A DOUBLE-BLIND, MULTICENTER STUDY IN PRIMARY-CARE COMPARING PAROXETINE AND CLOMIPRAMINE IN PATIENTS WITH DEPRESSION AND ASSOCIATED ANXIETY

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 sele ctive reuptake inhibitors have demonstrated efficacy in the treatment of both depression and certain anxiety states. Furthermore, in a metaa nalysis 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 t he present study was to prospectively compare the efficacy of paroxeti ne and clomipramine in patients specifically selected for coexisting d epression and anxiety. Method: This was a 12-week, double-blind, paral lel-group trial comparing paroxetine 20-40 mg/day with clomipramine 75 -150 mg/day in 1002 patients with a Montgomery-Asberg Depression Ratin g Scale (MADRS) score greater than or equal to 20 and a Clinical Anxie ty Score (CAS) greater than or equal to 11 after a 3-7 day placebo run -in period. Results: Both paroxetine and clomipramine reduced the MADR S and CAS ratings at 2, 6, and 12 weeks and at endpoint, with no signi ficant differences between treatment groups at any rime point. CGI sev erity of illness and global improvement ratings were also similar thro ughout the trial; however. there was a statistically significant diffe rence in the CGI efficacy index at. 6 weeks and at endpoint, favoring paroxetine (p=.015 and p=.015, respectively). Paroxetine resulted in f ewer treatment-emergent adverse experiences and related withdrawals th an clomipramine (p=.025 and p=.008, respectively). The number of serio us adverse experiences was not significantly different in the paroxeti ne 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 pat ients in the clomipramine group as in the paroxetine group (36.1% vs. 18.6%). Conclusion: There was no evidence of any significant differenc e in efficacy between paroxetine and clomipramine in patients with coe xisting depression and anxiety. However, paroxetine was better tolerat ed as shown by total treatment-emergent adverse experiences, anticholi nergic adverse experiences, and withdrawals due to adverse experiences .