BSN Tracker

clomipramine

Brand: Anafranil

⚠ BBW Beers Criteria TDM Required Prototype: amitriptyline
Drug Class: tricyclic antidepressant (TCA)
Drug Family: antidepressant
Subclass: chlorinated tertiary amine TCA
Organ Systems: cns

Mechanism of Action

Most potent SERT inhibitor among TCAs; also inhibits NET. The high serotonin selectivity, combined with its TCA structure, may explain its unique efficacy in OCD, a disorder with prominent serotonergic dysregulation. Additional dopamine D2 blockade may contribute to anti-obsessional effects.

SERT (serotonin transporter)NET (norepinephrine transporter)muscarinic receptorsD2 dopamine receptor

Indications

  • OCD (FDA-approved)
  • off-label: major depressive disorder
  • off-label: panic disorder
  • off-label: cataplexy (narcolepsy)

Contraindications

  • concurrent MAOI use
  • acute post-MI recovery
  • QT prolongation
  • seizure disorders (lowers seizure threshold)

Adverse Effects

Common

  • dry mouth
  • somnolence
  • tremor
  • ejaculation failure (90% in males)
  • constipation
  • weight gain

Serious

  • seizures (dose-dependent; higher risk than other TCAs)
  • QT prolongation
  • cardiac arrhythmias
  • serotonin syndrome

Pharmacokinetics (ADME)

Absorption well absorbed orally; bioavailability ~50% after first-pass metabolism
Distribution protein binding ~97%; highly lipophilic; large Vd
Metabolism demethylated to active desmethylclomipramine via CYP2D6 and CYP3A4
Excretion primarily renal as metabolites
Half-life 32 hours (range 19-37 hours); active metabolite 69 hours
Onset 4-10 weeks for OCD response
Peak 2-6 hours
Duration 24 hours
Protein Binding 97%
Vd 12-17 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
MAOIs serotonin syndrome and hypertensive crisis contraindicated
CYP2D6 inhibitors increase clomipramine levels and seizure risk major
tramadol additive seizure risk and serotonin syndrome major

Nursing Considerations

  1. Seizure risk is highest among TCAs — use with caution in patients with seizure history; maximum dose is 250 mg/day and doses above 250 mg significantly increase seizure risk.
  2. Sexual dysfunction is near-universal in males (90% ejaculatory dysfunction); counsel patients about this effect before initiating and discuss impact on quality of life and adherence.
  3. OCD response requires longer treatment trials (8-12 weeks) than depression (4-6 weeks); lack of early response should not prompt premature discontinuation.
  4. Monitor for serotonin syndrome symptoms at initiation and with any dose increase, as clomipramine's potent SERT inhibition makes this combination risk higher than with other TCAs.

Clinical Pearls

  • Clomipramine was the first pharmacological treatment proven effective for OCD in controlled trials, establishing serotonin dysregulation as central to OCD pathophysiology.
  • Its 90% rate of ejaculatory failure in males is the highest sexual adverse effect rate of any antidepressant, but this property is occasionally used therapeutically for premature ejaculation.

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

OCD (FDA-approved) Off-label: Cataplexy (narcolepsy) Off-label: Major Depressive Disorder Off-label: Panic Disorder Tricyclic Antidepressant (TCA)
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