Does levetiracetam (Keppra) cause nocturnal enuresis in children?

Levetiracetam (Keppra) Can Cause Nocturnal Enuresis in Some Children

Yes, levetiracetam (Keppra) can cause nocturnal enuresis in children, though it is an uncommon adverse effect. The FDA drug label for Keppra specifically lists enuresis as a reported side effect in pediatric patients, occurring in approximately 2% of children treated with the medication 1.

Evidence from FDA Drug Labeling

The official Keppra prescribing information documents enuresis as one of the neuropsychiatric adverse events associated with the medication 1. In pediatric clinical trials for partial onset seizures, enuresis was reported among the adverse effects, though it occurred less frequently than behavioral symptoms like hostility (11.9%), nervousness (9.9%), and somnolence (22.8%) 1.

Supporting Research Evidence

A 2016 retrospective study of 351 pediatric patients treated with levetiracetam found that enuresis occurred in 2% of patients as an adverse effect 2. This aligns precisely with the FDA drug label data, providing independent confirmation of this side effect.

More compelling evidence comes from a 2016 case report that documented two pediatric patients who developed diurnal frequent urination after starting levetiracetam 3. Both cases achieved a Naranjo score of 6, indicating levetiracetam was a "probable" cause of the urinary symptoms. In one case, a 6-year-old boy developed urinary frequency and urgency on the third day after starting levetiracetam, with symptoms worsening as the dose increased. When the drug was discontinued, urination frequency returned to normal. In the second case, reducing the levetiracetam dose to one-third resulted in a 60% reduction in urinary frequency 3.

Clinical Context and Mechanism

While the exact mechanism by which levetiracetam causes enuresis is not fully understood, it appears to be part of the broader spectrum of neuropsychiatric and behavioral adverse effects associated with this medication. The drug is well-documented to cause:

• Behavioral abnormalities (37.6% in pediatric patients) 1
• Somnolence (22.8% in children) 1
• Irritability (67% of adverse events) 2
• Mood and psychiatric disturbances 4

Important Clinical Considerations

The incidence of enuresis with levetiracetam is relatively low (2%), but clinicians should:

• Monitor for urinary symptoms when initiating or increasing levetiracetam doses in children
• Consider dose-dependent effects, as the case reports suggest symptoms may worsen with higher doses and improve with dose reduction 3
• Distinguish from primary enuresis, as levetiracetam-induced enuresis would represent secondary enuresis (new onset after a period of dryness)
• Rule out other causes before attributing enuresis solely to levetiracetam, including urinary tract infections, constipation, and sleep apnea 5

Management Approach

If enuresis develops after starting levetiracetam:

1. Document the temporal relationship between drug initiation/dose escalation and symptom onset
2. Assess whether seizure control justifies continuing the medication versus switching to an alternative antiepileptic drug
3. Consider dose reduction if seizure control permits, as this may reduce urinary symptoms while maintaining therapeutic benefit 3
4. Evaluate for other contributing factors such as fluid intake patterns, sleep disorders, or constipation 5
5. If enuresis persists and is clinically significant, consider discontinuing levetiracetam and selecting an alternative antiepileptic medication

The evidence clearly establishes that while uncommon, nocturnal enuresis is a recognized adverse effect of levetiracetam in children that warrants clinical awareness and appropriate monitoring.