Long-term administration of valproic acid in the treatment of affective symptoms in people with mental retardation

We report the results of an open trial of valproic acid in the treatment of affective symptoms in people with mental retardation. The study population consisted of 209 people with mental retardation who were serially referred to a tertiary-care medical center for the evaluation of behavioral symptoms. Criteria for treatment included the presence of three of the four following symptoms: irritability, sleep disturbance, aggressive or self-injurious behavior, and behavioral cycling. Twenty-one patients met enrollment criteria and were studied prospectively for a 2-year period. Two patients were lost to follow-up. One patient experienced severe drug side effects. Eighteen patients completed the study. Fourteen patients (78%) responded favorably to treatment and were maintained on valproic acid for the 2 years of the study (p < 0.001). Medications prescribed at the time of enrollment were usually discontinued, including neuroleptic medication in 9 of 10 patients and in all patients (N = 3) who were receiving phenobarbital. A history of epilepsy or a suspicion of seizures was strongly associated with a favorable response to valproic acid (p < 0.005). The results of this study suggest that people with mental retardation and concurrent affective disorders can be recognized by a cluster of developmentally appropriate symptoms such as those listed above. In addition, affective symptoms can be successfully treated with valproate with reductions in neuroleptic and barbiturate anticonvulsant medication. Further study of the comparative benefit of valproate and carbamazepine in this population is warranted.