A prospective test of the late effects of potentially antineuroplastic drugs in a stroke rehabilitation study

Background: Extensive data, primarily from animal studies, suggest that several classes of drugs may have antineuroplastic effects that could impede recovery from brain injury or reduce the efficacy of rehabilitation. Aims: The Locomotor Experience Applied Post-Stroke trial, a randomized controlled study of 408 subjects that tested the relative efficacy of two rehabilitation techniques on functional walking level at one-year poststroke, provided us the opportunity to prospectively assess the potential antineuroplastic effects of several classes of drug. Methods: Subjects were randomized to receive one of the two rehabilitation therapies at two-months poststroke. Drugs taken were recorded at time of randomization. Outcome was assessed at one-year poststroke. Regression models were used to determine the amount of variance in success in improving functional walking level, gains in walking speed, and declines in lower extremity, upper extremity, and cognitive impairment accounted for by α1 noradrenergic blockers+α2 noradrenergic agonists, benzodiazepines, voltage-sensitive sodium channel anticonvulsants, and α2δ voltage-sensitive calcium channel blockers. Results: The maximum variance accounted for by any drug class was 1·66%. Drug effects were not statistically significant when using even our most lenient standard for correction for multiple comparisons. Conclusions: Drugs in the classes we were able to assess do not appear to exert a clinically important effect on outcome over the period between two- and 12 months poststroke. However, the potential antineuroplastic effects of certain drugs remain an incompletely settled scientific question.