A randomized, double-blind, placebo-controlled study of the effect of sustained-release bupropion on blood pressure in individuals with mild untreated hypertension.

The effects of bupropion on blood pressure and heart rate were evaluated in a double-blind, placebo-controlled study of community volunteers with untreated mild (stage 1) hypertension (systolic blood pressure [SBP], 140-159 mm Hg, and/or diastolic blood pressure, 90-99 mm Hg). Three hundred subjects were randomly assigned (1:1:1:1) to 4 weeks of placebo or bupropion sustained release (SR) 150, 300, or 400 mg/d. Mean clinical blood pressures decreased from baseline to the end of protocol in all groups (n = 296): -6.53, -6.46, -4.20, -4.87 mm Hg for SBP; and -2.36, -2.27, -1.95, -1.55 mm Hg for diastolic blood pressure, for each group, respectively. Although decreases in mean clinical blood pressure were observed in all groups, the reduction in SBP was less on bupropion SR 300 mg/d than on placebo (-4.20 vs -6.53 mm Hg, respectively; Delta = 2.33, P = 0.020). Neither mean 24-hour ambulatory blood pressure measurements nor the proportion of subjects with clinically significant increases in blood pressure differed between any bupropion SR dose and placebo. Mean heart rate increases were small but statistically significant at 400 mg/d versus placebo (2.28 vs -0.64 beats/min; Delta = 2.92, P = 0.004). Although only minor effects on blood pressure were observed in this trial, an infrequent association of bupropion therapy and treatment-emergent hypertension cannot be ruled out.

Bupropion in pregnancy and the prevalence of congenital malformations.

PURPOSE: Reports from the GlaxoSmithKline Bupropion Pregnancy Registry suggested an increase in cardiovascular defects following exposure to bupropion during pregnancy. We conducted a study of congenital malformations among infants born to women exposed to bupropion during their first trimester. METHODS: The study used data from UnitedHealthcare between January 1995 and September 2004. We calculated the prevalence of all congenital malformations and cardiovascular malformations associated with bupropion exposure in the estimated first trimester (1213 infants), compared with (1) other antidepressant exposure in the first trimester (4743 infants) and (2) bupropion exposure outside the first trimester (1049 infants). Malformation cases were confirmed through medical record abstraction. We calculated adjusted odds ratios (AORs) using the GEE form of logistic regression. RESULTS: For all congenital malformations, the prevalence associated with bupropion first trimester was 23.1 per 1000 infants. The AORs were 0.95 (95%CI 0.62-1.45) and 1.00 (95%CI 0.57-1.73) in comparison to other antidepressants (prevalence 23.2 per 1000) and bupropion outside the first trimester (prevalence 21.9 per 1000), respectively. For cardiovascular malformations, the prevalence associated with bupropion first trimester was 10.7 per 1000 infants. The AORs were 0.97 (95%CI 0.52-1.80) and 1.07 (95%CI 0.48-2.40) in comparison to other antidepressants (prevalence 10.8 per 1000) and bupropion outside the first trimester (prevalence 9.5 per 1000), respectively. CONCLUSIONS: Results do not support a hypothesis of a teratogenic effect of first trimester bupropion exposure. The prevalence of malformations associated with bupropion exposure in the first trimester was not increased relative to the comparison groups.

A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability.

