The effects of methylphenidate on command following and yes/no communication in persons with severe disorders of consciousness: A meta-analysis of n-of-1 studies

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OBJECTIVE: To determine the effects of methylphenidate (MPH) on command following and yes/no communication in brain injured patients with severe disorders of consciousness (DOC). DESIGN: A meta-analysis of a series of single-subject repeated crossover trials, using doses ranging from 7.5 to 25 mg (median dose: 10 mg), generally given twice a day. A Wilcoxon signed ranks test was performed, comparing mean responsiveness and accuracy by drug condition. Drug effect sizes were calculated for the full group and for participant subgroups of interest. RESULTS: No significant effect of MPH was seen on either responsiveness or on accuracy in the whole group. None of the patient subgroups examined showed a substantial drug effect size. CONCLUSIONS: This study did not identify a clinically meaningful effect of MPH in the doses used on responsiveness or accuracy in standardized command-following protocols in the overall study group of patients with severe DOC, or in any subgroup that was assessed. Because MPH has been shown to have some positive effects in higher-level patients with TBI, more research is needed to define the types of individuals with TBI who do and do not benefit from this drug, and/or the dose that provides optimal benefit.

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