamin D-deficient.<ref name=Parker2017>{{cite journal | vauthors = Parker GB, Brotchie H, Graham RK | title = Vitamin D and depression | journal = Journal of Affective Disorders | volume = 208 | pages = 56–61 | date = January 2017 | pmid = 27750060 | doi = 10.1016/j.jad.2016.08.082 }}</ref> [[Lithium (medication)|Lithium]] appears effective at lowering the risk of suicide in those with bipolar disorder and unipolar depression by about 80%.<ref name="b789">{{cite journal | last1=Tondo | first1=Leonardo | last2=Baldessarini | first2=Ross J. | title=Prevention of suicidal behavior with lithium treatment in patients with recurrent mood disorders | journal=International Journal of Bipolar Disorders | volume=12 | issue=1 | date=9 March 2024 | issn=2194-7511 | pmid=38460088 | pmc=10924823 | doi=10.1186/s40345-024-00326-x | doi-access=free | page=6}}</ref> There is a narrow range of effective and safe dosages of lithium thus close monitoring may be needed.<ref name="x631">{{cite journal | last1=Nolen | first1=Willem A. | last2=Licht | first2=Rasmus W. | last3=Young | first3=Allan H. | last4=Malhi | first4=Gin S. | last5=Tohen | first5=Mauricio | last6=Vieta | first6=Eduard | last7=Kupka | first7=Ralph W. | last8=Zarate | first8=Carlos | last9=Nielsen | first9=René E. | last10=Baldessarini | first10=Ross J. | last11=Severus | first11=Emanuel | author12=the ISBD/IGSLI Task Force on the treatment with lithium | title=What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium | journal=Bipolar Disorders | volume=21 | issue=5 | date=2019 | issn=1398-5647 | pmid=31112628 | pmc=6688930 | doi=10.1111/bdi.12805 | doi-access=free | pages=394–409 }}</ref> Low-dose [[thyroid hormone]] may be added to existing antidepressants to treat persistent depression symptoms.<ref name="z385">{{cite journal | last1=Bauer | first1=M. | last2=Whybrow | first2=P. C. | title=Role of thyroid hormone therapy in depressive disorders | journal=Journal of Endocrinological Investigation | volume=44 | issue=11 | date=2021 | issn=1720-8386 | pmid=34129186 | pmc=8502157 | doi=10.1007/s40618-021-01600-w | doi-access=free | pages=2341–2347 | url=https://link.springer.com/content/pdf/10.1007/s40618-021-01600-w.pdf | access-date=17 March 2025}}</ref> Limited evidence suggests [[stimulants]], such as [[amphetamine]] and [[modafinil]], may be effective in the short term, or as [[adjuvant therapy]].<ref name="j433">{{cite journal | last1=Bahji | first1=Anees | last2=Mesbah-Oskui | first2=Lia | title=Comparative efficacy and safety of stimulant-type medications for depression: A systematic review and network meta-analysis | journal=Journal of Affective Disorders | volume=292 | date=2021 | doi=10.1016/j.jad.2021.05.119 | pages=416–423| pmid=34144366 }}</ref><ref>{{cite journal | vauthors = Malhi GS, Byrow Y, Bassett D, Boyce P, Hopwood M, Lyndon W, Mulder R, Porter R, Singh A, Murray G | title = Stimulants for depression: On the up and up? | journal = The Australian and New Zealand Journal of Psychiatry | volume = 50 | issue = 3 | pages = 203–207 | date = March 2016 | pmid = 26906078 | doi = 10.1177/0004867416634208 | s2cid = 45341424 }}</ref> Also, it is suggested that [[folate]] supplements may have a role in depression management.<ref>{{cite journal | vauthors = Taylor MJ, Carney S, Geddes J, Goodwin G | title = Folate for depressive disorders | journal = The Cochrane Database of Systematic Reviews | volume = 2003 | issue = 2 | pages = CD003390 | year = 2003 | pmid = 12804463 | pmc = 6991158 | doi = 10.1002/14651858.CD003390 }}</ref> There is tentative evidence for benefit from [[testosterone]] in males.<ref>{{cite journal | vauthors = Walther A, Breidenstein J, Miller R | title = Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men: A Systematic Review and Meta-analysis | journal = JAMA Psychiatry | volume = 76 | issue = 1 | pages = 31–40 | date = January 2019 | pmid = 30427999 | pmc = 6583468 | doi = 10.1001/jamapsychiatry.2018.2734 }}</ref>

===Electroconvulsive therapy===
[[Electroconvulsive therapy]] (ECT) is a standard [[psychiatry|psychiatric]] treatment in which [[seizure]]s are electrically induced in a person with depression to provide relief from psychiatric illnesses.<ref name="d505">{{cite journal | last1=Deng | first1=Zhi-De | last2=Robins | first2=Pei L. | last3=Regenold | first3=William | last4=Rohde | first4=Paul | last5=Dannhauer | first5=Moritz | last6=Lisanby | first6=Sarah H. | title=How electroconvulsive therapy works in the treatment of depression: is it the seizure, the electricity, or both? | journal=Neuropsychopharmacology | volume=49 | issue=1 | date=2024 | issn=0893-133X | pmid=37488281 | pmc=10700353 | doi=10.1038/s41386-023-01677-2 | doi-access=free | pages=150–162 | url=https://www.nature.com/articles/s41386-023-01677-2.pdf | access-date=15 March 2025}}</ref> ECT is used with [[informed consent]]<ref name="u822">{{cite journal | last1=Espinoza | first1=Randall T. | last2=Kellner | first2=Charles H. | title=Electroconvulsive Therapy | journal=New England Journal of Medicine | volume=386 | issue=7 | date=17 February 2022 | issn=0028-4793 | doi=10.1056/NEJMra2034954 | pages=667–672| pmid=35172057 }}</ref> as a last line of intervention for major depressive disorder.<ref name="o804" /> A round of ECT is effective for about 50% of people with treatment-resistant major depressive disorder, whether it is unipolar or [[Bipolar II disorder|bipolar]].<ref>{{cite journal |vauthors=Dierckx B, Heijnen WT, van den Broek WW, Birkenhäger TK |title=Efficacy of electroconvulsive therapy in bipolar versus unipolar major depression: a meta-analysis |journal=Bipolar Disorders |volume=14 |issue=2 |pages=146–50 |date=March 2012 |pmid=22420590 |doi=10.1111/j.1399-5618.2012.00997.x |s2cid=44280002 }}</ref> Follow-up treatment is still poorly studied, but about half of people who respond relapse within twelve months.<ref>{{cite journal |vauthors=Jelovac A, Kolshus E, McLoughlin DM |title=Relapse following successful electroconvulsive therapy for major depression: a meta-analysis |journal=Neuropsychopharmacology |volume=38 |issue=12 |pages=2467–74 |date=November 2013 |pmid=23774532 |pmc=3799066 |doi=10.1038/npp.2013.149 }}</ref> Aside from effects in the brain, the general physical risks of ECT are similar to those of brief [[general anesthesia]].<ref name="SG">Surgeon General (1999). [http://www.surgeongeneral.gov/library/mentalhealth/home.html ''Mental Health: A Report of the Surgeon General''] {{webarchive|url=https://web.archive.org/web/20070112012907/http://www.surgeongeneral.gov/library/mentalhealth/home.html |date=12 January 2007 }}, chapter 4.</ref>{{rp|259}} Immediately following treatment, the most common adverse effects are confusion and memory loss.<ref name=FDA2011rev>FDA. [https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/UCM240933.pdf FDA Executive Summary] {{webarchive|url=https://web.archive.org/web/20150924161659/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/UCM240933.pdf |date=24 September 2015 }}. Prepared for the 27–28 January 2011 meeting of the Neurological Devices Panel Meeting to Discuss the Classification of Electroconvulsive Therapy Devices (ECT). Quote, p38: "Three major practice guidelines have been published on ECT. These guidelines include: APA Task Force on ECT (2001); Third report of the Royal College of Psychiatrists' Special Committee on ECT (2004); National Institute for Health and Clinical Excellence (NICE 2003; NICE 2009). There is significant agreement between the three sets of recommendations."</ref><ref>{{cite book |title=The practice of electroconvulsive therapy: recommendations for treatment, training, and privileging|edition=2nd|location=Washington, DC|publisher=American Psychiatric Association |year=2001|url=https://books.google.com/books?id=iuuLJtmo_EYC|isbn=978-0-89042-206-9|author=Committee on Electroconvulsive Therapy }}</ref> ECT is considered one of the least harmful treatment options available for severely depressed pregnant women.<ref name=Pompili2014Rev>{{cite journal |vauthors=Pompili M, Dominici G, Giordano G, et al |title=Electroconvulsive treatment during pregnancy: a systematic review |journal=Expert Review of Neurotherapeutics |volume=14 |issue=12 |pages=1377–90 |date=December 2014 |pmid=25346216 |doi=10.1586/14737175.2014.972373 |s2cid=31209001 }}</ref>

A usual course of ECT involves multiple administrations, typically given two or three times per week, with a total of six to twelve treatments.<ref name="d426">{{cite book | last=Kroll | first=David S. | title=Caring for Patients with Depression in Primary Care | chapter=Treatment Resistance and Advanced Therapies | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-031-08494-2 | doi=10.1007/978-3-031-08495-9_6 | pages=61–73}}</ref> ECT is administered under [[anesthesia]] with a [[muscle relaxant]].<ref>{{cite web|url=http://psychcentral.com/lib/5-outdated-beliefs-about-ect/00011255|title=5 Outdated Beliefs About ECT|website=Psych Central.com|url-status=live|archive-url=https://web.archive.org/web/20130808042410/http://psychcentral.com/lib/5-outdated-beliefs-about-ect/00011255|archive-date=8 August 2013|date=17 May 2016}}</ref> Electroconvulsive therapy can differ in its application in three ways: electrode placement, frequency of treatments, and the electrical waveform of the stimulus. These three forms of application have significant differences in both adverse side effects and symptom remission. After treatment, drug therapy is usually continued, and some people receive maintenance ECT.<ref name=FDA2011rev />

