What is the recommended dose of clomipramine (tricyclic antidepressant) for Obsessive-Compulsive Disorder (OCD)?

Recommended Dosage of Clomipramine for OCD

For adults with OCD, clomipramine should be initiated at 25 mg daily and gradually increased to 100 mg during the first 2 weeks, with further titration up to a maximum of 250 mg daily as needed for symptom control. 1

Initial Dosing and Titration

• Treatment should begin with 25 mg daily and gradually increase to approximately 100 mg during the first 2 weeks 1
• Initial doses should be given in divided doses with meals to reduce gastrointestinal side effects 1
• After the initial 2 weeks, dosage may be increased gradually over several weeks up to a maximum of 250 mg daily 1
• After titration, the total daily dose may be given once daily at bedtime to minimize daytime sedation 1

Pediatric Dosing (Children and Adolescents)

• Starting dose is also 25 mg daily, gradually increased during the first 2 weeks 1
• Maximum dose for children and adolescents is 3 mg/kg or 200 mg daily, whichever is smaller 1
• As with adults, divided doses with meals are recommended initially, with transition to once-daily bedtime dosing after titration 1

Efficacy Considerations

• Higher doses of clomipramine are associated with greater treatment efficacy for OCD compared to doses used for other conditions 2
• Clomipramine was the first agent to show efficacy in OCD and some meta-analyses have suggested it may be more efficacious than SSRIs 2
• However, head-to-head trials directly comparing clomipramine with SSRIs indicate equivalent efficacy 2
• SSRIs have a higher safety and tolerability profile compared to clomipramine, which supports their use as first-line agents 2

Treatment Duration and Monitoring

• An 8-12 week trial is considered optimal to determine efficacy 2
• Significant improvement may be observed within the first 2-4 weeks of treatment 2, 3
• Recommended maintenance duration after achieving remission is a minimum of 12-24 months 2
• Longer treatment might be necessary due to risk of relapse after discontinuing medication 2

Safety Considerations and Adverse Effects

• Most common adverse effects are anticholinergic (dry mouth, constipation) 3, 4
• Other notable side effects include:
  • Nausea and gastrointestinal symptoms 3, 4
  • Sexual dysfunction 3
  • Sedation 1, 3
  • Potential for seizures at higher doses 3
• Careful assessment of adverse effects is crucial when establishing the best dose for each patient 2
• Clomipramine has a less favorable side effect profile compared to SSRIs, with higher withdrawal rates due to adverse effects (26% vs 11% for sertraline in comparative studies) 4

Treatment-Resistant Cases

• For patients with inadequate response to SSRIs, clomipramine may be used as an augmentation strategy 2
• In combination therapy with SSRIs, lower doses of clomipramine (25-50 mg) may be effective while minimizing adverse effects 5
• Caution is needed when combining clomipramine with SSRIs due to risk of serotonin syndrome 2

Important Precautions

• Allow at least 14 days between discontinuation of an MAOI and initiation of clomipramine 1
• Steady-state plasma levels may not be achieved until 2-3 weeks after dosage change 1
• Clomipramine requires careful monitoring due to its less favorable safety profile compared to SSRIs 2, 4