A systematic review of systematic reviews found preliminary evidence that ketamine may reduce suicidal thoughts in the short term, but long-term effects remain unknown. Most of the 27 reviewed studies reported positive effects, though only four showed mixed or negative results. Among nine reviews of esketamine, only five found significant benefit. Common side effects included a temporary rise in pulse and blood pressure, dissociation, confusion, blurred vision, nausea, and vertigo, mostly mild. Over two-thirds of the included reviews were rated low or critically low quality, highlighting the need for further research.
A systematic review of 38 randomized controlled trials found compelling evidence that ketamine (with or without electroconvulsive therapy, intravenous or other forms), nitrous oxide, amantadine, and rislenemdaz (MK-0657) are effective for treatment-resistant depression, though results for the latter three were each based on a single study. Lithium, lanicemine, D-cycloserine, and decoglurant showed mixed results, while riluzole and 7-chlorokynurenic acid were mostly comparable to placebo. High heterogeneity among trials prevented determining the difference between statistical and clinical significance. Ketamine appears efficacious, but optimal dosage, duration, and intervals remain unclear.