ECT appears to work in the short term via an [[anticonvulsant]] effect mostly in the [[frontal lobes]], and longer term via [[neurotrophic]] effects primarily in the [[medial temporal lobe]].<ref name=Abbott2014>{{cite journal |vauthors=Abbott CC, Gallegos P, Rediske N, Lemke NT, Quinn DK |title=A review of longitudinal electroconvulsive therapy: neuroimaging investigations |journal=Journal of Geriatric Psychiatry and Neurology |volume=27 |issue=1 |pages=33–46 |date=March 2014 |pmid=24381234 |pmc=6624835 |doi=10.1177/0891988713516542 }}</ref>

===Other===
[[Transcranial magnetic stimulation]] (TMS) or [[deep transcranial magnetic stimulation]] is a noninvasive method used to stimulate small regions of the brain.<ref>{{Cite web|url=http://www.nice.org.uk/guidance/ipg477/resources/guidance-transcranial-magnetic-stimulation-for-treating-and-preventing-migraine-pdf |title=NiCE. January 2014 Transcranial magnetic stimulation for treating and preventing migraine |archive-url=https://web.archive.org/web/20151004194631/http://www.nice.org.uk/guidance/ipg477/resources/guidance-transcranial-magnetic-stimulation-for-treating-and-preventing-migraine-pdf |archive-date=4 October 2015 }}</ref> TMS was approved by the FDA for treatment-resistant major depressive disorder (trMDD) in 2008.<ref name="g379" /> Recent systematic reviews have found that the effects of TMS on clinical response, remission, and severity in depression appear not to be statistically or clinically significant.<ref>{{cite web | title=Stimulation magnétique transcrânienne dans le traitement de la dépression de l'adulte | website={{interlanguage link|Haute Autorité de Santé|fr}} | date=25 July 2022 | url=https://www.has-sante.fr/jcms/p_3211966/fr/stimulation-magnetique-transcranienne-dans-le-traitement-de-la-depression-de-l-adulte | access-date=16 February 2025}}</ref><ref>{{cite journal | vauthors= Brini S, Brudasca NI, Hodkinson A, Kaluzinska K, Wach A, Storman D, Prokop-Dorner A, Jemioło P, Bala MM | title=Efficacy and safety of transcranial magnetic stimulation for treating major depressive disorder: An umbrella review and re-analysis of published meta-analyses of randomised controlled trials | journal = Clinical Psychology Review | volume = 100 | pages = 102236 | date = March 2023 | pmid = 36587461 | doi=10.1016/j.cpr.2022.102236 | doi-access=free}}</ref> The American Psychiatric Association,<ref>{{Cite web |url=http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf |publisher=American Psychiatric Association |year=2010 |veditors=Gelenberg AJ, Freeman MP, Markowitz JC, Rosenbaum JF, Thase ME, Trivedi MH, Van Rhoads RS |title=Practice Guidelines for the Treatment of Patients with Major Depressive Disorder |edition=3rd }}</ref> the Canadian Network for Mood and Anxiety Disorders,<ref>{{cite journal | vauthors=Kennedy SH, Lam RW, Parikh SV, Patten SB, Ravindran AV | title=Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults | journal=Journal of Affective Disorders | publisher=Elsevier BV | volume=117 | issue=Suppl 1 | year=2009 | issn=0165-0327 | doi=10.1016/j.jad.2009.06.043 | pages=S1–S64 | pmid=19682750 | url=http://www.canmat.org/resources/CANMAT%20Depression%20Guidelines%202009.pdf | archive-url=https://web.archive.org/web/20150823230409/http://www.canmat.org/resources/canmat%20depression%20guidelines%202009.pdf | archive-date=23 August 2015 }}</ref> and the Royal Australia and New Zealand College of Psychiatrists have endorsed TMS for trMDD.<ref>{{cite journal |vauthors=Rush AJ, Marangell LB, Sackeim HA, et al |title=Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial |journal=Biological Psychiatry |volume=58 |issue=5 |pages=347–54 |date=September 2005 |pmid=16139580 |doi=10.1016/j.biopsych.2005.05.025|s2cid=22066326 |url=http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1069&context=veterans }}</ref> [[Transcranial direct current stimulation]] (tDCS) is another noninvasive method used to stimulate small regions of the brain with a weak electric current. Several meta-analyses have concluded that active tDCS was useful for treating depression.<ref>{{cite journal |vauthors=Fregni F, El-Hagrassy MM, Pacheco-Barrios K, et al |title=Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders |journal=Int J Neuropsychopharmacol |volume=24 |issue=4 |pages=256–313 |date=April 2021 |pmid=32710772 |pmc=8059493 |doi=10.1093/ijnp/pyaa051 }}</ref><ref>{{cite journal | vauthors = Moffa AH, Martin D, Alonzo A, et al | title = Efficacy and acceptability of transcranial direct current stimulation (tDCS) for major depressive disorder: An individual patient data meta-analysis | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 99 | page = 109836 | date = April 2020 | pmid = 31837388 | doi = 10.1016/j.pnpbp.2019.109836 | s2cid = 209373871 | hdl = 1959.4/unsworks_81424 | url = https://unsworks.unsw.edu.au/bitstreams/967e9af1-ae7e-4a90-98f0-7f943f35d83b/download | hdl-access = free }}</ref>

There is a small amount of evidence that [[sleep deprivation]] may improve depressive symptoms in some individuals,<ref>{{cite journal |vauthors=Ioannou M, Wartenberg C, Greenbrook JT, et al |title=Sleep deprivation as treatment for depression: Systematic review and meta-analysis |journal=Acta Psychiatr Scand |volume=143 |issue=1 |pages=22–35 |date=January 2021 |pmid=33145770 |pmc=7839702 |doi=10.1111/acps.13253 }}</ref> with the effects usually showing up within a day. This effect is usually temporary. Besides sleepiness, this method can cause a side effect of [[mania]] or [[hypomania]].<ref>{{cite journal |vauthors=Giedke H, Schwärzler F |title=Therapeutic use of sleep deprivation in depression |journal=Sleep Medicine Reviews |volume=6 |issue=5 |pages=361–77 |date=October 2002 |pmid=12531127 |doi=10.1053/smrv.2002.0235 }}</ref> There is insufficient evidence for [[Reiki]]<ref>{{cite journal | vauthors = Joyce J, Herbison GP | title = Reiki for depression and anxiety | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD006833 | date = April 2015 | pmid = 25835541 | doi = 10.1002/14651858.cd006833.pub2 | pmc = 11088458 }}</ref> and [[dance movement therapy]] in depression.<ref>{{cite journal | vauthors = Meekums B, Karkou V, Nelson EA | title = Dance movement therapy for depression | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD009895 | date = February 2015 | volume = 2016 | pmid = 25695871 | doi = 10.1002/14651858.cd009895.pub2 | pmc = 8928931 | url = http://eprints.whiterose.ac.uk/87222/8/Meekums_et_al-2015-The_Cochrane_Library.pdf }}</ref> [[Medical cannabis|Cannabis]] is specifically not recommended as a treatment.<ref>{{cite journal | vauthors = Black N, Stockings E, Campbell G, et al | title = Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis | journal = The Lancet. Psychiatry | volume = 6 | issue = 12 | pages = 995–1010 | date = December 2019 | pmid = 31672337 | pmc = 6949116 | doi = 10.1016/S2215-0366(19)30401-8 }}</ref>

The [[Human microbiome|microbiome]] of people with major depressive disorder differs from that of healthy people, and [[probiotic]] and [[Synbiotics|synbiotic]] treatment may achieve a modest depressive symptom reduction.<ref>{{cite journal | vauthors = Sanada K, Nakajima S, Kurokawa S, Barceló-Soler A, Ikuse D, Hirata A, Yoshizawa A, Tomizawa Y, Salas-Valero M, Noda Y, Mimura M, Iwanami A, Kishimoto T | title = Gut microbiota and major depressive disorder: A systematic review and meta-analysis | journal = Journal of Affective Disorders | volume = 266 | pages = 1–13 | date = April 2020 | pmid = 32056863 | doi = 10.1016/j.jad.2020.01.102 }}</ref><ref>{{cite journal | vauthors = Alli SR, Gorbovskaya I, Liu JC, Kolla NJ, Brown L, Müller DJ | title = The Gut Microbiome in Depression and Potential Benefit of Prebiotics, Probiotics and Synbiotics: A Systematic Review of Clinical Trials and Observational Studies | journal = International Journal of Molecular Sciences | volume = 23 | issue = 9 | pages = 4494 | date = April 2022 | pmid = 35562885 | pmc = 9101152 | doi = 10.3390/ijms23094494 | doi-access = free }}</ref> With this, [[fecal microbiota transplant]]s (FMT) are being researched as add-on therapy treatments for people who do not respond to typical therapies. It has been shown that the patient's depressive symptoms improved, with minor gastrointestinal issues, after a FMT, with improvements in symptoms lasting at least 4 weeks after the transplant.<ref>{{cite journal | vauthors = Doll JP, Vázquez-Castellanos JF, Schaub AC, Schweinfurth N, Kettelhack C, Schneider E, Yamanbaeva G, Mählmann L, Brand S, Beglinger C, Borgwardt S, Raes J, Schmidt A, Lang UE | title = Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression-Case Report | journal = Frontiers in Psychiatry | volume = 13 | pages = 815422 | date = 17 February 2022 | pmid = 35250668 | pmc = 8891755 | doi = 10.3389/fpsyt.2022.815422 | doi-access = free }}</ref>

