Fatigue

Fatigue and depression may coexist in patients with cancer and other physical diseases, and considerable overlap of symptoms often occurs. Cancer-related fatigue is often experienced with additional symptoms, including sleep disturbance, pain, and depression, and may arise as a result both of the cancer itself and as a side effect of cancer treatment (Carroll et al. 2007). Breitbart and Alici-Evcimen (2007), in a review, reported that the prevalence of cancer-related fatigue ranges from 4% to 91% depending on the specific cancer population studied and the methods of assessment. These findings have led many researchers to examine the role of psychotropic medications to treat fatigue. Most of the research, however, has been based on work with adult patients, and results of studies listed must be interpreted cautiously before extrapolating treatment guidelines for pediatric patients.

Psychostimulants

Psychostimulant medications are commonly used as agents to treat symptoms of fatigue and depression in physically ill patients (Pliszka 2007). In a Cochrane database review, Minton et al. (2008) reviewed the existing data on the use of psychostimulants to treat cancer-related fatigue in adult patients during the years 1948-2007. The authors identified two studies that met criteria for inclusion in their review, and based on the participation of 264 subjects, they concluded that the findings were significant enough to support the use of methylphenidate to treat cancer-related fatigue (Bruera et al. 2006; Fleishman et al. 2005). Although there are fewer data on other diseases, Breitbart et al. (2001), in a randomized, controlled study of adults with HIV, found that psychostimulants improved both fatigue and quality of life in subjects. There is also interest in the use of modafinil, approved for the treatment of narcolepsy, in the management of fatigue in physically ill adults. Studies on patients with breast cancer and brain tumors have both shown positive responses to modafinil (Carroll et al. 2007).

Carroll et al. (2007) reviewed seven clinical trials of methylphenidate for the treatment of cancer-related fatigue and concluded that although methylphenidate was shown to improve fatigue in open-label studies in patients with cancer, there were mixed results for double-blind studies using methylpheni-date and dexmethylphenidate. These authors also noted the importance of considering potential side effects of psychostimulants, including irritability, anorexia, insomnia, labile mood, nausea, and tachycardia, when making treatment decisions. Auret et al. (2009), in a more recent randomized, controlled trial, looked at the effect of methylphenidate on 50 adult patients with advanced cancer who were receiving palliative care. Although subjects reported a transient improvement in the fatigue levels on the second day of the study, there was no evidence to suggest any sustained improvements in fatigue or quality of life.

Antidepressants

In the Cochrane database review, Minton et al. (2008) found no data to support the use of antidepressants for cancer-related fatigue. Breitbart and Alici (2008) in a recent review came to similar conclusions; however, they did report that paroxetine may show benefit for fatigue, but primarily when it is a symptom of clinical depression. There have also been two open-label studies on the use of the sustained-release preparation of bupropion, which has psychostimulant-like effects, showing benefits for the treatment of cancer-related fatigue (Cullum et al. 2004; Moss et al. 2006).

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