A new meta-analysis provides updated evidence that methylphenidate-type psychostimulants—a class of medications that increase dopamine and norepinephrine availability in the brain—can provide meaningful relief for cancer-related fatigue. The study was published in the May 2026 issue of JNCCN—Journal of the National Comprehensive Cancer Network.1
Cancer-related fatigue affects up to three-quarters of people living with cancer, according to some estimates, yet it remains one of the most undertreated symptoms in oncology.
According to the findings, treatment with methylphenidate or dexmethylphenidate was associated with significant improvements in fatigue scores across widely validated scales relative to placebo. Those effects were shown to increase over time.
“What makes this finding particularly noteworthy is the time dimension: the benefit isn’t fully apparent in the first couple of weeks, but by around 5 weeks it reaches a level that genuinely matters in terms of patients’ daily energy and function,” noted lead author Bruno Almeida Costa, MD, a hematology and medical oncology fellow at The University of Texas MD Anderson Cancer Center, Houston. “For people dealing with a symptom that can be profoundly disabling, that is a meaningful contribution.”
Bruno Almeida Costa, MD
He continued, “I would encourage cancer care professionals to think of methylphenidate as one piece of a broader approach to managing fatigue, not as a standalone solution. The strongest evidence still belongs to exercise, cognitive-behavioral therapy, and mind-body practices. But those take time—often 8 to 12 weeks of consistent engagement—to reach their full benefit. Methylphenidate could serve as a bridge during that window, providing earlier relief while the longer-term strategies take effect.”
Results were based on nine double-blind, individually randomized, parallel-group, placebo-controlled phase II/III trials evaluating methylphenidate or dexmethylphenidate in adults with advanced cancer or who were actively receiving cancer-directed treatment. A total of 823 patients were included.
The studies were published between May 2006 and July 2024 and primarily assessed fatigue using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) scale, a 13-item patient-reported questionnaire.
The authors pointed out that methylphenidate has one of the “longest-standing and best-documented safety records among actively prescribed controlled substances.” It has been on the market since 1955 and is approved for use in patients as young as 6 years old for attention-deficit/hyperactivity disorder (ADHD) and narcolepsy. The analysis found no statistically significant increase in side effects compared with placebo, though careful patient selection and regular monitoring remain important, according to the investigators.
Dr. Costa added, “We are seeing a worrying trend of cancer diagnoses in younger adults who are building careers, raising families, and leading very active lives. For this population, fatigue can be especially disruptive because there’s so much they need and want to do. 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.”
Chandana Banerjee, MD, MPA, HMDC, FAAHPM, of City of Hope in Duarte, California, and Vice-Chair of the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Panel forCancer-Related Fatigue—who was not involved with this research—commented, “The emerging evidence for [methylphenidate/dexmethylphenidate] underscores a broader principle in clinical care: that precision, thoughtful patient selection, and careful monitoring can transform modest effects into meaningful clinical impact and an improved patient experience.”
Chandana Banerjee, MD, MPA, HMDC, FAAHPM
The NCCN Guidelines® for Cancer-Related Fatigue include the option of considering methylphenidate in certain circumstances, while noting the need for caution, particularly with regard to dosing, scheduling, and investigation of underlying causes.2
REFERENCES
1. Costa BA, Sheppard R, Coelho HGB, et al: Methylphenidate-type psychostimulants for cancer-related fatigue: Updated meta-analysis of randomized controlled trials. J Natl Compr Canc Netw 24:163-171, 2026.
2. Jankowski C, Banerjee C, Aranha O, et al: NCCN Clinical Practice Guidelines in Oncology: Cancer-Related Fatigue. Version 2.2026. Available at www.nccn.org. Accessed May 18, 2026.
Of Note: JNCCN Evolves its Digital Platform
After years of publishing both in print and online, JNCCN has announced plans to focus solely on digital publication, beginning in July 2026. The June 2026 edition of JNCCN will be the final print issue.
JNCCN has also removed the paywall for all articles. This reflects a strengthened priority for sharing high-impact research that improves the quality of cancer care for all. By transitioning to online-only publication, JNCCN will share groundbreaking oncology data in a more timely and efficient manner while improving access and readability.
Register for email updates at https://www.nccn.org/education-research/jnccn/jnccn-email-updates and read JNCCN at JNCCN.org.
