Inadequate response to first- and second-line pharmacological treatments for psychiatric disorders is commonly observed. Ketamine has demonstrated efficacy in treating adults with treatment-resistant depression (TRD), with additional off-label benefits reported for various psychiatric disorders. Herein, we performed a systematic review and meta-analysis to examine the therapeutic applications of ketamine across multiple mental disorders, excluding mood disorders.

We conducted a multidatabase literature search of randomized controlled trials and open-label trials investigating the therapeutic use of ketamine in treating mental disorders. Studies utilizing the same psychological assessments for a given disorder were pooled using the generic inverse variance method to generate a pooled estimated mean difference.

The search in OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), EBSCO CINAHL Plus, Scopus, and Web of Science yielded 44 studies. Ketamine had a statistically significant effect on PTSD Checklist for DSM-5 (PCL-5) scores (pooled estimate = ‒28.07, 95% CI = [‒40.05, ‒16.11], p < 0.001), Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scores (pooled estimate = ‒14.07, 95% CI = [‒26.24, ‒1.90], p = 0.023), and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores (pooled estimate = ‒8.08, 95% CI = [‒13.64, ‒2.52], p = 0.004) in individuals with PTSD, treatment-resistant PTSD (TR-PTSD), and obsessive compulsive disorder (OCD), respectively. For alcohol use disorders and at-risk drinking, there was disproportionate reporting of decreased urge to drink, increased rate of abstinence, and longer time to relapse following ketamine treatment.

Extant literature supports the potential use of ketamine for the treatment of PTSD, OCD, and alcohol use disorders with significant improvement of patient symptoms. However, the limited number of randomized controlled trials underscores the need to further investigate the short- and long-term benefits and risks of ketamine for the treatment of psychiatric disorders.