Bupropion, an amphetamine, is authorised as an aid to smoking cessation, despite its negative harm-benefit balance. In 2004, data from a registry of pregnancies exposed to bupropion drew attention to an increased risk of congenital heart defects. In 2010, a case-control study including more than 10 000 children showed a higher incidence of in utero exposure to bupropion among children who had congenital left heart defects. Other, less reliable studies did not show such a link. In practice, this risk of congenital heart defects is yet another reason to avoid using bupropion, including during pregnancy, and to monitor the cardiac status of exposed fetuses and newborns.

BACKGROUND AND METHODS Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or "target quit date") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less. RESULTS At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01)-- but not the 100-mg group (P=0.09)-- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups. CONCLUSIONS A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year.

BACKGROUND AND METHODS: Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8. RESULTS: The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache. CONCLUSIONS: Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant.

BACKGROUND After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another. METHODS We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the study. Scores on the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16), obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less at exit) and response (a reduction of 50 percent or more on baseline scores). RESULTS Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events. CONCLUSIONS After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression.(ClinicalTrials.gov number, NCT00021528.).

BACKGROUND Although clinicians frequently add a second medication to an initial, ineffective antidepressant drug, no randomized controlled trial has compared the efficacy of this approach. METHODS We randomly assigned 565 adult outpatients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy (mean final dose, 55 mg per day) to receive sustained-release bupropion (at a dose of up to 400 mg per day) as augmentation and 286 to receive buspirone (at a dose of up to 60 mg per day) as augmentation. The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of this study; scores were obtained over the telephone by raters blinded to treatment assignment. The 16-item Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR-16) was used to determine the secondary outcomes of remission (defined as a score of less than 6 at the end of this study) and response (a reduction in baseline scores of 50 percent or more). RESULTS The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and 32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P<0.04), a lower QIDS-SR-16 score at the end of this study (8.0 vs. 9.1, P<0.02), and a lower dropout rate due to intolerance (12.5 percent vs. 20.6 percent, P<0.009). CONCLUSIONS Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events.(ClinicalTrials.gov number, NCT00021528.).

BACKGROUND Smoking relapse is common after successful pharmacologic treatment for smoking cessation. No previous studies have examined long-term drug therapy used expressly for prevention of smoking relapse. OBJECTIVE To evaluate the efficacy of bupropion to prevent smoking relapse. DESIGN Randomized, placebo-controlled trial. PARTICIPANTS 784 healthy community volunteers who were motivated to quit smoking and who smoked at least 15 cigarettes per day. INTERVENTION The participants received open-label, sustained-release bupropion, 300 mg/d, for 7 weeks. Participants who were abstinent throughout week 7 of open-label treatment were randomly assigned to receive bupropion, 300 mg/d, or placebo for 45 weeks and were subsequently followed for an additional year after the conclusion of the medication phase. Participants were briefly counseled at all follow-up visits. At the end of open-label bupropion treatment, 461 of 784 participants (58.8%) were abstinent from smoking. MEASUREMENT Self-reported abstinence was confirmed by an expired air carbon monoxide concentration of 10 parts per million or less. RESULTS The point prevalence of smoking abstinence was significantly higher in the bupropion group than in the placebo group at the end (week 52) of drug therapy (55.1% vs. 42.3%, respectively; P = 0.008) and at week 78 (47.7% vs. 37.7%; P = 0.034) but did not differ at the final (week 104) follow-up visit (41.6% vs. 40.0%). The median time to relapse was significantly greater for bupropion recipients than for placebo recipients (156 days vs. 65 days; P = 0.021). The continuous abstinence rate was higher in the bupropion group than in the placebo group at study week 24 (17 weeks after randomization)(52.3% vs. 42.3%; P = 0.037) but did not differ between groups after week 24. Weight gain was significantly less in the bupropion group than in the placebo group at study weeks 52 (3.8 kg vs. 5.6 kg; P = 0.002) and 104 (4.1 kg vs. 5.4 kg; P = 0.016). CONCLUSIONS In persons who stopped smoking with 7 weeks of bupropion treatment, sustained-release bupropion for 12 months delayed smoking relapse and resulted in less weight gain.

