BUPROPION FOR ADHD: MECHANISMS OF ACTION AND ITS POTENTIAL AS AN ALTERNATIVE TREATMENT — A REVIEW
Abstract
Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common psychiatric disorders in childhood. Its core symptoms are related to executive dysfunction and include inattention, hyperactivity, and impulsivity. As a neurodevelopmental disorder, ADHD requires chronic, long-term treatment. Therefore, it is essential to identify the most effective and safest therapeutic options that minimize the side effects of prolonged pharmacological intervention.
Aim of the Study: This article examines the potential role of bupropion in ADHD treatment, focusing on its mechanism of action, efficacy in symptom alleviation, and possible side effects.
Materials and Methods: This review was conducted using multiple databases, including PubMed, Scopus, and Google Scholar. The search terms used were: “ADHD”, “bupropion”, “methylphenidate”, “comorbidity”, “side effects”, and “non-stimulants”.
Summary of Current Knowledge: ADHD should be managed with both pharmacological and non-pharmacological methods. While methylphenidate is considered first-line pharmacological treatment, it is associated with a relatively high discontinuation rate. Bupropion, as an alternative, may offer effective symptom relief and better tolerability in patients who experience severe side effects from stimulant medications.
Conclusions: Bupropion appears to be effective in treating ADHD compared to placebo and is generally well tolerated, especially in contrast to first-line stimulant treatments. It may be a viable alternative for patients who do not tolerate stimulants. However, further research using objective comparative methods is necessary to evaluate the effectiveness and side effect profiles of bupropion versus methylphenidate.
References
Mohammadi, M.-R., Zarafshan, H., Khaleghi, A., Ahmadi, N., Hooshyari, Z., Mostafavi, S.-A., Ahmadi, A., Alavi, S.-S., Shakiba, A., & Salmanian, M. (2019). Prevalence of ADHD and Its Comorbidities in a Population-Based Sample. Journal of Attention Disorders, 25(8), 1058-1067. https://doi.org/10.1177/1087054719886372 (Original work published 2021)
Rowland, A. S., Skipper, B. J., Umbach, D. M., Rabiner, D. L., Campbell, R. A., Naftel, A. J., & Sandler, D. P. (2013). The Prevalence of ADHD in a Population-Based Sample. Journal of Attention Disorders, 19(9), 741-754. https://doi.org/10.1177/1087054713513799 (Original work published 2015)
Magnus W, Anilkumar AC, Shaban K. Attention Deficit Hyperactivity Disorder. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441838/
Song P, Zha M, Yang Q, Zhang Y, Li X, Rudan I; Global Health Epidemiology Reference Group (GHERG). The prevalence of adult attention-deficit hyperactivity disorder: A global systematic review and meta-analysis. J Glob Health. 2021 Feb 11;11:04009. doi: 10.7189/jogh.11.04009. PMID: 33692893; PMCID: PMC7916320.
Doernberg E, Hollander E. Neurodevelopmental Disorders (ASD and ADHD): DSM-5, ICD-10, and ICD-11. CNS Spectrums. 2016;21(4):295-299. doi:10.1017/S1092852916000262
Drechsler R, Brem S, Brandeis D, Grünblatt E, Berger G, Walitza S. ADHD: Current Concepts and Treatments in Children and Adolescents. Neuropediatrics. 2020 Oct;51(5):315-335. doi: 10.1055/s-0040-1701658. Epub 2020 Jun 19. PMID: 32559806; PMCID: PMC7508636.
Russell, J. (Ed.). (1997). Autism as an executive disorder. Oxford University Press.
Hosenbocus S, Chahal R. A review of executive function deficits and pharmacological management in children and adolescents. J Can Acad Child Adolesc Psychiatry. 2012 Aug;21(3):223-9. PMID: 22876270; PMCID: PMC3413474.
Pennington BF, Ozonoff S. Executive functions and developmental psychopathology. J Child Psychol Psychiatry. 1996 Jan;37(1):51-87. doi: 10.1111/j.1469-7610.1996.tb01380.x. PMID: 8655658.
Katzman MA, Bilkey TS, Chokka PR, Fallu A, Klassen LJ. Adult ADHD and comorbid disorders: clinical implications of a dimensional approach. BMC Psychiatry. 2017 Aug 22;17(1):302. doi: 10.1186/s12888-017-1463-3. PMID: 28830387; PMCID: PMC5567978.
