Clinical Information

Clomipramine (chlorimipramine, Anafranil) is a tricyclic antidepressant drug used primarily to treat obsessive-compulsive disorder. Clomipramine is also used to treat panic disorder and treatment-resistant depression.

Clomipramine preferentially blocks synaptic reuptake of serotonin; its pharmacologically active metabolite, norclomipramine (desmethylclomipramine) preferentially blocks synaptic reuptake of norepinephrine.

Clomipramine undergoes significant first-pass hepatic metabolism (up to 50%), which probably explains the high degree of interindividual variability observed between administered dose and steady-state serum concentrations of the drug and its metabolite. The serum ratio of clomipramine to norclomipramine is typically 1:2 to 1:2.5. The elimination half-lives of clomipramine and norclomipramine are 19 to 37 hours and 54 to 77 hours, respectively. When a patient is started on clomipramine or following an alteration in the dose, 1 to 2 weeks are required to achieve a steady-state condition.

Anticholinergic side effects (ie, dry mouth, excessive sweating, blurred vision, urinary retention, constipation) frequently accompany treatment. Other side effects may include tremor, nausea, orthostatic hypotension, dizziness, sexual dysfunction, and sleep disturbances. Signs and symptoms following overdose are similar to other tricyclic antidepressant drugs with cardiac toxicity (eg, tachycardia, arrhythmia, impaired conduction, congestive heart failure) the major concern.