==Prognosis==
Studies have shown that 80% of those with a first major depressive episode will have at least one more during their life,<ref>{{cite journal |vauthors=Fava GA, Park SK, Sonino N |title=Treatment of recurrent depression |journal=Expert Review of Neurotherapeutics |volume=6 |issue=11 |pages=1735–40 |date=November 2006 |pmid=17144786 |doi=10.1586/14737175.6.11.1735 |s2cid=22808803 }}</ref> with a lifetime average of four episodes.<ref>{{cite journal |vauthors=Limosin F, Mekaoui L, Hautecouverture S |title=[Prophylactic treatment for recurrent major depression] |journal=Presse Médicale |volume=36 |issue=11 Pt 2 |pages=1627–33 |date=November 2007 |pmid=17555914 |doi=10.1016/j.lpm.2007.03.032 }}</ref> Other general population studies indicate that around half those who have an episode recover (whether treated or not) and remain well, while the other half will have at least one more, and around 15% of those experience chronic recurrence.<ref>{{cite journal |vauthors=Eaton WW, Shao H, Nestadt G, et al |title=Population-based study of first onset and chronicity in major depressive disorder |journal=Archives of General Psychiatry |volume=65 |issue=5 |pages=513–20 |date=May 2008 |pmid=18458203 |pmc=2761826 |doi=10.1001/archpsyc.65.5.513 }}</ref> Studies recruiting from selective inpatient sources suggest lower recovery and higher chronicity, while studies of mostly outpatients show that nearly all recover, with a median episode duration of 11 months. Around 90% of those with severe or psychotic depression, most of whom also meet criteria for other mental disorders, experience recurrence.<ref>{{cite journal |vauthors=Holma KM, Holma IA, Melartin TK, Rytsälä HJ, Isometsä ET |title=Long-term outcome of major depressive disorder in psychiatric patients is variable |journal=The Journal of Clinical Psychiatry |volume=69 |issue=2 |pages=196–205 |date=February 2008 |pmid=18251627 |doi=10.4088/JCP.v69n0205 }}</ref><ref>{{cite journal |vauthors=Kanai T, Takeuchi H, Furukawa TA, et al |title=Time to recurrence after recovery from major depressive episodes and its predictors |journal=Psychological Medicine |volume=33 |issue=5 |pages=839–45 |date=July 2003 |pmid=12877398 |doi=10.1017/S0033291703007827 |s2cid=10490348 }}</ref> Cases when outcome is poor are associated with inappropriate treatment, severe initial symptoms including psychosis, early age of onset, previous episodes, incomplete recovery after one year of treatment, pre-existing severe mental or medical disorder, and [[family dysfunction]].<ref>{{cite web|url=http://www.mdguidelines.com/depression-major/prognosis|title=Depression, Major: Prognosis|website=MDGuidelines|publisher=[[The Guardian Life Insurance Company of America]]|access-date=16 July 2010|url-status=live|archive-url=https://web.archive.org/web/20100420055044/http://www.mdguidelines.com/depression-major/prognosis|archive-date=20 April 2010}}</ref>

A high proportion of people who experience full symptomatic remission still have at least one not fully resolved symptom after treatment.<ref name=Culpepper2015>{{cite journal | vauthors = Culpepper L, Muskin PR, Stahl SM | title = Major Depressive Disorder: Understanding the Significance of Residual Symptoms and Balancing Efficacy with Tolerability | journal = The American Journal of Medicine | volume = 128 | issue = 9 Suppl | pages = S1–S15 | date = September 2015 | pmid = 26337210 | doi = 10.1016/j.amjmed.2015.07.001 | doi-access = free }}</ref> Recurrence or chronicity is more likely if symptoms have not fully resolved with treatment.<ref name=Culpepper2015/> Current guidelines recommend continuing antidepressants for four to six&nbsp;months after remission to prevent relapse. Evidence from many [[randomized controlled trial]]s indicates continuing antidepressant medications after recovery can reduce the chance of relapse by 70% (41% on placebo vs. 18% on antidepressant). The preventive effect probably lasts for at least the first 36&nbsp;months of use.<ref>{{cite journal | vauthors = Geddes JR, Carney SM, Davies C, et al | title = Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review | journal = Lancet | volume = 361 | issue = 9358 | pages = 653–61 | date = February 2003 | pmid = 12606176 | doi = 10.1016/S0140-6736(03)12599-8 | s2cid = 20198748 }}</ref>

Major depressive episodes often resolve over time, whether or not they are treated. Outpatients on a waiting list show a 10–15% reduction in symptoms within a few months, with approximately 20% no longer meeting the full criteria for a depressive disorder.<ref>{{cite journal |vauthors=Posternak MA, Miller I |title=Untreated short-term course of major depression: a meta-analysis of outcomes from studies using wait-list control groups |journal=Journal of Affective Disorders |volume=66 |issue=2–3 |pages=139–46 |date=October 2001 |pmid=11578666 |doi=10.1016/S0165-0327(00)00304-9 }}</ref> The [[median]] duration of an episode has been estimated to be 23 weeks, with the highest rate of recovery in the first three months.<ref>{{cite journal |vauthors=Posternak MA, Solomon DA, Leon AC, et al |title=The naturalistic course of unipolar major depression in the absence of somatic therapy |journal=The Journal of Nervous and Mental Disease |volume=194 |issue=5 |pages=324–29 |date=May 2006 |pmid=16699380 |doi=10.1097/01.nmd.0000217820.33841.53 |s2cid=22891687 }}</ref> According to a 2013 review, 23% of untreated adults with mild to moderate depression will remit within 3 months, 32% within 6 months and 53% within 12 months.<ref>{{cite journal | vauthors= Whiteford HA, Harris MG, McKeon G, et al | title=Estimating remission from untreated major depression: a systematic review and meta-analysis | journal=Psychological Medicine | publisher=Cambridge University Press (CUP) | volume=43 | issue=8 | date=10 August 2012 | issn=0033-2917 | pmid=22883473 | doi=10.1017/s0033291712001717 | pages=1569–1585| s2cid=11068930 }}</ref>

===Ability to work===
Depression may affect people's ability to work. The combination of usual clinical care and support with return to work (like working less hours or changing tasks) probably reduces sick leave by 15%, and leads to fewer depressive symptoms and improved work capacity, reducing sick leave by an annual average of 25 days per year.<ref name=Nieuwenhuijsen2020>{{cite journal |vauthors=Nieuwenhuijsen K, Verbeek JH, Neumeyer-Gromen A, et al |title=Interventions to improve return to work in depressed people |journal=Cochrane Database Syst Rev |volume=10 |issue= 12|pages=CD006237 |date=October 2020 |pmid=33052607 |doi=10.1002/14651858.CD006237.pub4 |pmc=8094165 }}</ref> Helping depressed people return to work without a connection to clinical care has not been shown to have an effect on sick leave days. Additional psychological interventions (such as online cognitive behavioral therapy) lead to fewer sick days compared to standard management only. Streamlining care or adding specific providers for depression care may help to reduce sick leave.<ref name=Nieuwenhuijsen2020/>

===Life expectancy and the risk of suicide===
Depressed individuals have a shorter [[life expectancy]] than those without depression, in part because people who are depressed are at risk of dying of suicide.<ref>{{cite journal |vauthors=Cassano P, Fava M |title=Depression and public health: an overview |journal=Journal of Psychosomatic Research |volume=53 |issue=4 |pages=849–57 |date=October 2002 |pmid=12377293 |doi=10.1016/S0022-3999(02)00304-5 }}</ref> About 50% of people who die of suicide have a [[mood disorder]] such as major depression, and the risk is especially high if a person has a marked sense of hopelessness or has both depression and [[borderline personality disorder]].{{sfn|Barlow|Durand|2005|pp=248–49}}<ref>{{cite journal |vauthors=Bachmann S |title=Epidemiology of Suicide and the Psychiatric Perspective |journal=International Journal of Environmental Research and Public Health |date=6 July 2018 |volume=15 |issue=7 |page=1425 |doi=10.3390/ijerph15071425 |pmid=29986446|pmc=6068947 |quote=Half of all completed suicides are related to depressive and other mood disorders|doi-access=free }}</ref> About 2–8% of adults with major depression die by [[suicide]].<ref name="z273">{{cite journal |last1=Arnone |first1=Danilo |last2=Karmegam |first2=Sendhil Raj |last3=Östlundh |first3=Linda |last4=Alkhyeli |first4=Fatima |last5=Alhammadi |first5=Lamia |last6=Alhammadi |first6=Shama |last7=Alkhoori |first7=Amal |last8=Selvaraj |first8=Sudhakar |title=Risk of suicidal behavior in patients with major depression and bipolar disorder – A systematic review and meta-analysis of registry-based studies |journal=Neuroscience & Biobehavioral Reviews |volume=159 |date=2024 |doi=10.1016/j.neubiorev.2024.105594 |doi-access=free |page=105594|pmid=38368970 }}</ref><ref>{{cite book | vauthors = Strakowski S, Nelson E |title=Major Depressive Disorder |date=2015 |publisher=Oxford University Press |isbn=978-0-19-026432-1 |page=PT27 |url=https://books.google.com/books?id=nD8FCgAAQBAJ&pg=PT27 }}</ref> In the US, the lifetime risk of suicide associated with a diagnosis of major depression is estimated at 7% for men and 1% for women,<ref>{{cite journal |vauthors=Blair-West GW, Mellsop GW |title=Major depression: does a gender-based down-rating of suicide risk challenge its diagnostic validity? |journal=The Australian and New Zealand Journal of Psychiatry |volume=35 |issue=3 |pages=322–28 |date=June 2001 |pmid=11437805 |doi=10.1046/j.1440-1614.2001.00895.x |s2cid=36975913 }}</ref> even though suicide attempts are more frequent in women.<ref>{{cite journal |vauthors=Oquendo MA, Bongiovi-Garcia ME, Galfalvy H, et al |title=Sex differences in clinical predictors of suicidal acts after major depression: a prospective study |journal=The American Journal of Psychiatry |volume=164 |issue=1 |pages=134–41 |date=January 2007 |pmid=17202555 |pmc=3785095 |doi=10.1176/ajp.2007.164.1.134 }}</ref>

