Management of Imipramine-Responsive Nocturnal Enuresis with Relapse After Discontinuation
Continue imipramine treatment for a total duration of 4-6 months from initiation, then implement a gradual taper with scheduled drug holidays rather than abrupt discontinuation to minimize relapse risk. 1
Current Treatment Duration and Next Steps
Since the patient has been on imipramine for 5 months with good response but relapses upon discontinuation, you are approaching the recommended treatment endpoint but have not yet completed the full course:
- Standard imipramine treatment duration for enuresis is 4-6 months when effective 1
- At 5 months, you are within the appropriate treatment window 1
- The relapse you observed is expected—imipramine has a relapse rate as high as 50% upon discontinuation 1
Recommended Tapering Strategy
Do not abruptly stop imipramine; instead, implement a structured discontinuation protocol:
- Taper to the lowest effective dose gradually rather than stopping abruptly 2
- Institute regular drug holidays of at least 2 weeks every third month to decrease tolerance risk 2
- The FDA label specifically states "dosage should be tapered off gradually rather than abruptly discontinued; this may reduce the tendency to relapse" 3
Important Caveat About Relapse
Children who relapse when imipramine is discontinued do not always respond to a subsequent course of treatment 3. This is a critical consideration—the current response may not be reproducible if you stop and restart.
Alternative Strategies if Relapse Persists
If the patient continues to relapse despite proper tapering:
- Consider transitioning to an enuresis alarm, which has a 66% success rate with more than half experiencing long-term success and appears more durable than pharmacotherapy 4, 5
- Alarms are associated with one fewer wet night per week compared to imipramine after treatment discontinuation 5
- Combination therapy with desmopressin may be added to imipramine if there is partial response, provided fluid intake is restricted during evening and night 2
- For truly refractory cases after alarm and desmopressin failure, combination of solifenacin with low-dose imipramine (25 mg) has shown efficacy with lower relapse rates 6
Safety Monitoring Considerations
Given the 5-month treatment duration, ensure:
- ECG monitoring should have been performed before treatment initiation and periodically thereafter due to cardiac arrhythmia risk 1
- Secure medication storage away from younger siblings, as accidental ingestion can be fatal 1, 2
- The current 25 mg dose is appropriate and should not exceed 2.5 mg/kg/day 3
Why Not Just Continue Indefinitely?
While maintenance beyond 6 months might seem logical, the guidelines specifically recommend 4-6 months of treatment 1, and imipramine should only be used as third-line therapy due to safety concerns 2. The goal is to achieve sustained remission with the shortest necessary treatment duration, followed by transition to safer long-term strategies like behavioral interventions if needed.