Effects of Atomoxetine for Cognitive Function in Methamphetamine-dependent Patients: A Randomized Controlled Trial
International Journal of Medical Toxicology and Forensic Medicine,
Vol. 12 No. 1 (2022),
13 January 2022
,
Page 35883
https://doi.org/10.32598/ijmtfm.vi.35883
Abstract
Background: A substantial body of evidence indicates that methamphetamine abuse can lead to persistent and severe cognitive dysfunction. Preclinical studies and early pilot clinical investigations suggested that atomoxetine, a cognitive enhancer, may improve cognitive dysfunction. The present study evaluated whether atomoxetine would affect cognitive dysfunction in methamphetamine-dependent patients.
Methods: Participants with methamphetamine dependence (N=86) under Methadone Maintenance Therapy (MMT) were enrolled in a double-blind, placebo-controlled, randomized clinical trial. This investigation was performed on 86 subjects to consume either 40 mg/day atomoxetine (n=45) or placebo (n=41) for 8 weeks. Between January 2016 and June 2017, volunteers were selected from methamphetamine abusers in MMT centers in Kashan City, Iran. They completed the Cognitive Abilities Questionnaire at the first and each monthly visit to assess the cognitive functions. The collected data were analyzed using the Independent Samples t-test, Mann Whitney U test, and Chi-square in SPSS software.
Results: This study revealed that atomoxetine treatment improved some cognitive dysfunctions in methamphetamine users, including memory, inhibitory control, selective attention, decision-making, planning, sustained attention, and cognitive flexibility in methamphetamine users; however, social cognition improvement was less than others (P=0.107). There were only mild adverse effects in the placebo and atomoxetine groups.
Conclusion: The obtained findings indicated the efficacy of atomoxetine for improving cognitive dysfunction in methamphetamine users and suggest the potential effectiveness of atomoxetine for treating them.
- Atomoxetine
- Methamphetamine
- Cognitive Function
- Methadone
How to Cite
References
Drugs UNOo, Crime. World drug report 2010: United Nations Publications; 2010. https://www.unodc.org/documents/wdr/WDR_2010/World_Drug_Report_2010_lo-res.pdf
Davidson C, Gow AJ, Lee TH, Ellinwood EH. Methamphetamine neurotoxicity: Necrotic and apoptotic mechanisms and relevance to human abuse and treatment. Brain Research Reviews. 2001; 36(1):1-22. [DOI:10.1016/S0165-0173(01)00054-6]
Nakagawa T, Kaneko S. Neuropsychotoxicity of abused drugs: Molecular and neural mechanisms of neuropsychotoxicity induced by methamphetamine, 3, 4-methylenedioxymethamphetamine (ecstasy), and 5-methoxy-N, N-diisopropyltryptamine (foxy). Journal of Pharmacological Sciences. 2008; 106(1):2-8. [DOI:10.1254/jphs.FM0070141] [PMID]
Salo R, Nordahl TE, Possin K, Leamon M, Gibson DR, Galloway GP, et al. Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals. Psychiatry Research. 2002; 111(1):65-74. [DOI:10.1016/S0165-1781(02)00111-7]
Meredith CW, Jaffe C, Ang-Lee K, Saxon AJ. Implications of chronic methamphetamine use: A literature review. Harvard Review of Psychiatry. 2005; 13(3):141-54. [DOI:10.1080/10673220591003605] [PMID]
Scott JC, Woods SP, Matt GE, Meyer RA, Heaton RK, Atkinson JH, et al. Neurocognitive effects of methamphetamine: A critical review and meta-analysis. Neuropsychol Reviews. 2007; 17(3):275-97. [DOI:10.1007/s11065-007-9031-0] [PMID]
Burgess PW, Veitch E, de Lacy Costello A, Shallice TJN. The cognitive and neuroanatomical correlates of multitasking. Neuropsychologia. 2000; 38(6):848-63. [DOI:10.1016/S0028-3932(99)00134-7]
Damasio AR. Review: Toward a neurobiology of emotion and feeling: Operational concepts and hypotheses. The Neuroscientist. 1995; 1(1):19-25. [DOI:10.1177/107385849500100104]
Grafman J, Litvan IJTL. Importance of deficits in executive functions. Lancet. 1999; 354(9194):1921-3. [DOI:10.1016/S0140-6736(99)90438-5]
Stuss DT, Shallice T, Alexander MP, Picton TW. A Multidisciplinary approach to anterior attentional functions a. Annals of the New York Academy of Sciences. 1995; 769(1):191-212. [DOI:10.1111/j.1749-6632.1995.tb38140.x] [PMID]
Ornstein T, Iddon J, Baldacchino A, Sahakian B, London M, Everitt B, et al. Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers. Neuropsychopharmacology. 2000; 23(2):113-26. [DOI:10.1016/S0893-133X(00)00097-X]
Saxon AJ, Straits-Troster K, Rippeth JD, Romwall L, Rosenbaum G, Bush KR. Longitudinal cognitive changes among methamphetamine dependent patients in early abstinence. Inannual meeting of College on Problems of Drug Dependence, Bal Harbour, FL 2003 Jun 16.
