Paxil - Clinical Pharmacology

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Obsessive Compulsive Disorder:

The effectiveness of PAXIL in the treatment of obsessive compulsive disorder (OCD) was demonstrated in two 12-week multicenter placebo-controlled studies of adult outpatients (Studies 1 and 2). Patients in all studies had moderate to severe OCD (DSM-IIIR) with mean baseline ratings on the Yale Brown Obsessive Compulsive Scale (YBOCS) total score ranging from 23 to 26. Study 1, a dose-range finding study where patients were treated with fixed doses of 20, 40, or 60 mg of paroxetine/ day demonstrated that daily doses of paroxetine 40 and 60 mg are effective in the treatment of OCD.

Patients receiving doses of 40 and 60 mg paroxetine experienced a mean reduction of approximately 6 and 7 points, respectively, on the YBOCS total score which was significantly greater than the approximate 4-point reduction at 20 mg and a 3-point reduction in the placebo-treated patients. Study 2 was a flexible-dose study comparing paroxetine (20 to 60 mg daily) with clomipramine (25 to 250 mg daily). In this study, patients receiving paroxetine experienced a mean reduction of approximately 7 points on the YBOCS total score, which was significantly greater than the mean reduction of approximately 4 points in placebo-treated patients. The following table provides the outcome classification by treatment group on Global Improvement items of the Clinical Global Impression (CGI) scale for Study 1. Outcome Classification (%) on CGI-Global Improvement Item for Completers in Study 1 Outcome Classification Placebo (n = 74) PAXIL 20 mg (n = 75) PAXIL 40 mg (n = 66) PAXIL 60 mg (n = 66) Worse 14% 7% 7% 3%

No Change 44% 35% 22% 19% Minimally Improved 24% 33% 29% 34%

Much Improved 11% 18% 22% 24% Very Much Improved 7% 7% 20% 20%

Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age or gender.

The long-term maintenance effects of PAXIL in OCD were demonstrated in a long-term extension to Study 1. Patients who were responders on paroxetine during the 3-month double-blind phase and a 6-month extension on open-label paroxetine (20 to 60 mg/ day) were randomized to either paroxetine or placebo in a 6-month double-blind relapse prevention phase.