Resolution of sleepiness and fatigue: a comparison of bupropion and selective serotonin reuptake inhibitors in subjects with major depressive disorder achieving remission at doses approved in the European Union.

Unlike selective serotonin reuptake inhibitors (SSRIs), bupropion may be classified as a dual noradrenaline and dopamine reuptake inhibitor, a difference with potential implications for the treatment of residual sleepiness and fatigue in major depressive disorder (MDD). Post-hoc analysis of subjects with remitted MDD was performed on data pooled from six double-blind, randomized trials comparing the European Union (EU)-approved dose of ≤300 mg/day bupropion with SSRIs (sertraline, paroxetine or escitalopram) for the resolution of sleepiness and fatigue. Hypersomnia score was defined as the sum of scores of the Hamilton Depression Rating Scale (HDRS) items 22, 23, and 24; fatigue score as HDRS item 13 score; and remission as HDRS-17≤7. Similar proportions of bupropion- and SSRI-treated subjects achieved remission at study endpoint (169/343, 49.3% vs 324/656, 49.4%; last observation carried forward (LOCF), p=0.45). Fewer bupropion-treated remitters had residual symptoms of sleepiness (32/169, 18.9% vs 104/324, 32.1%; p<0.01) and fatigue (33/169, 19.5% vs 98/324, 30.2%; p<0.05). Bupropion-treated remitters also showed greater improvement (mean change from baseline) in sleepiness (p<0.05) and fatigue scores (p<0.01) at endpoint: benefits were evident from week 2 for sleepiness (p<0.01) and week 4 for fatigue (p<0.01). Bupropion treatment at the EU-approved dose of ≤300 mg/day may offer advantages over SSRIs in the resolution of sleepiness and fatigue in remitted MDD patients.

Efficacy of bupropion and the selective serotonin reuptake inhibitors in the treatment of major depressive disorder with high levels of anxiety (anxious depression): a pooled analysis of 10 studies.

OBJECTIVE: The goal of this work was to compare the efficacy of the norepinephrine and dopamine reuptake inhibitor bupropion with the selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder with high levels of anxiety (anxious depression). METHOD: Ten double-blind, randomized studies from 1991 through 2006 were combined (N = 2122). Anxious depression was defined as a 17-item Hamilton Rating Scale for Depression (HAM-D-17) anxiety-somatization factor score >or= 7. RESULTS: Among patients with anxious depression (N = 1275), response rates were greater following SSRI than bupropion treatment according to the HAM-D-17 (65.4% vs. 59.4%, p = .03) and the Hamilton Rating Scale for Anxiety (61.5% vs. 54.5%, p = .03). There was also a greater reduction in HAM-D-17 mean +/- SD scores (-14.1 +/- 7.6 vs. -13.2 +/- 7.9, p = .03) and a trend toward statistical significance for a greater reduction in HAM-A mean +/- SD scores (-10.5 +/- 7.4 vs. -9.6 +/- 7.6, p = .05) in favor of SSRI treatment among patients with anxious depression. There was no statistically significant difference in efficacy between bupropion and the SSRIs among patients with moderate/low levels of anxiety. CONCLUSIONS: There appears to be a modest advantage for the SSRIs compared to bupropion in the treatment of anxious depression (6% difference in response rates). Using the number-needed-to-treat (NNT) statistic as 1 indicator of clinical significance, nearly 17 patients would need to be treated with an SSRI than with bupropion in order to obtain 1 additional responder. This difference falls well above the limit of NNT = 10, which was suggested by the United Kingdom's National Institute of Clinical Excellence. Nevertheless, the present work is of theoretical interest because it provides preliminary evidence suggesting a central role for serotonin in the regulation of symptoms of negative affect such as anxiety.

Efficacy of bupropion and the selective serotonin reuptake inhibitors in the treatment of anxiety symptoms in major depressive disorder: a meta-analysis of individual patient data from 10 double-blind, randomized clinical trials.

The goal of this work was to compare the efficacy of the norepinephrine-dopamine reuptake inhibitor bupropion with the selective serotonin reuptake inhibitors (SSRIs) in the treatment of anxiety symptoms in major depressive disorder (MDD). Ten double-blind, randomized studies, involving a total of 2890 bupropion-, SSRI- or placebo- treated patients were pooled. Anxiety symptoms of depression were defined using the Hamilton depression rating scale (HDRS) Anxiety-Somatization factor (HDRS-AS) score, as well as the Hamilton anxiety scale (HAM-A) score. Both bupropion and the SSRIs led to a comparable degree of improvement in anxiety symptoms, defined using the HDRS-AS score (-3.8+/-2.8 vs. -3.9+/-2.8, p=0.130) or HAM-A score (-8.8+/-7.2 vs. -9.1+/-7.0, p=0.177). There was no consistent difference in the time to anxiolysis between the two treatment groups. In addition, there was no difference in the proportion of bupropion- and SSRI- remitters who continued to experience residual anxiety, defined as a HDRS-AS score >0 at endpoint (69.2% vs. 74.7%, p=0.081) or a HAM-A score >7 at endpoint (9.5% vs. 8.4%, p=0.284). Finally, there was no statistically significant difference in the severity of residual anxiety symptoms between bupropion- or SSRI- treated patients with remitted depression, defined using the HDRS-AS (1.15+/-1.14 vs. 1.25+/-1.09, p=0.569), or HAM-A scores at endpoint (3.30+/-2.89 vs. 3.31+/-2.89, p=0.552). Contrary to clinician impression, there does not appear to be any difference in the anxiolytic efficacy of bupropion and the SSRIs when used to treat MDD.

