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.