TaperCommunityclomipramine
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.
Clomipramine is a tricyclic antidepressant with the strongest serotonin reuptake inhibition of all TCAs. It is the only TCA FDA-approved for obsessive-compulsive disorder (OCD) and is considered a gold-standard treatment for severe OCD.
25mg, 50mg, 75mg, 100mg
Capsules: 25mg, 50mg, 75mg
Category C (risk cannot be ruled out)
Potent inhibitor of serotonin reuptake (most serotonergic TCA) and moderate inhibitor of norepinephrine reuptake. Its metabolite desmethylclomipramine is a potent norepinephrine reuptake inhibitor. Also has anticholinergic, antihistaminic, and alpha-adrenergic blocking activity.
Strong serotonergic TCA. Withdrawal can be severe. Capsules can be opened for bead counting.
Due to strong serotonin reuptake inhibition, withdrawal can resemble SSRI discontinuation. Slow hyperbolic taper recommended.
Toxicity
Cardiotoxic in overdose (QRS widening, arrhythmias). Seizures (dose-dependent, especially >250mg/day). Serotonin syndrome risk. Anticholinergic toxicity.
Pharmacokinetics
Well absorbed after oral administration. Extensive first-pass metabolism; bioavailability ~50%. Tmax 2–6 hours. Food does not significantly affect absorption.
~17 L/kg
Hepatic via CYP2D6, CYP1A2, CYP2C19, and CYP3A4 to the active metabolite desmethylclomipramine and hydroxylated metabolites.
Renal (~51–60% as metabolites) and fecal (~24–32%). Less than 1% excreted unchanged in urine.
~97–98%
Apparent oral clearance variable; auto-inhibition of CYP2D6 with chronic dosing.
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