Methylphenidate ER Improves Functional Capacity in Stable Schizophrenia

BACKGROUND: Cognitive impairment severely disrupts functioning and recovery in schizophrenia. Methylphenidate extended-release (ER) shows promise for cognition in attention-deficit/hyperactivity disorder but has limited, inconsistent evidence in schizophrenia. This study investigates low-dose methylphenidate ER's effects on cognitive and functional outcomes in schizophrenia, addressing a critical therapeutic gap. METHODS: In an 8-week, open-label, randomized crossover trial, 24 stable adults with Diagnostic and Statistical Manual of Mental Disorders, 5th edition, diagnosis of schizophrenia spectrum disorder received 4 weeks of methylphenidate ER or treatment-as-usual (TAU), with crossover at week 4, and follow-up at week 12. The primary outcome was improvement in functional capacity, measured by the Virtual Reality Functional Capacity Assessment Tool (VRFCAT), while secondary outcomes included cognitive performance, assessed by the Brief Assessment of Cognition in Schizophrenia (BACS), and symptom severity evaluated by Positive and Negative Symptoms Scale (PANSS). RESULTS: VRFCAT scores improved significantly over time; in the first period (baseline to week 4), the medication-first arm showed improvement versus the TAU-first arm, with overall gains from baseline to week 8 of 303.47 seconds and 159.91 seconds, respectively, sustained post medication. BACS showed significant improvements in the TAU-first arm during the medication phase for Symbol Coding and Tower of London. PANSS-6 improved significantly while on study medication, notably in delusions and social withdrawal, without psychosis exacerbation. At 2-month follow-up, 75% resumed methylphenidate ER. CONCLUSIONS: While results are interpreted cautiously due to the open-label design and small sample size, this trial suggests low-dose methylphenidate ER may enhance functional capacity, specific cognitive domains, and symptoms in schizophrenia without exacerbating psychosis.