Depressed people also have a higher [[mortality rate|rate of dying]] from other causes.<ref>{{cite journal |vauthors=Rush AJ |title=The varied clinical presentations of major depressive disorder |journal=The Journal of Clinical Psychiatry |volume=68 |issue=Supplement 8 |pages=4–10 |year=2007 |pmid=17640152 }}</ref> There is a 1.5- to 2-fold increased risk of [[cardiovascular disease]], independent of other known risk factors, and is itself linked directly or indirectly to risk factors such as smoking and obesity. People with major depression are less likely to follow medical recommendations for treating and preventing [[cardiovascular disorders]], further increasing their risk of medical complications.<ref>{{cite journal |vauthors=Swardfager W, Herrmann N, Marzolini S, et al |title=Major depressive disorder predicts completion, adherence, and outcomes in cardiac rehabilitation: a prospective cohort study of 195 patients with coronary artery disease |journal=The Journal of Clinical Psychiatry |volume=72 |issue=9 |pages=1181–88 |date=September 2011 |pmid=21208573 |doi=10.4088/jcp.09m05810blu}}</ref> [[Cardiologists]] may not recognize underlying depression that complicates a cardiovascular problem under their care.<ref>{{cite journal|vauthors=Schulman J, Shapiro BA|year=2008|journal=Psychiatric Times|volume=25|issue=9|title=Depression and Cardiovascular Disease: What Is the Correlation?|url=http://www.psychiatrictimes.com/depression/article/10168/1171821|access-date=10 June 2009|archive-date=6 March 2020|archive-url=https://web.archive.org/web/20200306051101/http://www.psychiatrictimes.com/depression/article/10168/1171821}}</ref>

==Epidemiology==
{{Main|Epidemiology of depression}}
[[File:Unipolar depressive disorders world map - DALY - WHO2004.svg|thumb|upright=1.15|[[Disability-adjusted life year]] for unipolar depressive disorders per 100,000 inhabitants in 2004:<ref>{{cite web |url=https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |title=WHO Disease and injury country estimates |year=2009 |website=World Health Organization |access-date=11 November 2009 |url-status=live |archive-url=https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |archive-date=11 November 2009 }}</ref>
{{Div col|colwidth=10em}}
{{legend|#b3b3b3|no data}}
{{legend|#ffff65|<700}}
{{legend|#fff200|700–775}}
{{legend|#ffdc00|775–850}}
{{legend|#ffc600|850–925}}
{{legend|#ffb000|925–1,000}}
{{legend|#ff9a00|1,000–1,075}}
{{legend|#ff8400|1,075–1,150}}
{{legend|#ff6e00|1,150–1,225}}
{{legend|#ff5800|1,225–1,300}}
{{legend|#ff4200|1,300–1,375}}
{{legend|#ff2c00|1,375–1,450}}
{{legend|#cb0000|>1,450}}
{{Div col end}}]]

Major depressive disorder affected approximately 163&nbsp;million people in 2017 (2% of the global population).<ref name="GBD 2017 prevalence">{{cite journal |author=((GBD 2017 Disease and Injury Incidence and Prevalence Collaborators)) |date=10 November 2018 |title=Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017 |journal=Lancet |volume=392 |issue=10159 |pages=1789–1858 |doi=10.1016/S0140-6736(18)32279-7 |pmc=6227754 |pmid=30496104}}</ref> The percentage of people who are affected at one point in their life varies from 7% in Japan to 21% in France. In most countries the number of people who have depression during their lives falls within an 8–18% range. Lifetime rates are higher in the [[developed world]] (15%) compared to the [[developing world]] (11%).<ref name="Kes2013" />

In the United States, 8.4% of adults (21&nbsp;million individuals) have at least one episode within a year-long period; the probability of having a major depressive episode is higher for females than males (10.5% to 6.2%), and highest for those aged 18 to 25 (17%).<ref name= NIMHMajorDepression>{{cite web |url= https://www.nimh.nih.gov/health/statistics/major-depression |publisher= U.S. [[National Institute of Mental Health]] (NIMH) |date= January 2022 |title= Major depression |archive-url=https://web.archive.org/web/20220809144808/https://www.nimh.nih.gov/health/statistics/major-depression |archive-date= 9 August 2022 |access-date= 14 August 2022}} {{Pd-notice}}</ref> 15% of adolescents, ages 12 to 17, in America are also affected by depression, which is equal to 3.7 million teenagers.<ref name="DP">{{Cite web |title=Depression |url=https://mhanational.org/conditions/depression |access-date=23 June 2024 |website=Mental Health America |language=en}}</ref> Among individuals reporting two or more races, the US prevalence is highest.<ref name=NIMHMajorDepression/> Out of all the people suffering from MDD, only about 35% seek help from a professional for their disorder.<ref name="DP" />

Major depression is about twice as common in women as in men, although it is unclear why this is so, and whether factors unaccounted for are contributing to this.<ref name="Kuehner03">{{cite journal |vauthors=Kuehner C |title=Gender differences in unipolar depression: an update of epidemiological findings and possible explanations |journal=Acta Psychiatrica Scandinavica |volume=108 |issue=3 |pages=163–74 |date=September 2003 |pmid=12890270 |doi=10.1034/j.1600-0447.2003.00204.x |s2cid=19538251}}</ref> The relative increase in occurrence is related to pubertal development rather than chronological age, reaches adult ratios between the ages of 15 and 18, and appears associated with psychosocial more than hormonal factors.<ref name="Kuehner03" /> In 2019, major depressive disorder was identified (using either the DSM-IV-TR or ICD-10) in the [[Global Burden of Disease Study]] as the fifth most common cause of [[years lived with disability]] and the 18th most common for [[disability-adjusted life years]].<ref>{{citation |author=Institute for Health Metrics and Evaluation |author-link=Institute for Health Metrics and Evaluation |year=2020 |title=Global Burden of Disease 2019 Cause and Risk Summary: Major depressive disorder — Level 4 cause |at=Table 3 |url=https://www.healthdata.org/results/gbd_summaries/2019/major-depressive-disorder-level-4-cause |publisher=University of Washington |place=Seattle, US |access-date=9 July 2022}}</ref><!-- the wording of this sentence is very janky, but this best mimics the source. -->

People are most likely to develop their first depressive episode between the ages of 30 and 40, and there is a second, smaller peak of incidence between ages 50 and 60.<ref>{{cite journal |vauthors=Eaton WW, Anthony JC, Gallo J, et al |title=Natural history of Diagnostic Interview Schedule/DSM-IV major depression. The Baltimore Epidemiologic Catchment Area follow-up |journal=Archives of General Psychiatry |volume=54 |issue=11 |pages=993–99 |date=November 1997 |pmid=9366655 |doi=10.1001/archpsyc.1997.01830230023003 }}</ref> The risk of major depression is increased with neurological conditions such as [[stroke]], [[Parkinson's disease]], or [[multiple sclerosis]], and during the first year after childbirth ([[Postpartum depression]]).<ref>{{cite journal |vauthors=Rickards H |title=Depression in neurological disorders: Parkinson's disease, multiple sclerosis, and stroke |journal=Journal of Neurology, Neurosurgery, and Psychiatry |volume=76 |issue=Suppl 1 |pages=i48–52 |date=March 2005 |pmid=15718222 |pmc=1765679 |doi=10.1136/jnnp.2004.060426}}</ref> It is also more common after cardiovascular illnesses, and is related more to those with a poor cardiac [[Prognosis|disease outcome]] than to a better one.<ref>{{cite journal |vauthors=Alboni P, Favaron E, Paparella N, Sciammarella M, Pedaci M |title=Is there an association between depression and cardiovascular mortality or sudden death? |journal=Journal of Cardiovascular Medicine |volume=9 |issue=4 |pages=356–62 |date=April 2008 |pmid=18334889 |doi=10.2459/JCM.0b013e3282785240 |s2cid=11051637 }}</ref><ref>{{cite journal |vauthors=Strik JJ, Honig A, Maes M |title=Depression and myocardial infarction: relationship between heart and mind |journal=Progress in Neuro-Psychopharmacology & Biological Psychiatry |volume=25 |issue=4 |pages=879–92 |date=May 2001 |pmid=11383983 |doi=10.1016/S0278-5846(01)00150-6 |s2cid=45722423 }}</ref> Depressive disorders are more common in urban populations than in rural ones and the prevalence is increased in groups with poorer socioeconomic factors, e.g., homelessness.<ref>Gelder, M, Mayou, R and Geddes, J (2005). ''Psychiatry''. 3rd ed. New York: Oxford. p. 105.</ref> Depression is common among those over 65 years of age and increases in frequency beyond this age.<ref name="SBU">{{Cite web |website=[[Swedish Agency for Health Technology Assessment and Assessment of Social Services]] (SBU) |date=27 January 2015 |title=Depression treatment for the elderly |url=http://www.sbu.se/en/publications/sbu-assesses/depression-treatment-for-the-elderly/ |url-status=live |archive-url=https://web.archive.org/web/20160618011954/http://www.sbu.se/en/publications/sbu-assesses/depression-treatment-for-the-elderly/ |archive-date=18 June 2016 |access-date=16 June 2016}}</ref> The risk of depression increases in relation to the [[Frailty syndrome|frailty]] of the individual.<ref>{{cite journal |vauthors=Soysal P, Veronese N, Thompson, et al |date=July 2017 |title=Relationship between depression and frailty in older adults: A systematic review and meta-analysis |url=http://www.repositorio.ufc.br/handle/riufc/25064 |journal=Ageing Res Rev |volume=36 |pages=78–87 |doi=10.1016/j.arr.2017.03.005 |pmid=28366616 |s2cid=205668529}}</ref> Depression is one of the most important factors which negatively impact quality of life in adults, as well as the elderly.<ref name="SBU" /> Both symptoms and treatment among the elderly differ from those of the rest of the population.<ref name="SBU" />

