A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy

Purpose: To assess the clinical impact of monitoring serum concentrations o f antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy. Methods: One-hundred eighty patients with partial or idiopathic generalized nonabsence epilepsy, aged 6 to 65 years, requiring initiation of treatment with carbamazepine (CBZ), valproate (VPA), phenytoin (PHT), phenobarbital (PB), or primidone (PRM) were randomly allocated to two groups according to an open, prospective parallel-group design. In one group, dosage was adjus ted to achieve serum AED concentration within a target range (10-20 mu g/ml for PHT, 15-40 mu g/ml for PB, 4-11 mu g/ml for CBZ, and 40-100 mu g/ml fo r VPA), whereas in the other group, dosage was adjusted on clinical grounds . Patients were followed up for 24 months or until a change in therapeutic strategy was clinically indicated. Results: Baseline characteristics did not differ between the two groups. Mo st patients with partial epilepsy were treated with CBZ, whereas generalize d epilepsies were most commonly managed with PB or VPA. PHT was used only i n a small minority of patients. A total of 116 patients completed 2-year fo llow-up, and there were no differences in exit rate from any cause between the monitored group and the control group. The proportion of assessable pat ients with mean serum drug levels outside the target range (mostly below ra nge) during the first 6 months of the study was 8% in the monitored group c ompared with 25% in the control group (p < 0.01). There were no significant differences between the monitored group and the control group with respect to patients achieving 12-month remission (60% vs. 61%), patients remaining seizure free since initiation of treatment (38% vs. 41%), and time to firs t seizure or 12-month remission. Frequency of adverse effects was almost id entical in the two groups. Conclusions: Only a small minority of patients were treated with PHT, the d rug for which serum concentration measurements are most likely to be useful . With the AEDs most commonly used in this study, early implementation of s erum AED level monitoring did not improve overall therapeutic outcome, and the majority of patients could be satisfactorily treated by adjusting dose on clinical grounds. Monitoring the serum levels of these drugs in selected patients and in special situations is likely to be more rewarding than rou tine measurements in a large clinic population.