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Fatigue is a common and highly distressing symptom of cancer associated with reduced quality of life and considerable psychological and functional morbidity. The reported prevalence of cancer-related fatigue ranges from 4% to 91%, depending on the specific cancer population studied and the methods of assessment. Cancer-related fatigue has typically been underreported, underdiagnosed, and undertreated. Fatigue and depression may coexist in cancer patients, and considerable overlap of symptoms occurs. This is partly the reason for the interest in examining the role of psychotropic medications in treating fatigue. Clarifying the relationship between depression and fatigue is necessary to effectively evaluate and treat cancer-related fatigue. Even with International Classification of Diseases criteria, differentiating cancer-related fatigue is difficult. Psychotropic drugs that have been studied for cancer-related fatigue include psychostimulants, wakefulness-promoting agents, and anti-depressants. Methylphenidate has been studied most and seems to be effective and well tolerated despite common side effects. Some preliminary data support using modafinil in cancer-related fatigue with less concern about tolerance or dependence. Antidepressant studies have shown mixed results. Paroxetine seems to show benefit for fatigue primarily when it is a symptom of clinical depression. Bupropion, a norepinephrine/dopamine reuptake inhibitor, may have psychostimulant-like effects, and therefore may be more beneficial for treating fatigue. However, studies are currently limited. Randomized, placebo-controlled trials with specific agents are needed to further assess the efficacy and tolerability of psychotropic medications in the treatment of cancer-related fatigue.

Fatigue is a highly prevalent and distressing symptom associated with significant psychological and functional morbidity and decreased quality of life among patients with cancer. Despite its impact on patients and caregivers, fatigue is underreported and underrecognized, and remains untreated among patients with cancer because of various patient- and clinician-related factors. In addition to assessment for potentially reversible medical causes or medications exacerbating fatigue, and the implementation of nonpharmacologic interventions, several pharmacologic treatment options have been considered for the treatment of cancer-related fatigue. Among traditional psychostimulants, methylphenidate has been studied the most and is effective and well tolerated among patients with cancer despite common side effects. Modafinil, a novel psychostimulant commonly referred to as wakefulness-promoting agents as a group, has also been studied and seems to be well tolerated among patients with cancer. A large placebo effect has been reported in most randomized controlled trials with psychostimulants. Thus, randomized placebo-controlled trials with large sample sizes are needed to further assess the efficacy and tolerability of psychostimulants in the treatment of cancer-related fatigue. This article presents a comprehensive review of the use of psychostimulant agents for fatigue among patients with cancer, including an overview of the clinical trials with psychostimulants and of the clinical guidelines available for treatment of cancer-related fatigue.