What is the recommended dosing for imipramine (tricyclic antidepressant) in the treatment of depression?

Imipramine Dosing for Depression

For depression treatment, start imipramine at 75 mg/day in outpatients (or 100 mg/day in hospitalized patients), increase gradually to 150 mg/day for outpatients (200 mg/day for hospitalized patients), with maximum doses of 200 mg/day for outpatients and 250-300 mg/day for hospitalized patients under close supervision. 1

Standard Adult Dosing Algorithm

Outpatient Depression

• Initial dose: 75 mg/day 1
• Target dose: 150 mg/day 1
• Maximum dose: 200 mg/day (doses above this are not recommended for outpatients) 1
• Maintenance: 50-150 mg/day after remission 1

Hospitalized Patients (Under Close Supervision)

• Initial dose: 100 mg/day in divided doses 1
• Titration: Gradually increase to 200 mg/day as required 1
• If no response after 2 weeks: Increase to 250-300 mg/day 1

Titration Strategy

• Increase dosage using increments of the initial dose every 5-7 days until therapeutic benefits or significant side effects appear 2
• A full therapeutic trial requires at least 4-8 weeks 2
• Monitor plasma levels of both imipramine and its active metabolite desipramine, with therapeutic range of 175-300 ng/mL combined 2

Special Populations

Elderly and Adolescent Patients

• Initial dose: 30-40 mg/day 1
• Maximum dose: Generally not necessary to exceed 100 mg/day 1
• Critical consideration: Elderly patients exhibit dose-dependent, non-linear kinetics with imipramine, where dose increases result in disproportionally higher plasma levels of the active metabolite desipramine 3
• Use lower starting doses and slower titration compared to younger adults 2

Geriatric-Specific Dosing from Guidelines

• Alternative recommendation: 10-25 mg in the morning initially 2
• Maximum: 150 mg in the morning 2
• Desipramine (imipramine's active metabolite) tends to be activating and may reduce apathy 2

Therapeutic Drug Monitoring

When to Monitor Plasma Levels

• Strongly recommended (Level 1 evidence) for imipramine plus desipramine combined 2
• Therapeutic range: 175-300 ng/mL (combined parent drug and metabolite) 2
• Monitor when approaching maximum doses, in elderly patients, with suspected non-compliance, or when response is inadequate 2
• At 225 mg/day, expected plasma levels are imipramine 6-268 ng/mL and desipramine 18-496 ng/mL 2

Pitfall: Non-Linear Kinetics in Elderly

• Dose increases in elderly patients cause unpredictable, disproportional rises in plasma levels, particularly affecting desipramine 3
• Plasma level monitoring is essential but may be difficult to interpret due to this non-linearity 3

Duration and Maintenance

• After 9 months of treatment, consider dosage reduction to reassess the need for continued medication 2
• Following remission, maintenance medication may be required for a longer period at the lowest dose that maintains remission 1
• When discontinuing, taper gradually over 10-14 days rather than abrupt cessation to limit withdrawal symptoms 2
• Most patients who achieve remission with 12 weeks of imipramine maintain it during 16 weeks of continuation treatment 4

Drug Interactions and Contraindications

Critical Interactions

• Perphenazine: Concomitant use (8-16 mg/day) causes marked rises in imipramine levels, particularly affecting desipramine 3
• MAO inhibitors: Contraindicated due to risk of serotonergic syndrome 2
• Cardiovascular disease: Use with extreme caution in patients with recent MI, arrhythmias, or heart block 5

Comparative Efficacy

• Imipramine demonstrates equal efficacy to sertraline in chronic depression, with 58.9% response rates in chronic major depression and 63.2% in double depression after 12 weeks 6
• Imipramine shows equal efficacy to moclobemide (300-600 mg/day) but with more side effects 7
• However, imipramine is associated with more anticholinergic side effects (dry mouth, orthostatic hypotension, constipation, urinary retention) compared to SSRIs 4

Common Pitfalls to Avoid

• Underdosing: Only 26.8% of chronic depression patients in community settings receive adequate trials (≥150 mg/day for ≥4 weeks) 6
• Premature dose escalation: Wait at least 2 weeks at 200 mg/day before increasing to 250-300 mg/day in hospitalized patients 1
• Ignoring age-related pharmacokinetics: Elderly patients require substantially lower doses due to non-linear metabolism 3
• Inadequate trial duration: Ensure at least 4-8 weeks at therapeutic doses before declaring treatment failure 2