Factors associated with lack of response to valproic acid monotherapy in juvenile myoclonic epilepsy.

Purpose: To determine factors associated with lack of response to valproic acid (VPA) in juvenile myoclonic epilepsy (JME).

Method: Retrospective analysis of clinical and EEG data of 201 patients with JME who had at least 3 years follow up was performed. Psychiatric evaluation was performed using ICD-10 by structured clinical interview. Patients were divided into two groups: VPA responders (seizure free for 2 or more years) and those with lack of response to VPA. Effect size for non-response and correlations for variables significantly different between the groups was performed, the findings were confirmed by ROC curves.

Results: The mean duration of follow up was 7.75 (range 3-12) years; 55.2% were males. Focal semiologic features were noted is 16%. EEG was abnormal in 67%; focal EEG abnormalities were noted in 32.8%. Coexisting psychiatric disorders (PDs) were found in 33.3%. Lack of response to VPA was noted in 19%. Diagnosis of PDs and focal EEG abnormalities significantly increased the risk of VPA non-responsiveness by 5.54 (95% CI of 2.60-11.80; p<0.0001) and 3.01 times respectively (95% CI of 1.40-6.47; p<0.008). Diagnosis of PDs showed significant correlation (r=0.332; p<0.0001) and association (AUC 0.700; p<0.0001) with lack of response to VPA. Though focal EEG abnormalities increased the chances, it did not correlate with lack of response to VPA.

Conclusion: Lack of response to VPA was noted 19% of patients with JME. Coexisting PDs showed significant correlation and association with lack of response to VPA.