Editing Major depressive disorder (section)

===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>