Methylphenidate-Based Interventions for Depressive Symptoms in Palliative Care: A Systematic Review and Meta-Analysis

Depressive symptoms are common in palliative care, but conventional antidepressants are limited by delayed onset and adverse effects. We evaluated randomized evidence on methylphenidate, a faster-acting intervention, for depressive symptoms in adults receiving palliative care.

This PRISMA 2020-compliant systematic review and meta-analysis (PROSPERO: CRD420261277228) included randomized controlled trials of methylphenidate-based interventions versus placebo, usual care, or background antidepressants in adults with advanced, life-limiting illness receiving palliative care. Depression-targeted trials provided direct evidence; fatigue-focused trials with depression outcomes provided indirect evidence. Continuous outcomes were pooled as standardized mean differences with random-effects models and Hartung-Knapp sensitivity analysis. Risk of bias was assessed with RoB 2.

Five trials (342 participants) were included. Methylphenidate-based interventions were associated with greater improvement in depressive symptoms overall (SMD -0.47, 95% CI -0.81 to -0.13; P = 0.006; I² = 58.9%). Depression-targeted (three trials; SMD -0.62, 95% CI -1.18 to -0.05) and fatigue-focused subgroups (two trials; SMD -0.30, 95% CI -0.53 to -0.07) did not differ significantly (P = 0.307). Depression response was more frequent with methylphenidate (RR 1.78, 95% CI 1.09-2.89; P = 0.021). Risk of bias was low in one, of some concern in three, and high in one.

Methylphenidate-based interventions may improve depressive symptoms in selected palliative-care patients, but evidence certainty is very low to low due to small samples, heterogeneity, and indirectness. Findings support cautious, individualized use rather than rapid antidepressant efficacy. Adequately powered trials with depression as a primary endpoint are needed.