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 #173, Fast Fact #259, and Fast Fact #309 for information on cancer fatigue, modafinil, and depression management. 

Uses of psychostimulants    Both fatigue and depression can be treated with one of the psychostimulants: dextroamphetamine, modafinil (see Fast Fact #259), methylphenidate, or pemoline. Psychostimulants are controlled 2 substances that act rapidly (within hours to days), are well-tolerated, and can be discontinued often without the need for a taper. These medications have several potentially beneficial effects for patients with terminal illness:  

• Mood elevation: meta-analyses suggest that psychostimulants can significantly reduce symptoms of depression when used off-label to treat depressive episodes in patients without serious illness, but the overall level of evidence is considered low.  Furthermore, long-term efficacy and efficacy in patients with serious illness is less established.
• Improved energy: a meta-analysis showed a small benefit of psychostimulants for cancer related fatigue and demonstrated little adverse effects.
• Counter opioid-induced sedation – studied regimen of methylphenidate 10 mg with breakfast 5 mg with lunch.
• Improve cognitive focus; data is less clear if it improves cognitive ability.
• Attention deficit disorder.

Practical tips      

• For depression, psychostimulants are often considered for patients with a relatively short life expectancy of weeks to months because they act quickly, usually within 24-48 hours. Some patients with a longer life expectancy benefit from starting a psycho-stimulant and then transitioning to a selective serotonin reuptake inhibitor anti-depressant (SSRI).  Psychostimulants may augment the action of SSRIs in patients with severe depression.
• Psychostimulants are generally safe.  However, they should be used with caution in patients with heart disease or cognitive disturbances (e.g., delirium). Psychostimulant use disorder has been described in the literature.  Clinicians should review state monitoring databases when prescribing psychostimulants and follow similar safe opioid prescribing best practices.
• Pemoline, a milder psychostimulant, can rarely cause hepatotoxicity, requiring regular monitoring of hepatic function.
• Patients should be generally advised to avoid doses after 12 PM to disruption in sleep.
• There is some published concern that the beneficial effects of psychostimulants can diminish over a couple years.

References:

1. Block S. Assessing and Managing Depression in the Terminally Ill Patient. Annals of Internal Medicine. 2000; 132(3):209-218.
2. 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.
3. 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.
4. McIntyre RS, Lee Y, Zhou A, et al.  The efficacy of psychostimulants in major depressive episodes: a systematic review and meta-analysis. Journal of Clin Psychopharm 2017; 37(4):412-8.
5. Sullivan DR, Mongoue-Tchokote S, Mori M, et al.  Randomized, double-blind, placebo-controlled study of methylphenidate for the treatment of depression in SSRI-treated cancer patients receiving palliative care.  Psycho-Oncology 2017; 26(11):1763-1769.
6. Lavretsky H, Reinlieb M, Cyr NS, et al.  Citalopram, methylphenidate, or their combination in geriatric depression: a randomized, double-blind, placebo-controlled trial.  American Journal of Psychiatry 2015; 172(6):561-9.
7. 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.
8. Tardelli VS, Bisaga A, Arcadepani FB, et al.  Prescription psychostimulant for the treatment of stimulant use disorder: a systematic review and meta-analysis. Psychopharmacology 2020; 237:2233-2255.

Version History:  This Fast Fact was originally edited by David E Weissman MD.   2nd Edition published September 2006; 3rd Edition May 2015; 4th Edition April 2025 .
Conflicts of Interest: None to report.