Methylphenidate for treating fatigue in palliative cancer care – effect and side effects in real-world data from a palliative care unit

Authors

  • Agneta Almerud ASIH Stockholm Södra, Palliative Home Care and Specialized Palliative Ward, Bergtallsvägen 12, SE-125 59 Älvsjö, Sweden
  • Gabriella Frisk ASIH Stockholm Södra, Palliative Home Care and Specialized Palliative Ward, Bergtallsvägen 12, SE-125 59 Älvsjö, Sweden; Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Blickagången 16, Neo floor 7, SE-141 83, Huddinge, Sweden
  • Caritha Klasson Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Blickagången 16, Neo floor 7, SE-141 83, Huddinge, Sweden
  • Linda Björkhem-Bergman Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Blickagången 16, Neo floor 7, SE-141 83, Huddinge, Sweden; Stockholms Sjukhem, Palliative Medicine, Mariebergsgatan 22, SE-112 19, Stockholm, Sweden

DOI:

https://doi.org/10.2340/1651-226X.2024.24156

Keywords:

Fatigue, palliative care, methylphenidate, dose-response, adverse effects

Abstract

Background: Methylphenidate can be used for the treatment of cancer-related fatigue (CRF), although randomized controlled trials have shown conflicting results. The aim of this study was to use ‘real-world’ data to evaluate the effect and side effects of using methylphenidate in palliative cancer care with a focus on the late palliative phase and dose-response.

Method: A retrospective review of medical records from a palliative care unit in Sweden was performed to evaluate the effect and adverse events (AEs) of using methylphenidate to treat CRF. Univariable and multivariable regression was performed and odds ratio (OR) calculated. Adjustments were made for sex, age, cancer type, dose and starting treatment <4 weeks before death.

Results: Of the 2,419 screened patients, 112 had been treated with methylphenidate for CRF. The treatment was assessed as being effective in 51 patients (46%). Twenty-six patients (23%) experienced AEs that were generally mild, including anxiety, palpitations, and insomnia. Patients starting the treatment <4 weeks before death (n = 54) were less likely to have an effect from treatment compared to those starting earlier; adjusted OR 0.24 (95% CI 0.10–0.55). Doses of 20 mg and above were well-tolerated and had a higher frequency of effect in the crude data but not after adjustment for confounding factors.

Conclusion: Methylphenidate is generally effective and well-tolerated for the treatment of CRF in palliative care. However, patients with a short life expectancy (<4 weeks) seem to benefit less from the treatment regardless of age, cancer type and dose.

Downloads

Download data is not yet available.

References

Al Maqbali M, Al Sinani M, Al Naamani Z, Al Badi K, Tanash MI. Prevalence of fatigue in patients with cancer: a systematic review and meta-analysis. J Pain Symptom Manage. 2021;61(1):167–89 e14. https://doi.org/10.1016/j.jpainsymman.2020.07.037 DOI: https://doi.org/10.1016/j.jpainsymman.2020.07.037

Bower JE. Cancer-related fatigue – mechanisms, risk factors, and treatments. Nat Rev Clin Oncol. 2014;11(10):597–609. https://doi.org/10.1038/nrclinonc.2014.127 DOI: https://doi.org/10.1038/nrclinonc.2014.127

de Raaf PJ, de Klerk C, Timman R, Hinz A, van der Rijt CC. Differences in fatigue experiences among patients with advanced cancer, cancer survivors, and the general population. J Pain Symptom Manage. 2012;44(6):823–30. https://doi.org/10.1016/j.jpainsymman.2011.12.279 DOI: https://doi.org/10.1016/j.jpainsymman.2011.12.279

de Raaf PJ, de Klerk C, van der Rijt CC. Elucidating the behavior of physical fatigue and mental fatigue in cancer patients: a review of the literature. Psychooncology. 2013;22(9):1919–29. https://doi.org/10.1002/pon.3225 DOI: https://doi.org/10.1002/pon.3225

Hagelin CL, Wengstrom Y, Ahsberg E, Furst CJ. Fatigue dimensions in patients with advanced cancer in relation to time of survival and quality of life. Palliat Med. 2009;23(2):171–8. https://doi.org/10.1177/0269216308098794 DOI: https://doi.org/10.1177/0269216308098794

Klasson C, Helde Frankling M, Lundh Hagelin C, Björkhem-Bergman L. Fatigue in cancer patients in palliative care – a review on pharmacological interventions. Cancers (Basel). 2021;13(5):985. https://doi.org/10.3390/cancers13050985 DOI: https://doi.org/10.3390/cancers13050985

Klasson C, Helde Frankling M, Warnqvist A, et al. Sex differences in the effect of vitamin D on fatigue in palliative cancer care – a post hoc analysis of the randomized, controlled trial ‘Palliative-D’. Cancers (Basel). 2022;14(3). https://doi.org/10.3390/cancers14030746 DOI: https://doi.org/10.3390/cancers14030746

