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Clomipramine (Anafranil)

TCA • Last reviewed 2025-09-27

General information

Clomipramine is a serotonin-preferring TCA approved for obsessive-compulsive disorder and used in treatment-resistant depression. Strong serotonergic, anticholinergic, and antihistamine effects increase side-effect burden.

Combined plasma levels (clomipramine + desmethylclomipramine) should stay within 150–300 ng/mL; higher concentrations significantly increase seizure and arrhythmia risk.

Patients require counseling regarding sexual dysfunction, orthostasis, and constipation.

Due to seizure risk, avoid rapid titration and use caution with other threshold-lowering drugs (bupropion, tramadol).

Dosing & administration

Start 25 mg at bedtime; increase by 25 mg every 3–4 days.

Target 100–250 mg/day divided; max 250 mg outpatient/300 mg inpatient.

Monitor plasma level after 3 weeks or with dose >150 mg/day.

Mechanism of action

Potent serotonin reuptake inhibition with secondary norepinephrine effect via active metabolite.

Metabolism & pharmacokinetics

Peak concentration 2–6 h post-dose. Half-life 32–37 h; hepatic metabolism via CYP2D6/CYP3A4 to desmethylclomipramine.

Drug interactions

Avoid MAOIs, cisapride, SSRIs (serotonin syndrome/QT).

CYP2D6/CYP3A4 inhibitors (fluoxetine, fluvoxamine, ketoconazole) increase levels; reduce dose.

Use caution with other anticholinergic or QT-prolonging agents.

Monitoring & safety checks

  • ECG baseline and after dose increases

  • Plasma level (goal 150–300 ng/mL)

  • Assess anticholinergic side effects and bowel regimen

Discontinuation guidance

Taper ≥4 weeks. Abrupt stop can provoke cholinergic rebound, anxiety, and insomnia.

References

  1. Clomipramine Prescribing Information — DailyMed
  2. APA OCD guideline (2020)
  3. Clomipramine therapeutic monitoring and safety — CNS Spectrums (2023)

Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.