In this double-blind, multicenter study, bupropion XL, a norepinephrine-dopamine reuptake inhibitor, and venlafaxine XR, a serotonin-norepinephrine reuptake inhibitor, were compared with regard to sexual functioning, efficacy, and tolerability. A total of 348 sexually active adult outpatients with depression were randomized to receive bupropion XL (titrated to a target dose of 300-450 mg/d) or venlafaxine XR (titrated to a target dose of 150-225 mg/d) for 12 weeks. Total scores on the primary dependent variable, the Changes in Sexual Functioning Questionnaire (self-report), increased for subjects receiving bupropion XL and decreased for those treated with venlafaxine XR; the mean change scores differed significantly between groups from week 2 onward. Among subjects with normal pretreatment sexual functioning, Changes in Sexual Functioning Questionnaire total scores remained essentially unchanged for the bupropion XL group but were decreased significantly for the venlafaxine XR group; mean change scores also differed between groups from week 2 onward. Although the therapies resulted in similar change on the 17-item Hamilton Depression Rating Scale, remission rates were significantly higher among those treated with bupropion XL (46%) versus venlafaxine XR (33%) (odds ratio, 1.93; 95% confidence interval, 1.07-3.46). Aside from adverse effects of venlafaxine XR on sexual function, both treatments were reasonably well tolerated. In conclusion, in this patient population (ie, relatively young, sexually active outpatients), bupropion XL was at least as effective as venlafaxine XR and had a significantly more favorable sexual side effect profile.

Use of bupropion in combination with serotonin reuptake inhibitors.

Incomplete symptom remission and sexual side effects are common problems for which bupropion often is added to treatment with selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs) for patients with major depressive disorder (MDD). This article reviews the literature on combining bupropion with SSRIs or SNRIs. We used MEDLINE to select studies that included patients diagnosed with MDD treated with any combination of bupropion and an SSRI or SNRI, either to enhance antidepressant response or to ameliorate antidepressant-associated sexual dysfunction. Bibliographies of located articles were searched for additional studies. Controlled and open-label studies support the effectiveness of bupropion in reversing antidepressant-associated sexual dysfunction, whereas open trials suggest that combination treatment with bupropion and an SSRI or SNRI is effective for the treatment of MDD in patients refractory to the SSRI, SNRI, or bupropion alone. The available data suggest that, although not an approved indication, the combination of bupropion and either an SSRI or an SNRI is generally well tolerated, can boost antidepressant response, and can reduce SSRI or SNRI-associated sexual side effects. Additional randomized controlled studies are needed to answer important questions, such as those regarding optimal dose and duration of treatment.

Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: a meta-analysis of original data from 7 randomized controlled trials.

BACKGROUND: Although it is widely believed that the various classes of antidepressants are equally effective, clinically meaningful differences may be obscured in individual studies because of a lack of statistical power. The present report describes a meta-analysis of original data from a complete set of studies comparing the norepinephrine/dopamine reuptake inhibitor (NDRI) bupropion with selective serotonin reuptake inhibitors (SSRIs; sertraline, fluoxetine, or paroxetine). METHOD: Individual patient data were pooled from a complete set of 7 randomized, double-blind studies comparing bupropion (N = 732) with SSRIs (fluoxetine, N = 339; sertraline, N = 343; paroxetine, N = 49) in outpatients with major depressive disorder (DSM-III-R or DSM-IV); 4 studies included placebo (N = 512). Response and remission rates were compared at week 8 or endpoint in both the intent-to-treat sample, using the last-observation-carried-forward (LOCF) method to account for attrition, and the observed cases. Tolerability data, including incidence of sexual side effects, were also compared. RESULTS: The LOCF response and remission rates for the bupropion (62% and 47%) and SSRI (63% and 47%) groups were similar; both active therapies were superior to placebo (51% and 36%; all comparisons, p < .001). The same pattern of results was demonstrated on the observed cases analyses. Although bupropion and SSRIs were generally well tolerated, SSRI therapy resulted in significantly higher rates of sexual side effects as compared to both bupropion and placebo. SSRIs were also associated with more somnolence and diarrhea, and bupropion was associated with more dry mouth. CONCLUSION: Bupropion and the SSRIs were equivalently effective and, overall, both treatments were well tolerated. The principal difference between these treatments was that sexual dysfunction commonly complicated SSRI therapy, whereas treatment with bupropion caused no more sexual dysfunction than placebo.

Does pretreatment insomnia or anxiety predict acute response to bupropion SR?

