PAROXETINE VERSUS PLACEBO - A DOUBLE-BLIND COMPARISON IN DEPRESSED-PATIENTS

Background. Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI). The present study assessed the efficacy and tolerability of paroxetine against placebo in depressed outpatients. Method. A double-blind, parallel-group study was undertaken in four stand-alone centers. Patients aged 18-65 years, meeting DSM-III criteria for major depression, and having a Hamilton Rating Scale for Depression (HAM-D) score greater-than-or-equal-to 18 on the first 17 items of the HAM-D-21 were randomized to paroxetine or placebo for 6 weeks of treatment. Efficacy outcome variables included the HAM-D, the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impressions Scale (CGI), and the Covi Anxiety Scale. Tolerability was assessed by asking a nonleading question. Routine laboratory safety and vital sign data from all four centers were pooled. The primary analysis used the intention-to-treat sample and for efficacy variables the last-observation-carried forward data set was employed. Statistical methods included one-way analysis of variance for parametric and Fisher exact test for nonparametric variables. Results: Significant differences (p less-than-or-equal-to .05) were found between paroxetine and placebo on the HAM-D and CGI by Week 2 and on all efficacy outcome variables by Week 4. Improvement on the HAM-D sleep factor occurred 2 weeks prior to that seen on the retardation factor. Similar results were obtained when an adequate treatment group (therapy for greater-than-or-equal-to 28 days) was considered. A full clinical response (CGI-severity of illness score 1 or 2) was seen in over 40% of subjects. Adverse events were more common for paroxetine compared with placebo (p less-than-or-equal-to .01). Somnolence was twice more common than nervousness. Dropout due to adverse events was similar between therapies. Paroxetine had no clinically significant effect on laboratory safety data or vital signs. Conclusion: Paroxetine was an effective, well tolerated, and safe antidepressant. Side effects were typical of the SSRI class of drugs. Symptoms indicative of a nonalerting profile were more common than those associated with alerting effects.