Major depression was the leading cause of [[disease burden]] in North America and other high-income countries, and the fourth-leading cause worldwide as of 2006. In the year 2030, it is predicted to be the second-leading cause of disease burden worldwide after [[HIV]], according to the WHO.<ref>{{cite journal |vauthors=Mathers CD, Loncar D |title=Projections of global mortality and burden of disease from 2002 to 2030 |journal=PLOS Medicine |volume=3 |issue=11 |page=e442 |date=November 2006 |pmid=17132052 |pmc=1664601 |doi=10.1371/journal.pmed.0030442 |doi-access=free }}</ref> Delay or failure in seeking treatment after relapse and the failure of health professionals to provide treatment are two barriers to reducing disability.<ref>{{cite journal |vauthors=Andrews G |title=Reducing the burden of depression |journal=Canadian Journal of Psychiatry |volume=53 |issue=7 |pages=420–27 |date=July 2008 |pmid=18674396 |doi=10.1177/070674370805300703|doi-access=free }}</ref>

===Comorbidity===
Major depression frequently [[Comorbidity|co-occurs]] with other psychiatric problems. The 1990–92 ''[[National Comorbidity Survey]]'' (US) reported that half of those with major depression also have lifetime [[anxiety]] and its associated disorders, such as [[generalized anxiety disorder]].<ref>{{cite journal |vauthors=Kessler RC, Nelson CB, McGonagle KA, et al|title=Comorbidity of DSM-III-R major depressive disorder in the general population: results from the US National Comorbidity Survey |journal=The British Journal of Psychiatry. Supplement |volume=168 |issue=30 |pages=17–30 |date=June 1996 |pmid=8864145 |doi=10.1192/S0007125000298371 |s2cid=19525295 }}</ref> Anxiety symptoms can have a major impact on the course of a depressive illness, with delayed recovery, increased risk of relapse, greater disability and increased suicidal behavior.<ref>{{cite journal |vauthors=Hirschfeld RM |title=The Comorbidity of Major Depression and Anxiety Disorders: Recognition and Management in Primary Care |journal=Primary Care Companion to the Journal of Clinical Psychiatry |volume=3 |issue=6 |pages=244–54 |date=December 2001 |pmid=15014592 |pmc=181193 |doi=10.4088/PCC.v03n0609 }}</ref> Depressed people have increased rates of alcohol and substance use, particularly dependence,<ref>{{cite journal |vauthors=Grant BF |title=Comorbidity between DSM-IV drug use disorders and major depression: results of a national survey of adults |journal=Journal of Substance Abuse |volume=7 |issue=4 |pages=481–97 |year=1995 |pmid=8838629 |doi=10.1016/0899-3289(95)90017-9 }}</ref><ref>{{cite journal | vauthors = Boden JM, Fergusson DM | title = Alcohol and depression | journal = Addiction | volume = 106 | issue = 5 | pages = 906–14 | date = May 2011 | pmid = 21382111 | doi = 10.1111/j.1360-0443.2010.03351.x | hdl = 10523/10319 | hdl-access = free }}</ref> and around a third of individuals diagnosed with [[attention deficit hyperactivity disorder]] (ADHD) develop comorbid depression.<ref>{{cite book |title=Delivered from distraction: Getting the most out of life with Attention Deficit Disorder |url=https://archive.org/details/deliveredfromdis00edwa |url-access=registration |vauthors=Hallowell EM, Ratey JJ |year=2005 |publisher=Ballantine Books |location=New York|isbn=978-0-345-44231-4 |pages=[https://archive.org/details/deliveredfromdis00edwa/page/253 253–55]}}</ref> [[Post-traumatic stress disorder]] and depression often co-occur.<ref name=NIMHPub/> Depression may also coexist with ADHD, complicating the diagnosis and treatment of both.<ref>{{cite journal |vauthors=Brunsvold GL, Oepen G |title=Comorbid Depression in ADHD: Children and Adolescents |journal=Psychiatric Times |volume=25 |issue=10 |year=2008 |url=http://www.psychiatrictimes.com/adhd/article/10168/1286863 |url-status=live |archive-url=https://web.archive.org/web/20090524050341/http://www.psychiatrictimes.com/adhd/article/10168/1286863 |archive-date=24 May 2009 }}</ref> Depression is also frequently comorbid with [[alcohol use disorder]] and [[personality disorder]]s.<ref>{{cite journal |vauthors=Melartin TK, Rytsälä HJ, Leskelä US, Lestelä-Mielonen PS, Sokero TP, Isometsä ET |title=Current comorbidity of psychiatric disorders among DSM-IV major depressive disorder patients in psychiatric care in the Vantaa Depression Study |journal=The Journal of Clinical Psychiatry |volume=63 |issue=2 |pages=126–34 |date=February 2002 |pmid=11874213 |doi=10.4088/jcp.v63n0207 }}</ref> Depression can also be exacerbated during particular months (usually winter) in those with [[seasonal affective disorder]]. While [[Digital media use and mental health|overuse of digital media]] has been associated with depressive symptoms, using digital media may also improve mood in some situations.<ref>{{cite journal | vauthors = Hoge E, Bickham D, Cantor J | title = Digital Media, Anxiety, and Depression in Children | journal = Pediatrics | volume = 140 | issue = Suppl 2 | pages = S76–S80 | date = November 2017 | pmid = 29093037 | doi = 10.1542/peds.2016-1758G | doi-access = free }}</ref><ref>{{cite journal | vauthors = Elhai JD, Dvorak RD, Levine JC, Hall BJ | title = Problematic smartphone use: A conceptual overview and systematic review of relations with anxiety and depression psychopathology | journal = Journal of Affective Disorders | volume = 207 | pages = 251–259 | date = January 2017 | pmid = 27736736 | doi = 10.1016/j.jad.2016.08.030 | s2cid = 205642153 }}</ref>

Depression and [[pain]] often co-occur. One or more pain symptoms are present in 65% of people who have depression, and anywhere from 5 to 85% of people who are experiencing pain will also have depression, depending on the setting—a lower prevalence in general practice, and higher in specialty clinics. Depression is often underrecognized, and therefore undertreated, in patients presenting with pain.<ref>{{cite journal |vauthors=Bair MJ, Robinson RL, Katon W, Kroenke K |title=Depression and pain comorbidity: a literature review |journal=Archives of Internal Medicine |volume=163 |issue=20 |pages=2433–45 |date=November 2003 |pmid=14609780 |doi=10.1001/archinte.163.20.2433 |url=http://archinte.ama-assn.org/cgi/content/full/163/20/2433(fulltext) |doi-access=free }}</ref> Depression often coexists with physical disorders common among the elderly, such as [[stroke]], other [[cardiovascular diseases]],<ref>{{Cite journal |last1=Krittanawong |first1=Chayakrit |last2=Maitra |first2=Neil Sagar |last3=Qadeer |first3=Yusuf Kamran |last4=Wang |first4=Zhen |last5=Fogg |first5=Sonya |last6=Storch |first6=Eric A. |last7=Celano |first7=Christopher M. |last8=Huffman |first8=Jeff C. |last9=Jha |first9=Manish |last10=Charney |first10=Dennis S. |last11=Lavie |first11=Carl J. |date=1 September 2023 |title=Association of Depression and Cardiovascular Disease |url=https://linkinghub.elsevier.com/retrieve/pii/S0002934323003340 |journal=The American Journal of Medicine |language=English |volume=136 |issue=9 |pages=881–895 |doi=10.1016/j.amjmed.2023.04.036 |issn=0002-9343 |pmid=37247751}}</ref> [[Parkinson's disease]], and [[chronic obstructive pulmonary disease]].<ref>{{cite journal|vauthors=Yohannes AM, Baldwin RC|title=Medical Comorbidities in Late-Life Depression|journal=Psychiatric Times|volume=25|issue=14|year=2008|url=http://www.psychiatrictimes.com/depression/article/10168/1358135|access-date=10 June 2009|archive-date=14 June 2020|archive-url=https://web.archive.org/web/20200614095605/https://www.psychiatrictimes.com/10168/1358135}}</ref>

