Chemistry:List of investigational fatigue drugs

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Short description: Investigational fatigue drugs
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This is a list of investigational fatigue drugs, or drugs that are currently under development for clinical use for the treatment of fatigue but are not yet approved.

This list includes drugs for idiopathic or general fatigue and/or for fatigue related to medical conditions such as depression, cancer, autoimmune diseases, neurodegenerative diseases, stroke, and traumatic brain injury. This list does not include investigational drugs for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or long COVID, which can instead be found here and here, respectively.

Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. The format of list items is "Name (Synonyms) – Mechanism of Action [Reference]".

This list was last comprehensively updated in September 2025. It is likely to become outdated with time.

Under development

Phase 2

  • Anamorelin (Adlumiz; ANAM; ONO-7643; RC-1291; ST-1291) – ghrelin receptor agonist[1]
  • Anhydrous enol oxaloacetate (AEO; oxaloacetate) – oxaloacetate replacement[2]
  • BP-1.3656B (BP13656) – histamine H3 receptor antagonist[3]
  • Laromestrocel (Lomecel-B; Longeveron human mesenchymal stem cells; LMSC) – cell replacement[4]
  • Reparixin (DF-1681Y; Repertaxin) – CXC chemokine receptor CXCR1 and CXCR2 negative allosteric modulator[5]

Phase 1

  • Coacillium (LH-10; LH-4; LH-8) – various actions[6]

Preclinical

  • AVA-291 – androgen (androgen receptor agonist)[7]
  • DAT inhibitor therapeutic – dopamine reuptake inhibitor[8]

Not under development

Suspended

  • Clazakizumab (ALD-518; Anti-IL-6 mAb; BMS-945429; CSL-300) – monoclonal antibody against interleukin-6[9]

No development reported

  • MRZ-9547 ((R)-phenylpiracetam, (R)-phenotropil, or (R)-fonturacetam) – atypical dopamine reuptake inhibitor[10]

Discontinued

  • Armodafinil (CEP-10953; Nuvigil; (R)-modafinil) – atypical dopamine reuptake inhibitor[11]
  • Levacecarnine (acetyl-L-carnitine; ALC; ALCAR; Branigen; L-acetylcarnitine; Nicetile; RO-447190; ST-200; ST-211; Zibren) – carnitine acetyltransferase stimulant[12]

