Meta-Analysis Supports Potential Use of Ketamine for PTSD, OCD

A recent study supports ketamine’s potential for treating post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD); however, the evidence is limited by the number of randomized controlled trials.¹

“Despite the variations in the number of ketamine infusions in each study, treatment with ketamine consistently demonstrated a significant reduction in within-group symptom severity, as measured by multiple validated external mood assessments over time,” wrote investigators, led by Angela T.H. Kwan, MD, from the Brain and Cognition Discovery Foundation in Toronto and a faculty member at the University of Ottawa.

Ketamine has demonstrated efficacy in treating adults with treatment-resistant depression, along with alleviating symptoms for several psychiatric disorders.² Investigators performed a systematic review and meta-analysis to examine the efficacy of ketamine across multiple mental disorders, excluding mood disorders.¹

Investigators searched for randomized controlled trials and open-label trials in OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), EBSCO CINAHL Plus, Scopus, and Web of Science from inception to June 10, 2023. They focused on trials evaluating ketamine use in participants aged ≥ 18 years for alcohol use disorder, PTSD, substance use disorders (opiate use disorder/opiate withdrawal, nicotine dependency, and cocaine dependency), eating disorders, borderline personality disorder, and schizophrenia spectrum disorder. Participants had some sort of pharmacological treatment involving ketamine therapy, whether that be oral, subcutaneous, intramuscular, or intravenous.

After exclusion, the study included 37 studies, with trials on PTSD (n = 6), treatment-resistant PTSD (n = 9), alcohol use disorder (n = 4), at-risk drinking, SI (n = 2), cocaine dependence/use disorder (n = 3), opiate use disorder (n = 2), anxiety disorders (n = 3), borderline personality disorder (n = 1), schizophrenia (n = 2), and OCD (n = 4). Sample sizes ranged from 8 – 223 participants.

Ketamine brought statistically significant therapeutic effects for PTSD based on the PTSD Checklist for DSM-5 (pooled estimate, -28.07; 95% confidence interval [CI], -40.05 to -16.11; P < .001) and Clinician-Administered PTSD Scale for DSM-5 scores (pooled estimate, -14.07; 95% CI, -26.24 to -1.90; P = .023). The Yale-Brown Obsessive Compulsive Scale scores reflected significant therapeutic effects for individuals with PTSD, treatment-resistant PTSD, and OCD (pooled estimate, -8.08; 95% CI, -13.64 to -2.52; P = .004).

“Notably, these studies only measured the acute effects of ketamine treatment, so further study should be performed to establish efficacy and safety for long-term usage, as well as in repeat ketamine infusions,” investigators wrote.

The study also showed a disproportionate reporting of decreased urge to drink, increased rate of abstinence, and longer time to relapse following ketamine treatment among individuals with alcohol use disorders and at-risk drinking. Additionally, ketamine brought improvement in symptom severity in cocaine dependence/cocaine use disorder and anxiety disorders.

As for suicidal ideation, opiate use disorder, nicotine dependence, borderline personality disorder, schizophrenia, and eating disorders, the study could not evaluate the safety and efficacy of ketamine for these disorders due to an insufficient number of studies.

In general, current randomized controlled trials examining the effects of ketamine on psychiatric disorders, excluding major depressive disorder, remain insufficient. Although studies include a diverse set of study populations—and there is a high level of heterogeneity across the studies for those focusing on PTSD (P < .0001), treatment-resistant depression (P < .0001), and OCD (P = .02)—there is a lack of data on the efficacy and safety of ketamine in real-world settings.

“Overall, the current evidence suggests that ketamine has transdiagnostic efficacy and safety across many mental disorders,” investigators concluded.

References

1. ^{Kwan ATH, Lakhani M, Singh G, Le GH, Wong S, Teopiz KM, Dev DA, Manku AS, Sidhu G, McIntyre RS. Ketamine for the Treatment of Psychiatric Disorders: A Systematic Review and Meta-Analysis. CNS Spectr. 2024 Nov 20:1-8. doi: 10.1017/S1092852924000580. Epub ahead of print. PMID: 39564613.}
2. ^{Albott CS, Lim KO, Forbes MK, Erbes C, Tye SJ, Grabowski JG, Thuras P, Batres-Y-Carr TM, Wels J, Shiroma PR. Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression. J Clin Psychiatry. 2018 May/Jun;79(3):17m11634. doi: 10.4088/JCP.17m11634. PMID: 29727073.}