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.