Imipramine Dosage and Side Effects in Children
For childhood enuresis, imipramine should be dosed at 25-50 mg at bedtime for children aged 6 and older, with the higher dose given to children older than 9 years. 1, 2
Dosing Guidelines for Enuresis
- Initial oral dose of 25 mg/day should be tried in children aged 6 and older, given one hour before bedtime 2
- If no satisfactory response occurs within one week, increase the dose to 50 mg nightly in children under 12 years; children over 12 may receive up to 75 mg nightly 2
- For early night bedwetters, the drug may be more effective given earlier and in divided amounts (25 mg in midafternoon, repeated at bedtime) 2
- A daily dose greater than 75 mg does not enhance efficacy and tends to increase side effects 2
- A dose of 2.5 mg/kg/day should not be exceeded in childhood 2
- Treatment should be evaluated after 1 month 1
- If treatment is successful, taper to the lowest effective dose and ensure regular drug holidays of at least 2 weeks every third month to decrease the risk of tolerance 1
Important Safety Considerations
- Imipramine should only be used as third-line therapy for enuresis at tertiary care facilities due to safety concerns and side effects 1
- The drug should be kept securely locked and out of reach of smaller siblings due to potential cardiotoxicity and fatal overdose risk 1
- ECG monitoring is essential before starting treatment if there is any history of palpitations or syncope in the child, or any sudden cardiac death or unstable arrhythmia in the family 1, 2
- ECG changes of unknown significance have been reported in pediatric patients with doses exceeding 2.5 mg/kg/day 2
Side Effects
Serious Side Effects
- Potentially cardiotoxic - can cause conduction defects, arrhythmias, tachycardia 1, 2
- Overdose may prove fatal 1
- May lower seizure threshold in patients with seizure disorders 2
Common Side Effects
- Mood changes 1
- Nausea 1
- Insomnia 1
- Anticholinergic effects (urinary retention, increased intraocular pressure) 2
- These side effects often appear earlier than the beneficial effects 1
- Moderate side effects often gradually disappear even if treatment is continued 1
Efficacy and Monitoring
- Approximately 50% of unselected children with enuresis respond to imipramine 1
- Response rate seems to be the same in children with therapy-resistant enuresis 1, 3
- Older children (mean age 11.4 years) tend to respond better than younger children (mean age 8.7 years) 3
- Serum level monitoring may be useful in some cases, with better responses typically seen at combined imipramine and desipramine levels above 60-80 ng/ml 4, 5, 6
- When there is a partial response, desmopressin at the standard dose may be added, provided that fluid intake is restricted during evening and night 1
Special Precautions
- Screen patients for bipolar disorder before initiating treatment 2
- Monitor for suicidality and unusual changes in behavior, especially during the initial few months of therapy 2
- Use extreme caution in patients with cardiovascular disease 2
- May interact with guanethidine, clonidine, and methylphenidate 2
- May enhance CNS depressant effects of alcohol 2
Remember that imipramine should only be considered after first-line therapies (enuresis alarm and desmopressin) have failed, due to its potential for serious side effects and the availability of safer alternatives 1.