The effect of ketamine on cognition, anxiety, and social functioning in adults with psychiatric disorders: A systematic review and meta-analysis

Abstract

BackgroundIt has been shown that ketamine can improve suicidality and depression. Evidence for other dimensions of psychopathology is lacking. We undertook a systematic review to investigate the effect of ketamine on cognition, anxiety, quality of life, and social functioning in adults with psychiatric disorders.MethodsPubMed (Medline), Scopus, PsycINFO, and EMBASE were searched up to April 2022. Randomized controlled trials (RCTs) on ketamine [or its S (+) enantiomer] reporting data on cognition, anxiety, quality of life, social functioning in adults with psychiatric disorders were included. Standardized mean difference (SMD) was used for summarizing continuous outcomes.ResultsTwenty-two reports were included in the final selection, of which 20, corresponding to 1,298 participants, were included in the quantitative synthesis. Affective disorders were the predominant diagnostic category. Median follow-up time was 21 days. The evidence was rated moderate to very low. In most trials, ketamine was administered intravenously or as adjuvant to electro-convulsant therapy (ECT). Only 2 trials of intranasal esketamine were identified. The effect of ketamine on depression was confirmed (SMD: −0.61 [95% CI: −1.06; −0.16]). Furthermore, by pooling results of 6 RCTs, ketamine may be effective in reducing anxiety symptoms (SMD: −0.42 [95% CI: −0.84; 0.003]), particularly when administered not within ECT (5 trials; SMD: −0.58 [95% CI: −1.07; −0.09]). However, there was moderate heterogeneity of results. Patients treated with ketamine also had an improvement in social functioning (SMD: −0.31 [95% CI: −0.52; −0.10]), although the estimate was based only on 2 studies. No difference to comparators was found with respect to cognition and quality of life.ConclusionAlongside the antidepressant effect, ketamine may also improve anxiety and social functioning in adults with affective disorders.

Ketamine for Adults With Treatment-Resistant Depression or Posttraumatic Stress Disorder: A 2023 Update

“…This report includes 4 SRs, [30][31][32][33] 7 RCTs, [34][35][36][37][38][39][40] 1 economic evaluation, 41 and 2 evidence-based guidelines. 42,43 Study selection details are presented in Appendix 1.…”

“…• 2 SRs 30,33 and 1 guideline 43 had broader inclusion criteria for the population than the present review, with 1 SR and the guideline 43 on major depressive disorder (MDD) and the other SR on psychiatric disorders. 33 We included findings specific to TRD 30,33,43 • the RCT by Harvey et al 36 was a substudy of the larger RCT by Loo et al 38 Different outcomes were reported in each trial; therefore, we included both studies in this Rapid Review. We did not include data from a third comparison group of healthy adults in the RCT by Harvey et al 36 • 2 RCTs 37,39 were authored by the same group of researchers.…”

“…Three SRs 30,31,33 and 5 RCTs [35][36][37][38][39] compared ketamine with midazolam. The studies took place in Australia, 36,38 Taiwan, 37,39 and the US.…”

“…The studies took place in Australia, 36,38 Taiwan, 37,39 and the US. 33,35 Two SRs 30,33 and 4 RCTs [36][37][38][39] included adults with treatment-resistant major depression. One SR 31 and 1 RCT 35 included adults with chronic PTSD.…”

“…One study in 1 SR 30 was a crossover trial. Baseline characteristics between the intervention and comparator groups in the parallel trials were not described in the 3 SRs; 30,31,33 the participants in the 2 groups were balanced in baseline demographics in the 5 RCTs. [35][36][37][38][39] The interventions included single-dose IV ketamine, 30,33,35,37,39 single-dose subcutaneous ketamine, 30,36 single-dose IM ketamine, repeated doses of IV ketamine, 30,31 and repeated subcutaneous ketamine injections.…”