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Classification: A

Drug products: Bupropion Accord, Bupropion Bluefish, Bupropion Ebb, Bupropion hydrochloride, Bupropion Orion, Bupropion Paranova, Bupropion Pharmachim, Bupropion Sandoz, Bupropion Teva, Bupropion Zentiva, Mysimba, Wellbutrin, WELLBUTRIN, Voxra, Zyban, Zyban®

ATC code: A08AA62, N06AX12

Substances: bupropion, bupropion hydrochloride


Most studies show that the effect of bupropion treatment is equal among men and women. However, some studies have shown better effect among men but also one study indicating a better effect among women. Prescribing of bupropion is higher among women in Sweden as well as internationally.

Additional information

There seems to be gender differences in smoking cessation. One randomized controlled study (649 men, 875 women) showed higher education in women and no previous depression or a relative lack of negative affect such as anxiousness, irritability and hopelessness during quitting in men to be predictors for success in smoking cessation [1].A cross-sectional survey study of smokers (451 men, 222 women) showed that women had higher expectancies of effect of pharmacotherapy and a greater motivation to quit smoking than men [2]. However, a high degree of motivation was not equal to success in smoking cessation. In a controlled trial of the impact of cost (negative)- or benefit (positive)-messages on smoking cessation rate (120 men, 129 women), participants were treated with bupropion and randomized to receive messages addressing either benefits of quitting or costs of continuing smoking.  Women who expected low smoking cessation discomfort and received benefit-messages had a higher quit rate than women who received cost-messages (68.4% vs 31.6%). Type of message had no effect in women who expected high smoking cessation discomfort and in men regardless of expectancies [3].

Pharmacokinetics and dosing

In a study of single-dose bupropion in smoking and nonsmoking adults (18 men, 16 women) the half-life for bupropion that was 15% shorter in men than in women (17 ± 3 hours and 20 ± 5 hours, respectively) while the AUC, Cmax, t max and the metabolite hydroxybupropion (approximately 50% as effective as bupropion) were similar in men and women [4, 5]. In contrast to this, another study of single-dose of bupropion in smoking and nonsmoking teenagers (37 males, 38 females) showed that the mean AUC and Cmax were higher in women than in men. The bupropion volume of distribution (Vd) normalized to body weight and the half-life were also higher in women than in men, while clearance normalized to body weight (CL/f) was the only parameter showing similar values in men and women. The authors suggested that the protein binding and the metabolism by the CYP2B6 isoenzyme could explain the sex difference [6]. Despite the pharmacokinetic differences of bupropion, the clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested [7].


Studies show conflicting results regarding sex differences of smoking cessation rate. Some studies show a similar smoking cessation rate in men and women. Two randomized controlled trials (482 men, 475 women) [8, 9] and one survey study (94 men, 129 women) [10] comparing bupropion treatment with nicotine replacement therapy or cognitive behavioral therapy showed no difference in smoking cessation between men and women. In two randomized controlled trials of supportive counseling combined with varenicline 2 mg/day (in all 228 men, 209 women), bupropion 300 mg/day (in all 252 men, 179 women) or placebo (in all 253 men, 197 women) the smoking cessation frequency was similar in men and women [11, 12].However, there are also studies showing a higher quit rate in men than in women.  In a randomized placebo controlled trial of bupropion treatment (224 men, 380 women) women were less likely to quit smoking [13]. In another randomized controlled trial (629 men, 875 women) the risk of relapse was higher in women (odds ratio 1.29) even though the initial quit rate was similar in men and women [14]. In an observational study of a 6-week cognitive behavioral program with opportunity to add nicotine replacement therapy, bupropion or varenicline (552 men, 730 women), predictors for success in smoking cessation were investigated. Follow-up interviews carried out at 12, 26, and 52 weeks showed that women were 1.5 times more likely to continue smoking than men despite similar baseline characteristics and treatments [15].In a double-blind trial excluding responders to one week nicotine patch treatment, smokers were randomized to varenicline (46 men, 62 women) or a combination of varenicline and bupropion (55 men, 58 women). The result showed the quit rate with the combination of  varenicline and bupropion to be higher in men (odds ratio compared to monotherapy for successful quitting 4.3 in men and 0.9 in women), contrary, the quit rate with varenicline in monotherapy seemed to be higher in women than in men [16].

Adverse effects

In a placebo-controlled clinical trial of smoking cessation discomfort, volunteers highly motivated to quit were randomized to treatment with monotherapy (nicotine lozenge, nicotine patch or bupropion), combined therapy (lozenge+patch or lozenge+bupropion) or placebo (in total, 412 men, 592 women). Compared to men, women experienced more cessation fatigue, had a stronger association between craving and cessation fatigue, and a greater reduction of symptoms with pharmacotherapy. In men the association between cessation fatigue and negative affect (such as anxiousness, irritability and hopelessness during quitting), and reduction of symptoms with monotherapy was greater, with an even more pronounced sex difference with the combined therapy [17].No sex differences in self-harm was observed in cohort study during 1.5 years of 80 660 smokers (approximately equal sex distribution) who were prescribed nicotine replacement therapy, varenicline or bupropion [18].Women who quit smoking without pharmacological treatment have been shown to gain 1 kg more than men [19].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

In a study patients with major depressive disorder (28 men, 25 women) and non-depressed controls (20 men, 23 women) were randomized to treatment with bupropion, escitalopram or bupropion+ escitalopram during 12 weeks. The results showed sustained attention/concentration to be higher in women than in men and that reaction time to unexpected stimuli at baseline was predictive of depression treatment response in men but not in women [20].A Swedish study of smokers treated with varenicline (8639 men, 9287 women) or bupropion (8674 men, 9252 women) showed  that the rate of cardiovascular events per 1000 person years was higher in women than in men six months after treatment with varenicline (4.9 men, 9.1 women) or bupropion (5.8 men, 8.6 women) [21]. No comparison to non-treated smokers was made.A cross-sectional survey study that investigated awareness of smoking cessation treatments among parents of pre-adolescent children showed that female smokers had higher awareness of older nicotine replacement therapies, acupuncture and a quit smoking telephone support line than men. There was no sex difference in awareness of varenicline, bupropion, nortriptyline or newer nicotine replacement therapies. Male smokers experienced to a greater degree than female smokers that nicotine gum and lozenge was effective while other treatments were experienced as equally effective among men and women [22].Several studies have shown that the use of any smoking cessation medication (varenicline, bupropion or nicotine replacement therapies) to quit was less likely in men than in women [18, 23-26] with the exception of one study where prescription of varenicline and bupropion was equally common in men and women [27].A randomized placebo-controlled study in African American light smokers receiving health counseling and bupropion (81 men, 133 women) showed that the risk of discontinuing medication at treatment week 3 was more common in men than in women (odds ratio 2.02) [28].

Updated: 2020-08-28

Date of litterature search: 2015-08-17


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Authors: Maria Enghag, Desirée Loikas

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson