Correlation between Breakthrough Seizures and Serum Level of Phenytoin and Valproate in Indian Patients

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.