### Major Depressive Disorder

The efficacy of paroxetine hydrochloride extended-release tablets as a treatment for major depressive disorder has been established in two 12 week, flexible dose, placebo-controlled studies of patients with DSM-IV Major Depressive Disorder. One study included patients in the age range 18 to 65 years and a second study included elderly patients, ranging in age from 60 to 88. In both studies, paroxetine hydrochloride extended-release tablets were shown to be significantly more effective than placebo in treating major depressive disorder as measured by the following: Hamilton Depression Rating Scale (HDRS), the Hamilton depressed mood item and the Clinical Global Impression (CGI)–Severity of Illness score. 

A study of outpatients with major depressive disorder who had responded to immediate-release paroxetine tablets (HDRS total score < 8) during an initial 8 week open treatment phase and were then randomized to continuation on immediate-release paroxetine tablets or placebo for one year demonstrated a significantly lower relapse rate for patients taking immediate-release paroxetine tablets (15%) compared to those on placebo (39%). Effectiveness was similar for male and female patients. 

### Panic Disorder

The effectiveness of paroxetine hydrochloride extended-release tablets in the treatment of panic disorder was evaluated in three 10 week, multicenter, flexible dose studies (Studies 1, 2 and 3) comparing paroxetine extended-release tablets (12.5 mg to 75 mg daily) to placebo in adult outpatients who had panic disorder (DSM-IV), with or without agoraphobia. These trials were assessed on the basis of their outcomes on three variables: (1) the proportions of patients free of full panic attacks at endpoint; (2) change from baseline to endpoint in the median number of full panic attacks; and (3) change from baseline to endpoint in the median Clinical Global Impression Severity score. For Studies 1 and 2, paroxetine hydrochloride extended-release tablets were consistently superior to placebo on 2 of these 3 variables. Study 3 failed to consistently demonstrate a significant difference between paroxetine hydrochloride extended-release tablets and placebo on any of these variables. 

For all three studies, the mean dose of paroxetine hydrochloride extended-release tablets for completers at endpoint was approximately 50 mg/day. Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age or gender. 

Long-term maintenance effects of the immediate-release formulation of paroxetine in panic disorder were demonstrated in an extension study. Patients who were responders during a 10 week double-blind phase with immediate-release paroxetine and during a 3 month double-blind extension phase were randomized to either immediate-release paroxetine or placebo in a 3 month double-blind relapse prevention phase. Patients randomized to paroxetine were significantly less likely to relapse than comparably treated patients who were randomized to placebo. 

### Social Anxiety Disorder

The efficacy of paroxetine hydrochloride extended-release tablets as a treatment for social anxiety disorder has been established, in part, on the basis of extrapolation from the established effectiveness of the immediate-release formulation of paroxetine. In addition, the effectiveness of paroxetine hydrochloride extended-release tablets in the treatment of social anxiety disorder was demonstrated in a 12 week, multicenter, double-blind, flexible dose, placebo-controlled study of adult outpatients with a primary diagnosis of social anxiety disorder (DSM-IV). In the study, the effectiveness of paroxetine hydrochloride extended-release tablets (12.5 mg to 37.5 mg daily) compared to placebo was evaluated on the basis of (1) change from baseline in the Liebowitz Social Anxiety Scale (LSAS) total score and (2) the proportion of responders who scored 1 or 2 (very much improved or much improved) on the Clinical Global Impression (CGI) Global Improvement score. 

Paroxetine hydrochloride extended-release tablets demonstrated statistically significant superiority over placebo on both the LSAS total score and the CGI Improvement responder criterion. For patients who completed the trial, 64% of patients treated with paroxetine hydrochloride extended-release tablets compared to 34.7% of patients treated with placebo were CGI Improvement responders. 

Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of gender. Subgroup analyses of studies utilizing the immediate-release formulation of paroxetine generally did not indicate differences in treatment outcomes as a function of age, race or gender. 

### Premenstrual Dysphoric Disorder

The effectiveness of paroxetine hydrochloride extended-release tablets for the treatment of PMDD utilizing a continuous dosing regimen has been established in two placebo-controlled trials. Patients in these trials met DSM-IV criteria for PMDD. In a pool of 1,030 patients, treated with daily doses of paroxetine hydrochloride extended-release tablets 12.5 or 25 mg/day or placebo the mean duration of the PMDD symptoms was approximately 11 ± 7 years. Patients on systemic hormonal contraceptives were excluded from these trials. Therefore, the efficacy of paroxetine hydrochloride extended-release tablets in combination with systemic (including oral) hormonal contraceptives for the continuous daily treatment of PMDD is unknown. In both positive studies, patients (n = 672) were treated with 12.5 mg/day or 25 mg/day of paroxetine hydrochloride extended-release tablets or placebo continuously throughout the menstrual cycle for a period of 3 menstrual cycles. The VAS-Total score is a patient-rated instrument that mirrors the diagnostic criteria of PMDD as identified in the DSM-IV and includes assessments for mood, physical symptoms and other symptoms. 12.5 mg/day and 25 mg/day of paroxetine hydrochloride extended-release tablets were significantly more effective than placebo as measured by change from baseline to the endpoint on the luteal phase VAS-Total score. 

In a third study employing intermittent dosing, patients (n = 366) were treated for the 2 weeks prior to the onset of menses (luteal phase dosing, also known as intermittent dosing) with 12.5 mg/day or 25 mg/day of paroxetine hydrochloride extended-release tablets or placebo for a period of 3 months. 12.5 mg/day and 25 mg/day of paroxetine hydrochloride extended-release tablets, as luteal phase dosing, was significantly more effective than placebo as measured by change from baseline luteal phase VAS total score. 

There is insufficient information to determine the effect of race or age on outcome in these studies.