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TOPLINE:

An updated systematic review and meta-analysis of randomized trials found that methylphenidate (MPH; Ritalin) and dexmethylphenidate (d-MPH; Focalin) were associated with modest improvements in cancer-related fatigue compared with placebo, with effects reaching clinically meaningful levels by about 5 weeks of treatment and no significant increase in treatment-emergent adverse events.

METHODOLOGY:

• Cancer-related fatigue affects nearly three quarters of people living with cancer but remains one of the most undertreated symptoms in oncology. Recommended interventions are typically nonpharmacologic and include exercise, mind-body practices, and psychosocial approaches; to date, no drug has received regulatory approval for cancer-related fatigue and prior evidence on psychostimulants has been mixed, with one recent study finding that MPH was not superior to placebo at about 6 weeks in patients with advanced cancer.
• To assess further, researchers conducted an updated meta-analysis of nine double-blind, individually randomized, placebo-controlled phase II/III trials evaluating MPH or d-MPH in adults with cancer, including those with advanced disease or receiving active cancer-directed treatment.
• A total of 823 patients were included in the analysis, across studies published between May 2006 and July 2024.
• Outcomes included between-group differences in fatigue score changes measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and self-rated 0-10 scales as well as treatment-emergent adverse events.
• Exploratory subanalyses examined FACIT-F score changes at various timepoints after treatment initiation (around 2, 5, and 8 weeks).

TAKEAWAY:

• Compared with placebo, MPH or d-MPH was associated with modest but statistically significant improvements in FACIT-F scores (pooled mean difference [MD], 2.43 points) and reductions in self-rated fatigue severity on 0-10 scales (pooled MD, -1.52 points).
• At approximately 2 weeks, pooled FACIT-F score improvements modestly favored psychostimulants (MD, 2.34 points; P = .0008), while larger benefits were observed at approximately 5 weeks (MD, 3.56 points; P = .0005) and 8 weeks or longer (MD, 3.89 points; P = .0003). After approximately 5 weeks, improvements were large enough to meet established benchmarks for clinically meaningful reductions in fatigue.
• No statistically significant increase in adverse effects was observed with psychostimulants compared with placebo, although investigators emphasized the importance of gradual dose titration, careful patient selection, and regular monitoring.

IN PRACTICE:

“Our findings show that a well-established, accessible medication can provide meaningful relief within weeks, giving clinicians a practical tool to help preserve daily functioning and support engagement with other treatments,” the lead author said in a press release. Although not a replacement for ‌established approaches such as exercise, cognitive behavioral therapy, and mind-body practices — where the strongest evidence exists — “methylphenidate could serve as a bridge during that window, providing earlier relief while the longer-term strategies take effect.”

SOURCE:

The study, led by Bruno Almeida Costa, MD, The University of Texas MD Anderson Cancer Center, Houston, was published online in May 2026 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The authors noted several limitations, including heterogeneity across the nine trials in psychostimulant regimens, patient and disease characteristics, and fatigue measures; relatively short treatment durations with many assessments within 2-4 weeks; predominant enrollment of older adults; substantial placebo‑related improvements in fatigue; lack of individual patient data for subgroup/meta‑regression analyses; and notable dropout rates in these palliative‑care populations. These factors may limit generalizability and complicate interpretation of treatment effects across patient subgroups.

DISCLOSURES:

No disclosures or conflicts-of-interest statements were provided in the study document.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.