Document Type : Original Article

Authors

1 Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

2 Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Department of Neurology, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

4 Department of Epidemiology and Biostatistics, School of Public Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Background: Recent research shows that most of the patients with multiple sclerosis (MS) have cognitive-like disorders. Due to the beneficial effects of atomoxetine on improving cognition in limited animal and human surveys, the aim of the present study was to investigate the effect of the atomoxetine on improving cognitive disorders of MS.
Methods: This study was a parallel, randomized clinical trial, designed to investigate the effect of atomoxetine drug on the improvement of cognitive impairment (CI) in MS, from April 2021 to March 2022. According to the inclusion and exclusion criteria, a total of 52 participants were involved in the study and then randomly divided in two groups of 26. Experimental group was treated with atomoxetine and the control group was treated with placebo. The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) test was performed for assessment at the beginning and after 3 months. The California Verbal Learning Test (CVLT), the CVLT-delay, the Brief Visuospatial Memory Test-Revised (BVMT-R), and the Symbol Digit Modalities Test (SDMT) were used to evaluate the CI and changes following medication. Finally, data were analyzed by SPSS software at significance level of 0.05.
Results: The mean age of patients in the experimental group was 37.7 ± 8.5 and in the placebo group was 37.8 ± 7.6 (P = 0.32). The results showed significant changes in cognitive levels before and after the use of atomoxetine and also in comparison to the placebo group (P < 0.05).
Conclusion: This study showed that atomoxetine improved the cognitive domains after administration compared to placebo.

