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

Background: It 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. Methods: PubMed (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. Results: Twenty-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. Conclusion: Alongside the antidepressant effect, ketamine may also improve anxiety and social functioning in adults with affective disorders.