==History==
{{Main|History of depression}}

The Ancient Greek physician [[Hippocrates]] described a syndrome of [[melancholia]] ({{lang|grc|μελαγχολία}}, {{transliteration|grc|melankholía}}) as a distinct disease with particular mental and physical symptoms; he characterized all "fears and despondencies, if they last a long time" as being symptomatic of the ailment.<ref>Hippocrates, ''Aphorisms'', Section 6.23</ref> It was a similar but far broader concept than today's depression; prominence was given to a clustering of the symptoms of sadness, dejection, and despondency, and often fear, anger, delusions and obsessions were included.<ref name= Radden2003>{{cite journal | vauthors = Radden J |year=2003 |title=Is this dame melancholy? Equating today's depression and past melancholia |journal=Philosophy, Psychiatry, & Psychology |volume=10 |issue=1 |pages=37–52 |doi=10.1353/ppp.2003.0081|s2cid=143684460 }}</ref>
[[File:Hippocrates pushkin02.jpg|alt=|thumb|left|Diagnoses of depression go back at least as far as [[Hippocrates]].]]
The term ''depression'' itself was derived from the Latin verb {{lang|la|deprimere}}, meaning "to press down".<ref>{{Cite web |title=Definition of depress {{!}} Dictionary.com |url=https://www.dictionary.com/browse/depress |access-date=14 August 2022 |website=www.dictionary.com |language=en}}</ref> From the 14th century, "to depress" meant to subjugate or to bring down in spirits. It was used in 1665 in English author [[Richard Baker (chronicler)|Richard Baker's]] ''Chronicle'' to refer to someone having "a great depression of spirit", and by English author [[Samuel Johnson's health|Samuel Johnson]] in a similar sense in 1753.<ref>{{cite web| vauthors = Wolpert L|year=1999|title=Malignant Sadness: The Anatomy of Depression|website=The New York Times|url=https://www.nytimes.com/books/first/w/wolpert-sadness.html|access-date=30 October 2008|url-status=live|archive-url=https://web.archive.org/web/20090409111218/http://www.nytimes.com/books/first/w/wolpert-sadness.html|archive-date=9 April 2009}}</ref> The term also came into use in [[depression (physiology)|physiology]] and [[depression (economics)|economics]]. An early usage referring to a psychiatric symptom was by French psychiatrist [[Louis Delasiauve]] in 1856, and by the 1860s it was appearing in medical dictionaries to refer to a physiological and metaphorical lowering of emotional function.<ref>{{cite journal |vauthors=Berrios GE |title=Melancholia and depression during the 19th century: a conceptual history |journal=The British Journal of Psychiatry |volume=153 |issue=3 |pages=298–304 |date=September 1988 |pmid=3074848 |doi=10.1192/bjp.153.3.298 |s2cid=145445990 }}</ref> Since [[Aristotle]], melancholia had been associated with men of learning and intellectual brilliance, a hazard of contemplation and creativity. However, by the 19th century, this association has largely shifted and melancholia became more commonly linked with women.<ref name=Radden2003/>

Although ''melancholia'' remained the dominant diagnostic term, ''depression'' gained increasing currency in medical treatises and was a synonym by the end of the century; German psychiatrist [[Emil Kraepelin]] may have been the first to use it as the overarching term, referring to different kinds of melancholia as ''depressive states''.<ref name="Davison2006">{{cite journal |vauthors=Davison K|year=2006|title=Historical aspects of mood disorders |journal=Psychiatry |volume=5 |issue=4 |pages=115–18 |doi=10.1383/psyt.2006.5.4.115}}</ref> Freud likened the state of melancholia to mourning in his 1917 paper ''Mourning and Melancholia''. He theorized that [[object (philosophy)|objective]] loss, such as the loss of a valued relationship through death or a romantic break-up, results in [[subject (philosophy)|subjective]] loss as well; the depressed individual has identified with the object of affection through an [[unconscious mind|unconscious]], [[narcissism|narcissistic]] process called the ''libidinal [[cathexis]]'' of the [[Id, ego and super-ego|ego]]. Such loss results in severe melancholic symptoms more profound than mourning; not only is the outside world viewed negatively but the ego itself is compromised.<ref>{{cite journal |vauthors=Carhart-Harris RL, Mayberg HS, Malizia AL, Nutt D |title=Mourning and melancholia revisited: correspondences between principles of Freudian metapsychology and empirical findings in neuropsychiatry |journal=Annals of General Psychiatry |volume=7 |page=9 |date=July 2008 |pmid=18652673 |pmc=2515304 |doi=10.1186/1744-859X-7-9 |doi-access=free }}</ref> The person's decline of self-perception is revealed in his belief of his own blame, inferiority, and unworthiness.<ref>{{cite book |veditors=Richards A |vauthors=Freud S |title=11. On Metapsychology: The Theory of Psycholoanalysis |chapter=Mourning and Melancholia|pages=245–69 |publisher=Pelican |location=Aylesbury, Bucks |year=1984 |isbn=978-0-14-021740-7}}</ref> He also emphasized early life experiences as a predisposing factor.<ref name=Radden2003/> [[Adolf Meyer (psychiatrist)|Adolf Meyer]] put forward a mixed social and biological framework emphasizing ''reactions'' in the context of an individual's life, and argued that the term ''depression'' should be used instead of ''melancholia''.<ref name="Lewis1934">{{cite journal |vauthors=Lewis AJ|year=1934|title=Melancholia: A historical review |journal=Journal of Mental Science |volume=80 |issue=328|pages=1–42|doi=10.1192/bjp.80.328.1|doi-access=free}}</ref> The first version of the DSM (DSM-I, 1952) contained ''depressive reaction'' and the DSM-II (1968) ''depressive neurosis'', defined as an excessive reaction to internal conflict or an identifiable event, and also included a depressive type of manic-depressive psychosis within Major affective disorders.<ref name="DSMII">{{cite book|title=Diagnostic and statistical manual of mental disorders: DSM-II |author=American Psychiatric Association |publisher=American Psychiatric Publishing, Inc. |location=Washington, DC |year=1968 |chapter=Schizophrenia |series=DSM Library |chapter-url=http://dsm.psychiatryonline.org/doi/pdf/10.1176/appi.books.9780890420355.dsm-ii |chapter-format=PDF |pages=36–37, 40 |doi=10.1176/appi.books.9780890420355.dsm-ii |doi-broken-date=1 November 2024 |isbn=978-0-89042-035-5 }}</ref>

The term ''unipolar'' (along with the related term ''bipolar'') was coined by the neurologist and psychiatrist [[Karl Kleist]], and subsequently used by his disciples [[Edda Neele]] and [[Karl Leonhard]].<ref>[[Jules Angst|Angst J.]] Terminology, history and definition of bipolar spectrum. In: Maj M, Akiskal HS, López-Ibor JJ, Sartorius N (eds.), ''Bipolar disorders''. Chichester: Wiley & Sons, LTD; 2002. pp. 53–55.</ref>

The term ''major depressive disorder'' was introduced by a group of US clinicians in the mid-1970s as part of proposals for diagnostic criteria based on patterns of symptoms (called the "Research Diagnostic Criteria", building on earlier [[Feighner Criteria]]),<ref name= Spitzer/> and was incorporated into the DSM-III in 1980.<ref name="Philipp1991">{{cite journal |vauthors=Philipp M, Maier W, Delmo CD |title=The concept of major depression. I. Descriptive comparison of six competing operational definitions including ICD-10 and ''DSM-III-R'' |journal=European Archives of Psychiatry and Clinical Neuroscience |volume=240 |issue=4–5 |pages=258–65 |year=1991 |pmid=1829000 |doi=10.1007/BF02189537 |s2cid=36768744 }}</ref> The [[American Psychiatric Association]] added "major depressive disorder" to the ''[[Diagnostic and Statistical Manual of Mental Disorders]]'' (DSM-III),<ref name=Her2008/> as a split of the previous [[depressive neurosis]] in the DSM-II, which also encompassed the conditions now known as dysthymia and [[adjustment disorder with depressed mood]].<ref name=Her2008>{{cite book| vauthors = Hersen M, Rosqvist J |title=Handbook of Psychological Assessment, Case Conceptualization, and Treatment, Volume 1: Adults|publisher=John Wiley & Sons|isbn=978-0-470-17356-5|page=32|date=2008|url=https://books.google.com/books?id=zOBdVdjGf4oC&pg=PA32}}</ref> To maintain consistency the ICD-10 used the same criteria, with only minor alterations, but using the DSM diagnostic threshold to mark a ''mild depressive episode'', adding higher threshold categories for moderate and severe episodes.<ref name="DSMvsICD">{{Cite book|vauthors=Gruenberg AM, Goldstein RD, Pincus HA |pages=1–12 |year=2005 |chapter-url=http://media.wiley.com/product_data/excerpt/50/35273078/3527307850.pdf |archive-url=https://web.archive.org/web/20050503192112/http://media.wiley.com/product_data/excerpt/50/35273078/3527307850.pdf |archive-date=3 May 2005 |url-status=live |title=Biology of Depression: From Novel Insights to Therapeutic Strategies | veditors = Licinio J, Wong ML |publisher=Wiley-VCH Verlag GmbH|access-date=30 October 2008|doi=10.1002/9783527619672.ch1|isbn=978-3-527-61967-2 |chapter=Classification of Depression: Research and Diagnostic Criteria: DSM-IV and ICD-10 }}</ref><ref name="Philipp1991" /> The ancient idea of ''melancholia'' still survives in the notion of a melancholic subtype.

