Augmentation strategies for intravenous ketamine in treatment-resistant depression: A systematic review and meta-analysis.
Reinhard Janssen-Aguilar, Jithin Joseph, Huda F Al-Shamali et al.
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In 30 seconds
This systematic review and meta-analysis assessed augmentation strategies intended to sustain or improve the effects of intravenous ketamine in adults with treatment-resistant depression. Seven randomized controlled trials involving 346 participants evaluated pharmacological agents and ketamine combined with psychotherapy. Across seven heterogeneous comparisons, augmentation did not significantly improve depressive symptoms relative to control (SMD = -0.12; 95% CI, -0.37 to 0.12; p = 0.323; I² = 0.0%). Pharmacological strategies showed no additional benefit at primary endpoints; CBT- and ASAT-based approaches had preliminary maintenance signals, each from a single study. The authors judged the randomized evidence low-certainty and insufficient to support routine augmentation.
Key findings
- The pooled analysis found no significant symptom difference between augmentation and control: SMD = -0.12; 95% CI, -0.37 to 0.12; p = 0.323; I² = 0.0%.
- Pharmacological augmentation strategies did not show additional benefit at primary endpoints.
- CBT- and ASAT-based ketamine psychotherapy showed preliminary signals of maintained antidepressant effects, but each approach was evaluated in one study.
- No clear new safety signal emerged, although adverse-event reporting varied across trials.
Why it matters
Ketamine’s antidepressant benefits may be transient, making strategies to extend them clinically relevant. This review indicates that current randomized evidence does not establish an overall benefit from adding pharmacological or psychotherapy-based approaches. The preliminary psychotherapy signals may warrant further study, but the small and heterogeneous evidence base limits confidence about which, if any, strategies can sustain benefit.
What to keep in mind
The evidence comprised seven heterogeneous trials, and CBT- and ASAT-based approaches were each assessed in a single study. Adverse-event reporting was heterogeneous, and the authors characterize the evidence as low-certainty.