Kaisari P, Dourish CT, Higgs S. Attention Deficit Hyperactivity Disorder (ADHD) and disordered eating behaviour: A systematic review and a framework for future research. Clin Psychol Rev. 2017 Apr;53:109-121. doi: 10.1016/j.cpr.2017.03.002. Epub 2017 Mar 6. PMID: 28334570.
Nazarova VA, Sokolov AV, Chubarev VN, Tarasov VV, Schiöth HB. Treatment of ADHD: Drugs, psychological therapies, devices, complementary and alternative methods as well as the trends in clinical trials. Front Pharmacol. 2022 Nov 17;13:1066988. doi: 10.3389/fphar.2022.1066988. PMID: 36467081; PMCID: PMC9713849.
Kosheleff AR, Mason O, Jain R, Koch J, Rubin J. Functional Impairments Associated With ADHD in Adulthood and the Impact of Pharmacological Treatment. J Atten Disord. 2023 May;27(7):669-697. doi: 10.1177/10870547231158572. Epub 2023 Mar 6. PMID: 36876491; PMCID: PMC10173356.
Nickel K, Maier S, Endres D, Joos A, Maier V, Tebartz van Elst L, Zeeck A. Systematic Review: Overlap Between Eating, Autism Spectrum, and Attention-Deficit/Hyperactivity Disorder. Front Psychiatry. 2019 Oct 10;10:708. doi: 10.3389/fpsyt.2019.00708. PMID: 31649563; PMCID: PMC6796791.
Verbeeck W, Bekkering GE, Van den Noortgate W, Kramers C. Bupropion for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2017 Oct 2;10(10):CD009504. doi: 10.1002/14651858.CD009504.pub2. PMID: 28965364; PMCID: PMC6485546.
Huecker MR, Smiley A, Saadabadi A. Bupropion. 2024 Sep 2. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 29262173.
Enriquez-Geppert S, Smit D, Pimenta MG, Arns M. Neurofeedback as a Treatment Intervention in ADHD: Current Evidence and Practice. Curr Psychiatry Rep. 2019 May 28;21(6):46. doi: 10.1007/s11920-019-1021-4. PMID: 31139966; PMCID: PMC6538574.
Catalá-López F, Hutton B, Núñez-Beltrán A, Page MJ, Ridao M, Macías Saint-Gerons D, Catalá MA, Tabarés-Seisdedos R, Moher D. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials. PLoS One. 2017 Jul 12;12(7):e0180355. doi: 10.1371/journal.pone.0180355. PMID: 28700715; PMCID: PMC5507500.
Austerman J. ADHD and behavioral disorders: Assessment, management, and an update from DSM-5. Cleve Clin J Med. 2015 Nov;82(11 Suppl 1):S2-7. doi: 10.3949/ccjm.82.s1.01. PMID: 26555810.
Thapar A, Cooper M, Eyre O, Langley K. What have we learnt about the causes of ADHD? J Child Psychol Psychiatry. 2013 Jan;54(1):3-16. doi: 10.1111/j.1469-7610.2012.02611.x. Epub 2012 Sep 11. PMID: 22963644; PMCID: PMC3572580.
Volkow ND, Wang GJ, Kollins SH, Wigal TL, Newcorn JH, Telang F, Fowler JS, Zhu W, Logan J, Ma Y, Pradhan K, Wong C, Swanson JM. Evaluating dopamine reward pathway in ADHD: clinical implications. JAMA. 2009 Sep 9;302(10):1084-91. doi: 10.1001/jama.2009.1308. Erratum in: JAMA. 2009 Oct 7;302(13):1420. PMID: 19738093; PMCID: PMC2958516.
Kollins SH, Adcock RA. ADHD, altered dopamine neurotransmission, and disrupted reinforcement processes: implications for smoking and nicotine dependence. Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jul 3;52:70-8. doi: 10.1016/j.pnpbp.2014.02.002. Epub 2014 Feb 18. PMID: 24560930; PMCID: PMC4004668.
