Side Effects of Zonisamide in Adolescents with Juvenile Myoclonic Epilepsy
Zonisamide commonly causes somnolence, anorexia, dizziness, ataxia, and cognitive issues in adolescents with JME, with approximately 12% of patients discontinuing treatment due to adverse effects. 1
Common Side Effects and Their Frequency
Most Common Side Effects (>4% higher than placebo)
- Somnolence/drowsiness - Very common
- Anorexia/weight loss - Very common
- Dizziness - Common
- Ataxia/coordination problems - Common
- Agitation/irritability - Common
- Cognitive issues (memory and concentration difficulties) - Common 1
Leading Causes of Discontinuation
- Somnolence, fatigue, and/or ataxia (6%)
- Anorexia (3%)
- Concentration difficulties (2%)
- Memory problems, mental slowing, nausea/vomiting (2%)
- Weight loss (1%) 1
Neurological Side Effects
- Tremor - Frequent
- Abnormal gait - Frequent
- Hyperesthesia - Frequent
- Incoordination - Frequent
- Convulsions - Frequent 1
Many of these side effects are dose-related, with higher doses increasing risk of adverse events.
Psychiatric and Cognitive Side Effects
- Mood problems - Can include depression, mood changes, or irritability
- Cognitive impairment - Problems with concentration, memory, mental slowing
- Speech and language problems - Can occur in some patients 1
These cognitive side effects are particularly important to monitor in adolescents, as they may impact academic performance.
Other System Effects
Digestive System
- Vomiting - Frequent
- Nausea - Common
- Abdominal pain - Common 1
Metabolic Effects
- Weight loss - Common and significant in adolescents
- Peripheral edema - Infrequent
- Weight gain - Infrequent (less common than weight loss) 1
Efficacy vs. Side Effect Profile in JME
In a retrospective study of adolescents with JME treated with zonisamide:
- 80% of patients on zonisamide monotherapy showed good seizure control (≥50% reduction)
- 69% became free of generalized tonic-clonic seizures
- 62% became free of myoclonic seizures
- Only 20% experienced side effects (weight loss, headache, dizziness), which resolved during maintenance therapy 2
Long-term Safety in Pediatric Population
A long-term safety study in children and adolescents with epilepsy found:
- Mean dose received was 8.5 mg/kg/day
- 48% of patients completed 15 months of treatment
- Treatment-related adverse events were mostly mild to moderate
- Only 7% discontinued due to treatment-related adverse events
- Serious adverse events (pancreatitis, decreased sweating, vertigo) were rare, reported in only 3 patients 3
Clinical Monitoring Recommendations
Baseline assessment before starting zonisamide:
- Complete medical history, particularly regarding depression, mood problems, or suicidal thoughts
- Kidney and liver function tests
- Assessment for history of metabolic acidosis
- Bone health evaluation
- Growth parameters
Ongoing monitoring:
- Weight and appetite changes (monthly initially)
- Cognitive function and mood changes
- Kidney function (risk of kidney stones)
- Hydration status (recommend increased fluid intake)
Warning signs requiring immediate attention:
- Severe rash
- Signs of metabolic acidosis
- Significant weight loss
- Suicidal ideation
- Severe cognitive impairment
Practical Considerations for Adolescents with JME
- Start with low doses and titrate slowly to minimize side effects
- Consider once-daily dosing (possible due to long half-life) to improve adherence in adolescents
- Monitor academic performance due to potential cognitive side effects
- Ensure adequate hydration to prevent kidney stones
- Consider the impact of weight loss on adolescent development and body image
Conclusion
While zonisamide can be effective for JME in adolescents with 80% showing good seizure control, clinicians must carefully monitor for common side effects, particularly somnolence, anorexia, cognitive issues, and weight loss. Most side effects are mild to moderate and often resolve during maintenance therapy, but approximately 12% of patients may discontinue treatment due to adverse effects.