Venlafaxine clinical studies

# Clinical Studies

## major depressive disorder
The efficacy of Effexor XR (venlafaxine hydrochloride) extended-release capsules as a treatment for major depressive disorder was established in two placebo-controlled, short-term, flexible-dose studies in adult outpatients meeting DSM-III-R or DSM-IV criteria for major depressive disorder.
A 12-week study utilizing Effexor XR doses in a range 75 to 150 mg/day (mean dose for completers was 136 mg/day) and an 8-week study utilizing Effexor XR doses in a range 75 to 225 mg/day (mean dose for completers was 177 mg/day) both demonstrated superiority of Effexor XR over placebo on the HAM-D total score, HAM-D Depressed Mood Item, the MADRS total score, the Clinical Global Impressions (CGI) Severity of Illness item, and the CGI Global Improvement item. In both studies, Effexor XR was also significantly better than placebo for certain factors of the HAM-D, including the anxiety/somatization factor, the cognitive disturbance factor, and the retardation factor, as well as for the psychic anxiety score.
A 4-week study of inpatients meeting DSM-III-R criteria for major depressive disorder with melancholia utilizing Effexor (immediate release) in a range of 150 to 375 mg/day (t.i.d. schedule) demonstrated superiority of Effexor over placebo. The mean dose in completers was 350 mg/day.
Examination of gender subsets of the population studied did not reveal any differential responsiveness on the basis of gender.
In one longer-term study, adult outpatients meeting DSM-IV criteria for major depressive disorder who had responded during an 8-week open trial on Effexor XR (75, 150, or 225 mg, qAM) were randomized to continuation of their same Effexor XR dose or to placebo, for up to 26 weeks of observation for relapse. Response during the open phase was defined as a CGI Severity of Illness item score of 3 and a HAM-D-21 total score of 10 at the day 56 evaluation. Relapse during the double-blind phase was defined as follows: (1) a reappearance of major depressive disorder as defined by DSM-IV criteria and a CGI Severity of Illness item score of 4 (moderately ill), (2) 2 consecutive CGI Severity of Illness item scores of 4, or (3) a final CGI Severity of Illness item score of 4 for any patient who withdrew from the study for any reason. Patients receiving continued Effexor XR treatment experienced significantly lower relapse rates over the subsequent 26 weeks compared with those receiving placebo.
In a second longer-term trial, adult outpatients meeting DSM-III-R criteria for major depressive disorder, recurrent type, who had responded (HAM-D-21 total score 12 at the day 56 evaluation) and continued to be improved  during an initial 26 weeks of treatment on Effexor (immediate release)  were randomized to continuation of their same Effexor dose or to placebo. The follow-up period to observe patients for relapse, defined as a CGI Severity of Illness item score 4, was for up to 52 weeks. Patients receiving continued Effexor treatment experienced significantly lower relapse rates over the subsequent 52 weeks compared with those receiving placebo.
Generalized Anxiety Disorder
The efficacy of Effexor XR capsules as a treatment for Generalized Anxiety Disorder (GAD) was established in two 8-week, placebo-controlled, fixed-dose studies, one 6-month, placebo-controlled, fixed-dose study, and one 6-month, placebo-controlled, flexible-dose study in adult outpatients meeting DSM-IV criteria for GAD.
One 8-week study evaluating Effexor XR doses of 75, 150, and 225 mg/day, and placebo showed that the 225 mg/day dose was more effective than placebo on the Hamilton Rating Scale for Anxiety (HAM-A) total score, both the HAM-A anxiety and tension items, and the Clinical Global Impressions (CGI) scale. While there was also evidence for superiority over placebo for the 75 and 150 mg/day doses, these doses were not as consistently effective as the highest dose. A second 8-week study evaluating Effexor XR doses of 75 and 150 mg/day and placebo showed that both doses were more effective than placebo on some of these same outcomes; however, the 75 mg/day dose was more consistently effective than the 150 mg/day dose. A dose-response relationship for effectiveness in GAD was not clearly established in the 75 to 225 mg/day dose range utilized in these two studies.
Two 6-month studies, one evaluating Effexor XR doses of 37.5, 75, and 150 mg/day and the other evaluating Effexor XR doses of 75 to 225 mg/day, showed that daily doses of 75 mg or higher were more effective than placebo on the HAM-A total, both the HAM-A anxiety and tension items, and the CGI scale during 6 months of treatment. While there was also evidence for superiority over placebo for the 37.5 mg/day dose, this dose was not as consistently effective as the higher doses.
Examination of gender subsets of the population studied did not reveal any differential responsiveness on the basis of gender.

## Social Anxiety Disorder (Social Phobia)
The efficacy of Effexor XR capsules as a treatment for Social Anxiety Disorder (also known as Social Phobia) was established in four double-blind, parallel-group, 12-week, multicenter, placebo-controlled, flexible-dose studies and one double-blind, parallel-group, 6-month, placebo-controlled, fixed/flexible-dose study in adult outpatients meeting DSM-IV criteria for Social Anxiety Disorder. Patients received doses in a range of 75 to 225 mg/day. Efficacy was assessed with the Liebowitz Social Anxiety Scale (LSAS). In these five trials, Effexor XR was significantly more effective than placebo on change from baseline to endpoint on the LSAS total score. There was no evidence for any greater effectiveness of the 150 to 225 mg/day group compared to the 75 mg/day group in the 6-month study.
Examination of subsets of the population studied did not reveal any differential responsiveness on the basis of gender. There was insufficient information to determine the effect of age or race on outcome in these studies.

## Panic Disorder
The efficacy of Effexor XR capsules as a treatment for panic disorder was established in two double-blind, 12-week, multicenter, placebo-controlled studies in adult outpatients meeting DSM-IV criteria for panic disorder, with or without agoraphobia. Patients received fixed doses of 75 or 150 mg/day in one study and 75 or 225 mg/day in the other study.
Efficacy was assessed on the basis of outcomes in three variables: (1) percentage of patients free of full-symptom panic attacks on the Panic and Anticipatory Anxiety Scale (PAAS); (2) mean change from baseline to endpoint on the Panic Disorder Severity Scale (PDSS) total score; and (3) percentage of patients rated as responders (much improved or very much improved) on the Clinical Global Impressions (CGI) Improvement scale. In these two trials, Effexor XR was significantly more effective than placebo in all three variables.
In the two 12-week studies described above, one evaluating Effexor XR doses of 75 and 150 mg/day and the other evaluating Effexor XR doses of 75 and 225 mg/day, efficacy was established for each dose. A dose-response relationship for effectiveness in patients with panic disorder was not clearly established in fixed-dose studies.
Examination of subsets of the population studied did not reveal any differential responsiveness on the basis of gender. There was insufficient information to determine the effect of age or race on outcome in these studies.
In a longer-term study, adult outpatients meeting DSM-IV criteria for panic disorder who had responded during a 12-week open phase with Effexor XR (75 to 225 mg/day) were randomly assigned to continue the same Effexor XR dose (75, 150, or 225 mg) or switch to placebo for observation for relapse under double-blind conditions. Response during the open phase was defined as  1 full-symptom panic attack per week during the last 2 weeks of the open phase and a CGI Improvement score of 1 (very much improved) or 2 (much improved). Relapse during the double-blind phase was defined as having 2 or more full-symptom panic attacks per week for 2 consecutive weeks or having discontinued due to loss of effectiveness as determined by the investigators during the study. Randomized patients were in response status for a mean time of 34 days prior to being randomized. In the randomized phase following the 12-week open-label period, patients receiving continued Effexor XR experienced a significantly longer time to relapse.