Methylphenidate Versus Placebo for Treating Fatigue in Patients With Advanced Cancer: Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial

Author(s): Patrick Charles Stone, MD, MA, MRCP¹; Ollie Minton, PhD, FRCP, FHEA²; Alison Richardson, PhD, MSc, BN (Hons), PGDipEd, RGN³; Peter Buckle¹; Zinat E. Enayat, PhD, MSc, BSc¹; Louise Marston, PhD, MSc, BSc⁴; Nick Freemantle, PhD, MA(Dist), BA(Hons)⁴

Source: https://doi.org/10.1200/JCO.23.02639

Dr. Anjan Patel's Thoughts

Stimulant therapy with methylphenidate did not improve fatigue in a well-done, prospective, placebo-controlled trial. This refutes prior practices of using ADD medications to mitigate fatigue for patients on chemotherapy. I rarely use these in my own practice given the concern for weight loss and mood disorder.

PURPOSE

To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer.

METHODS

This is a randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients had advanced incurable cancer and fatigue >3/10. Principal exclusions were hypertension; psychiatric, cardiovascular, cerebrovascular, renal, liver, or blood disorders; substance dependency; and epilepsy. Patients were randomly assigned 1:1 methylphenidate or placebo starting at 5 mg twice daily. Dose of methylphenidate/placebo was titrated once per week, over 6 weeks, up to a maximum of 20 mg three times daily. Trial ended at 10 weeks. Primary outcome was the difference in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores between groups at 6 ± 2 weeks. Secondary outcomes included adverse effects, quality of life, and mood.

RESULTS

One hundred sixty-two patients (73 men; mean, 65.8; standard deviation [SD], 10.3 years) were randomly assigned, and three were excluded from analysis. Seventy-seven were allocated placebo (baseline FACIT-F = 22 [SD, 10]); 82 were allocated methylphenidate (FACIT-F = 20 [SD, 9]). After 6 ± 2 weeks, FACIT-F scores were 1.97 points (95% CI, –0.95 to 4.90; P = .186) higher (better) on methylphenidate than placebo. Across 10 weeks of the study, FACIT-F was nominally higher in the methylphenidate group versus placebo (Diff, 2.20 [95% CI, 0.39 to 4.01]), but this did not reach the minimally clinically important difference (5-points). At 6 weeks, there were no differences between groups in quality-of-life or symptom domains except for depression scores (nominally reduced in the methylphenidate group: Diff, –1.35 [95% CI, –2.41 to –0.30]). There were no differences in mortality or serious adverse events.

CONCLUSION

After 6 ± 2 weeks of treatment, methylphenidate was not superior to placebo for treating fatigue in advanced cancer. Methylphenidate was safe and well-tolerated.

Author Affiliations

¹Marie Curie Palliative Care Research Department, Division of Psychiatry, University College London (UCL), London, United Kingdom; ²University Hospitals Sussex NHS Foundation Trust, Worthing Hospital, Lyndhurst Road, Worthing, West Sussex, United Kingdom; ³University of Southampton & University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton, United Kingdom; ⁴Department of Primary Care & Population Health, Institute of Epidemiology & Health Care, Faculty of Population Health Sciences, University College London (UCL), London, United Kingdom; ⁵Comprehensive Clinical Trials Unit, University College London (UCL), London, United Kingdom

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