Determination of valproic acid reference range and predictors for good seizure control among patients with epilepsy at Hospital Kuala Lumpur

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Date
2014-02
Authors
Ahmad, Mastura
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Abstract
Valproic acid, a broad spectrum anti-epileptic drug, had been proven efficacious and tolerable, but its serum drug concentration monitoring value remains obscure. This study was carried out to determine valproic acid concentration range associated with efficacy and tolerability, and the prognostic factors associated with seizure control. A retrospective cohort, observational study was conducted in patients who received valproic acid treatment in Neurology Clinic, Hospital Kuala Lumpur. ‗Good response‘ group were patients experiencing 50% or more seizure reductions. ‗Poor response‘ group were patients who did not achieve the definition of ‗good response‘. Seizure frequency was assessed from medical record, patients‘ own diary and verified by seizure diary supplied during this study. Blood sampling for determination of valproic acid concentration was done on the first encounter with the patient and/or at any time during the study period. Seizure diary was used as a tool to improve patient‘s adherence and record side effects occurrence. A total of 242 patients were recruited from January 2011 and followed up for a year. Seventy-six patients with ‗good response‘ and consented to serum concentration monitoring were included for reference range determination. Several approaches were exercised to generate reference ranges, (i) mean or median concentration, (ii) range associated with a sudden increase in response with increasing valproic acid concentration, (iii) a composite concentration range based on (i) and ( determined arbitrarily to produce majority of patients with ‗good response‘ and minimal side effects. When more than one concentration ranges of potential exists, they were tabulated and statistically analyzed to find the most acceptable concentration range. The reference range provided by this population is 40 to 85mg/L. Tremor was associated with valproic acid serum concentration above 80mg/L and the presence of other side effects. Significant prognostic factors associated with good seizure response in patients with epilepsy on valproic acid were age at the initiation of AED [Adjusted OR 0.96, 95% CI (0.920, 0.995), P=0.027], on valproic acid monotherapy [Adjusted OR 4.74, 95% CI (2.258, 9.947), P<0.001], normal MRI/CT-scan [Adjusted OR 5.83, 95% CI (2.507, 13.552), P<0.001], non-smoking [Adjusted OR 3.23, 95% CI (1.099, 9.473) P=0.033] and absence of stress [Adjusted OR 19.98, 95% CI (9.255, 42.764), P<0.001]. This study described valproic acid reference range for this population and highlighted the important prognostic factors that were associated with favorable seizure response in patients with epilepsy on valproic acid.
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Valproic acid, a broad spectrum anti-epileptic drug , had been proven efficacious and tolerable
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