Combining Cyproheptadine Hydrochloride With Targeted Muscle Activation Training to Treat Upper Extremity Stroke: A Randomized, Placebo-Controlled Trial.

Abstract

Objective: To examine a treatment for upper extremity impairment in stroke survivors that combines administration of cyproheptadine hydrochloride with repetitive practice focused on control of muscle activation patterns.

Design: Double-blind, randomized controlled trial.

Settings: Laboratory within a free-standing rehabilitation hospital.

Participants: A total of 94 stroke survivors with severe, chronic hand impairment were randomly assigned to 1 of 4 treatment groups.

Interventions: Participants received either a placebo or cyproheptadine hydrochloride in identical pill form. The daily dosage of cyproheptadine/placebo was gradually increased from 8 to 24 mg/d over 3 weeks and then maintained over the next 6 weeks while participants completed 18 therapy sessions. Therapy consisted of either (1) active practice of muscle activation patterns to play "serious" computer games or control a custom hand exoskeleton or (2) passive, cyclical finger stretching imposed by the exoskeleton.

Main outcome measures: Hand control was evaluated with the primary outcome measure of time to complete the Graded Wolf Motor Function Test (GWMFT) and secondary outcome measures including finger strength and spasticity.

Results: Across the 88 participants who completed the study, a repeated-measures analysis of variance revealed a significant effect of GroupxEvaluation interaction on GWMFT (F=1.996, P=.026). The 3 groups receiving cyproheptadine and/or actively practicing muscle activation pattern control exhibited significant reduction in mean time to complete the GWMFT tasks; roughly one-third of these participants experienced at least a 10% reduction in completion time. Gains were maintained at the 1-month follow-up evaluation. The group receiving placebo and passive stretching did not show improvement. No significant differences among groups were observed in terms of changes in strength or spasticity.

Conclusions: Despite chronic, severe impairment, stroke survivors were able to complete the therapy focused on muscle activations and achieved statistically significant improvement in hand motor control. Cyproheptadine hydrochloride is a potential complementary treatment modality for stroke survivors with hand impairment.