BACKGROUND: Although treatment of bipolar depression is a frequent clinical problem, double-blind studies of the treatment of bipolar depression are scarce. Some case series and uncontrolled data suggest antidepressants may differ in their propensity to induce mania or their efficacy for bipolar depression. METHOD: The authors conducted a prospective double-blind trial to assess efficacy and rate of treatment-emergent mood elevation in depressed bipolar patients when bupropion or desipramine was added to an ongoing therapeutic regimen of lithium or an anticonvulsant. Results were assessed after 8 weeks of acute treatment and during maintenance treatment up to 1 year. RESULTS: No difference was found for acute efficacy between the two drugs. Mania/hypomania was observed in 5 of 10 desipramine-treated patients, but only 1 of 9 bupropion-treated patients. The occurrence of hypomania or mania was correlated with treatment group (Kendall's tau correlation = 0.42; Z =-2.5, p <.012). CONCLUSION: These pilot findings suggest that bupropion is less likely to induce mood elevation than desipramine. For treatment of bipolar depression, bupropion and desipramine appear to have similar antidepressant efficacy.

OBJECTIVE: This is a multisite, double-blind, placebo-controlled trial to determine the safety and efficacy of bupropion in the treatment of children with attention deficit disorder with hyperactivity (ADDH). METHOD: In a four-center, double-blind comparison of bupropion (n = 72) and placebo (n = 37), children aged 6 to 12 years meeting DSM-III criteria for ADDH were randomized to receive bupropion 3 to 6 mg/kg per day or placebo, administered twice daily, at 7 A.M. and 7 P.M. Measures of efficacy included the Conners Parent and Teacher Questionnaires (93-item, 39-item, and 10 item), Clinical Global Impressions Scales of Severity and Improvement, the Sternberg Short-Term Memory Task, and the Continuous Performance Test. Screen and posttreatment physical examinations, electrocardiograms, electroencephalograms, and clinical laboratory evaluations were performed. Height, weight, and vital signs were measured and adverse experiences were assessed weekly. RESULTS: A significant treatment effect, apparent as early as day 3, was present for both conduct problems and hyperactivity on the Conners 10-item and 39-item teacher's checklist, and at day 28 for conduct problems and restless-impulsive behavior on the 93-item parent questionnaire. Findings were of smaller magnitude for parent ratings than teacher ratings. Significant treatment effects were present on both the Continuous Performance Test and memory retrieval test. Effect sizes of bupropion/placebo differences for teacher and parent ratings in this study were somewhat smaller than for standard stimulant drugs used to treat ADDH. Bupropion appeared to be well tolerated in most children. Dermatological reactions were twice as frequent in the drug group as the placebo group, with four reactions involving rash and urticaria that were serious enough to require discontinuation of medication. CONCLUSIONS: Bupropion may be a useful addition to available treatments for ADDH. Comparative trials with such standard drugs as methylphenidate are warranted to determine the relative clinical merits of bupropion.

Drug development in psychiatry has evolved from a process dependent on chance discovery to one based on rationally targeting specific mechanisms of action believed to be important in the pathophysiology underlying psychiatric syndromes. Antidepressant pharmacotherapy is the first area to have substantially benefited from this evolution. Serotonin selective reuptake inhibitors (SSRIs) were the first class of psychiatric medications developed based on such molecular targeting. Nefazodone is a new antidepressant that combines blockade of the serotonin-2 receptor with serotonin uptake inhibition. Perhaps as a result of this dual action, nefazodone caused fewer complaints of nervousness (e.g., agitation, anxiety), insomnia, and tremors and a higher incidence of confusion, dizziness, and vision disturbance than do other advanced generation antidepressants based on several different ways of assessing the relative incidence of these adverse effects. Reports of sexual dysfunction on nefazodone and bupropion treatment were lower than on treatment with other recently released antidepressants.

