Lower, E. E., Fleishman, S., Cooper, A., Zeldis, J., Faleck, H., Yu, Z., & Manning, D. (2009). Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. Journal of Pain and Symptom Management, 38, 650–662.
To test the hypothesis that d-methylphenidate (d-MPH) would produce a significant reduction in fatigue compared to placebo.
Patients were randomized to receive the study drug or an identical appearing placebo; packaging and labeling were done by a pharmacist not involved in other aspects of the study. Patients received 5 mg of the drug twice daily by mouth. Measures were performed at baseline and at weeks 1 and 8, which was the end of the double-blind treatment phase. Weekly dose modifications were performed at the investigators' discretion based on the magnitude and duration of response assessed weekly by Clinical Global Improvement–Impression (CGI-I) scores. The maximum allowable total daily dosage was 50 mg/day in two to three doses per day.
This was a double-blind, randomized, controlled study.
D-MPH–treated patients had lower ECOG performance status scores than placebo-treated patients (p = 0.03), indicating better performance. The mean highest dose achieved in d-MPH–treated patients was 27.7 mg/day (range 10–70). A significantly greater improvement in FACIT scores from baseline was seen in patients who received d-MPH compared to placebo at week 8 (p = 0.02). In the study group, there was a mean 10.5-point score reduction in the d-MPH group. Reduction in fatigue was seen at an average dose of 27.7 mg/day of the study drug. All patients had reduction in CGI scores, indicating decreased severity of symptoms from baseline to week 8. Improvement in these scores was seen in a significantly greater percentage of those given d-MPH (p = 0.02). The most frequent adverse events were headache, nausea, and dry mouth in the treatment group and headache, diarrhea, and insomnia in the placebo group. There was a higher rate of adverse events in the d-MPH group. Eleven percent of the treatment group experienced serious adverse events that led to study discontinuation. Events that led to discontinuation were nausea, vomiting, feeling jittery, and abnormal electrocardiogram.
D-MPH treatment in an individualized dosing regimen based on therapeutic response and side effects was associated with a significant improvement in fatigue.
Future studies need to be performed that address a broader range of patient types. The effectiveness of d-MPH in combination with other interventions, such as exercise, should be examined.