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Tricyclic Antidepressant (TCA) — OCD Specialist Pregnancy: Avoid — neonatal anticholinergic effects and withdrawal syndrome. Sertraline preferred.

Clomipramine

Brand names: Anafranil

Adult dose

Dose: OCD: 25mg OD initially; increase over 2 weeks to 100–150mg OD; maximum 250mg OD. Depression: 10mg OD initially; increase to 30–150mg daily (divided or single dose at night); maximum 250mg daily. Phobic and anxiety states: 75–150mg daily.
Route: Oral
Frequency: Once daily at night or divided doses
Max: 250mg OD
Most serotonergic of all TCAs — gold standard pharmacotherapy for OCD, with the strongest evidence base. NICE recommends clomipramine as second-line (after SSRI failure) for OCD. Higher seizure risk than other TCAs at doses above 250mg. Therapeutic plasma levels 230–450 nanograms/mL (clomipramine + N-desmethylclomipramine).

Paediatric dose

Route: Oral
Frequency: Once daily at night
Max: 200mg OD or 3mg/kg (whichever is lower)
BNFc: OCD (10–17 years): 25mg OD initially; increase over 2 weeks to 3mg/kg OD (max 200mg OD). Seek specialist child and adolescent psychiatry opinion.

Dose adjustments

Renal

Use with caution — risk of accumulation in severe impairment.

Hepatic

Avoid in severe hepatic impairment.

Clinical pearls

  • NICE CG31: clomipramine is second-line for OCD after one or two SSRI trials fail — strongest evidence of any TCA for OCD due to its serotonin selectivity
  • OCD doses are typically higher than antidepressant doses (up to 250mg) — seizure risk increases significantly above this dose
  • Overdose: as per other TCAs — IV sodium bicarbonate for QRS widening (cardiac toxicity antidote)
  • Serotonin syndrome risk: highest of all TCAs — avoid combining with tramadol, lithium, other serotonergic drugs

Contraindications

  • Recent MI
  • Arrhythmias, heart block
  • Mania (risk of switch)
  • Closed-angle glaucoma
  • MAOIs within 14 days
  • Hypersensitivity to clomipramine

Side effects

  • Sedation
  • Dry mouth, constipation (anticholinergic)
  • QTc prolongation
  • Seizures (dose-related, >250mg)
  • Sexual dysfunction (very common)
  • Weight gain
  • Orthostatic hypotension

Interactions

  • MAOIs — contraindicated
  • SSRIs (especially fluvoxamine) — significantly increase clomipramine levels; avoid combination
  • Antiarrhythmics — additive cardiac toxicity
  • Tramadol — serotonin syndrome + seizure risk

Monitoring

  • ECG (QTc)
  • Plasma levels (clomipramine + N-desmethylclomipramine)
  • Seizure history (dose above 200mg)
  • OCD symptom rating (Y-BOCS score)

Reference: BNFc; BNF 90; NICE CG31 (OCD). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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