OBJECTIVES: The aims of this work were to assess the efficacy and tolerability of controlled-release paroxetine (paroxetine CR) in the treatment of outpatients with severe major depressive disorder (MDD). METHODS: This was a retrospective analysis of pooled data from 4 previously published, double-blind, randomized, placebo-controlled, 8- to 12-week outpatient studies of paroxetine CR (12.5-62.5 mg) in MDD. However, the studies were designed to assess the efficacy of paroxetine CR overall, rather than specifically in those with severe MDD. Subjects were categorized according to their baseline mean 17-item Hamilton Depression Rating Scale (HAMD-17) total score as having severe (> or =25) or nonsevere (<25) depression. Changes in depressive symptomatology were assessed, based on the mean change from baseline in HAMD-17 total scores and the proportion of responders (> or =50% reduction from baseline in HAMD-17 total scores or Clinical Global Impression [CGI] of Improvement scores of 1 or 2), for each study and pooled across the studies. The pooled analysis of data also assessed the proportion of patients achieving remission (HAMD-17 total score < or =7 or CGI-Improvement score of 1) at last-observation-carried-forward end point. RESULTS: A total of 1083 subjects participated in the 4 studies; 303 had severe MDD (paroxetine CR, n = 174; placebo, n = 129). Among the patients with severe MDD, most were women, had a mean HAMD-17 score between 26.3 and 27.7, and had a mean CGI of Severity score between 4.5 and 4.9. In 3 studies, the mean age of such participants was between 35 and 43 years. However, the fourth study was an evaluation in late-life depression in which the mean age was 71.3 years in the paroxetine CR group and 70.0 years in the placebo group. In the overall pooled sample, significantly greater improvements in depressive symptoms were observed among those with severe MDD who were treated with paroxetine CR compared with those who received placebo (HAMD-17 total treatment difference, -4.37 [95% CI, -6.31 to -2.42; P < 0.001]). The odds of CGI-Improvement response were also significantly higher for patients receiving paroxetine CR than those receiving placebo, regardless of baseline depressive symptomatology (severe MDD: odds ratio [OR], 2.42 [95% CI, 1.50-3.91; P < 0.001]; nonsevere MDD: OR, 1.63 [95% CI, 1.21-2.19; P < 0.002] ). Withdrawal rates due to adverse events were 9.8% versus 5.4% (severe) and 5.2% versus 4.5% (nonsevere), paroxetine CR versus placebo, respectively. CONCLUSIONS: This post hoc analysis of pooled data suggests that paroxetine CR was effective and well tolerated in these outpatients with severe MDD.
RCT Entities:
OBJECTIVES: The aims of this work were to assess the efficacy and tolerability of controlled-release paroxetine (paroxetine CR) in the treatment of outpatients with severe major depressive disorder (MDD). METHODS: This was a retrospective analysis of pooled data from 4 previously published, double-blind, randomized, placebo-controlled, 8- to 12-week outpatient studies of paroxetine CR (12.5-62.5 mg) in MDD. However, the studies were designed to assess the efficacy of paroxetine CR overall, rather than specifically in those with severe MDD. Subjects were categorized according to their baseline mean 17-item Hamilton Depression Rating Scale (HAMD-17) total score as having severe (> or =25) or nonsevere (<25) depression. Changes in depressive symptomatology were assessed, based on the mean change from baseline in HAMD-17 total scores and the proportion of responders (> or =50% reduction from baseline in HAMD-17 total scores or Clinical Global Impression [CGI] of Improvement scores of 1 or 2), for each study and pooled across the studies. The pooled analysis of data also assessed the proportion of patients achieving remission (HAMD-17 total score < or =7 or CGI-Improvement score of 1) at last-observation-carried-forward end point. RESULTS: A total of 1083 subjects participated in the 4 studies; 303 had severe MDD (paroxetine CR, n = 174; placebo, n = 129). Among the patients with severe MDD, most were women, had a mean HAMD-17 score between 26.3 and 27.7, and had a mean CGI of Severity score between 4.5 and 4.9. In 3 studies, the mean age of such participants was between 35 and 43 years. However, the fourth study was an evaluation in late-life depression in which the mean age was 71.3 years in the paroxetine CR group and 70.0 years in the placebo group. In the overall pooled sample, significantly greater improvements in depressive symptoms were observed among those with severe MDD who were treated with paroxetine CR compared with those who received placebo (HAMD-17 total treatment difference, -4.37 [95% CI, -6.31 to -2.42; P < 0.001]). The odds of CGI-Improvement response were also significantly higher for patients receiving paroxetine CR than those receiving placebo, regardless of baseline depressive symptomatology (severe MDD: odds ratio [OR], 2.42 [95% CI, 1.50-3.91; P < 0.001]; nonsevere MDD: OR, 1.63 [95% CI, 1.21-2.19; P < 0.002] ). Withdrawal rates due to adverse events were 9.8% versus 5.4% (severe) and 5.2% versus 4.5% (nonsevere), paroxetine CR versus placebo, respectively. CONCLUSIONS: This post hoc analysis of pooled data suggests that paroxetine CR was effective and well tolerated in these outpatients with severe MDD.