Editing Ketamine (section)

=== Depression ===
{{See also|Esketamine#Depression|Ketamine-assisted psychotherapy}}

Ketamine is a rapid-acting [[antidepressant]],<ref name="Sachdeva_2023" /> but its effect is transient.<ref name="pmid28249076">{{cite journal | vauthors = Sanacora G, Frye MA, McDonald W, Mathew SJ, Turner MS, Schatzberg AF, Summergrad P, Nemeroff CB | title = A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | journal = JAMA Psychiatry | volume = 74 | issue = 4 | pages = 399–405 | date = April 2017 | pmid = 28249076 | doi = 10.1001/jamapsychiatry.2017.0080 | s2cid = 28320520 }}</ref> Intravenous ketamine infusion in [[treatment-resistant depression]] may result in improved mood within 4 hours reaching the peak at 24 hours.<ref name=Zhang2018 /><ref name="pmid33065824">{{cite journal |vauthors=Marcantoni WS, Akoumba BS, Wassef M, Mayrand J, Lai H, Richard-Devantoy S, Beauchamp S |title=A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: January 2009 – January 2019 |journal=J Affect Disord |volume=277 |pages=831–841 |date=December 2020 |pmid=33065824 |doi=10.1016/j.jad.2020.09.007 |s2cid=223557698 }}</ref> A single dose of intravenous ketamine has been shown to result in a response rate greater than 60% as early as 4.5 hours after the dose (with a sustained effect after 24 hours) and greater than 40% after 7 days.<ref name="pmid29736744"/> Although only a few pilot studies have sought to determine the optimal dose, increasing evidence suggests that 0.5&nbsp;mg/kg dose injected over 40 minutes gives an optimal outcome.<ref name="Sanacora Katz 2018 pp. 243–250">{{cite journal | vauthors = Sanacora G, Katz R | title = Ketamine: A Review for Clinicians | journal = Focus | volume = 16 | issue = 3 | pages = 243–250 | date = July 2018 | pmid = 31975918 | pmc = 6493090 | doi = 10.1176/appi.focus.20180012 | publisher = American Psychiatric Association Publishing }}</ref> The antidepressant effect of ketamine is diminished at 7 days, and most people relapse within 10 days. However, for a significant minority, the improvement may last 30 days or more.<ref name="pmid33065824" /><ref name="pmid33174760">{{cite journal |vauthors=Swainson J, McGirr A, Blier P, Brietzke E, Richard-Devantoy S, Ravindran N, Blier J, Beaulieu S, Frey BN, Kennedy SH, McIntyre RS, Milev RV, Parikh SV, Schaffer A, Taylor VH, Tourjman V, van Ameringen M, Yatham LN, Ravindran AV, Lam RW |title=The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L'humeur Et De L'anxiété (Canmat) Concernant L'utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur |journal=Can J Psychiatry |pages=113–125 |date=November 2020 |volume=66 |issue=2 |pmid=33174760 |doi=10.1177/0706743720970860 |pmc=7918868 }}</ref><ref name="pmid29736744">{{cite journal | vauthors = Molero P, Ramos-Quiroga JA, Martin-Santos R, Calvo-Sánchez E, Gutiérrez-Rojas L, Meana JJ | title = Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review | journal = CNS Drugs | volume = 32 | issue = 5 | pages = 411–420 | date = May 2018 | pmid = 29736744 | doi = 10.1007/s40263-018-0519-3 | s2cid = 13679905 }}</ref><ref name="pmid28395988">{{cite journal | vauthors = Singh I, Morgan C, Curran V, Nutt D, Schlag A, McShane R | title = Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight | journal = The Lancet. Psychiatry | volume = 4 | issue = 5 | pages = 419–426 | date = May 2017 | pmid = 28395988 | doi = 10.1016/S2215-0366(17)30102-5 | url = http://discovery.ucl.ac.uk/1552865/ | hdl-access = free | hdl = 10871/30208 | s2cid = 28186580 | access-date = 10 September 2018 | archive-date = 9 March 2019 | archive-url = https://web.archive.org/web/20190309081101/http://discovery.ucl.ac.uk/1552865/ | url-status = live }}</ref>

