What is the appropriate dosing of Afranil (imipramine) for depression?

Appropriate Dosing of Imipramine (Afranil) for Depression

For adults with depression, imipramine should be initiated at 75 mg/day and increased to 150 mg/day for outpatients, with a maximum recommended dose of 200 mg/day. 1

Dosing Algorithm by Patient Population

Adult Outpatients

• Initial dose: 75 mg/day
• Target therapeutic dose: 150 mg/day
• Maximum dose: 200 mg/day (doses above this are not recommended)
• Maintenance dose: 50-150 mg/day

Hospitalized Adults

• Initial dose: 100 mg/day in divided doses
• Increase gradually to 200 mg/day as required
• If no response after two weeks, may increase to 250-300 mg/day
• Higher doses are justified in the inpatient setting due to closer monitoring capabilities

Elderly Patients and Adolescents

• Initial dose: 30-40 mg/day
• Maximum dose: Generally not necessary to exceed 100 mg/day
• Use lower doses in these populations due to increased sensitivity to side effects

Administration Guidelines

• Administer once daily at bedtime to minimize daytime sedation
• A single bedtime dose is effective and may improve adherence 2
• For optimal therapeutic effect, gradually increase the dose using increments of the initial dose every 5-7 days until therapeutic benefits are achieved or side effects become apparent 1
• A full therapeutic trial requires at least 4-8 weeks 1

Monitoring and Dose Adjustment

• Evaluate response after 4-8 weeks of treatment at an adequate dose
• If partial response, continue for additional 2-4 weeks before considering dose increase
• Monitor for side effects, particularly:
  • Cardiovascular effects (tachycardia, orthostatic hypotension)
  • Anticholinergic effects (constipation, dry mouth, urinary retention)
  • Sedation and dizziness
• Consider ECG monitoring, especially in elderly patients or those with cardiac history
• After 9 months of successful treatment, consider gradual dose reduction to assess continued need 1

Important Considerations

• Discontinuation: Taper gradually over 10-14 days to limit withdrawal symptoms 1
• Treatment failures: If no response after 4-8 weeks at maximum tolerated dose, consider switching to another antidepressant class
• Therapeutic blood levels: May be helpful in some cases, particularly when using desipramine (a metabolite of imipramine) 1
• Safety concerns: Imipramine is potentially cardiotoxic and overdose may be fatal; secure storage is essential, especially in households with children 1

Special Populations

• Patients with psychotic depression: Require concomitant antipsychotic medication in addition to imipramine 1
• Adolescents: Studies show variable response with a mean dose of 246 mg/day (4.5 mg/kg/day), but only 44% showed significant improvement 3
• Elderly patients: More susceptible to side effects; lower doses are essential to minimize risks

Common Side Effects to Monitor

• Cardiovascular: Tachycardia, orthostatic hypotension
• Anticholinergic: Dry mouth, constipation, urinary hesitancy
• Neurological: Sedation, dizziness
• Sexual dysfunction: May occur in 26% of males and 14% of females, appears to be dose-related 4

By following this dosing algorithm and monitoring protocol, clinicians can optimize the therapeutic benefits of imipramine while minimizing potential adverse effects in patients with depression.