Efficacy and safety of adjunctive orexin receptor antagonist therapy in major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.
Samuel Izaias Dos Santos Pereira, Martin Kotochinsky, Wellgner Fernandes Oliveira Amador et al.
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In 30 seconds
This systematic review and meta-analysis evaluated the efficacy and safety of adjunctive orexin receptor antagonists (ORAs) in adults with major depressive disorder (MDD) who inadequately responded to SSRIs or SNRIs. The analysis found that ORA therapy led to significant improvements in depressive symptoms measured by MADRS (MD -1.96) and sleep disturbance (MD -3.39 on PROMIS-SD), with no significant increase in adverse events compared to placebo.
Key findings
- Adjunctive ORA therapy improved depressive symptoms on MADRS with a mean difference of -1.96.
- Significant sleep improvement was observed with a mean difference of -3.39 on PROMIS-SD.
- No significant difference in safety outcomes compared to placebo was reported.
- An exploratory analysis suggested a small effect favoring ORA therapy (SMD -0.15).
Why it matters
The findings suggest that orexin receptor antagonists may provide a modest benefit for patients with major depressive disorder who do not respond adequately to standard treatments, particularly in improving sleep and depressive symptoms.
What to keep in mind
The evidence is limited by the small number of studies included in the analysis.