Clinically used drugs

Approved drugs

  • None

Off-label drugs

See also

References

  1. ↑ "Anamorelin - Helsinn Therapeutics/Ono Pharmaceutical - AdisInsight". https://adisinsight.springer.com/drugs/800021124. 
  2. ↑ "Anhydrous enol oxaloacetate - MetVital - AdisInsight". https://adisinsight.springer.com/drugs/800055090. 
  3. ↑ "BP 1.3656B - AdisInsight". https://adisinsight.springer.com/drugs/800044195. 
  4. ↑ "Laromestrocel - Longeveron - AdisInsight". https://adisinsight.springer.com/drugs/800043748. 
  5. ↑ "Reparixin - Dompe Farmaceutici - AdisInsight". https://adisinsight.springer.com/drugs/800010313. 
  6. ↑ "Coacillium - Legacy Healthcare - AdisInsight". https://adisinsight.springer.com/drugs/800050081. 
  7. ↑ "AVA 291 - AdisInsight". https://adisinsight.springer.com/drugs/800083242. 
  8. ↑ "DAT inhibitor therapeutic - Theracryf - AdisInsight". https://adisinsight.springer.com/drugs/800079689. 
  9. ↑ "Clazakizumab - CSL Behring - AdisInsight". https://adisinsight.springer.com/drugs/800029304. 
  10. ↑ "MRZ 9547 - AdisInsight". https://adisinsight.springer.com/drugs/800044857. 
  11. ↑ "Armodafinil - Teva Pharmaceutical Industries - AdisInsight". https://adisinsight.springer.com/drugs/800022302. 
  12. ↑ "Levacecarnine - AdisInsight". https://adisinsight.springer.com/drugs/800004527. 
  13. ↑ 13.0 13.1 13.2 13.3 13.4 "Pharmacological treatments for fatigue associated with palliative care". Cochrane Database Syst Rev 2015 (5). May 2015. doi:10.1002/14651858.CD006788.pub3. PMID 26026155. 
  14. ↑ "Fatigue in Alzheimer's disease: biological basis and clinical management-a narrative review". Aging Clin Exp Res 35 (10): 1981–1989. October 2023. doi:10.1007/s40520-023-02482-z. PMID 37395951. 
  15. ↑ "Fatigue in older cancer patients: etiology, assessment, and treatment". Semin Oncol 35 (6): 633–642. December 2008. doi:10.1053/j.seminoncol.2008.08.005. PMID 19027467. 
  16. ↑ "Caffeine: a valuable tool to study central fatigue in humans?". Exerc Sport Sci Rev 32 (4): 143–147. October 2004. doi:10.1097/00003677-200410000-00004. PMID 15604932. 
  17. ↑ "Fatigue: an overview". Am Fam Physician 78 (10): 1173–1179. November 2008. PMID 19035066. 
  18. ↑ 18.0 18.1 "New Pharmacological Approaches to Treating Non-Motor Symptoms of Parkinson's Disease". Curr Pharmacol Rep 2 (6): 253–261. December 2016. doi:10.1007/s40495-016-0071-0. PMID 28534003. 
  19. ↑ "Preladenant, a novel adenosine A(2A) receptor antagonist for the potential treatment of parkinsonism and other disorders". IDrugs 13 (10): 723–731. October 2010. PMID 20878595. 
  20. ↑ 20.0 20.1 20.2 "Efficacy of pharmacologic treatments for fatigue in multiple sclerosis: A systematic review and meta-analysis". Mult Scler Relat Disord 96. April 2025. doi:10.1016/j.msard.2025.106352. PMID 40043557. 
  21. ↑ "Amantadine: reappraisal of the timeless diamond-target updates and novel therapeutic potentials". J Neural Transm (Vienna) 128 (2): 127–169. February 2021. doi:10.1007/s00702-021-02306-2. PMID 33624170. 
  22. ↑ "Recommendations | Multiple sclerosis in adults: management | Guidance | NICE". June 22, 2022. https://www.nice.org.uk/guidance/ng220/chapter/Recommendations#ms-symptom-management-and-rehabilitation. 
  23. ↑ 23.0 23.1 23.2 23.3 23.4 "Fatigue in Parkinson disease, stroke, and traumatic brain injury". Phys Med Rehabil Clin N Am 20 (2): 347–361. May 2009. doi:10.1016/j.pmr.2008.12.006. PMID 19389616. 
  24. ↑ "Symptoms of fatigue and cognitive/executive dysfunction in major depressive disorder before and after antidepressant treatment". J Clin Psychiatry 64 Suppl 14: 30–34. 2003. PMID 14658933. 
  25. ↑ "Fatigue, a major still underestimated issue". Curr Opin Oncol 30 (4): 219–225. July 2018. doi:10.1097/CCO.0000000000000451. PMID 29877886. 
  26. ↑ "Symptoms of fatigue and sleepiness in major depressive disorder". J Clin Psychiatry 67 Suppl 6: 9–15. 2006. PMID 16848671. 
  27. ↑ "Cancer and Non-cancer Fatigue Treated With Bupropion: A Systematic Review". J Pain Symptom Manage 65 (1): e21–e28. January 2023. doi:10.1016/j.jpainsymman.2022.09.011. PMID 36198335. 
  28. ↑ "Fatigue in chronically ill patients". Curr Opin Support Palliat Care 2 (3): 180–186. September 2008. doi:10.1097/SPC.0b013e32830baed0. PMID 18685418. 
