Abstracts

Rationale: Pregabalin (PGB) is approved for adjunctive treatment of partial seizures. However, there are no reports of its efficacy in the unique population of mentally retarded, developmentally disabled (MRDD) patients with multiple handicaps and a wide variety of seizure types. This study evaluated the efficacy and tolerability of adjunctive PGB therapy in institutionalized, MRDD patients.Methods: We retrospectively reviewed our database to select the patients. The evaluation time frame and outcome measures were defined a priori, with each patient serving as their own control. We defined baseline phase (BP) as the 8-week period prior to initiating PGB, and treatment phase (TP) as the 12-week period following the initiation of PGB when PGB was titrated and maintained. The inclusion criteria were profound mental retardation (IQ <40), documented epilepsy under treatment, at least 1 seizure during BP, and newly-initiated treatment with PGB without history of prior exposure to the drug. The primary outcome measure of efficacy was the change in median frequency of weekly seizure days (of all seizures) between BP and TP. Since seizure clusters were common in many patients, seizure days were counted instead of the absolute number of seizures. Seizure frequency data were obtained from the daily seizure logs documented by the nursing staff in a standardized format. Tolerability was evaluated over a longer term, until the last follow-up cutoff date of April 1, 2007.Results: Seven patients (4 female and 3 male, mean age 43 years, range 25-59 years) met the inclusion criteria. The seizure types included generalized tonic-clonic (n=7), partial (n=6), tonic (n=2) and atypical absence (n=1). One patient had Lennox-Gastaut syndrome based on slow spike-wave on EEG and tonic seizures. The initial starting dose of PGB was 150 mg/d (n=7), and the mean maintenance dose was 293 mg/d (150-350 mg/d). The number of concomitant AEDs was 2-5, and included lamotrigine (n=6), levetiracetam (n=4), phenytoin (n=2), gabapentin (n=2), zonisamide (n=2), topiramate (n=2), valproate (n=2), clonazepam (n=1) and diazepam (n=1). Four patients had VNS implants. The change in median frequency of weekly seizure days between BP and TP was statistically significant (1.38 vs 0.50, p=0.018, Wilcoxon signed rank test). The median percent reduction in weekly seizure days was 56% during TP compared to BP, and the 50% responder rate was 71%. Concomitant AEDs and VNS were unchanged except in 2 patients. At last follow-up (mean 13 months, range 9-17 months), the adverse effects included sedation (n=1) and myoclonus (n=2). Sedation improved with dose reduction. Myoclonus resolved with dose reduction in 1 patient, while PGB was discontinued in the second patient after 5 months of treatment. No behavioral problems or weight gain were seen.Conclusions: Adjunctive PGB therapy is effective and well tolerated in MRDD patients with refractory epilepsy and multiple seizure types. The adverse effects included sedation and myoclonus. Positive results of this preliminary study warrant prospective evaluation of PGB in this unique population.