Augmenting selective serotonin reuptake inhibitors with clomipramine in obsessive-compulsive disorder: benefits and risks.

A small body of literature suggests that clomipramine may usefully augment selective serotonin reuptake inhibitor (SSRI) treatment in obsessive-compulsive disorder (OCD) patients who do not respond to SSRI monotherapy. The combination, however, is associated with the risk of clinically significant drug interactions. Clomipramine can raise the blood levels and hence the adverse effects of most SSRIs, and many SSRIs can raise the blood levels and hence the adverse effects of clomipramine. The latter situation is more important because certain dose-dependent adverse effects of clomipramine, such as seizures, can be life-threatening. This article presents an evidence-based discussion of the pharmacodynamic and pharmacokinetic adverse effects of the SSRI-clomipramine combination along with suggestions for dosing and monitoring when the combination is used in OCD.