Editing Major depressive disorder (section)

==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>