The Effect of Methylphenidate on Fatigue in Advanced Cancer: An Aggregated N-of-1 Trial

Geoffrey K Mitchell; Janet R Hardy; Catherine J Nikles; Sue-Ann S Carmont; Hugh E Senior; Philip J Schluter; Phillip Good; David C Currow

doi:10.1016/j.jpainsymman.2015.03.009

The Effect of Methylphenidate on Fatigue in Advanced Cancer: An Aggregated N-of-1 Trial

J Pain Symptom Manage. 2015 Sep;50(3):289-96. doi: 10.1016/j.jpainsymman.2015.03.009. Epub 2015 Apr 18.

Authors

Geoffrey K Mitchell¹, Janet R Hardy², Catherine J Nikles³, Sue-Ann S Carmont³, Hugh E Senior³, Philip J Schluter⁴, Phillip Good⁵, David C Currow⁶

Affiliations

¹ School of Medicine, University of Queensland, Brisbane, Queensland, Australia. Electronic address: g.mitchell@uq.edu.au.
² Department of Palliative and Supportive Care, Mater Health Services, South Brisbane, Queensland, Australia; Mater Research, University of Queensland, South Brisbane, Queensland, Australia.
³ School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
⁴ School of Health Sciences, University of Canterbury, Christchurch, New Zealand.
⁵ Department of Palliative and Supportive Care, Mater Health Services, South Brisbane, Queensland, Australia; Mater Research, University of Queensland, South Brisbane, Queensland, Australia; St. Vincent's Private Hospital, Brisbane, Queensland, Australia.
⁶ Cancer Institute of New South Wales, Sydney, New South Wales, Australia; Department of Palliative and Supportive Care, Flinders University, Adelaide, South Australia, Australia.

PMID: 25896104
DOI: 10.1016/j.jpainsymman.2015.03.009

Abstract

Context: Fatigue is common in life-limiting cancer. Methylphenidate (MPH), a psychostimulant, may be a useful therapy. Gathering evidence in patients with advanced cancer can be challenging.

Objectives: To determine if MPH improves cancer-related fatigue in people with advanced cancer.

Methods: N-of-1 trials are multicycle, double-blind, randomized, controlled crossover trials using standardized measures of effect in individuals. They are normally used to assess treatment effects in individuals. Aggregated N-of-1 trials from participants with end-stage cancer suffering fatigue were used to assess the group effect of MPH, producing an estimate of equivalent power to a parallel-group randomized controlled trial (RCT) but requiring less than half of the sample size. Up to three cycles of MPH 5 mg twice daily (three days) vs. identical placebo (three days) capsules were offered to participants. Primary outcome was improvement in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale and the Wu Cancer Fatigue Scale. Analysis used Bayesian statistical methods using intention-to-treat principles.

Results: Forty-three participants completed 84 cycles of MPH and placebo in random order, exceeding sample size estimates. Overall, MPH did not improve fatigue (mean difference 3.2; 95% credible interval -2.0, 9.0; posterior probability of favorable effect 0.890). Eight participants showed important improvement, and one participant showed important worsening of fatigue on MPH. There were no features that distinguished participants whose fatigue responded to MPH compared with those who did not.

Conclusion: MPH does not improve fatigue in the population of patients with end-stage cancer. Aggregated N-of-1 trial methodology is feasible and produces population-based sample estimates with less than half the sample size required for the equivalent parallel-group RCT. It also identified individuals who did and did not respond to MPH, which is a feature difficult to achieve in a standard RCT. The study was registered with the Australian Clinical Trials Registry (12609000794202).

Keywords: Methylphenidate; N-of-1 trial; advanced cancer; fatigue; palliative care.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Australia
Central Nervous System Stimulants / adverse effects
Central Nervous System Stimulants / therapeutic use*
Cross-Over Studies
Double-Blind Method
Drug Administration Schedule
Fatigue / drug therapy*
Fatigue / physiopathology*
Female
Humans
Male
Methylphenidate / adverse effects
Methylphenidate / therapeutic use*
Middle Aged
Neoplasms / drug therapy
Neoplasms / physiopathology*
Palliative Care / methods*
Severity of Illness Index
Terminal Care / methods
Treatment Outcome

Substances

Central Nervous System Stimulants
Methylphenidate