One of the main challenges with ketamine treatment can be the length of time that the antidepressant effects last after finishing a course of treatment. A possible option may be maintenance therapy with ketamine, which usually runs twice a week to once in two weeks.<ref name="pmid33065824"/><ref name="pmid33174760"/><ref name="pmid33162856">{{cite journal |vauthors=Bobo WV, Riva-Posse P, Goes FS, Parikh SV |title=Next-Step Treatment Considerations for Patients With Treatment-Resistant Depression That Responds to Low-Dose Intravenous Ketamine |journal=Focus (Am Psychiatr Publ) |volume=18 |issue=2 |pages=181–192 |date=April 2020 |pmid=33162856 |doi=10.1176/appi.focus.20190048 |pmc=7587874 }}</ref> Ketamine may decrease [[suicidal thought]]s for up to three days after the injection.<ref name="pmid31729893">{{cite journal |vauthors=Witt K, Potts J, Hubers A, Grunebaum MF, Murrough JW, Loo C, Cipriani A, Hawton K |title=Ketamine for suicidal ideation in adults with psychiatric disorders: A systematic review and meta-analysis of treatment trials |journal=Aust N Z J Psychiatry |volume=54 |issue=1 |pages=29–45 |date=January 2020 |pmid=31729893 |doi=10.1177/0004867419883341 |s2cid=208035394 |url=https://ora.ox.ac.uk/objects/uuid:25219d6c-5c8f-4842-91d9-41a9fd7fb1bd |access-date=18 January 2021 |archive-date=2 July 2022 |archive-url=https://web.archive.org/web/20220702024708/https://ora.ox.ac.uk/objects/uuid:25219d6c-5c8f-4842-91d9-41a9fd7fb1bd |url-status=live |hdl=1959.4/unsworks_76229 |hdl-access=free }}</ref>

An [[enantiomer]] of ketamine {{ndash}} [[esketamine]] {{ndash}} was approved as an antidepressant by the [[European Medicines Agency]] in 2019.<ref>{{cite web|title=Spravato (esketamine)|publisher=European Medicines Agency|date=8 July 2022|accessdate=20 July 2022|url=https://www.ema.europa.eu/en/medicines/human/EPAR/spravato|archive-date=23 November 2020|archive-url=https://web.archive.org/web/20201123231245/https://www.ema.europa.eu/en/medicines/human/EPAR/spravato|url-status=live}}</ref> Esketamine was approved as a nasal spray for treatment-resistant depression in the United States<ref name="fda-spravato">{{cite web |title=FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor's office or clinic |url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified |publisher=US Food and Drug Administration |access-date=29 July 2022 |date=5 March 2019 |archive-date=23 July 2021 |archive-url=https://web.archive.org/web/20210723022112/https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified |url-status=live }}</ref> and elsewhere in 2019. The Canadian Network for Mood and Anxiety Treatments (CANMAT) recommends esketamine as a third-line treatment for depression.<ref name="pmid33174760"/>

A [[Cochrane (organisation)|Cochrane review]] of [[randomized controlled trial]]s in adults with [[major depressive disorder]]<ref name="Sachdeva_2023" /> found that when compared with placebo, people treated with either ketamine or esketamine experienced reduction or remission of symptoms lasting 1 to 7 days.<ref name="dean2">{{cite journal | vauthors = Dean RL, Hurducas C, Hawton K, Spyridi S, Cowen PJ, Hollingsworth S, Marquardt T, Barnes A, Smith R, McShane R, Turner EH, Cipriani A| title = Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder | journal = The Cochrane Database of Systematic Reviews | volume = 9 | pages = CD011612 | date = September 2021 | issue = 11 | pmid = 34510411 | pmc = 8434915 | doi = 10.1002/14651858.CD011612.pub3 }}</ref> There were 18.7% (4.1 to 40.4%) more people reporting some benefit and 9.6% (0.2 to 39.4%) more who achieved remission within 24 hours of ketamine treatment. Among people receiving esketamine, 12.1% (2.5 to 24.4%) encountered some relief at 24 hours, and 10.3% (4.5 to 18.2%) had few or no symptoms. These effects did not persist beyond one week, although a higher dropout rate in some studies means that the benefit duration remains unclear.<ref name=dean2/>

Ketamine may partially improve depressive symptoms<ref name="Sachdeva_2023" /> among people with [[bipolar depression]] at 24 hours after treatment, but not three or more days.<ref name="dean">{{cite journal | vauthors = Dean RL, Marquardt T, Hurducas C, Spyridi S, Barnes A, Smith R, Cowen PJ, McShane R, Hawton K, Malhi GS, Geddes J, Cipriani A | title = Ketamine and other glutamate receptor modulators for depression in adults with bipolar disorder | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | pages = CD011611 | date = October 2021 | issue = 10 | pmid = 34623633 | pmc = 8499740 | doi = 10.1002/14651858.CD011611.pub3 }}</ref> Potentially, ten more people with bipolar depression per 1000 may experience brief improvement, but not the cessation of symptoms, one day following treatment. These estimates are based on limited available research.<ref name=dean/>

In February 2022, the US [[Food and Drug Administration]] (FDA) issued an alert to healthcare professionals concerning [[compounding|compounded]] nasal spray products containing ketamine intended to treat depression.<ref name="fda-2/22">{{cite web |title=FDA alerts health care professionals of potential risks associated with compounded ketamine nasal spray |url=https://www.fda.gov/drugs/human-drug-compounding/fda-alerts-health-care-professionals-potential-risks-associated-compounded-ketamine-nasal-spray |publisher=US Food and Drug Administration |access-date=29 July 2022 |date=16 February 2022 |archive-date=31 August 2022 |archive-url=https://web.archive.org/web/20220831210903/https://www.fda.gov/drugs/human-drug-compounding/fda-alerts-health-care-professionals-potential-risks-associated-compounded-ketamine-nasal-spray |url-status=live }}</ref>