ABSTRACT
Objectives: To determine the optimum range of phenytoin (PHT) and valproate (VAP) levels and find out the critical drug levels below which chances of breakthrough seizures increase in North Indian population. Methodology: A cross-sectional, case-controlled, record-based study was conducted in a quaternary care hospital from September 2018–2019. The case group comprised epilepsy patients on monotherapy with PHT/VAP presenting with breakthrough seizures after at least 6 months of seizure control. Noncompliant, overdose, toxicity, no or partial response, any other psychiatric or neurological disorder, adverse effects, and patients taking two or more antiepileptic drugs were excluded. Results: Data of 100 patients in each group were analyzed. Significantly lower mean levels in cases were observed in PHT (5.74 ± 3.68 mg/L vs. 13.75 ± 4.27 mg/L control) and VAP (24.13 ± 27.39 mg/L vs. 76.37 ± 17.71 mg/L control). A negative correlation of drug levels was observed with age and weight in both the groups. The level/dose ratio in controls (0.05 ± 0.03; 0.09 ± 0.06) was significantly (P < 0.0001) higher than cases (0.02 ± 0.01; 0.02 ± 0.03) in PHT and VAP, respectively. Conclusions: This study identifies the critical levels and level/dose ratio at which the risk of breakthrough seizures increases. A wide level/dose ratio was found in controls, more so in the VAP group. A prospective study with larger group size along with genetic studies should be done to evaluate further.
ABSTRACT
Background: The prevalence of breakthrough seizures in persons with epilepsyis very high in developing countries. Consequently, patients and physicians should be aware of the possible factors that may cause breakthrough seizures.Objective: The aim of our study is to determine the possible factors that may be a precipitating cause for breakthrough seizures in patients with epilepsy.Methods: This cross-sectional study included 100 persons with epilepsywith idiopathic epilepsy receiving antiepileptic drugs (AEDs). They were divided into two groups. Group 1 included 50 persons with epilepsywith a history of recent breakthrough seizures. Group 2 included 50 persons with epilepsywho had not experienced any recent breakthrough seizures. Patients were subjected to a thorough questionnaire addressing precipitating factors. All participants were subjected to an electroencephalogram (EEG) and medication adherence assessment.Results: There was no significant differences between group 1 and group 2 regarding age, sex, ageOriginal Research Article of onset of epilepsy, occupation and marital status (P value range 0.5 –0.2). The patients in group 1 were found to have longer durations of epilepsy, lower adherence to AEDs (P= 0.001), moremissed doses of AEDs (P= 0.0001), more side effects of AEDs (P = 0.0005), more sleep deprivation, lower level of AEDs (P= 0.0006), more frequently on AED polytherapy (P = 0.0002), and more flickering lights(P= 0.04) than the participants in group 2. In terms of the EEG, group 1 showed a higher percentage of abnormal EEGs and more frequent focal epileptiform discharges (P = 0.003). Also, pathological findings in MRI brain were associated with higher breakthrough seizures (P = 0.005). No significant difference was found in both group1 and group 2 regarding emotional stress (P = 0.55), substitution of brand AEDs by generic one (P = 0.83), concurrent illness (P = 1), or the use of non AEDs (P = 0.79). Conclusion: The precipitating factors of breakthrough seizures are multifactorial and it is very important to educate patients about these precipitating factors to achieve better control of epilepsy