The new definitions of depression were widely accepted, albeit with some conflicting findings and views. There have been some continued empirically based arguments for a return to the diagnosis of melancholia.<ref name="ActaPsychiatrica06">{{cite journal |vauthors=Bolwig TG |title=Melancholia: Beyond DSM, Beyond Neurotransmitters. Proceedings of a conference, May 2006, Copenhagen, Denmark |journal=Acta Psychiatrica Scandinavica. Supplementum |volume=115 |issue=433 |pages=4–183 |year=2007 |pmid=17280564 |doi=10.1111/j.1600-0447.2007.00956.x |s2cid=221452354 }}</ref><ref>{{cite journal |vauthors=Fink M, Bolwig TG, Parker G, Shorter E |title=Melancholia: restoration in psychiatric classification recommended |journal=Acta Psychiatrica Scandinavica |volume=115 |issue=2 |pages=89–92 |date=February 2007 |pmid=17244171 |pmc=3712974 |doi=10.1111/j.1600-0447.2006.00943.x }}</ref> There has been some criticism of the expansion of coverage of the diagnosis, related to the development and promotion of antidepressants and the biological model since the late 1950s.<ref>{{cite book |title=The Antidepressant Era | vauthors = Healy D |author-link=David Healy (psychiatrist)|year=1999 |publisher=Harvard University Press |location=Cambridge, MA |isbn=978-0-674-03958-2 |page=42}}</ref>

==Society and culture==
{{Further|Depression and culture}}

===Terminology===
[[File:Abraham Lincoln O-60 by Brady, 1862.jpg|thumb|The 16th [[President of the United States|American president]], [[Abraham Lincoln]], had "[[Depression (mood)|melancholy]]", a condition that now may be referred to as clinical depression.<ref>Wolf, Joshua [https://www.theatlantic.com/doc/200510/lincolns-clinical-depression "Lincoln's Great Depression"] {{webarchive|url=https://web.archive.org/web/20111009044732/http://www.theatlantic.com/magazine/archive/2005/10/lincoln-apos-s-great-depression/4247/ |date=9 October 2011 }}, ''The Atlantic'', October 2005. Retrieved 10 October 2009</ref>]]

The term ''depression'' is used in a number of different ways. It is often used to mean this syndrome but may refer to other [[mood disorder]]s or simply to a low mood. People's conceptualizations of depression vary widely, both within and among cultures. "Because of the lack of scientific certainty," one commentator has observed, "the debate over depression turns on questions of language. What we call it—'disease,' 'disorder,' 'state of mind'—affects how we view, diagnose, and treat it."<ref>{{Cite journal|url=http://www.slate.com/id/2129377|title=The Depression Wars: Would Honest Abe Have Written the Gettysburg Address on Prozac?|author=Maloney F|date=3 November 2005|journal=Slate|access-date=3 October 2008|url-status=live|archive-url=https://web.archive.org/web/20080925012423/http://www.slate.com/id/2129377/|archive-date=25 September 2008}}</ref> There are cultural differences in the extent to which serious depression is considered an illness requiring personal professional treatment, or an indicator of something else, such as the need to address social or moral problems, the result of biological imbalances, or a reflection of individual differences in the understanding of distress that may reinforce feelings of powerlessness, and emotional struggle.<ref>{{cite journal |vauthors=Karasz A |title=Cultural differences in conceptual models of depression |journal=Social Science & Medicine |volume=60 |issue=7 |pages=1625–35 |date=April 2005 |pmid=15652693 |doi=10.1016/j.socscimed.2004.08.011 }}</ref><ref>{{cite journal| vauthors = Tilbury F, Rapley M | year = 2004 | title = 'There are orphans in Africa still looking for my hands': African women refugees and the sources of emotional distress|journal=Health Sociology Review|volume=13|issue=1|pages=54–64|doi=10.5172/hesr.13.1.54| s2cid = 145545714 }}</ref>

===Cultural dimension===
Cultural differences contribute to different prevalence of symptoms. "Do the Chinese [[Somatization|somatize]] depression? A cross-cultural study" by Parker ''et al.'' discusses the cultural differences in prevalent symptoms of depression between [[Individualistic culture|individualistic]] and [[collectivistic culture]]s. The authors reveal that individuals with depression in collectivistic cultures tend to present more somatic symptoms and less affective symptoms compared to those in individualistic cultures. The finding suggests that individualistic cultures 'warranting' or [[Emotional validation|validating]] one's expression of emotions explains this cultural difference since collectivistic cultures see this as a taboo against the social cooperation it deems one of the most significant values.<ref>{{cite journal | vauthors = Parker G, Cheah YC, Roy K | title = Do the Chinese somatize depression? A cross-cultural study | journal = Social Psychiatry and Psychiatric Epidemiology | volume = 36 | issue = 6 | pages = 287–293 | date = June 2001 | pmid = 11583458 | doi = 10.1007/s001270170046 | s2cid = 24932164 }}</ref>

===Stigma===
Historical figures were often reluctant to discuss or seek treatment for depression due to [[social stigma]] about the condition, or due to ignorance of diagnosis or treatments. Nevertheless, analysis or interpretation of letters, journals, artwork, writings, or statements of family and friends of some historical personalities has led to the presumption that they may have had some form of depression. People who may have had depression include English author [[Mary Shelley]],<ref>{{cite book | vauthors = Seymour M |title=Mary Shelley|publisher=Grove Press|year=2002 |pages=560–61 |isbn=978-0-8021-3948-1}}</ref> American-British writer [[Henry James]],<ref>{{cite web|url=https://www.pbs.org/wgbh/masterpiece/americancollection/american/genius/henry_bio.html|title=Biography of Henry James|publisher=[[Public Broadcasting Service|PBS]]|access-date=19 August 2008|archive-url=https://web.archive.org/web/20081008042925/http://www.pbs.org/wgbh/masterpiece/americancollection/american/genius/henry_bio.html|archive-date=8 October 2008}}</ref> and American president [[Abraham Lincoln]].<ref>{{cite book | vauthors = Burlingame M |title=The Inner World of Abraham Lincoln |publisher=University of Illinois Press |location=Urbana |year=1997 |isbn=978-0-252-06667-2 |pages=xvii, 92–113 }}</ref> Some well-known contemporary people with possible depression include Canadian songwriter [[Leonard Cohen]]<ref>{{cite web |author=Pita E |url=http://www.webheights.net/10newsongs/press/elmunmag.htm |title=An Intimate Conversation with...Leonard Cohen |date=26 September 2001 |access-date=3 October 2008 |url-status=live |archive-url=https://web.archive.org/web/20081011082500/http://www.webheights.net/10newsongs/press/elmunmag.htm |archive-date=11 October 2008 }}</ref> and American playwright and novelist [[Tennessee Williams]].<ref>{{cite journal |vauthors=Jeste ND, Palmer BW, Jeste DV |title=Tennessee Williams |journal=The American Journal of Geriatric Psychiatry |volume=12 |issue=4 |pages=370–75 |year=2004 |pmid=15249274 |doi=10.1097/00019442-200407000-00004 }}</ref> Some pioneering psychologists, such as Americans [[William James]]<ref>{{cite book |vauthors=James H |title=Letters of William James (Vols. 1 and 2) |publisher=Kessinger Publishing Co|location=Montana |pages=147–48|isbn=978-0-7661-7566-2 |year=1920}}</ref><ref name="HistoryJames">{{Harvnb |Hergenhahn|2005|p=311}}</ref> and [[John B. Watson]],<ref>{{cite book |vauthors=Cohen D |title=J. B. Watson: The Founder of Behaviourism |publisher=Routledge & Kegan Paul |location=London |year=1979 |page=7 |isbn=978-0-7100-0054-5}}</ref> dealt with their own depression.

[[File:Norges statsminister Kjell Magne Bondevik.jpg|thumb|150px|In 1998, the Norwegian PM [[Kjell Magne Bondevik]] publicly announced he would take a leave of absence in order to recover from a depressive episode.]]

There has been a continuing discussion of whether neurological disorders and mood disorders may be linked to [[creativity]], a discussion that goes back to [[Aristotle|Aristotelian]] times.<ref>{{cite journal |vauthors=Andreasen NC |title=The relationship between creativity and mood disorders |journal=Dialogues in Clinical Neuroscience |volume=10 |issue=2 |pages=251–5 |year=2008 |doi=10.31887/DCNS.2008.10.2/ncandreasen |pmid=18689294 |pmc=3181877 }}</ref><ref>{{cite journal |vauthors=Simonton DK |year=2005 |title=Are genius and madness related? Contemporary answers to an ancient question |journal=Psychiatric Times |volume=22 |issue=7 |url=http://www.psychiatrictimes.com/display/article/10168/52456?pageNumber=1 |url-status=live |archive-url=https://web.archive.org/web/20090114065333/http://www.psychiatrictimes.com/display/article/10168/52456?pageNumber=1 |archive-date=14 January 2009 }}</ref> British literature gives many examples of reflections on depression.<ref>{{cite book |vauthors=Heffernan CF |title=The melancholy muse: Chaucer, Shakespeare and early medicine |publisher=Duquesne University Press |location=Pittsburgh|year=1996 |isbn=978-0-8207-0262-9}}</ref> English philosopher [[John Stuart Mill]] experienced a several-months-long period of what he called "a dull state of nerves", when one is "unsusceptible to enjoyment or pleasurable excitement; one of those moods when what is pleasure at other times, becomes insipid or indifferent". He quoted English poet [[Samuel Taylor Coleridge]]'s "Dejection" as a perfect description of his case: "A grief without a pang, void, dark and drear, / A drowsy, stifled, unimpassioned grief, / Which finds no natural outlet or relief / In word, or sigh, or tear."<ref>{{cite book |chapter-url=http://www.gutenberg.org/files/10378/10378-8.txt |title=Autobiography |author=Mill JS |chapter-format=txt |publisher=Project Gutenberg EBook |pages=1826–32 |chapter=A crisis in my mental history: One stage onward |access-date=9 August 2008 |isbn=978-1-4212-4200-2 |year=2003 |url-status=live |archive-url=https://web.archive.org/web/20080921084533/http://www.gutenberg.org/files/10378/10378-8.txt |archive-date=21 September 2008 |author-link=John Stuart Mill }}</ref><ref>{{cite journal |author=Sterba R |title=The 'Mental Crisis' of John Stuart Mill |journal=Psychoanalytic Quarterly |volume=16 |issue=2 |pages=271–72 |year=1947 |url=http://www.pep-web.org/document.php?id=PAQ.016.0271C |access-date=5 November 2008 |url-status=live |archive-url=https://web.archive.org/web/20090112164603/http://www.pep-web.org/document.php?id=PAQ.016.0271C |archive-date=12 January 2009 }}</ref> English writer [[Samuel Johnson]] used the term "the black dog" in the 1780s to describe his own depression,<ref name=McKinlay05>{{cite web |url=http://www.blackdoginstitute.org.au/docs/McKinlay.pdf |title=Churchill's Black Dog?: The History of the 'Black Dog' as a Metaphor for Depression |year=2005 |access-date=18 August 2008 |website=Black Dog Institute website |publisher=Black Dog Institute |archive-url=https://web.archive.org/web/20080910170230/http://www.blackdoginstitute.org.au/docs/McKinlay.pdf |archive-date=10 September 2008 }}</ref><ref name=HistoryCollection>{{cite web |url=https://historycollection.com/these-20-historical-figures-with-severe-mental-issues-helped-shape-the-world/ |title=These 20 Historical Figures With Severe Mental Issues Helped Shape The World |date=27 November 2018 |access-date=5 December 2024 |website=History Collection }}</ref> and it was subsequently popularized by British Prime Minister Sir [[Winston Churchill]], who also had the disorder.<ref name=McKinlay05 /><ref name=HistoryCollection /> [[Johann Wolfgang von Goethe]] in his ''[[Faust, Part One]]'', published in 1808, has [[Mephistopheles]] assume the form of a black dog, specifically a [[poodle]].