Sigurdardottir HL, Kranz GS, Rami-Mark C, James GM, Vanicek T, Gryglewski G, Kautzky A, Hienert M, Traub-Weidinger T, Mitterhauser M, Wadsak W, Hacker M, Rujescu D, Kasper S, Lanzenberger R. Effects of norepinephrine transporter gene variants on NET binding in ADHD and healthy controls investigated by PET. Hum Brain Mapp. 2016 Mar;37(3):884-95. doi: 10.1002/hbm.23071. Epub 2015 Dec 17. PMID: 26678348; PMCID: PMC4949568.
Faraone SV. The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. Neurosci Biobehav Rev. 2018 Apr;87:255-270. doi: 10.1016/j.neubiorev.2018.02.001. Epub 2018 Feb 8. PMID: 29428394; PMCID: PMC8063758.
Lee J, Grizenko N, Bhat V, Sengupta S, Polotskaia A, Joober R. Relation between therapeutic response and side effects induced by methylphenidate as observed by parents and teachers of children with ADHD. BMC Psychiatry. 2011 Apr 21;11:70. doi: 10.1186/1471-244X-11-70. PMID: 21510895; PMCID: PMC3095543.
Mechler K, Banaschewski T, Hohmann S, Häge A. Evidence-based pharmacological treatment options for ADHD in children and adolescents. Pharmacol Ther. 2022 Feb;230:107940. doi: 10.1016/j.pharmthera.2021.107940. Epub 2021 Jun 23. PMID: 34174276.
Miklós M, Futó J, Komáromy D, Balázs J. Executive Function and Attention Performance in Children with ADHD: Effects of Medication and Comparison with Typically Developing Children. Int J Environ Res Public Health. 2019 Oct 10;16(20):3822. doi: 10.3390/ijerph16203822. PMID: 31658722; PMCID: PMC6843761.
Clark A, Tate B, Urban B, Schroeder R, Gennuso S, Ahmadzadeh S, McGregor D, Girma B, Shekoohi S, Kaye AD. Bupropion Mediated Effects on Depression, Attention Deficit Hyperactivity Disorder, and Smoking Cessation. Health Psychol Res. 2023 Jul 1;11:81043. doi: 10.52965/001c.81043. PMID: 37405312; PMCID: PMC10317506.
Shalabi AR, Walther D, Baumann MH, Glennon RA. Deconstructed Analogues of Bupropion Reveal Structural Requirements for Transporter Inhibition versus Substrate-Induced Neurotransmitter Release. ACS Chem Neurosci. 2017 Jun 21;8(6):1397-1403. doi: 10.1021/acschemneuro.7b00055. Epub 2017 Feb 27. PMID: 28220701; PMCID: PMC7261150.
Stahl SM, Pradko JF, Haight BR, Modell JG, Rockett CB, Learned-Coughlin S. A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor. Prim Care Companion J Clin Psychiatry. 2004;6(4):159-166. doi: 10.4088/pcc.v06n0403. PMID: 15361919; PMCID: PMC514842.
Hamedi M, Mohammdi M, Ghaleiha A, Keshavarzi Z, Jafarnia M, Keramatfar R, Alikhani R, Ehyaii A, Akhondzadeh S. Bupropion in adults with Attention-Deficit/Hyperactivity Disorder: a randomized, double-blind study. Acta Med Iran. 2014;52(9):675-80. PMID: 25325205.
Wilens TE, Haight BR, Horrigan JP, Hudziak JJ, Rosenthal NE, Connor DF, Hampton KD, Richard NE, Modell JG. Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study. Biol Psychiatry. 2005 Apr 1;57(7):793-801. doi: 10.1016/j.biopsych.2005.01.027. PMID: 15820237.
Wilens TE, Prince JB, Waxmonsky J, Doyle R, Spencer T, Martelon M, Evans M. An Open Trial of Sustained Release Bupropion for Attention-Deficit/Hyperactivity Disorder in Adults with ADHD plus Substance Use Disorders. J ADHD Relat Disord. 2010 Apr 1;1(3):25-35. PMID: 22500195; PMCID: PMC3322541.
Maneeton N, Maneeton B, Srisurapanont M, Martin SD. Bupropion for adults with attention-deficit hyperactivity disorder: meta-analysis of randomized, placebo-controlled trials. Psychiatry Clin Neurosci. 2011 Dec;65(7):611-7. doi: 10.1111/j.1440-1819.2011.02264.x. PMID: 22176279.
