Tofranil (Imipramine) Dosing
For depression in adults, the dose range is 75-300 mg/day, with hospitalized patients typically requiring 100-300 mg/day and outpatients 75-200 mg/day; for childhood enuresis, the dose is 25-75 mg/day at bedtime, not to exceed 2.5 mg/kg/day. 1
Depression Dosing
Outpatients
- Start: 75 mg/day
- Target: 150 mg/day
- Maximum: 200 mg/day (doses above this are not recommended) 1
Hospitalized Patients
- Start: 100 mg/day in divided doses
- Increase gradually to: 200 mg/day as required
- If no response after 2 weeks: Increase to 250-300 mg/day 1
Adolescents and Elderly
- Start: 30-40 mg/day
- Maximum: Generally not necessary to exceed 100 mg/day 1
Maintenance
- Range: 50-150 mg/day 1
Childhood Enuresis Dosing (Age ≥6 years)
Start with 25 mg/day one hour before bedtime 1
If inadequate response after 1 week:
- Children <12 years: Increase to 50 mg nightly
- Children ≥12 years: May increase up to 75 mg nightly 1
Critical safety limit: Do not exceed 2.5 mg/kg/day 1
Important: Doses >75 mg do not enhance efficacy and increase side effects 1
Alternative timing for early-night bedwetters: 25 mg in mid-afternoon, repeated at bedtime 1
The more recent 2010 International Children's Continence Society guideline recommends a simpler fixed-dose approach of 25-50 mg at bedtime, with the larger dose for children >9 years 2. This represents third-line therapy due to cardiac toxicity concerns 2.
Weight-Based Dosing for Enuresis
Multiple guidelines consistently recommend 1.0-2.5 mg/kg/day as a single bedtime dose for enuresis 3. If no effect occurs at 2.5 mg/kg/day, serum level assessment is indicated 3.
Critical Safety Considerations
Obtain baseline ECG before initiating treatment to exclude underlying rhythm disorders, particularly given reports of unexpected cardiac deaths in children on tricyclic antidepressants 3, 1. This is especially crucial since the maximum safe dose of 2.5 mg/kg/day should never be exceeded in children—ECG changes of unknown significance have been reported at twice this dose 1.
Keep medication securely locked away from younger siblings, as accidental ingestion can be fatal 3.
Important Dosing Nuances
The evidence reveals significant interindividual variability in plasma levels at the same dose 3. Research demonstrates nonlinear kinetics, particularly in the low-to-medium plasma level range, meaning dose adjustments based on simple linear predictions can result in 0-130% overestimates 4. For depression, therapeutic plasma levels (imipramine + desipramine combined) should be ≥200 ng/ml, typically achieved with mean doses around 248 mg/day (range 50-450 mg) 5.
For panic disorder with agoraphobia, optimal plasma levels are 110-140 ng/ml; higher levels may have detrimental effects 6. Interestingly, high desipramine metabolite levels may negatively impact treatment response 7.