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Bupropion for ADHD


Bupropion for ADHD

Trade names: Elontril, Wellbutrin, Zyban
Active ingredient name before 2000: Amfebutamone

The active ingredient bupropion is an amphetamine derivative.1
It is not classically classified as a stimulant, although it has a stimulating effect - like nicotine and caffeine.
Bupropion does not require a narcotic prescription.

Bupropion is active as the active ingredient itself and is metabolized to hydroxybupropion as well as threohydrobupropion. All three are potent norepinephrine reuptake inhibitors.2 Hydroxybupropion, for example, can reach concentrations up to 16-20 times that of bupropion.[7]

Bupropion acts as a dopamine and norepinephrine reuptake inhibitor. In rats, the dopamine : norepinephrine effect ratio is 2:13

However, one study showed a very weak affinity for DAT in humans (DAT exposure of 14%), so it is questionable whether bupropion actually acts as a dopamine reuptake inhibitor in humans at usual drug doses.4 In rhesus monkeys, on the other hand, DAT occupancy was found to be 85%, and 35% in rodents5
These findings could conclusively explain why bupropion is not very successfully used as an ADHD medication in practice and requires very high doses. Therefore, bupropion should only be used for ADHD when all better alternatives are ineffective.

In addition, bupropion also has a weak dopamine and norepinephrine secreting effect,6 as well as a minor serotonergic effect.

Bupropion decreases TNF-alpha levels.7

Bupropion is further a non-competitive antagonist of several nicotinic acetylcholine receptors (AChR).8

Bupropion is reported to have comparable effect sizes with respect to ADHD as methylphenidate, according to three studies; another study found a weaker effect than methylphenidate9

Bupropion has an (even) stronger activating / drive-increasing effect than nortryptiline and is thus indicated for more severe symptoms of ADHD-I (without hyperactivity). The administration of bupropion in ADHD-HI or ADHD-C sufferers (with hyperactivity) can trigger aggression or jitteriness.

Two studies in 30 and 47 adults with AD(HS) with 300 mg and up to 400 mg bupropion/day, respectively, found trends for efficacy of bupropion in ADHD without statistical significance.1011

Useful results when used alone in ADHD have been found in practice only at quite high doses of 400 to 450 mg/day, which is why the updated European consensus on the diagnosis and treatment of ADHD in adults recommends using bupropion only when neither MPH nor amphetamine medications are effective (double nonresponding).12

Bupropion can be a helpful adjunct to stimulant medication in individual cases.
In combination drug use for ADHD, a much lower dosage is required than would be usual for use as an antidepressant.
In ADHD with comorbid depression, bupropion may be helpful.

In depression, a serum hydroxybupropion concentration greater than 860 ng/ml should be achieved for a positive response. The therapeutic reference range for depression is between 850 and 1500 ng/ml hydroxybupropion.5

Bupropion is a CYP2D6 inhibitor, so caution should be exercised when administering other drugs that affect CYP2B6. Concomitant administration of CYP2B6 inhibitors such as clopidogrel or ticlopidine increased bupropion AUC levels by 60% and 90%, respectively. Concomitant administration of carbamazepine (inducer of CYP2B6 and CYP3A4) decreased bupropion AUC by 90% and an increase hydroxybupropion AUC by 50%.5


  2. Caye, Swanson, Coghill, Rohde (2019): Treatment strategies for ADHD: an evidence-based guide to select optimal treatment. Mol Psychiatry. 2019 Mar;24(3):390-408. doi: 10.1038/s41380-018-0116-3. PMID: 29955166.

  3. Wikipedia: Buprorion

  4. Meyer, Goulding, Wilson, Hussey, Christensen, Houle (2002): Bupropion occupancy of the dopamine transporter is low during clinical treatment. Psychopharmacology (Berl). 2002 Aug;163(1):102-5. doi: 10.1007/s00213-002-1166-3. PMID: 12185406.

  5. Eap, Gründer, Baumann, Ansermot, Conca, Corruble, Crettol, Dahl, de Leon, Greiner, Howes, Kim, Lanzenberger, Meyer, Moessner, Mulder, Müller, Reis, Riederer, Ruhe, Spigset, Spina, Stegman, Steimer, Stingl, Suzen, Uchida, Unterecker, Vandenberghe, Hiemke (2021): Tools for optimising pharmacotherapy in psychiatry (therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests): focus on antidepressants. World J Biol Psychiatry. 2021 Oct;22(8):561-628. doi: 10.1080/15622975.2021.1878427. PMID: 33977870.

  6. Arias, Santamaría, Ali (2009): Chapter 9 – Pharmacological and Neurotoxicological Actions Mediated By Bupropion and Diethylpropion; International Review of Neurobiology; Volume 88, 2009, Pages 223-255

  7. Wilkes (2006): Bupropion. Drugs Today (Barc). 2006 Oct;42(10):671-81.

  8. Arias, Santamaría, Ali (2009); Pharmacological and neurotoxicological actions mediated by bupropion and diethylpropion. Int Rev Neurobiol. 2009;88:223-55. doi: 10.1016/S0074-7742(09)88009-4. PMID: 19897080.

  9. Ng (2017): A Systematic Review of the Use of Bupropion for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. J Child Adolesc Psychopharmacol. 2017 Mar;27(2):112-116. doi: 10.1089/cap.2016.0124. EPMID: 27813651. REVIEW

  10. Kuperman, Perry, Gaffney, Lund, Bever-Stille, Arndt, Holman, Moser, Paulsen (2001): Bupropion SR vs. methylphenidate vs. placebo for attention deficit hyperactivity disorder in adults. Ann Clin Psychiatry. 2001 Sep;13(3):129-34. doi: 10.1023/a:1012239823148. PMID: 11791949. n = 30

  11. Reimherr, Hedges, Strong, Marchant, Williams (2005): Bupropion SR in adults with ADHD: a short-term, placebo-controlled trial. Neuropsychiatr Dis Treat. 2005 Sep;1(3):245-51. PMID: 18568102; PMCID: PMC2416755.

  12. Kooij, Bijlenga, Salerno, Jaeschke, Bitter, Balázs, Thome, Dom, Kasper, Filipe, Stes, Mohr, Leppämäki, Brugué, Bobes, Mccarthy, Richarte, Philipsen, Pehlivanidis, Niemela, Styr, Semerci, Bolea-Alamanac, Edvinsson, Baeyens, Wynchank, Sobanski, Philipsen, McNicholas, Caci, Mihailescu, Manor, Dobrescu, Krause, Fayyad, Ramos-Quiroga, Foeken, Rad, Adamou, Ohlmeier, Fitzgerald, Gill, Lensing, Mukaddes, Brudkiewicz, Gustafsson, Tania, Oswald, Carpentier, De Rossi, Delorme, Simoska, Pallanti, Young, Bejerot, Lehtonen, Kustow, Müller-Sedgwick, Hirvikoski, Pironti, Ginsberg, Félegeházy, Garcia-Portilla, Asherson (2018): Updated European Consensus Statement on diagnosis and treatment of adult ADHD, European Psychiatrie, European Psychiatry 56 (2019) 14–34,, Seite 22, 7.4.6.