Clomipramine

Brand Names: Anafranil

Drug Class: Tricyclic antidepressant (TCA), Serotonin reuptake inhibitor

Overview

Clomipramine is a tricyclic antidepressant primarily used for the treatment of obsessive-compulsive disorder (OCD). It works by inhibiting serotonin reuptake, which is thought to reduce obsessions and compulsions. Treatment requires careful dose titration and monitoring due to risks including seizures, serotonin syndrome, and suicidality.

Mechanism of Action

Clomipramine inhibits the reuptake of serotonin (5-HT) at presynaptic neuronal membranes, increasing synaptic serotonin concentrations. This serotonergic activity is believed to mediate its anti-obsessional effects in OCD, though its exact neurochemical mechanism remains unknown.

Indications

  • Treatment of obsessions and compulsions in patients with Obsessive-Compulsive Disorder (OCD)

Common Doses

  • 25 mg
  • 50 mg
  • 75 mg

Dosage

Start at 25 mg daily, titrate gradually to 100 mg over first 2 weeks, then increase as tolerated up to 250 mg daily in adults or 3 mg/kg/day (max 200 mg) in children/adolescents. Give divided doses with meals initially; once-daily bedtime dosing may be used after titration to minimize sedation. Wait 2-3 weeks between dosage adjustments due to long half-life.

Contraindications

  • Hypersensitivity to clomipramine or other tricyclic antidepressants
  • Concomitant use with MAOIs or within 14 days of MAOI therapy
  • During acute recovery period after myocardial infarction
  • Initiation in patients receiving linezolid or intravenous methylene blue

Side Effects

  • Common: Dry mouth, constipation, nausea, somnolence, tremor, dizziness, increased sweating, fatigue, weight gain, visual changes
  • Serious: Seizures, suicidal ideation, serotonin syndrome, cardiac arrhythmias, hypotension, angle-closure glaucoma
  • Genitourinary: Ejaculatory failure, impotence, libido changes, micturition disorders

Interactions

  • MAOIs: Contraindicated due to serotonin syndrome risk
  • Other serotonergic drugs (SSRIs, SNRIs, triptans, tramadol, lithium): Increased serotonin syndrome risk
  • CNS depressants: Additive sedation
  • Drugs that inhibit CYP2D6 (fluoxetine, paroxetine, quinidine): Increased clomipramine levels
  • Anticholinergics/sympathomimetics: Enhanced effects requiring dose adjustment
  • Warfarin/digoxin: Potential displacement from protein binding

Counseling Points

  • Take with food to reduce stomach upset
  • Do not stop abruptly; taper under medical supervision
  • Report worsening depression, suicidal thoughts, or unusual behavior changes
  • Avoid alcohol and other CNS depressants
  • Use caution when driving or operating machinery due to sedation
  • Maintain adequate hydration and monitor for constipation
  • Allow 2-3 weeks for full therapeutic effect
  • Use sun protection due to photosensitivity risk