Simon SL, Domier C, Carnell J, Brethen P, Rawson R, Ling W. Cognitive impairment in individuals currently using methamphetamine. American Journal on Addictions. 2000; 9(3):222-31. [DOI:10.1080/10550490050148053] [PMID]
Volkow ND, Chang L, Wang G-J, Fowler JS, Franceschi D, Sedler M, et al. Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. The Journal of Neuroscience. 2001; 21(23):9414-8. [DOI:10.1523/JNEUROSCI.21-23-09414.2001] [PMID] [PMCID]
Volkow ND, Chang L, Wang G-J, Fowler JS, Leonido-Yee M, Franceschi D, et al. Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. The American Journal of Psychiatry. 2001; 158(3):377-82. [DOI:10.1176/appi.ajp.158.3.377] [PMID]
Fredriksen M, Halmøy A, Faraone SV, Haavik JJEN. Long-term efficacy and safety of treatment with stimulants and atomoxetine in adult ADHD: A review of controlled and naturalistic studies. European Neuropsychopharmacology. 2013; 23(6):508-27. [DOI:10.1016/j.euroneuro.2012.07.016] [PMID]
Simpson D, Plosker GLJD. Atomoxetine: A review of its use in adults with attention deficit hyperactivity disorder. Drugs. 2004; 64(2):205-23. [DOI:10.2165/00003495-200464020-00005] [PMID]
Rabiey A, Hassani-Abharian P, Farhad M, Moravveji AR, Akasheh G, Banafshe HR. [Atomoxetine efficacy in methamphetamine dependence during methadone maintenance therapy (Persian)]. Archives of Iranian medicine. 2019; 22(12):692-8. http://www.aimjournal.ir/Article/aim-4266
DeVito EE, Herman AI, Konkus NS, Zhang H, Sofuoglu M. Atomoxetine in abstinent cocaine users: Cognitive, subjective and cardiovascular effects. Pharmacology Biochemistry and Behavior. 2017; 159:55-61. [DOI:10.1016/j.pbb.2017.07.002] [PMID] [PMCID]
Weintraub D, Mavandadi S, Mamikonyan E, Siderowf A, Duda J, Hurtig H, et al. Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson disease. Neurology. 2010; 75(5):448-55. [DOI:10.1212/WNL.0b013e3181ebdd79] [PMID] [PMCID]
Liu F, Conley RR. A randomized double-blind trial of atomoxetine for cognitive impairments in 32 people with schizophrenia. The Journal of Clinical Psychiatry. 2009; 70(4):518-25. [DOI:10.4088/JCP.08m04358] [PMID]
Sacco KA, Creeden C, Reutenauer EL, Vessicchio JC, Weinberge AH, George TP. Effects of atomoxetine on cognitive function and cigarette smoking in schizophrenia. Schizophrenia Research. 2009; 107(2-3):332-3 [DOI:10.1016/j.schres.2008.09.026] [PMID]
Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: A potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002; 27(5):699-711. [DOI:10.1016/S0893-133X(02)00346-9]
Higgins GA, Brown M, St John J, MacMillan C, Silenieks LB, Thevarkunnel S. Effects of 5-HT2C receptor modulation and the NA reuptake inhibitor atomoxetine in tests of compulsive and impulsive behaviour. Neuropharmacology. 2020; 170:108064. [DOI:10.1016/j.neuropharm.2020.108064] [PMID]
Talabari ZK, Khajavi MN, Rafiei H. [Reasons of Methadone Maintenance Therapy drop out in clients of Iranian national center for addiction studies (INCAS): A qualitative study (Persian)]. Iranian Journal of Psychiatry & Clinical Psychology. 2013; 18(4). https://ijpcp.iums.ac.ir/article-1-1935-fa.pdf
Nejati V. [Cognitive Abilities Questionnaire: Development and Evaluation of Psychometric Properties (Persian)]. Advances in Cognitive Sciences. 2013; 15(2):11-19. http://icssjournal.ir/article-1-289-en.html
Sofuoglu M, Poling J, Hill K, Kosten T. Atomoxetine attenuates dextroamphetamine effects in humans. The American Journal of Drug and Alcohol Abuse. 2009; 35(6):412-6. [DOI:10.3109/00952990903383961] [PMID] [PMCID]
Zhukovsky P, Morein-Zamir S, Ziauddeen H, Fernandez-Egea E, Meng C, Regenthal R, et al. Prefrontal Cortex Activation and Stopping Performance Underlie the Beneficial Effects of Atomoxetine on Response Inhibition in Healthy Volunteers and Those With Cocaine Use Disorder. Biological Psychiatry. Cognitive Neuroscience and Neuroimaging. 2021; S2451-9022(21)00252-4. [DOI:10.1016/j.bpsc.2021.08.010] [PMID]
Cantilena L, Kahn R, Duncan CC, Li S-H, Anderson A, Elkashef A. Safety of atomoxetine in combination with intravenous cocaine in cocaine-experienced participants. Journal of Addiction Medicine. 2012; 6(4):265. [DOI:10.1097/ADM.0b013e31826b767f] [PMID] [PMCID]
Stoops WW, Blackburn JW, Hudson DA, Hays LR, Rush CR. Safety, tolerability and subject-rated effects of acute intranasal cocaine administration during atomoxetine maintenance. Drug and Alcohol Dependence 2008; 92(1-3):282-5. [DOI:10.1016/j.drugalcdep.2007.07.005] [PMID] [PMCID]
Han DD, Gu HH. Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs. BMC Pharmacology. 2006; 6(1):1-7. [DOI:10.1186/1471-2210-6-6] [PMID] [PMCID]
Vanderschuren LJ, Beemster P, Schoffelmeer AN. On the role of noradrenaline in psychostimulant-induced psychomotor activity and sensitization. Psychopharmacology . 2003; 169(2):176-85. [DOI:10.1007/s00213-003-1509-8] [PMID]
Szabo ST, Blier P. Effect of the selective noradrenergic reuptake inhibitor reboxetine on the firing activity of noradrenaline and serotonin neurons. European Journal of Neuroscience. 2001; 13(11):2077-87. [DOI:10.1046/j.0953-816x.2001.01583.x] [PMID]
- Abstract Viewed: 511 times
- pdf Downloaded: 342 times