There is growing interest in glutamatergic agents as a treatment for depression, especially intranasal ketamine, which has become a hot topic in recent years. We aim to assess the efficacy and safety of intranasal ketamine in the treatment of major depressive disorder (MDD), especially treatment-resistant depression (TRD).
We searched Medline, EMBASE, and the Cochrane Library until April 1, 2020 to identify double-blind, randomized controlled trials with allocation concealment evaluating intranasal ketamine in major depressive episodes. Clinical remission, response, and depressive symptoms were extracted by two independent raters. The outcome measures were Montgomery–Asberg Depression Rating Scale (MADRS) score improved from baseline, clinical response and remission, dissociative symptoms, and common adverse events. The analyses employed a random-effects model.
Data were synthesized from five randomized controlled trials (RCTs) employing an intranasal esketamine and one RCT employing intranasal ketamine, representing 840 subjects in parallel arms, and 18 subjects in cross-over designs (
Our meta-analysis suggests that repeated intranasal ketamine conducted a fast-onset antidepression effect in unipolar depression, while the mild and transient adverse effects were acceptable.
PROSPERO, CRD42020196856.