Minton, O., Richardson, A., Sharpe, M., Hotopf, M., & Stone, P. C. (2011). Psychostimulants for the management of cancer-related fatigue: a systematic review and meta-analysis. Journal of Pain and Symptom Management, 41, 761–767.

To focus on the role of psychostimulants, particularly methylphenidate, in the treatment of cancer-related fatigue (CRF).

Databases searched were MEDLINE, EMBASE, CINAHL, and Cochrane Register from inception to 2009.

Search keywords were not stated but appeared to be related to cancer-related fatigue and psychostimulants. According to the authors, “An exhaustive list of search terms was used and a systematic review methodology was applied.”

Studies were included if they were randomized, controlled trials testing a psychostimulant against a placebo or usual care in the treatment of CRF.

No exclusion criteria were stated.
 

The total number of references retrieved was not stated. One author screened relevant titles and abstracts. The final list of included studies was agreed on by all the authors. Data were “extracted and independently reviewed using predesigned data extraction forms. Data were entered into Cochrane review manager software.” More information on search terms and numbers of articles initially reviewed would have been helpful; it was unclear as to who designed the “predesigned data extraction forms.”

• The final number of studies included was five.
• The sample range across studies was 50 to 152 patients (N = 426 patients).
• Minimal information was provided.
• Mean age ranged from 50 to 71 years for the various studies (no range was provided).
• There appeared to be various tumor types and treatment both current and past.
• No other demographic data were provided.
   

• Patients were undergoing the transitional phase of care after initial treatment.
• The study has clinical applicability for late effects and survivorship and palliative care.

Four studies measured CRF with the Functional Assessment of Cancer Therapy–Fatigue (FACT-F), and one used the Brief Fatigue Inventory (BFI). There was a significant effect of psychostimulants over placebo (standardized mean difference = –0.28; 95% confidence interval [CI] [–0.48, –0.09]; p = 0.005). There was no difference in the rate of adverse effects between the drug and the placebo.

According to the authors, “evidence suggests that methylphenidate may be effective in management of CRF”; however, there was no large well-conducted clinical trial, and evidence from smaller trials was somewhat contradictory; thus, the authors stated “this advice must be considered to be tentative and provisional.”

Generally, this was a weak systematic review because the authors talked about performing an extensive search but provided no details about that search. The meta-analysis was also weak because only one (the largest) of the five studies showed improvement with psychostimulants compared to placebo.

Because there was no evidence about the long-term side effects of the medications, methylphenidate may best be used in patients with advanced disease or short-term use in those on active treatment. However, there was a trend toward benefit in some patients, and it may be worth a trial in selected patients as suggested by the authors.