[18][19] Bupropion has several features that distinguish it from other antidepressants: it does not usually cause sexual dysfunction,[18] it is not associated with weight gain[18] and sleepiness,[20] and it is more effective than SSRIs at improving symptoms of hypersomnia and fatigue.

[2][3] Common adverse effects of bupropion with the greatest difference from placebo are dry mouth, nausea, constipation, insomnia, anxiety, tremor, and excessive sweating.

[39] In 2022, the US Food and Drug Administration (FDA) approved the combination dextromethorphan/bupropion to serve as a rapid-acting antidepressant in patients with major depressive disorder.

[20] Bupropion is more effective than selective serotonin reuptake inhibitors (SSRIs) at improving symptoms of hypersomnia and fatigue in depressed patients.

[53][further explanation needed] Prescribed as an aid for smoking cessation, bupropion reduces the severity of craving for nicotine and withdrawal symptoms[54][55][56] such as depressed mood, irritability, difficulty concentrating, and increased appetite.

[30][64][65][66] Similarly to atomoxetine, bupropion has a delayed onset of action for ADHD, and several weeks of treatment are required for therapeutic effects.

[71] According to an expert consensus recommendation from the International Society for the Study of Women's Sexual Health, bupropion can be considered as an off-label treatment for HSDD despite limited safety and efficacy data.

[75][76] Bupropion is not effective in the treatment of cocaine dependence,[77] but it is showing promise in reducing drug use in treating amphetamine-type stimulant use and cravings.

[10] The common adverse effects of bupropion with the greatest difference from placebo are dry mouth, nausea, constipation, insomnia, anxiety, tremor, and excessive sweating.

[26] For significant overdoses, seizures have been reported in about a third of all cases; other serious effects include hallucinations, loss of consciousness, and abnormal heart rhythms.

[10] Since bupropion is metabolized to hydroxybupropion by the enzyme CYP2B6, drug interactions with CYP2B6 inhibitors are possible: this includes such medications as paroxetine, sertraline, norfluoxetine (active metabolite of fluoxetine), diazepam, clopidogrel, and orphenadrine.

The reverse effect (decrease of bupropion and increase of hydroxybupropion) can be expected with CYP2B6 inducers such as carbamazepine, clotrimazole, rifampicin, ritonavir, St John's wort, and phenobarbital.

[112] As another example, the ratio of dextromethorphan (a drug that is mainly metabolized by CYP2D6) to its major metabolite dextrorphan increased approximately 35-fold when it was administered to people being treated with 300 mg/day bupropion.

[109][115] Bupropion prevents norepinephrine and dopamine release induced by amphetamines and has been found to reduce the subjective and sympathomimetic effects of methamphetamine in humans.

[2] However, it is thought to be related to the fact that bupropion is a norepinephrine–dopamine reuptake inhibitor (NDRI) and negative allosteric modulator of several nicotinic acetylcholine receptors.

[129] Pharmacological actions of bupropion, to a substantial degree, are due to its active metabolites hydroxybupropion, threo-hydrobupropion, and erythro-hydrobupropion that are present in the blood plasma at comparable or much higher levels.

[30] In accordance with its low DAT occupancy, no measurable dopamine release in the human brain was detected with bupropion (one 150 mg dose) in a PET study.

[132] These findings raise questions about the role of dopamine reuptake inhibition in the pharmacology of bupropion, and suggest that other actions may be responsible for its therapeutic effects.

[150] After oral administration, bupropion is rapidly and completely absorbed reaching the peak blood plasma concentration after 1.5 hours (tmax).

This might explain why abuse is unfeasible due to a short "high", as well as support the use of extended-release formulas to maintain a consistent concentration of bupropion.

The alpha position adjacent to the ketone is first brominated followed by nucleophilic displacement of the resulting alpha-bromoketone with t-butylamine and treated with hydrochloric acid to give bupropion as the hydrochloride salt in 75–85% overall yield.

Subsequently, the risk of seizures was found to be highly dose-dependent, and bupropion was re-introduced to the market in 1989 with a lower maximum recommended daily dose of 450 mg/day.

[184][185] In October 2007, two providers of consumer information on nutritional products and supplements, ConsumerLab.com and The People's Pharmacy, released the results of comparative tests of different brands of bupropion.

[186] The People's Pharmacy received multiple reports of increased side effects and decreased efficacy of generic bupropion, which prompted it to ask ConsumerLab.com to test the products in question.

[12][190][191] In 2009, the FDA issued a health advisory warning that the prescription of bupropion for smoking cessation has been associated with reports of unusual behavior changes, agitation, and hostility.

[194] In 2012, the US Justice Department announced that GlaxoSmithKline had agreed to plead guilty and pay a $3 billion fine, in part for promoting the unapproved use of Wellbutrin for weight loss and sexual dysfunction.

[197] Following EMA's call for an industry-wide review of medicines for the possible presence of nitrosamines,[198] GlaxoSmithKline paused batch release and distribution of bupropion 150 mg tablets in November 2022.

In July 2023, EMA raised the acceptable daily intake of nitrosamine impurities, leading GlaxoSmithKline to announce that distribution of bupropion 150 mg tablets would resume "across the EU and Europe" by the end of 2023.

[201] However, bupropion, by non-conventional routes of administration like injection or insufflation, has been reported to be misused in the United States and Canada, notably in prisons.

[207][208][209] Brand names include Wellbutrin,[10][11] Aplenzin,[12] Budeprion, Buproban, buprapan, Forfivo, Voxra, Zyban,[8] Bupron, Bupisure, Bupep, Smoquite, Elontril, Oribion and Buxon.