Clomipramine (Anafranil)

Class

Tricyclic antidepressant (TCA)

Mechanism

Inhibits the reuptake of serotonin and norepinephrine, with a strong serotonin reuptake inhibition profile, contributing to its efficacy in obsessive-compulsive disorder (OCD). Also exhibits anticholinergic, antihistaminic, and alpha-1 adrenergic blocking effects.

FDA-Approved Use

Obsessive-compulsive disorder (OCD)

Off-Label Use

Treatment-resistant depression (augmentation), panic disorder

Formulation

Oral tablets

Titration

Start at 25 mg p.o. nightly, titrate slowly based on clinical response, typically up to 250 mg/day

Dose Range

25–250 mg/day

Kinetics

Half-life approximately 19–37 hours; metabolized hepatically mainly via CYP2D6; steady state reached in ~1 week

Common AEs

Sedation, dry mouth, constipation, weight gain, orthostatic hypotension, blurred vision, sexual dysfunction

Serious/Rare AEs

Cardiac conduction abnormalities, QT prolongation, seizures, serotonin syndrome risk when combined with other serotonergic agents

Monitoring

ECG monitoring recommended in patients >40 years old or with cardiac risk factors; monitor for signs of serotonin syndrome, especially with serotonergic augmentation; serum levels may guide dosing due to narrow therapeutic index; review concomitant medications for CYP450 interactions; monitor for orthostatic hypotension and fall risk especially in elderly

Black Box Warning

Increased risk of suicidal ideation and behavior in children, adolescents, and young adults

Considerations

Increased sensitivity in elderly patients with higher risk of sedation, falls, cognitive impairment, and potential worsening of delirium or dementia symptoms. Use with caution in patients with cardiac conduction issues, glaucoma, or seizure history.