Social stigma of major depression is widespread, and contact with mental health services reduces this only slightly. Public opinions on depression treatment vary. While some remain skeptical about antidepressants, recent studies show a more balanced view. Many patients recognize their benefits but have concerns about side effects and personality changes.<ref>{{Cite journal |last1=Jacob |first1=Sabrina Anne |last2=Hassali |first2=Mohamed Azmi Ahmad |last3=Ab Rahman |first3=Ab Fatah |date=May 2015 |title=Attitudes and beliefs of patients with chronic depression toward antidepressants and depression |journal=Neuropsychiatric Disease and Treatment |volume=11 |language=en |pages=1339–1347 |doi=10.2147/NDT.S82563 |doi-access=free |pmid=26064052 |pmc=4455848 |issn=1178-2021}}</ref><ref>{{cite book |title=Unmet Need in Psychiatry:Problems, Resources, Responses |veditors=Andrews G, Henderson S |year=2000 |publisher=Cambridge University Press |page=[https://archive.org/details/unmetneedinpsych0000unse/page/409 409] |chapter=Public knowledge of and attitudes to mental disorders: a limiting factor in the optimal use of treatment services |vauthors=Jorm AF, Angermeyer M, Katschnig H |isbn=978-0-521-66229-1 |chapter-url=https://archive.org/details/unmetneedinpsych0000unse/page/409 }}</ref> In the UK, the [[Royal College of Psychiatrists]] and the [[Royal College of General Practitioners]] conducted a joint Five-year Defeat Depression campaign to educate and reduce stigma from 1992 to 1996;<ref>{{cite journal |vauthors=Paykel ES, Tylee A, Wright A, et al |title=The Defeat Depression Campaign: psychiatry in the public arena |journal=The American Journal of Psychiatry |volume=154 |issue=6 Suppl |pages=59–65 |date=June 1997 |pmid=9167546 |doi=10.1176/ajp.154.6.59 |doi-access=free }}</ref> a [[Ipsos MORI|MORI]] study conducted afterwards showed a small positive change in public attitudes to depression and treatment.<ref>{{cite journal |vauthors=Paykel ES, Hart D, Priest RG |title=Changes in public attitudes to depression during the Defeat Depression Campaign |journal=The British Journal of Psychiatry |volume=173 |issue=6 |pages=519–22 |date=December 1998 |pmid=9926082 |doi=10.1192/bjp.173.6.519 |s2cid=21172113 }}</ref>

While serving his first term as Prime Minister of Norway, [[Kjell Magne Bondevik]] attracted international attention in August 1998 when he announced that he was suffering from a depressive episode, becoming the highest ranking world [[leadership|leader]] to admit to suffering from a mental illness while in office. Upon this revelation, [[Anne Enger]] became acting Prime Minister for three weeks, from 30 August to 23 September, while he recovered from the depressive episode. Bondevik then returned to office. Bondevik received thousands of supportive letters, and said that the experience had been positive overall, both for himself and because it made mental illness more publicly acceptable.<ref name=Jones2011Fighting>{{cite journal | vauthors = Bondevik KM | title = Fighting stigma with openness. Interview by Ben Jones | journal = Bulletin of the World Health Organization | volume = 89 | issue = 12 | pages = 862–863 | date = December 2011 | pmid = 22271941 | pmc = 3260893 | doi = 10.2471/BLT.11.041211 | url = https://www.who.int/bulletin/volumes/89/12/11-041211/en/index.html | access-date = 19 July 2013 | archive-url = https://web.archive.org/web/20131031035031/http://www.who.int/bulletin/volumes/89/12/11-041211/en/index.html | archive-date = 31 October 2013 }}</ref><ref>[[BBC]] [[Newsnight]], 21 January 2008.</ref>

==References==
{{Reflist}}

===Cited works===
{{Spoken Wikipedia|Mdd2 003.ogg|date=6 October 2014}}
{{refbegin}}
* {{cite book |title=Diagnostic and statistical manual of mental disorders |edition=Fourth Edition, Text Revision: DSM-IV-TR |publisher=American Psychiatric Publishing, Inc. |location=Washington, DC |year=2000a|isbn=978-0-89042-025-6 |author=American Psychiatric Association}}
* {{cite book |title=Diagnostic and statistical manual of mental disorders |edition=Fifth Edition: DSM-5 |publisher=American Psychiatric Publishing, Inc. |location=Washington, DC |year=2013|isbn=978-0-89042-555-8 |author=American Psychiatric Association}}
* {{cite book |vauthors=Barlow DH, Durand VM |title=Abnormal psychology: An integrative approach |edition=5th |publisher=Thomson Wadsworth |location=Belmont, CA |year=2005 |isbn=978-0-534-63356-1 }}
* {{cite book |vauthors=Beck AT, Rush J, Shaw BF, Emery G |title=Cognitive therapy of depression |publisher=Guilford Press |location=New York|year=1987|orig-date=1979 |isbn=978-0-89862-919-4}}
* {{cite book |author=Hergenhahn BR|title=An Introduction to the History of Psychology |edition=5th |publisher=Thomson Wadsworth |location=Belmont, CA |year=2005|isbn=978-0-534-55401-9|ref=CITEREFHergenhahn2005}}
* {{cite book |veditors=Parker G, Hadzi-Pavlovic D |title=Melancholia: a disorder of movement and mood: a phenomenological and neurobiological review |publisher=Cambridge University Press |location=Cambridge |year=1996 |isbn=978-0-521-47275-3|ref=CITEREFParker1996}}
* {{cite book |title=British National Formulary (BNF 56) |author=Royal Pharmaceutical Society of Great Britain |year=2008 |publisher=BMJ Group and RPS Publishing |location=UK |isbn=978-0-85369-778-7 |url=https://archive.org/details/britishnationalf0000unse_k4e9 |url-access=registration }}
* {{cite book | vauthors = Sadock VA, Sadock BJ, Kaplan HI |title=Kaplan & Sadock's synopsis of psychiatry: behavioral sciences/clinical psychiatry |publisher=Lippincott Williams & Wilkins |location=Philadelphia |year=2003 |isbn=978-0-7817-3183-6|ref=CITEREFSadock2002}}
* {{cite encyclopedia |title=6A70 Single episode depressive disorder |date=February 2022<!-- The most recent update as of the access date --> |orig-date=adopted in 2019<!-- This is when it was adopted by the World Health Assembly --> |url=https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/578635574 |encyclopedia=International Classification of Diseases 11th Revision |publisher=World Health Organization |access-date=9 July 2022 |ref=CITEREF-ICD11-6A70 }}
* {{cite encyclopedia |title=6A71 Recurrent depressive disorder |date=February 2022<!-- The most recent update as of the access date --> |orig-date=adopted in 2019<!-- This is when it was adopted by the World Health Assembly --> |url=https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/578635574 |encyclopedia=International Classification of Diseases 11th Revision |publisher=World Health Organization |access-date=9 July 2022 |ref=CITEREF-ICD11-6A71 }}
{{refend}}
{{Medical condition classification and resources
|DiseasesDB=3589
|ICD10={{ICD10|F|32||f|30}}, {{ICD10|F|33||f|30}}
|ICD9={{ICD9|296.2}}, {{ICD9|296.3}}
|ICDO=
|OMIM=608516
|MedlinePlus=003213
|eMedicineSubj=med
|eMedicineTopic=532
|MeshID=D003865
|ICD11={{ICD11|6A70}}, {{ICD11|6A71}}}}
{{Mental and behavioural disorders|selected=mood}}
{{Mood disorders}}
{{Digital media use and mental health}}
{{Authority control}}

[[Category:Major depressive disorder| ]]
[[Category:Mood disorders]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Wikipedia neurology articles ready to translate]]