Keywords

  1. National Multiple Sclerosis Society. Understanding Multiple Sclerosis [Online]. [cited 2016]; Available from: URL: https://www.nationalmssociety.org/What-is-MS/MS-FAQ-s
  2. Rogers JM, Panegyres PK. Cognitive impairment in multiple sclerosis: Evidence-based analysis and recommendations. J Clin Neurosci 2007; 14(10): 919-27.
  3. Kantarci O, Wingerchuk D. Epidemiology and natural history of multiple sclerosis: New insights. Curr Opin Neurol 2006; 19(3): 248-54.
  4. Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol 2008; 7(12): 1139-51.
  5. Beatty WW, Krull KR, Wilbanks SL, Blanco CR, Hames KA, Paul RH. Further validation of constructs from the selective reminding test. J Clin Exp Neuropsychol 1996; 18(1): 52-5.
  6. Miller E. Multiple sclerosis. Adv Exp Med Biol 2012; 724: 222-38.
  7. Peedicayil J. Epigenetic drugs for multiple sclerosis. Curr Neuropharmacol 2016; 14(1): 3-9.
  8. Bartko D, Combor I, Kubovicova K, Gombosova Z. Multiple sclerosis and cognitive disorders: What should neurologists advice patient with ms about his risk of developing dementia. Act Nerv Super Rediviva 2012; 54(4): 143-9.
  9. Zakzanis KK. Distinct neurocognitive profiles in multiple sclerosis subtypes. Arch Clin Neuropsychol 2000; 15(2): 115-36.
  10. Ruano L, Portaccio E, Goretti B, Niccolai C, Severo M, Patti F, et al. Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes. Mult Scler 2017; 23(9): 1258-67.
  11. Staff NP, Lucchinetti CF, Keegan BM. Multiple sclerosis with predominant, severe cognitive impairment. Arch Neurol 2009; 66(9): 1139-43.
  12. Foley JF, Brandes DW. Redefining functionality and treatment efficacy in multiple sclerosis. Neurology 2009; 72(23 Suppl 5): S1-11.
  13. Bethoux F, Bennett S. Evaluating walking in patients with multiple sclerosis: which assessment tools are useful in clinical practice? Int J MS Care 2011; 13(1): 4-14.
  14. Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 1991; 41(5): 685-91.
  15. Benedict RH, Cookfair D, Gavett R, Gunther M, Munschauer F, Garg N, et al. Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS). J Int Neuropsychol Soc 2006; 12(4): 549-58.
  16. Deloire MS, Ruet A, Hamel D, Bonnet M, Dousset V, Brochet B. MRI predictors of cognitive outcome in early multiple sclerosis. Neurology 2011; 76(13): 1161-7.
  17. Hamilton F, Rochester L, Paul L, Rafferty D, O'Leary CP, Evans JJ. Walking and talking: an investigation of cognitive-motor dual tasking in multiple sclerosis. Mult Scler 2009; 15(10): 1215-27.
  18. Patel VP, Zambrana A, Walker LA, Herrmann N, Feinstein A. Distraction adds to the cognitive burden in multiple sclerosis. Mult Scler 2017; 23(1): 106-13.
  19. Langdon DW, Amato MP, Boringa J, Brochet B, Foley F, Fredrikson S, et al. Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Mult Scler 2012; 18(6): 891-8.
  20. Rao SM, Losinski G, Mourany L, Schindler D, Mamone B, Reece C, et al. Processing speed test: Validation of a self-administered, iPad((R))-based tool for screening cognitive dysfunction in a clinic setting. Mult Scler 2017; 23(14): 1929-37.
  21. Penner IK, Stemper B, Calabrese P, Freedman MS, Polman CH, Edan G, et al. Effects of interferon beta-1b on cognitive performance in patients with a first event suggestive of multiple sclerosis. Mult Scler 2012; 18(10): 1466-71.
  22. Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue EW, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006; 354(9): 911-23.
  23. Krupp LB, Christodoulou C, Melville P, Scherl WF, Pai LY, Muenz LR, et al. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis. Neurology 2011; 76(17): 1500-7.
  24. Tzavara ET, Bymaster FP, Overshiner CD, Davis RJ, Perry KW, Wolff M, et al. Procholinergic and memory enhancing properties of the selective norepinephrine uptake inhibitor atomoxetine. Mol Psychiatry 2006; 11(2): 187-95.
  25. Vaughan B, Fegert J, Kratochvil CJ. Update on atomoxetine in the treatment of attention-deficit/hyperactivity disorder. Expert Opin Pharmacother 2009; 10(4): 669-76.
  26. Callahan PM, Plagenhoef MR, Blake DT, Terry AV. Atomoxetine improves memory and other components of executive function in young-adult rats and aged rhesus monkeys. Neuropharmacology 2019; 155: 65-75.
  27. Marsh L, Biglan K, Gerstenhaber M, Williams JR. Atomoxetine for the treatment of executive dysfunction in Parkinson's disease: A pilot open-label study. Mov Disord 2009; 24(2): 277-82.
  28. Weintraub D, Mavandadi S, Mamikonyan E, Siderowf AD, Duda JE, Hurtig HI, et al. Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson disease. Neurology 2010; 75(5): 448-55.
  29. Hinson VK, Delambo A, Elm J, Turner T. A randomized clinical trial of atomoxetine for mild cognitive impairment in Parkinson's disease. Mov Disord Clin Pract 2017; 4(3): 416-23.
  30. Warner CB, Ottman AA, Brown JN. The role of atomoxetine for parkinson disease-related executive dysfunction: A systematic review. J Clin Psychopharmacol 2018; 38(6): 627-31.
  31. Borchert RJ, Rittman T, Passamonti L, Ye Z, Sami S, Jones SP, et al. Atomoxetine enhances connectivity of prefrontal networks in Parkinson's disease. Neuropsychopharmacology 2016; 41(8): 2171-7.
  32. Miller E, Morel A, Redlicka J, Miller I, Saluk J. Pharmacological and Non-pharmacological therapies of cognitive impairment in multiple sclerosis. Curr Neuropharmacol 2018; 16(4): 475-83.
  33. Benedict RH, Fischer JS, Archibald CJ, Arnett PA, Beatty WW, Bobholz J, et al. Minimal neuropsychological assessment of MS patients: A consensus approach. Clin Neuropsychol 2002; 16(3): 381-97.
  34. Kehagia AA, Housden CR, Regenthal R, Barker RA, Muller U, Rowe J, et al. Targeting impulsivity in Parkinson's disease using atomoxetine. Brain 2014; 137(Pt 7): 1986-97.
  35. Greenfield AL, Hauser SL. B-cell therapy for multiple sclerosis: Entering an era. Ann Neurol 2018; 83(1): 13-26.