Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review

Abstract

Background In the past two decades, subanaesthetic doses of ketamine have been demonstrated to have rapid and sustained antidepressant effects, and accumulating research has demonstrated ketamine's therapeutic effects for a range of psychiatric conditions. Aims In light of these findings surrounding ketamine's psychotherapeutic potential, we systematically review the extant evidence on ketamine's effects in treating mental health disorders. Method The systematic review protocol was registered in PROSPERO (identifier CRD42019130636). Human studies investigating the therapeutic effects of ketamine in the treatment of mental health disorders were included. Because of the extensive research in depression, bipolar disorder and suicidal ideation, only systematic reviews and meta-analyses were included. We searched Medline and PsycINFO on 21 October 2020. Risk-of-bias analysis was assessed with the Cochrane Risk of Bias tools and A Measurement Tool to Assess Systematic Reviews (AMSTAR) Checklist. Results We included 83 published reports in the final review: 33 systematic reviews, 29 randomised controlled trials, two randomised trials without placebo, three non-randomised trials with controls, six open-label trials and ten retrospective reviews. The results were presented via narrative synthesis. Conclusions Systematic reviews and meta-analyses provide support for robust, rapid and transient antidepressant and anti-suicidal effects of ketamine. Evidence for other indications is less robust, but suggests similarly positive and short-lived effects. The conclusions should be interpreted with caution because of the high risk of bias of included studies. Optimal dosing, modes of administration and the most effective forms of adjunctive psychotherapeutic support should be examined further.

Suizidpräventive Effekte von Ketamin und Esketamin

“…Studien wurden dabei anhand dreier aktueller systematischer Reviews ausgewählt. Der Review von Siegel et al beinhaltet RKS mit Patienten mit Suizidgedanken zu Studienbeginn [ 9 ], das Cochrane-Review von Dean et al Studien zu Depressionen [ 10 ] und schließlich der Review von Walsh et al zu Ketamin bei verschiedenen psychischen Störungen und Suizidalität [ 11 ]. Walsh et al geben einen systematischen Überblick zu anderen Reviews, darunter 6 Reviews zu Suizidalität, die wir ebenfalls berücksichtigen [ 5 , 12 – 16 ].…”

“…Die Studienlage zu Ketamin ist heterogen bezüglich Anwendung (einfache oder wiederholte Verabreichung, Monotherapie oder Augmentation), Applikation (oral, nasal, intramuskulär, intravenös), psychischer Störungen (Major/bipolare/behandlungsresistente/suizidale Depression) und Vergleichsgruppen (Placebo, Midazolam, Elektrokrampftherapie). Einige Reviews sahen daher von einer metaanalytischen Synthese ab [ 9 , 11 , 15 , 16 ]. Bis auf die Cochrane-Analyse [ 10 ] kommen alle Reviews und die Metaanalyse von Witt et al [ 14 ] zu dem Schluss, dass Ketamin kurzfristig eine moderate bis starke Reduktion von Suizidgedanken bewirkt, jedoch nicht über den Zeitraum von einer halben bis einer Woche hinaus ( Abb.…”

Ketamine as a Novel Psychopharmacotherapy for Eating Disorders: Evidence and Future Directions

“…In particular, AN presentation consisted of no comorbidity ( n = 5), BN comorbidity ( n = 2), OCD comorbidity ( n = 5), BN and OCD multicomorbidity ( n = 1), and BN and AUD multicomorbidity ( n = 2). Patients received 2–15 ketamine infusions scheduled at 5–21-day intervals, dependent upon clinical response, and were delivered at 20 mg/h over 10 h. This was a fairly intense drug regimen—relative to current studies on ketamine and mental health [ 141 ] previously used to treat postoperative pain [ 142 ] and acute war injuries [ 143 ]. Marked and sustained remissions were observed in responders ( n = 9) compared to nonresponders ( n = 6), with no-to-minimal disease activity at 7–24 months follow-up.…”

Ketamine as a Novel Psychopharmacotherapy for Eating Disorders: Evidence and Future Directions

“…Patients received 2-15 ketamine infusions scheduled at 5-21-day intervals, depending on clinical response, that were delivered at 20 mg/hour over 10 hours. This was a fairly intense drug regimen-relative to current studies on ketamine and mental health [122]-previously used to treat post-operative pain [123] and acute war injuries [124]. Marked and sustained remission were observed in responders (n = 9) compared to non-responders (n = 6), with no-to-minimal disease activity at 7-24 months follow-up.…”