Am Fam Physician. 2014 Jan 15;89(2):124-127.
Does methylphenidate (Ritalin) improve fatigue in the palliative care setting?
No recent evidence demonstrates that methylphenidate improves fatigue in patients receiving palliative care. Methylphenidate can be used to minimally improve fatigue symptom scores in patients with cancer-related fatigue. (Strength of Recommendation [SOR]: C, based on a meta-analysis of multiple randomized controlled trials [RCTs] with heterogeneous results.) Methylphenidate can also be used to modestly improve fatigue scores in patients with human immunodeficiency virus infection, Parkinson disease, and sarcoidosis. (SOR: C, based on a single small RCT for each condition.) Approximately 5% to 30% of medically ill older adults receiving methylphenidate experience adverse effects (e.g., agitation, tachycardia, insomnia). Methylphenidate rarely produces non–life-threatening cardiovascular and central nervous system–activating adverse effects.
Fatigue is associated with diverse illnesses and is common in palliative care settings. No recent studies have evaluated methylphenidate in the treatment of fatigue in general palliative care settings.1 One small double-blind crossover trial (n = 61) found that methylphenidate given for four days improved lethargy, fatigue, and depression in chronically ill older patients in care facilities.2 However, this study was performed in 1958, before palliative care was defined, and the authors did not describe how fatigue was assessed.
A Cochrane review of five RCTs (N = 426) evaluating the use of psychostimulants for the management of cancer-related fatigue (i.e., a persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with normal functioning and is not relieved by rest3) found that methylphenidate slightly improved symptom scores.4 Four of the included studies evaluated methylphenidate, and one evaluated dexamphetamine.3,5–8 All of the studies used standardized survey instruments to measure fatigue symptoms. Although only one study demonstrated a significant difference (3.7-point improvement vs. placebo out of 52 possible points for fatigue symptom scores on the non–disease-specific Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-F] Scale), the meta-analysis favored methylphenidate over placebo. There was a reduction in fatigue scores of −0.28 standard deviations (95% confidence interval, −0.48 to −0.09). The methylphenidate group had a two-point reduction in fatigue symptom scores on the FACIT-F; this was the minimum clinically significant difference that was detectable.4
High-quality but small RCTs demonstrated that methylphenidate modestly reduced fatigue symptom scores in ambulatory adult patients with human immunodeficiency virus infection,9 older patients with Parkinson disease,10 and adults with sarcoidosis.11 Patients with human immunodeficiency virus who were treated with methylphenidate had a 1.3-point improvement (out of 10 possible points) on the Piper Fatigue Scale. Those with Parkinson disease had a 4.6-point improvement (out of 54 possible points) on the Fatigue Severity Scale and a 5.2-point improvement (out of 80 possible points) on the Multidimensional Fatigue Inventory. Patients with sarcoidosis who were treated with dexmethylphenidate (Focalin) in a crossover trial had a five-point improvement (out of 52 possible points) on the FACIT-F.
A systematic review of the use of methylphenidate in medically ill older adults (44 studies, 1,355 patients) found that adverse effects were reported in 5% to 30% of patients.12 However, controlled studies found no significant differences in rates of adverse effects compared with placebo. The most common adverse effects were agitation or restlessness, sinus tachycardia or palpitations, delirium or confusion, and insomnia. One serious but uncommon adverse effect was arrhythmia, which was reversible with discontinuation.
Recommendations from Others
Guidelines from the National Comprehensive Cancer Network state that treatment with methylphenidate or modafinil (Provigil) may be considered in select patients with terminal cancer and fatigue.13 A statement from the British Columbia Medical Services Commission states that psychostimulants such as methylphenidate, dextroamphetamine, and modafinil may be beneficial in managing fatigue when no correctable underlying cause can be found.14 The European Association for Palliative Care guidelines state that methylphenidate may have a role in the management of opioid-induced sedation and cognitive failure in patients for whom opioid dose reduction or dose rotation is impractical or inappropriate.15
Copyright Family Physicians Inquiries Network. Used with permission.
REFERENCESshow all references
1. Peuckmann V, Elsner F, Krumm N, Trottenberg P, Radbruch L. Pharmacological treatments for fatigue associated with palliative care. Cochrane Database Syst Rev. 2010;(11):CD006788....
2. Landman ME, Preisig R, Perlman M. A practical mood stimulant. J Med Soc N J. 1958;55(2):55–58.
3. Auret KA, Schug SA, Bremner AP, Bulsara M. A randomized, double-blind, placebo-controlled trial assessing the impact of dexamphetamine on fatigue in patients with advanced cancer. J Pain Symptom Manage. 2009;37(4):613–621.
4. Minton O, Richardson A, Sharpe M, Hotopf M, Stone P. Drug therapy for the management of cancer-related fatigue. Cochrane Database Syst Rev. 2010; (7):CD006704.
5. Bruera E, Valero V, Driver L, et al. Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial. J Clin Oncol. 2006;24(13):2073–2078.
6. Butler JM Jr, Case LD, Atkins J, et al. A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy. Int J Radiat Oncol Biol Phys. 2007;69(5):1496–1501.
7. Lower EE, Fleishman S, Cooper A, et al. Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. J Pain Symptom Manage. 2009;38(5):650–662.
8. Mar Fan HG, Clemons M, Xu W, et al. A randomised, placebo-controlled, double-blind trial of the effects of d-methylphenidate on fatigue and cognitive dysfunction in women undergoing adjuvant chemotherapy for breast cancer. Support Care Cancer. 2008;16(6):577–583.
9. Breitbart W, Rosenfeld B, Kaim M, Funesti-Esch J. A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease. Arch Intern Med. 2001;161(3):411–420.
10. Mendonça DA, Menezes K, Jog MS. Methylphenidate improves fatigue scores in Parkinson disease: a randomized controlled trial. Mov Disord. 2007;22(14):2070–2076.
11. Lower EE, Harman S, Baughman RP. Double-blind, randomized trial of dexmethylphenidate hydrochloride for the treatment of sarcoidosis-associated fatigue. Chest. 2008;133(5):1189–1195.
12. Hardy SE. Methylphenidate for the treatment of depressive symptoms, including fatigue and apathy, in medically ill older adults and terminally ill adults. Am J Geriatr Pharmacother. 2009;7(1):34–59.
13. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: cancer-related fatigue. http://www.nccn.org/professionals/physician_gls/pdf/fatigue.pdf (subscription required). Accessed October 29, 2013.
14. British Columbia Medical Services Commission. Palliative care for the patient with incurable cancer or advanced disease. Part 2: pain and symptom management. http://www.bcguidelines.ca/guideline_palliative2.html. Accessed October 30, 2013.
15. Radbruch L, Strasser F, Elsner F, et al.; Research Steering Committee of the European Association for Palliative Care. Fatigue in palliative care patients—an EAPC approach. Palliat Med. 2008;22(1):13–32.
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