Clomipramine: a tricyclic antidepressant effective in obsessive compulsive disorder.

Clomipramine hydrochloride, a chlorinated analog of imipramine, is a widely used antidepressant recently approved for use in the U.S. for the treatment of obsessive-compulsive disorder (OCD), a potentially incapacitating affliction. Its primary pharmacologic action is blockade of the reuptake of the neurotransmitter serotonin. Its metabolite, desmethylclomipramine, is a potent norepinephrine reuptake inhibitor. Significant first-pass metabolism reduces oral bioavailability to less than 62 percent. The drug is widely distributed throughout the body (volume of distribution 9-25 L/kg) and is 90-98 percent protein-bound. Clomipramine follows first-order elimination pharmacokinetics, with a plasma half-life of 20-24 hours. Recent double-blind controlled clinical trials have demonstrated the drug's effectiveness in the treatment of OCD. Response is most often associated with doses greater than 75 mg/d, with 250 mg the maximum recommended daily dose. Relapse upon withdrawal is frequently reported. The adverse effect profile of clomipramine is similar to other tricyclic antidepressants, with anticholinergic, cardiovascular, sexual, and central nervous system effects the most prominent.