Mustian KM, Alfano CM, Heckler C, et al. Comparison of pharmaceutical, psychological, and exercise treatments for cancer-related fatigue: a meta-analysis. JAMA Oncol. 2017;3(7):961–8. https://doi.org/10.1001/jamaoncol.2016.6914 DOI: https://doi.org/10.1001/jamaoncol.2016.6914

Mücke M, Cuhls H, Peuckmann-Post V, Minton O, Stone P, Radbruch L. Pharmacological treatments for fatigue associated with palliative care. Cochrane Database Syst Rev. 2015;5:CD006788. https://doi.org/10.1002/14651858.CD006788.pub3 DOI: https://doi.org/10.1002/14651858.CD006788.pub3

Radbruch L, Strasser F, Elsner F, et al. Fatigue in palliative care patients – an EAPC approach. Palliat Med. 2008;22(1):13–32. https://doi.org/10.1177/0269216307085183 DOI: https://doi.org/10.1177/0269216307085183

Mock V, Atkinson A, Barsevick A, et al. NCCN Practice Guidelines for Cancer-Related Fatigue. Oncology (Williston Park). 2000;14(11A):151-61.

Fabi A, Bhargava R, Fatigoni S, et al. Cancer-related fatigue: ESMO clinical practice guidelines for diagnosis and treatment. Ann Oncol. 2020;31(6):713–23. https://doi.org/10.1016/j.annonc.2020.02.016 DOI: https://doi.org/10.1016/j.annonc.2020.02.016

Bruera E, Yennurajalingam S, Palmer JL, et al. Methylphenidate and/or a nursing telephone intervention for fatigue in patients with advanced cancer: a randomized, placebo-controlled, phase II trial. J Clin Oncol. 2013;31(19):2421–7. https://doi.org/10.1200/JCO.2012.45.3696 DOI: https://doi.org/10.1200/JCO.2012.45.3696

Centeno C, Roji R, Portela MA, et al. Improved cancer-related fatigue in a randomised clinical trial: methylphenidate no better than placebo. BMJ Support Palliat Care. 2022;12(2):226–34. https://doi.org/10.1136/bmjspcare-2020-002454 DOI: https://doi.org/10.1136/bmjspcare-2020-002454

Escalante CP, Meyers C, Reuben JM, et al. A randomized, double-blind, 2-period, placebo-controlled crossover trial of a sustained-release methylphenidate in the treatment of fatigue in cancer patients. Cancer J. 2014;20(1):8–14. https://doi.org/10.1097/PPO.0000000000000018 DOI: https://doi.org/10.1097/PPO.0000000000000018

Mitchell GK, Hardy JR, Nikles CJ, et al. The effect of methylphenidate on fatigue in advanced cancer: an aggregated N-of-1 trial. J Pain Symptom Manage. 2015;50(3):289–96. https://doi.org/10.1016/j.jpainsymman.2015.03.009 DOI: https://doi.org/10.1016/j.jpainsymman.2015.03.009

Pedersen L, Lund L, Petersen MA, Sjogren P, Groenvold M. Methylphenidate as needed for fatigue in patients with advanced cancer. A prospective, double-blind, and placebo-controlled study. J Pain Symptom Manage. 2020;60(5):992–1002. https://doi.org/10.1016/j.jpainsymman.2020.05.023 DOI: https://doi.org/10.1016/j.jpainsymman.2020.05.023

Richard PO, Fleshner NE, Bhatt JR, Hersey KM, Chahin R, Alibhai SM. Phase II, randomised, double-blind, placebo-controlled trial of methylphenidate for reduction of fatigue levels in patients with prostate cancer receiving LHRH-agonist therapy. BJU Int. 2015;116(5):744–52. https://doi.org/10.1111/bju.12755 DOI: https://doi.org/10.1111/bju.12755

Roth AJ, Nelson C, Rosenfeld B, et al. Methylphenidate for fatigue in ambulatory men with prostate cancer. Cancer. 2010;116(21):5102–10. https://doi.org/10.1002/cncr.25424 DOI: https://doi.org/10.1002/cncr.25424

Hovey E, de Souza P, Marx G, et al. Phase III, randomized, double-blind, placebo-controlled study of modafinil for fatigue in patients treated with docetaxel-based chemotherapy. Support Care Cancer. 2014;22(5):1233–42. https://doi.org/10.1007/s00520-013-2076-0 DOI: https://doi.org/10.1007/s00520-013-2076-0

Lee EQ, Muzikansky A, Drappatz J, et al. A randomized, placebo-controlled pilot trial of armodafinil for fatigue in patients with gliomas undergoing radiotherapy. Neuro Oncol. 2016;18(6):849–54. https://doi.org/10.1093/neuonc/now007 DOI: https://doi.org/10.1093/neuonc/now007

