Is extended-release (ER) valproic acid (valproate) associated with less weight gain in adolescents with juvenile myoclonic epilepsy (JME)?

Extended-Release Valproic Acid and Weight Gain in Adolescents with JME

There is no evidence that extended-release (ER) valproic acid is associated with less weight gain compared to immediate-release formulations in adolescents with juvenile myoclonic epilepsy (JME).

Valproic Acid and Weight Gain in Epilepsy

Valproic acid (valproate) remains the most effective medication for JME, with control rates of 70-90% for all seizure types associated with this condition 1. However, weight gain is a well-documented adverse effect of valproic acid therapy that particularly impacts adolescents:

• Valproic acid is specifically listed among anti-epileptic medications associated with weight gain 2
• Weight gain and obesity from valproate have direct negative effects on health and life expectancy 2
• Weight increase from valproate reduces insulin sensitivity and can promote polycystic ovary syndrome (PCOS) development in predisposed women 2

Extended-Release vs. Immediate-Release Formulations

Despite the suggestion in some literature that extended-release preparations might be less likely to produce weight gain 1, there is no robust clinical evidence demonstrating that ER valproic acid causes less weight gain than immediate-release formulations in adolescents with JME.

Treatment Considerations for JME in Adolescents

When treating adolescents with JME, clinicians should consider:

1. Efficacy vs. Side Effects

   • Valproic acid remains the most effective treatment for JME 1, 3
   • Low-dose valproate (500-1000mg daily) may be as effective as higher doses while potentially minimizing side effects 4

2. Alternative Medications

   • For female adolescents, particularly those of childbearing potential, alternative medications should be considered due to valproate's teratogenic potential and endocrine effects
   • Levetiracetam has shown better efficacy than lamotrigine for JME patients previously controlled on valproate 5
   • However, valproate still shows higher overall seizure freedom rates compared to levetiracetam 3

3. Monitoring for Endocrine Effects

   • Regular monitoring for weight gain, insulin resistance, and signs of PCOS is essential
   • Up to 45% of women on valproate monotherapy may experience menstrual irregularities 2
   • Polycystic ovaries or hyperandrogenemia have been found in up to 64% of women taking valproate monotherapy 2

Clinical Approach for Adolescents with JME

For adolescents with JME requiring medication:

1. For male adolescents: Valproate remains first-line therapy, starting with lower doses (500-1000mg daily) and monitoring for weight gain

2. For female adolescents: Consider alternatives to valproate:

   • Levetiracetam appears to be the most effective alternative, particularly for controlling myoclonic seizures 5, 3
   • If valproate is necessary due to seizure control issues, use the lowest effective dose and monitor closely for weight gain and endocrine effects

3. If weight gain occurs on valproate:

   • Consider switching to levetiracetam, which has shown good efficacy in JME without weight gain concerns
   • Monitor for breakthrough seizures during medication transitions

Weight management should be addressed proactively with all patients on valproate through dietary counseling and regular physical activity, regardless of the formulation used.