What is the maximum recommended dose of Imipramine (tricyclic antidepressant) per day?

Maximum Recommended Dose of Imipramine

The maximum recommended dose of imipramine is 300 mg per day for hospitalized patients under close supervision, while outpatients should not exceed 200 mg per day. 1

Standard Dosing by Patient Population

Hospitalized Adults

• Start at 100 mg/day in divided doses 1
• Gradually increase to 200 mg/day as required 1
• If no response after two weeks, increase to 250-300 mg/day (maximum dose) 1
• Maintenance: 50-150 mg/day 1

Outpatients

• Start at 75 mg/day 1
• Increase to 150 mg/day as tolerated 1
• Dosages over 200 mg/day are not recommended for outpatients 1
• Maintenance: 50-150 mg/day 1

Elderly and Adolescent Patients

• Start at 30-40 mg/day 1
• It is generally not necessary to exceed 100 mg/day in these populations 1
• Alternative recommendation for elderly: 10-25 mg in the morning, with maximum of 150 mg in the morning 2
• Use lower starting doses and slower titration compared to younger adults 3

Children (Enuresis Only)

• Ages 6-12: Start 25 mg/day, may increase to 50 mg nightly 1
• Ages >12: May receive up to 75 mg nightly 1
• A dose of 2.5 mg/kg/day should not be exceeded 1
• Daily doses greater than 75 mg do not enhance efficacy and increase side effects 1

Titration Strategy

Increase dosage using increments of the initial dose every 5-7 days until therapeutic benefits or significant side effects appear. 2, 3

• A full therapeutic trial requires at least 4-8 weeks 2, 3
• Monitor for clinical response and any evidence of intolerance 1
• Dosage should be initiated at a low level and increased gradually 1

Therapeutic Drug Monitoring

Therapeutic drug monitoring is strongly recommended (Level 1 evidence) for imipramine plus its active metabolite desipramine combined. 3

• The therapeutic range for combined parent drug and metabolite is 175-300 ng/mL 3
• At a dose of 225 mg/day, expected plasma levels are imipramine 6-268 ng/mL and desipramine 18-496 ng/mL 3
• Monitor plasma levels when approaching maximum doses, in elderly patients, with suspected non-compliance, or when response is inadequate 3
• Elderly patients may experience dose-dependent kinetics with disproportional rises in desipramine levels when doses are increased 4

Critical Safety Considerations

Cardiovascular Monitoring

• Obtain baseline ECG before initiating imipramine, particularly in patients with cardiac history 3
• Recent reports of unexpected deaths due to cardiac arrhythmia in children suggest pretreatment ECG to determine underlying rhythm disorder, with periodic monitoring thereafter 2
• Use with extreme caution in patients with recent myocardial infarction, arrhythmias, or heart block 3

Contraindications

• MAO inhibitors are contraindicated due to risk of serotonergic syndrome 3

Common Pitfalls

• Elderly patients are prone to dose-dependent kinetics: Increased doses result in disproportionally higher plasma levels of desipramine, making dose changes unpredictable 4
• Plasma level monitoring may be difficult in elderly patients due to non-linear kinetics 4
• The most serious problem is accidental ingestion by younger siblings, leading to serious or fatal consequences 2

Duration and Discontinuation

• After 9 months of treatment, consider dosage reduction to reassess the need for continued medication 2, 3
• Taper gradually over 10-14 days rather than abrupt cessation to limit withdrawal symptoms 2, 3
• Following remission, maintenance medication may be required for a longer period at the lowest dose that will maintain remission 1

Evidence Quality Note

Research evidence shows that 300 mg/day is more effective than 150 mg/day in hospitalized depressed patients, with greater and more consistent improvement noted in the higher dose group 5. However, the FDA label clearly restricts outpatients to a maximum of 200 mg/day due to safety considerations when patients are not under close hospital supervision 1.