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.

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