Roth, A. J., Nelson, C., Rosenfeld, B., Scher, H., Slovin, S., Morris, M., . . . Breitbart, W. (2010). Methylphenidate for fatigue in ambulatory men with prostate cancer. Cancer, 116, 5102–5110.

To test the potential benefit of psychostimulants in managing fatigue in men with prostate cancer.

Patients were randomly assigned to receive methylphenidate or placebo for up to six weeks. Methylphenidate was started at 5 mg once daily and titrated upward by 5 mg every two to three days to a maximum of 30 mg/day. The physician or research nurse was in contact with each patient at least twice weekly for dosage and patient safety evaluation. Study data were collected at the time of study entry and at the end of the six-week study period.

• The study was comprised of 39 men with advanced prostate cancer receiving either chemotherapy or hormonal therapy.
• Mean age was 70 years (standard deviation = 9 years). 
• Of the patients, 90% were Caucasian, 71% were married, and 70% had a college education.
• Patients were eligible if they rated an average level of fatigue of 4 or greater on a 10-point scale over the past two weeks.
• Patients were excluded if they had cognitive impairment, major depression, or medical conditions or were taking medications that contraindicated use of a psychostimulant. 

• Single site
• Outpatient 
• Memorial Sloan Kettering

This was a randomized, double-blind, placebo-controlled, intervention study.

• Brief Fatigue Inventory (BFI)
• Fatigue Severity Scale (FSS)
• Hospital Anxiety and Depression Scale (HADS)
• Beck Depression Inventory (BDI)
• Functional Assessment of Cancer Therapy–Prostate (FACT-P)
• Systematic Assessment for Treatment of Emergent Events (SAFTEE) questionnaire

Of the eligible patients screened, 54% declined to participate. Of the patients in the methylphenidate group, 31% were discontinued due to increased blood pressure, and another 16% were removed due to tachycardia. The methylphenidate group showed significant reduction in BFI fatigue scores from 5.13 to 2.19 (p = 0.01). The placebo group also showed significant reduction in scores (p = 0.02). There was a difference between groups in the changes in fatigue during the study, with those in the methylphenidate group showing greater reduction in fatigue (p = 0.07; d = .80). There were no significant differences between groups in depression, anxiety, quality of life, or measures of cognitive function. The separation of study drug and placebo effects emerged at weeks 3 and 6.

The results suggested that methylphenidate was associated with a decline in fatigue; however, it was also associated with substantial cardiovascular side effects in almost half of the patients. A significant placebo effect was also observed.

• The study had a small sample size, with less than 100 patients. 
• There was substantial difficulty accruing patients for the study, and the sample was not sufficiently powered.

Psychostimulants may be helpful to some patients in managing fatigue, but their use should be accompanied by close monitoring of potential side effects.