OBJECTIVE Antiepileptic drugs (AEDs) are commonly employed in the treatment of bipolar disorder. The efficacy and tolerability of topiramate, a novel anticonvulsant, and bupropion SR when added to mood stabilizer therapy were compared under single-blind conditions (rater-blinded) in patients meeting DSM-IV criteria for bipolar I/II depression. METHODS A total of 36 out-patients with Hamilton Depression Rating Scale (HDRS-17) scores > or = 16 were randomized to receive escalating doses of either topiramate (50-300 mg/day) or bupropion SR (100-400 mg/day) for 8 weeks. Data were analyzed on an intent-to-treat basis using the last observation carried forward method. RESULTS The percentage of patients meeting a priori response criteria (> or = 50% decrease from baseline in mean HDRS-17 total score) was significant for both topiramate (56%) and bupropion SR (59%)[t(17)= 2.542, p = 0.04 and t(17)= 2.661, p = 0.03, respectively]. Baseline demographic and clinical parameters were comparable between the two treatment groups. The mean doses of study medication were 176 mg/day (SD = 102 mg/day) for the topiramate-treated group and 250 mg/day (SD = 133 mg/day) for the bupropion SR-treated group. A significant and comparable reduction in depressive symptoms was observed from baseline to endpoint following topiramate and bupropion SR treatment, according to a > or = 50% reduction in the HDRS-17. Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups (p = 0.001), however, differences between the topiramate-treated group and the bupropion SR-treated group were not significant [t(36)= 1.754, p = 0.097]. Both topiramate and bupropion SR were generally well tolerated. Thirteen patients discontinued the study: 2 because of lack of efficacy, 1 due to withdrawal of consent and 10 following side-effects (six in the topiramate and four in the bupropion SR-treated group). There were no cases of affective switch in either arm. Weight loss was experienced by patients in both groups (mean weight loss at endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate)[t(17)= 2.325, p = 0.061 and t(17)= 2.481, p = 0.043, respectively]. CONCLUSIONS These preliminary data suggest that adjunctive topiramate may reduce depressive symptom severity in acute bipolar depression. The antidepressant efficacy of this compound requires confirmation via double-blind placebo controlled investigation.

Sexual dysfunction, a frequently reported side effect of many antidepressants, may result in patient dissatisfaction and noncompliance with treatment regimens. This paper describes the results of the first placebo-controlled comparison of the efficacy, safety, and effects on sexual functioning of sustained-release bupropion (bupropion SR) and the selective serotonin reuptake inhibitor sertraline. This randomized, double-masked, double-dummy, parallel-group, multicenter trial enrolled 360 patients with moderate-to-severe recurrent major depression. Patients were treated with bupropion SR 150 to 400 mg/d, sertraline 50 to 200 mg/d, or placebo for up to 8 weeks. Patients' depression and sexual functioning were assessed at weekly or biweekly clinic visits; safety was assessed by regular monitoring of adverse events, vital signs, and body weight. Treatment groups were similar at baseline in terms of age, sex, and race, and most patients had a diagnosis of moderate uncomplicated depression. Patients treated with bupropion SR or sertraline showed similar improvements on all efficacy measures; both active treatments were superior to placebo in improving scores on all rating scales for depression at various time points. Significantly more patients treated with sertraline experienced orgasmic dysfunction throughout the study than did patients treated with bupropion SR or placebo (P < 0.001). Headache was the most frequently reported adverse event in all 3 treatment groups and occurred with similar frequency in each group (30% to 40%). Nausea (31%), diarrhea (26%), insomnia (18%), and somnolence (17%) occurred in significantly more patients in the sertraline group than in the bupropion SR group (18%, 7%, 13%, and 3%, respectively) and the placebo group (10%, 11%, 4%, and 6%, respectively). Dry mouth occurred more frequently with bupropion SR (19%) than with sertraline (14%) or placebo (12%), although the differences were not significant. Changes in vital signs were similar in all groups. Similar (small, but not statistically significant) decreases in mean body weight were seen in both the bupropion SR (-1.06 kg) and sertraline (-0.79 kg) groups, whereas the placebo group experienced a minor increase (0.21 kg). Although bupropion SR and sertraline were similarly well tolerated and effective in the treatment of depression, sertraline treatment was more often associated with sexual dysfunction and certain other adverse events compared with bupropion SR and placebo. Therefore, bupropion SR may be an appropriate choice as an antidepressant for the treatment of sexually active patients.