BACKGROUND: This retrospective analysis was conducted to determine whether pretreatment levels of insomnia or anxiety were associated with likelihood of or time to antidepressant response with bupropion sustained release (SR). METHODS: Data from an open-label, 8-week, acute phase multicenter study of 797 adult outpatients with recurrent, nonpsychotic major depressive disorder who received bupropion SR (300 mg/day) were used. Depressive symptom severity was measured by the 17-item Hamilton Rating Scale for Depression (HAM-D17), insomnia by totaling the three HAM-D17 insomnia items (early, middle, late), and anxiety by the 14-item Hamilton Rating Scale forAnxiety. RESULTS: Overall, 67% (533/797) of patients responded (defined as > or = 50% reduction in baseline HAM-D17). Neither baseline insomnia nor baseline anxiety was related to the likelihood of achieving response. Higher baseline insomnia and lower baseline anxiety were associated with an earlier onset of response (about one week sooner in each). CONCLUSIONS: Predicting the likelihood of antidepressant response with bupropion SR cannot be based on either baseline insomnia or anxiety levels.

Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study.

BACKGROUND: Data remain limited on treatment strategies for adults with attention-deficit/hyperactivity disorder (ADHD). This study evaluated the efficacy and safety of an extended-release, once-daily formulation of bupropion (XL) in the treatment of adults with ADHD. METHODS: This multisite, placebo-controlled, 8-week prospective trial evaluated 162 adult patients diagnosed with ADHD (combined and inattentive types). Subjects were treated with up to 450 mg/day of bupropion XL. The primary efficacy endpoint was the proportion of ADHD responders (defined as at least a 30% reduction in the investigator-rated ADHD Rating Scale score) at week 8 (last observation carried forward [LOCF]). RESULTS: Bupropion XL responders (53%) exceeded placebo responders (31%) (p =.004 at week 8) with a significantly greater proportion of bupropion XL responders as early as week 2 (p = .01). Treatment effect size calculated for the ADHD Rating Scale total score was .6. Bupropion XL appeared to provide sustained benefit throughout the day compared with placebo (morning p =.033, afternoon p =.004, evening p = .024). Bupropion XL was safe and well tolerated, with no serious or unexpected adverse events and a low rate of drug-related study discontinuation (5%). CONCLUSIONS: The results from this multisite study indicate that bupropion XL is an effective and well-tolerated nonstimulant treatment for adult ADHD.

Bupropion SR vs. placebo for weight loss in obese patients with depressive symptoms.

OBJECTIVE: This randomized, double-blind, placebo-controlled study evaluated the efficacy and tolerability of bupropion sustained-release (bupropion SR) in reducing weight and depressive symptoms in obese adults. RESEARCH METHODS AND PROCEDURES: Obese adults (body mass index, 30 to 44 kg/m(2)) not currently meeting criteria for major depression but with depressive symptoms (Beck Depression Inventory score 10-30) received bupropion SR 300 mg/d or placebo for 26 weeks with a 500 kcal/d-deficit diet. Patients who lost <5% of baseline weight at week 12 had bupropion SR dosage or placebo increased to 400 mg/d in a blinded fashion. RESULTS: The bupropion SR group (n = 193) lost an average of 4.4 kg (4.6% of baseline weight) vs. 1.7 kg (1.8% of baseline weight) on placebo (n = 191, p < 0.001, last-observation-carried-forward analysis). More patients in the bupropion SR group than in the placebo group (40% vs. 16% of intent-to-treat sample, 50% vs. 28% of completers, respectively) lost at least 5% of baseline weight (p < 0.05 at week 4, p < 0.001 at weeks 6 to 26). The percentage of patients reporting > or =50% decrease in depressive symptoms did not differ between groups, but depressive symptoms improved more with bupropion SR than with placebo among patients with a history of major depression (p < 0.05, weeks 4 to 26). In the sample as a whole, improvement in depressive symptoms was related to weight loss of > or =5% regardless of treatment (p < 0.0001). Bupropion SR was well-tolerated. DISCUSSION: Bupropion SR in combination with a 500 kcal/d-deficit diet facilitated weight loss. Weight loss of > or =5% may improve mood in obese patients with depressive symptoms.