So how special is special K? A systematic review and meta-analysis of ketamine for PTSD RCTs

Jan 15, 2024European journal of psychotraumatology

Ketamine's effects in treating PTSD: A review and analysis of clinical trials

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Abstract

A small advantage for ketamine over control conditions in reducing PTSD symptoms was observed, with an effect size of 0.27.

Meta-analysis included 52 effect sizes from six randomized control trials, involving a total of 221 participants.
Bias-correction estimates reduced the initial effect size to 0.20, suggesting potential overestimation in smaller studies.
At 24-hours post-initial infusion, ketamine demonstrated a small relative advantage over controls with an effect size of 0.35.
Significant differences favoring ketamine were found when compared to passive controls (effect size = 0.44), but not active controls (effect size = 0.24).
No meaningful differences were noted between ketamine and control groups at one week or two weeks post-infusion.

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PTSD is a significant mental health problem worldwide. Current evidence-based interventions suffer various limitations. Ketamine is a novel agent that is hoped to be incrementally better than extant interventions.Several randomized control trials (RCTs) of ketamine interventions for PTSD have now been published. We sought to systematically review and meta-analyse results from these trials to evaluate preliminary evidence for ketamine's incremental benefit above-and-beyond control interventions in PTSD treatment.Omnibus findings from 52 effect sizes extracted across six studies (= 221) yielded a small advantage for ketamine over control conditions at reducing PTSD symptoms (= 0.27, 95% CI = 0.03, 0.51). However, bias-correction estimates attenuated this effect (adjusted= 0.20, 95%, CI = -0.08, 0.48). Bias estimates indicated smaller studies reported larger effect sizes favouring ketamine. The only consistent timepoint assessed across RCTs was 24-hours post-initial infusion. Effects at 24-hours post-initial infusion suggest ketamine has a small relative advantage over controls (= 0.35, 95% CI = 0.06, 0.64). Post-hoc analyses at 24-hours post-initial infusion indicated that ketamine was significantly better than passive controls (= 0.44, 95% CI = 0.03, 0.85), but not active controls (= 0.24, 95% CI = -0.30, 0.78). Comparisons one-week into intervention suggested no meaningful group differences (= 0.24, 95% CI = 0.00, 0.48). No significant differences were evident for RCTs that examined effects two-weeks post initial infusion (= 0.17, 95% CI = -0.10, 0.44).Altogether, ketamine-for-PTSD RCTs reveal a nominal initial therapeutic advantage relative to controls. However, bias and heterogeneity appear problematic. While rapid acting effects were observed, all control agents (including saline) also evidenced rapid acting effects. We argue blind penetration to be a serious concern, and that placebo is the likely mechanism behind reported therapeutic effects. Background: Objective: Results: Conclusions: n g g g g g g g

Key numbers

0.27

Effect Size

Omnibus effect size for ketamine vs. controls

0.35

24-Hour Effect Size

Effect size at 24 hours post-infusion compared to controls

0.20

Adjusted Effect Size

Bias-corrected effect size for ketamine vs. controls

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So how special is special K? A systematic review and meta-analysis of ketamine for PTSD RCTs

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