Fatigue (PDQ®): Supportive care - Health Professional Information [NCI] - Intervention
With both methylphenidate and modafinil, there have been exploratory data suggesting that patients with more severe fatigue or more advanced disease may receive more benefit from these drugs.[7,8] A small (n = 13), randomized, placebo-controlled study  using methylphenidate (titrated up to 30 mg/day) as an intervention failed to show statistical difference on the primary outcome measure, the brief fatigue inventory (BFI) total score, or activity interference subscale. However, the methylphenidate group showed significant reductions in the BFI severity subscale scores compared with the placebo group. The mean severity score at baseline was 6.5 for the methylphenidate group and 5.7 for the placebo group, placing these patients in a more severe fatigue category. A secondary analysis of the phase III trial evaluating modafinil versus placebo for CRF also revealed that patients with more severe fatigue may have benefited from modafinil. More research is needed to further evaluate whether psychostimulants are beneficial for patients experiencing more severe CRF.
The side effects most commonly described with psychostimulants include insomnia, euphoria, headache, nausea, anxiety, and mood lability.[5,7,8,13,14] High doses and long-term use may produce anorexia, nightmares, insomnia, euphoria, paranoia, and possible cardiovascular complications. Patients with cancer carry a higher risk of cardiovascular complications, depending on the type of cancer and cancer treatment (e.g., cardiotoxic chemotherapy regimens). Cardiovascular complications with psychostimulants can arise even in patients without any significant risk factors. In the study using methylphenidate as an intervention for the treatment of CRF in patients with prostate cancer, 6 subjects (27%) out of a total of 16 subjects in the methylphenidate group were discontinued because of increased blood pressure and tachycardia. It is important to note that none of these subjects were being treated with known cardiotoxic chemotherapeutic regimens such as anthracyclines. Careful and continuous monitoring of certain cardiovascular parameters (mainly blood pressure and heart rate) is critical when psychostimulants are used to treat CRF. In certain complex cases, consulting with cardiology services may be considered. Cardiovascular issues are thought to be less of a risk with modafinil and armodafinil. It is important to consider risk-benefit ratio and to evaluate patients for response and side effects when these agents are used to treat CRF.