Cortese S, Adamo N, Del Giovane C, Mohr-Jensen C, Hayes AJ, Carucci S, Atkinson LZ, Tessari L, Banaschewski T, Coghill D, Hollis C, Simonoff E, Zuddas A, Barbui C, Purgato M, Steinhausen HC, Shokraneh F, Xia J, Cipriani A. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018 Sep;5(9):727-738. doi: 10.1016/S2215-0366(18)30269-4. Epub 2018 Aug 7. PMID: 30097390; PMCID: PMC6109107.
Conners CK, Casat CD, Gualtieri CT, Weller E, Reader M, Reiss A, Weller RA, Khayrallah M, Ascher J. Bupropion hydrochloride in attention deficit disorder with hyperactivity. J Am Acad Child Adolesc Psychiatry. 1996 Oct;35(10):1314-21. doi: 10.1097/00004583-199610000-00018. PMID: 8885585.
Daviss WB, Bentivoglio P, Racusin R, Brown KM, Bostic JQ, Wiley L. Bupropion sustained release in adolescents with comorbid attention-deficit/hyperactivity disorder and depression. J Am Acad Child Adolesc Psychiatry. 2001 Mar;40(3):307-14. doi: 10.1097/00004583-200103000-00010. PMID: 11288772.
Jafarinia M, Mohammadi MR, Modabbernia A, Ashrafi M, Khajavi D, Tabrizi M, Yadegari N, Akhondzadeh S. Bupropion versus methylphenidate in the treatment of children with attention-deficit/hyperactivity disorder: randomized double-blind study. Hum Psychopharmacol. 2012 Jul;27(4):411-8. doi: 10.1002/hup.2242. PMID: 22806822.
Barrickman LL, Perry PJ, Allen AJ, Kuperman S, Arndt SV, Herrmann KJ, Schumacher E. Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1995 May;34(5):649-57. doi: 10.1097/00004583-199505000-00017. PMID: 7775360.
Stuhec M, Munda B, Svab V, Locatelli I. Comparative efficacy and acceptability of atomoxetine, lisdexamfetamine, bupropion and methylphenidate in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis with focus on bupropion. J Affect Disord. 2015 Jun 1;178:149-59. doi: 10.1016/j.jad.2015.03.006. Epub 2015 Mar 13. PMID: 25813457.
Maji S, Mishra A, Ramasubbu MK, Mohapatra D, Maiti R. Efficacy and safety of monoamine reuptake inhibitors in attention deficit hyperactivity disorder: A Bayesian network meta-analysis. J Psychiatr Res. 2024 Aug;176:403-410. doi: 10.1016/j.jpsychires.2024.06.048. Epub 2024 Jun 27. PMID: 38950507.
Verpeut JL, Bello NT. Drug safety evaluation of naltrexone/bupropion for the treatment of obesity. Expert Opinion on Drug Safety. 2014;13(6):831-841. http://doi.org/10.1517/14740338.2014.909405
Aubin, HJ. Tolerability and Safety of Sustained-Release Bupropion in the Management of Smoking Cessation. Drugs 62 (Suppl 2), 45–52 (2002). https://doi.org/10.2165/00003495-200262002-00005
Trivedi MH, Walker R, Ling W, Dela Cruz A, Sharma G, Carmody T, Ghitza UE, Wahle A, Kim M, Shores-Wilson K, Sparenborg S, Coffin P, Schmitz J, Wiest K, Bart G, Sonne SC, Wakhlu S, Rush AJ, Nunes EV, Shoptaw S. Bupropion and Naltrexone in Methamphetamine Use Disorder. N Engl J Med. 2021 Jan 14;384(2):140-153. doi: 10.1056/NEJMoa2020214. PMID: 33497547; PMCID: PMC8111570.
Ross, S., & Williams, D. (2005). Bupropion: risks and benefits. Expert Opinion on Drug Safety, 4(6), 995–1003. https://doi.org/10.1517/14740338.4.6.995
Views:
6
Downloads:
1
Copyright (c) 2025 Martyna Narożniak, Bartłomiej Czerwiec, Julia Skowrońska-Borsuk, Adam Borsuk, Joanna Pergoł, Malwina Wojtas, Adrianna Ewa Pękacka, Julia Borkowska, Zuzanna Krupa, Julia Sposób
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
