Parenteral clomipramine for depression or obsessive-compulsive disorder: a systematic review and meta-analysis

In severe cases of depression and obsessive-compulsive disorder (OCD), clomipramine is sometimes administered parenterally. This systematic review aimed to investigate whether parenteral clomipramine is superior to oral clomipramine or other treatments, primarily in terms of reducing depressive/OCD symptoms within two weeks (CRD420250654029). Medline, Embase, the Cochrane Library, and PsycInfo were searched for relevant publications. Randomized controlled trials (RCTs) without a high risk of bias formed the primary basis for the conclusions. Meta-analyses were performed when applicable. Certainty of evidence was assessed according to GRADE. The literature search identified 4973 unique publications, whereof 14 RCTs contributed data regarding the question at issue in this systematic review. The evidence synthesis revealed that parenteral clomipramine may not be superior to oral administration in terms of reducing depressive symptoms within two weeks, but a clinically relevant effect cannot be excluded (low certainty of evidence; five RCTs including 70 patients; mean difference of change in Hamilton depression rating scale scores (meta-analysis based on three RCTs): -1.27 (95% confidence interval: -3.09 to 0.54; 2, I2 = 22%). Regarding patients with OCD, no conclusion could be drawn (very low certainty of evidence; two RCTs including 47 patients; meta-analysis not conducted due to heterogeneity). Regarding comparisons with other treatments, the available RCT (depression) did not allow for conclusions, or no RCTs (OCD) were available. Current evidence indicates that parenteral administration of clomipramine may not be favourable compared to oral administration, and RCTs with relevant comparisons such as electroconvulsive therapy and ketamine are lacking.