Imipramine Dosing and Monitoring for Depression

Titration Strategy

• Increase imipramine dosage using increments of the initial dose every 5-7 days until therapeutic benefits or significant side effects appear 1
• A full therapeutic trial of imipramine requires at least 4-8 weeks 1
• Monitor plasma levels of both imipramine and its active metabolite desipramine, with therapeutic range of 175-300 ng/mL combined 2

Special Populations

• In elderly and adolescent patients, use lower starting doses and slower titration compared to younger adults 3
• For geriatric patients, an alternative initial recommendation is 10-25 mg in the morning, with maximum of 150 mg in the morning 1
• Desipramine (imipramine's active metabolite) tends to be activating and may reduce apathy 1

Therapeutic Drug Monitoring

• Therapeutic drug monitoring is strongly recommended (Level 1 evidence) for imipramine plus desipramine combined 2
• The therapeutic range for combined parent drug and metabolite is 175-300 ng/mL 2
• Monitor plasma levels when approaching maximum doses, in elderly patients, with suspected non-compliance, or when response is inadequate 4, 2
• At a dose of 225 mg/day, expected plasma levels are imipramine 6-268 ng/mL and desipramine 18-496 ng/mL 5, 4

Duration and Maintenance

• After 9 months of treatment, consider dosage reduction to reassess the need for continued medication 1
• When discontinuing imipramine, taper gradually over 10-14 days rather than abrupt cessation to limit withdrawal symptoms 1

Drug Interactions and Contraindications

• MAO inhibitors are contraindicated with imipramine due to risk of serotonergic syndrome 6
• Use imipramine with extreme caution in patients with recent myocardial infarction, arrhythmias, or heart block 7

Treatment Adequacy

• Ensure at least 4-8 weeks at therapeutic doses before declaring treatment failure 1