A double-blind, multicenter study in primary care comparing paroxetine and clomipramine in patients with depression and associated anxiety. Paroxetine Study Group.

BACKGROUND

60%-90% of patients with a primary diagnosis of depression also experience symptoms of anxiety, and such patients have a poorer prognosis than those with uncomplicated depression. The serotonin selective reuptake inhibitors have demonstrated efficacy in the treatment of both depression and certain anxiety states. Furthermore, in a metaanalysis of the paroxetine clinical trial database of 2963 patients in whom depression predominated, there was a concomitant reduction in the Hamilton Rating Scale for Depression anxiety factor. The purpose of the present study was to prospectively compare the efficacy of paroxetine and clomipramine in patients specifically selected for coexisting depression and anxiety.

METHOD

This was a 12-week, double-blind, parallel-group trial comparing paroxetine 20-40 mg/day with clomipramine 75-150 mg/day in 1002 patients with a Montgomery-Asberg Depression Rating Scale (MADRS) score > or = 20 and a Clinical Anxiety Score (CAS) > or = 11 after a 3-7 day placebo run-in period.

RESULTS

Both paroxetine and clomipramine reduced the MADRS and CAS ratings at 2, 6, and 12 weeks and at endpoint, with no significant differences between treatment groups at any time point. CGI severity of illness and global improvement ratings were also similar throughout the trial; however, there was a statistically significant difference in the CGI efficacy index at 6 weeks and at endpoint, favoring paroxetine (p = .015 and p = .015, respectively). Paroxetine resulted in fewer treatment-emergent adverse experiences and related withdrawals than clomipramine (p = .025 and p = .008, respectively). The number of serious adverse experiences was not significantly different in the paroxetine group compared with the clomipramine group (14 [2.8%] vs. 27 [5.4%]), but did approach statistical significance (p = .056). Anticholinergic-emergent adverse experiences were reported twice as frequently by patients in the clomipramine group as in the paroxetine group (36.1% vs. 18.6%).

CONCLUSION

There was no evidence of any significant difference in efficacy between paroxetine and clomipramine in patients with coexisting depression and anxiety. However, paroxetine was better tolerated as shown by total treatment-emergent adverse experiences, anticholinergic adverse experiences, and withdrawals due to adverse experiences.