Background: Depressive symptoms, fatigue, and apathy are common symptoms among medically ill older adults and patients with advanced disease, and have been associated with morbidity and mortality. Methylphenidate has been used to treat these symptoms because of its rapid effect. Despite the long history of methylphenidate use for the treatment of depressive symptoms, fatigue, and apathy, there is little definitive evidence to support its use.

Objective: The aim of this paper was to review the efficacy and tolerability of methylphenidate in the treatment of depressive symptoms, fatigue, and apathy in medically ill older adults and adults receiving palliative care.

Methods: English-language articles presenting systematic reviews, clinical trials, or case series describing the use of methylphenidate for the treatment of depressive symptoms, fatigue, or apathy in medically ill older adults or adults receiving palliative care were identified. The key words methylphenidate and either depressive, depression, fatigue, or apathy were used to search the Cochrane Database, MEDLINE, PsycINFO, and International Pharmaceutical Abstracts. Included articles addressed depressive symptoms, fatigue, or apathy in (1) older adults (generally, age > or =65 years), particularly those with comorbid medical illness; (2) adults receiving palliative care; and (3) adults with other chronic illnesses. I excluded articles regarding treatment of depression in healthy young adults; bipolar disorder and attention-deficit/hyperactivity disorder; and narcolepsy, chronic fatigue syndrome, and related disorders.

Results: A total of 19 controlled trials of methylphenidate in medically ill older adults or patients in palliative care were identified. Unfortunately, their conflicting results, small sample sizes, and poor methodologic quality limited the ability to draw inferences regarding the efficacy of methylphenidate, although evidence of tolerability was stronger. The available evidence suggests possible effectiveness of methylphenidate for depressive symptoms, fatigue, and apathy in various medically ill populations.

Conclusion: In the absence of definitive evidence of effectiveness, trials of low-dose methylphenidate in medically ill adults with depression, fatigue, or apathy, with monitoring for response and adverse effects, are appropriate.