  29. ↑ "Fatigue as a core symptom in major depressive disorder: overview and the role of bupropion". Expert Rev Neurother 7 (10): 1251–1263. October 2007. doi:10.1586/14737175.7.10.1251. PMID 17939764. 
  30. ↑ "Carnitine for fatigue in multiple sclerosis". Cochrane Database Syst Rev 2012 (5). May 2012. doi:10.1002/14651858.CD007280.pub3. PMID 22592719. 
  31. ↑ "Management of Fatigue in Patients with Advanced Cancer". Curr Treat Options Oncol 24 (2): 93–107. February 2023. doi:10.1007/s11864-022-01045-0. PMID 36656503. 
  32. ↑ "Corticosteroids for the management of cancer-related fatigue in adults with advanced cancer". Cochrane Database Syst Rev 1 (1). January 2023. doi:10.1002/14651858.CD013782.pub2. PMID 36688471. 
  33. ↑ "Reducing fatigue in pediatric rheumatic conditions: a systematic review". Pediatr Rheumatol Online J 19 (1). July 2021. doi:10.1186/s12969-021-00580-8. PMID 34238314. 
  34. ↑ "The problem of fatigue in patients suffering from neoplastic disease". Contemp Oncol (Pozn) 21 (2): 131–135. 2017. doi:10.5114/wo.2017.68621. PMID 28947882. 
  35. ↑ "Identifying and responding to fatigue and apathy in Parkinson's disease: a review of current practice". Expert Rev Neurother 20 (5): 477–495. May 2020. doi:10.1080/14737175.2020.1752669. PMID 32290717. 
  36. ↑ "Fatigue in Parkinson's disease and potential interventions". NeuroRehabilitation 37 (1): 25–34. 2015. doi:10.3233/NRE-151238. PMID 26409691. 
  37. ↑ "Interventions for fatigue in Parkinson's disease". Cochrane Database Syst Rev 2015 (10). October 2015. doi:10.1002/14651858.CD010925.pub2. PMID 26447539. 
  38. ↑ "The Role of MAO-B Inhibitors in Fatigue in Parkinson's Disease: A Narrative Review". J Clin Med 14 (8): 2598. April 2025. doi:10.3390/jcm14082598. PMID 40283428. 
  39. ↑ "Effects of MAO-B inhibitors on non-motor symptoms and quality of life in Parkinson's disease: A systematic review". npj Parkinsons Dis 8 (1). June 2022. doi:10.1038/s41531-022-00339-2. PMID 35697709. 
  40. ↑ "Fatigue interventions in long term, physical health conditions: A scoping review of systematic reviews". PLOS ONE 13 (10). 2018. doi:10.1371/journal.pone.0203367. PMID 30312325. Bibcode: 2018PLoSO..1303367H. 
  41. ↑ 41.0 41.1 "Efficacy of pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases". RMD Open 9 (4). December 2023. doi:10.1136/rmdopen-2023-003349. PMID 38056919. 
  42. ↑ "Managing fatigue in sarcoidosis - A systematic review of the evidence". Chron Respir Dis 14 (2): 161–173. May 2017. doi:10.1177/1479972316661926. PMID 27507833. 
  43. ↑ "Review article: Description and management of fatigue in inflammatory bowel disease". Aliment Pharmacol Ther 37 (5): 505–516. March 2013. doi:10.1111/apt.12205. PMID 23311461. 
  44. ↑ "Fatigue in Patients with Major Depressive Disorder: Prevalence, Burden and Pharmacological Approaches to Management". CNS Drugs 32 (1): 65–74. January 2018. doi:10.1007/s40263-018-0490-z. PMID 29383573. 
  45. ↑ "Residual Fatigue in Unipolar and Bipolar Depression: A Systematic Review". Neuropsychopharmacol Rep 45 (1). March 2025. doi:10.1002/npr2.12519. PMID 39783764. 
  46. ↑ "The Utility of Methylphenidate for Fatigue in Long-Term Neurological Conditions: A Meta-analytical Review". Clin Neuropharmacol 46 (6): 239–252. 2023. doi:10.1097/WNF.0000000000000572. PMID 37962311. 
  47. ↑ "Fatigue After Traumatic Brain Injury: A Systematic Review". J Head Trauma Rehabil 37 (4): E249–E257. 2022. doi:10.1097/HTR.0000000000000710. PMID 34354018. 
  48. ↑ "The use of stimulant medications for non-core aspects of ADHD and in other disorders". Neuropharmacology 87: 161–172. December 2014. doi:10.1016/j.neuropharm.2014.06.014. PMID 24951855. 
  49. ↑ "Predictors and treatment strategies of HIV-related fatigue in the combined antiretroviral therapy era". AIDS 24 (10): 1387–1405. June 2010. doi:10.1097/QAD.0b013e328339d004. PMID 20523204. 
  50. ↑ "Efficacy of modafinil on fatigue and excessive daytime sleepiness associated with neurological disorders: a systematic review and meta-analysis". PLOS ONE 8 (12). 2013. doi:10.1371/journal.pone.0081802. PMID 24312590. Bibcode: 2013PLoSO...881802S. 




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