Comparing the rapidity of response during treatment of major depressive disorder with bupropion and the SSRIs: a pooled survival analysis of 7 double-blind, randomized clinical trials.

OBJECTIVE: Several controlled studies, as well as a meta-analysis, suggest that the efficacy of bupropion, a norepinephrine-dopamine reuptake inhibitor, is comparable to that of the selective serotonin reuptake inhibitors (SSRIs). The current analysis was undertaken to determine if these antidepressants differ in rapidity of clinical effect. METHOD: Individual patient data were obtained from 7 double-blind, randomized studies of 8 weeks' duration that compared bupropion (N = 836) and SSRIs (sertraline, paroxetine, fluoxetine, and escitalopram; N = 836). Time to first response and first remission were compared between treatment groups with the use of Cox proportional hazards regression models, stratified by trial number, with depression severity at baseline as a covariate. A secondary analysis compared outcomes in the 2 bupropion versus escitalopram studies. Random-effects meta-analyses were then conducted to confirm the survival-analysis findings. RESULTS: There was no statistically significant difference between bupropion and the SSRIs in time to first response (hazard ratio [HR] = 0.955; p = .43) and first remission (HR = 1.00; p = .97). Similarly, there was no statistically significant difference between bupropion and escitalopram in time to first response (HR = 0.897; p = .29), and first remission (HR = 0.999; p = .99). These results were confirmed with the use of random-effects meta-analyses (p > .05, all 4 analyses). CONCLUSION: There does not appear to be any statistically detectable difference in the rapidity of antidepressant effect between bupropion and the SSRIs overall or escitalopram specifically.

Relative antidepressant efficacy of bupropion and the selective serotonin reuptake inhibitors in major depressive disorder: gender-age interactions.

To determine whether age/gender-based differences in efficacy exist between bupropion and the selective serotonin reuptake inhibitors for major depressive disorder, we pooled the findings of 10 double-blind studies comparing bupropion with a selective serotonin reuptake inhibitor. Men (N=943) and women (N=1179) were divided into three age groups (younger than 40, 40-55, older than 55). Improvement in terms of the 17-item Hamilton Depression Rating Scale, as well as the Bech melancholia, anxiety-somatization, and insomnia factors of the Hamilton Depression Rating Scale was compared between the two treatment groups. Of 64 pair-wise comparisons, only one was statistically significant. Specifically, more women treated with a selective serotonin reuptake inhibitor experienced a 50% or greater decrease in Hamilton Depression Rating Scale Anxiety-Somatization scores (58.8 versus 63.8%, P=0.0394). No difference, however, was seen in the degree of resolution of Hamilton Depression Rating Scale Anxiety-Somatization scores (continuous measure) between women treated with bupropion versus a selective serotonin reuptake inhibitor (P=0.114). Bupropion and the selective serotonin reuptake inhibitors, thus, appear to be equally effective in treating depressive symptoms, as well as anxious/somatic symptoms and insomnia in depression. No gender-related or age-related differences were found except that greater improvement was seen in anxious/somatic symptoms of depression among women during selective serotonin reuptake inhibitor treatment. This finding could, however, not be replicated when improvement in anxious/somatic symptoms was defined as a continuous measure.

Resolution of sleepiness and fatigue in major depressive disorder: A comparison of bupropion and the selective serotonin reuptake inhibitors.

BACKGROUND: The purpose of this study was to examine whether the treatment of major depressive disorder (MDD) with the norepinephrine-dopamine reuptake inhibitor (NDRI) bupropion results in a greater resolution of sleepiness and fatigue than with the selective serotonin reuptake inhibitors (SSRIs). METHODS: Six double-blind, randomized clinical trials comparing bupropion (n = 662) with an SSRI (n = 655) for the treatment of MDD were pooled. Hypersomnia scores were defined as the sum of scores of the Hamilton Depression Rating Scale (HDRS) items #22, 23, and 24. Fatigue scores were defined as the score of HDRS item #13. RESULTS: There was a greater improvement in hypersomnia scores among bupropion-treated than SSRI-treated (p < .0001) or placebo-treated patients (p = .0008). There was also a greater improvement in fatigue scores among bupropion-treated (p < .0001) and SSRI-treated (p = .0005) than placebo-treated patients as well as a greater improvement in fatigue scores among bupropion-treated than SSRI-treated patients (p = .0078). Fewer bupropion-remitters than SSRI-remitters experienced residual hypersomnia (20.5% vs. 32.1%; p = .0014) or residual fatigue (19.5% vs. 30.2%; p = .0020). CONCLUSION: Treatment of MDD with the NDRI bupropion resulted in a greater resolution of sleepiness and fatigue than SSRIs treatment. Although preliminary, these results warrant prospectively designed studies examining potential differences between bupropion and the SSRIs on these specific depressive symptoms.