Abstract
This systematic review and meta-analysis evaluated the efficacy and safety of methylphenidate in patients with brain disease. A comprehensive search up to November 4, 2024 identified 33 randomized controlled trials involving 1,369 participants with traumatic brain injury (TBI), stroke, Parkinson's disease (PD), Alzheimer's disease (AD), other dementias, and multiple sclerosis. Methylphenidate was administered at 10-80 mg/day or 0.1-1 mg/kg/day for durations ranging from a single dose to 6 months. Data were synthesized using a random-effects model, with study quality evaluated via the Revised Cochrane Risk of Bias Tool. Methylphenidate significantly improved attention (standardized mean difference [SMD], 0.43; 95% confidence interval [CI], 0.03 to 0.84), particularly in TBI. Motor function improved in stroke populations (mean difference [MD], 0.66; 95% CI, 0.13 to 1.18), while activities of daily living (ADL) significantly improved in stroke and AD (SMD, 0.71; 95% CI, 0.37 to 1.06). Apathy was significantly reduced in AD (SMD, -0.60; 95% CI, -0.95 to -0.26), and depression improved across patients with PD, stroke, and TBI (SMD, -0.50; 95% CI, -0.94 to -0.05). No significant effects were observed for consciousness, global cognition, executive function, fatigue, or quality of life. Side effects were mild, with a slight increase in pulse rate (MD, 0.28; 95% CI, 0.10 to 0.47). In summary, methylphenidate improves attention (TBI), motor function (stroke), ADL (stroke, AD), and mood, especially apathy (AD) and depression, with a favorable safety profile. Its effects appear condition-specific, and further research is needed to confirm long-term efficacy and establish standardized protocols. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews Identifier: CRD42024563826.