Chesika J. Crump, M.D. – PGY-3 Psychiatry Resident

Steven Lippmann, M.D. – Emeritus Professor of Psychiatry, University of Louisville School of Medicine, Louisville, Kentucky

Bupropion was approved for clinical prescribing in 1985. This antidepressant medication has been widely prescribed for treating adults with major depression, seasonal affective disorder, and promotion of smoking cessation. It is prescribed also for many off-label indications, such as antidepressant drug-induced sexual dysfunction, attention-deficit/hyperactivity disorder, bipolar depression, and obesity.1 Bupropion evidences a pharmacology that may target alternative applications.
           While bupropion’s mechanism of action is not fully clear, it inhibits norepinephrine-dopamine reuptake by blocking the norepinephrine and dopamine reuptake pumps. It does not inhibit monoamine oxidase or the reuptake of serotonin. Metabolized by cytochrome P-2D6 enzymes, active metabolites are excreted in urine.1
           Beyond psychiatry, bupropion pharmacotherapies are also prescribed by neurologists and internists. Recently approved is a combined dextromethorphan-bupropion medicine indicated for patients with major depression, agitation during Alzheimer’s disease, and mitigating nicotine withdrawal. Dextromethorphan is a N-methyl-D-aspartate (NMDA) receptor antagonist, serotonin norepinephrine reuptake inhibitor, and may induce many other actions. Abnormal glutamate levels are identified in the cortex among depressed subjects using magnetic resonance spectroscopy. This pharmaceutical also affects the glutamatergic system by blocking the NMDA receptor.2
           A combination drug of bupropion and naltrexone is being investigated for usefulness during methamphetamine abuse. One randomized trial measuring methamphetamine-negative urine samples evidenced little difference compared to placebo treatment.3 Further research is ongoing.
Another drug study combining bupropion and naltrexone has revealed efficacy in helping people diminish binge eating disorders and assisting others with weight loss. One trial comparing this combination versus placebo, with and without behavioral weight loss therapy (BWT), revealed that bupropion/naltrexone with BWT resulted in significantly greater remission rates and more weight loss than alternative therapies.4
Other studies document that this same combination medication is effective as an augmenting agent for antidepressant drug effects, including decreasing antidepressant agent-induced weight gain. These trials evidenced some efficacy, but the results were not significant.5 Bupropion with naltrexone investigations were inconclusive at managing antipsychotic drug-induced weight gain in patients with psychotic disorders.6
The pharmacology of bupropion is still being investigated. The results of these studies remain undetermined.


1.    Huecker MR, Smiley A, Saadabadi A. Bupropion. [Updated 2022 Oct 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470212/ . Date last accessed 11/28/2022
2.    Iosifescu DV, Jones, A, O’Gorman C, et al. Efficacy and safety of AXS-05 (dextromethorphan-bupropion) in patients with major depressive disorder: a phase 3 randomized clinical trial (GEMINI). J Clin Psychiatry. 2022;83(4):21m14345. Date last accessed 11/28/2022
3.    Trivedi MH, Walker R, Ling W, et al. Bupropion and Naltrexone in Methamphetamine Use Disorder. N Engl J Med. 2021;384(2):140-153. doi:10.1056/NEJMoa2020214. Date last accessed 11/29/2022
4.    Grilo CM, Lydecker JA, Fineberg SK, et al. Naltrexone-Bupropion and Behavior Therapy, Alone and Combined, for Binge-Eating Disorder: Randomized Double-Blind Placebo-Controlled Trial [published online ahead of print, 2022 Oct 26]. Am J Psychiatry.2022;appiajp20220267. doi:10.1176/appi.ajp.20220267. Date last accessed 11/28/2022
5.    McIntyre RS, Paron E, Burrows M, et al. Psychiatric Safety and Weight Loss Efficacy of Naltrexone/bupropion as Add-on to Antidepressant Therapy in Patients with Obesity or Overweight. J Affect Disord. 2021;289:167-176. doi:10.1016/j.jad.2021.04.017. Date last accessed 11/28/2022
6.    Lee K, Abraham S, Cleaver R. A systematic review of licensed weight-loss medications in treating antipsychotic-induced weight gain and obesity in schizophrenia and psychosis. Gen Hosp Psychiatry. 2022;78:58-67. doi:10.1016/j.genhosppsych.2022.07.006. Date last accessed 11/28/2022