Spathis A, Fife K, Blackhall F, et al. Modafinil for the treatment of fatigue in lung cancer: results of a placebo-controlled, double-blind, randomized trial. J Clin Oncol. 2014;32(18):1882–8. https://doi.org/10.1200/JCO.2013.54.4346 DOI: https://doi.org/10.1200/JCO.2013.54.4346

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):613–21. https://doi.org/10.1016/j.jpainsymman.2008.03.016 DOI: https://doi.org/10.1016/j.jpainsymman.2008.03.016

Homsi J, Nelson KA, Sarhill N, et al. A phase II study of methylphenidate for depression in advanced cancer. Am J Hosp Palliat Care. 2001;18(6):403–7. https://doi.org/10.1177/104990910101800610 DOI: https://doi.org/10.1177/104990910101800610

Bjorkhem-Bergman L, Wallin C. [Methylphenidate and cannabinoids may have a place in palliative care. Literature review and clinical experience provides evidence]. Lakartidningen. 2013;110(32–33):1409–11.

Storebo OJ, Ramstad E, Krogh HB, et al. Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). Cochrane Database Syst Rev. 2015;11:CD009885. https://doi.org/10.1002/14651858.CD009885.pub2 DOI: https://doi.org/10.1002/14651858.CD009885.pub2

Kapur A. Is methylphenidate beneficial and safe in pharmacological cognitive enhancement? CNS Drugs. 2020;34(10):1045–62. https://doi.org/10.1007/s40263-020-00758-w DOI: https://doi.org/10.1007/s40263-020-00758-w

Kis B, Lucke C, Abdel-Hamid M, Hessmann P, Graf E, Berger M, et al. Safety profile of methylphenidate under long-term treatment in adult ADHD patients – results of the COMPAS study. Pharmacopsychiatry. 2020;53(6):263–71. https://doi.org/10.1055/a-1207-9851 DOI: https://doi.org/10.1055/a-1207-9851

Seeman P. Schizophrenia and dopamine receptors. Eur Neuropsychopharmacol. 2013;23(9):999–1009. https://doi.org/10.1016/j.euroneuro.2013.06.005 DOI: https://doi.org/10.1016/j.euroneuro.2013.06.005

Sterpu B, Lindman P, Bjorkhem-Bergman L. A comparative study on decision and documentation of refraining from resuscitation in two medical home care units in Sweden. BMC Palliat Care. 2019;18(1):80. https://doi.org/10.1186/s12904-019-0472-z DOI: https://doi.org/10.1186/s12904-019-0472-z

Flatt T. A new definition of aging? Front Genet. 2012;3:148. https://doi.org/10.3389/fgene.2012.00148 DOI: https://doi.org/10.3389/fgene.2012.00148

Lunney JR, Lynn J, Foley DJ, Lipson S, Guralnik JM. Patterns of functional decline at the end of life. JAMA. 2003;289(18):2387–92. https://doi.org/10.1001/jama.289.18.2387 DOI: https://doi.org/10.1001/jama.289.18.2387

Mukherjee J, Christian BT, Dunigan KA, et al. Brain imaging of 18F-fallypride in normal volunteers: blood analysis, distribution, test-retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors. Synapse. 2002;46(3):170–88. https://doi.org/10.1002/syn.10128 DOI: https://doi.org/10.1002/syn.10128

Hoenemeyer TW, Kaptchuk TJ, Mehta TS, Fontaine KR. Open-label placebo treatment for cancer-related fatigue: a randomized-controlled clinical trial. Sci Rep. 2018;8(1):2784. https://doi.org/10.1038/s41598-018-20993-y DOI: https://doi.org/10.1038/s41598-018-20993-y

Ching C, Eslick GD, Poulton AS. Evaluation of methylphenidate safety and maximum-dose titration rationale in attention-deficit/hyperactivity disorder: a meta-analysis. JAMA Pediatr. 2019;173(7):630–9. https://doi.org/10.1001/jamapediatrics.2019.0905 DOI: https://doi.org/10.1001/jamapediatrics.2019.0905

Mattos P, Louza MR, Palmini AL, de Oliveira IR, Rocha FL. A multicenter, open-label trial to evaluate the quality of life in adults with ADHD treated with long-acting methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) study. J Atten Disord. 2013;17(5):444–8. https://doi.org/10.1177/1087054711434772 DOI: https://doi.org/10.1177/1087054711434772

Tripp G, Wickens JR. Neurobiology of ADHD. Neuropharmacology. 2009;57(7–8):579–89. https://doi.org/10.1016/j.neuropharm.2009.07.026 DOI: https://doi.org/10.1016/j.neuropharm.2009.07.026

Published

2024-02-13

How to Cite

Almerud, A., Frisk, G., Klasson, C., & Björkhem-Bergman, L. (2024). Methylphenidate for treating fatigue in palliative cancer care – effect and side effects in real-world data from a palliative care unit. Acta Oncologica, 63(1), 9–16. https://doi.org/10.2340/1651-226X.2024.24156

Funding data