Background More than 95% of patients experience fatigue near the end of life. Chemotherapy, radiation, and administration of opioids all tend to increase tiredness. Depression is also a common cause of suffering at the end of life; about 25% of cancer patients with early stage disease develop depression, in advanced illness more than three-quarters of all patients have symptoms of depression. See also Fast Fact #259 on modafinil.
Uses of Psycho-stimulants Both fatigue and depression can be treated with one of the psycho-stimulants: dextroamphetamine, methylphenidate, or pemoline. Psycho-stimulants act rapidly and are well-tolerated. These medications have 6 potentially beneficial effects for patients with terminal illness:
- Mood elevation: a Cochrane analysis suggested that psychostimulants significantly reduce symptoms of depression, but long term efficacy is not established.
- Improved energy: a meta-analysis showed a small benefit of psychostimulants for cancer related fatigue and demonstrated little adverse effects.
- Potentiate analgesic effect of opioids
- Counter opioid-induced sedation
- Increase appetite
- Improve cognition
Practical Tips For depression, psycho-stimulants are the drug of choice for patients with a relatively short life expectancy of weeks to months because they act quickly, usually within 24-48 hours. Psycho-stimulants are generally safe. However, they should be used with caution in patients with heart disease or cognitive disturbances (e.g. delirium). Pemoline, a milder psycho-stimulant, can rarely cause hepatotoxicity, requiring regular monitoring of hepatic function. Some patients with severe depression and a longer life expectancy benefit from starting a psycho-stimulant and then transitioning to a selective serotonin reuptake inhibitor anti-depressant (SSRI). Psycho-stimulants are also useful to augment the action of SSRIs in patients with severe depression.

References:
- Block S. Assessing and Managing Depression in the Terminally Ill Patient. Annals of Internal Medicine. 2000; 132(3):209-218.
- Roszans M, Dreisbach A, Lertora JJL, Kahn MJ. Palliative uses of methylphenidate in patients with cancer: a review. J Clin Onc. 2002;20:335-339.
- Minton O, Richardson, A, et al. Psychostimulants for the Management of Cancer-Related Fatigue: A Systematic Review and Meta-Analysis. J of Pain and Symptom Manage 2011; 41: 761–767
- Candy B, Jones L, Williams R, Tookman A, King M. Psychostimulants for depression. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD006722. DOI: 10.1002/14651858.CD006722.pub2.
Version History: This Fast Fact was originally edited by David E Weissman MD. 2nd Edition published September 2006; 3rd Edition May 2015. Current version re-copy-edited April 2009; then again May 2015 with additional references added and incorporated into the text.
Fast Facts and Concepts are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School), with the generous support of a volunteer peer-review editorial board, and are made available online by the Palliative Care Network of Wisconsin (PCNOW); the authors of each individual Fast Fact are solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at Palliative Care Network of Wisconsin with contact information, and how to reference Fast Facts.
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