Cognitive effects of antipsychotic agents in persons with traumatic brain injury.

Over 1 million survivors of traumatic brain injury receive maintenance pharmacotherapy, of which a substantial number receive antipsychotic agents for the treatment of psychoses, agitation and aggression, and other maladaptive behaviours. In spite of the common clinical uses of antipsychotics, the cognitive risks versus benefits are unclear. The purpose of this study was to assess differences in cognitive functioning before, during, and after discontinuation of antipsychotic agents in inpatients undergoing rehabilitation for traumatic brain injury. Neuropsychiatric tests (Reys Auditory-Verbal Learning, Trail Making A&B, Digit Span Forwards and Backward) evaluating cognitive skills of verbal ability, visuomotor speed, memory, learning, attention, and spatial ability were administered to each subject at baseline (immediately prior to tapering or discontinuing antipsychotic), when taper reached 50% of baseline dose, 1 week after antipsychotic discontinuation, and 3 weeks after discontinuation. These data suggest that select areas of cognition improve after antipsychotic discontinuation in subjects with traumatic brain injury. The magnitude of improvement appeared to be greater after discontinuation with thioridazine, a low-potency agent, compared to haloperidol, a high-potency agent. Results, although very preliminary, support the hypothesis of cholinergic involvement in regulating cognitive processes, and this underscores the need for more systematic research in this area.