These studies present the first time an SNRI has been evaluated in SAD. SNRIs are believed to work by increasing the levels of two brain chemicals – serotonin and norepinephrine – a deficiency of which is thought to play a role in causing depression and anxiety disorders.
"Alternative therapies for social anxiety disorder are important because health care providers have limited options available to treat this crippling illness," said lead investigator Michael R. Liebowitz, M.D., professor of clinical psychiatry at Columbia University and director of the Anxiety Disorders Clinic at the New York State Psychiatric Institute. "In these studies, venlafaxine XR significantly reduced fear and anxiety-related symptoms in social phobic patients."
SAD is the third most common psychiatric disorder in the United States, occurring in approximately 10 million Americans each year. People with SAD experience overwhelming and disabling fear of scrutiny, embarrassment, or humiliation in social situations, which are often avoided or endured with dread. Approximately 70 to 80 percent of all social phobics have coexisting psychiatric conditions. In particular, SAD patients have a 40 to 50 percent lifetime prevalence of coexisting major depressive disorder.
Study results
In the two 12-week studies, venlafaxine XR significantly reduced patients' SAD symptoms compared to placebo as early as four or six weeks, with continued improvements through week 12, as measured by declines in their mean scores on several standard measures including the Liebowitz Social Anxiety Scale (LSAS).
In the first study, treated patients had significant reductions in mean LSAS scores at week six, and even greater reductions occurred by week 12. In the second study, the significant reduction in mean LSAS scores with venlafaxine XR occurred at the fourth week; by week 12, the treated patients averaged even greater reductions compared to the placebo group.
In addition to LSAS scores, the studies used such standard measures as the Clinical Global Impressions – Severity (CGI-S) score, CGI-Improvement (CGI-I) score and Social Phobia Inventory (SPIN). As with their LSAS scores, venlafaxine XR patients made significant progress within weeks of starting treatment and continued to improve through the studies' 12 weeks.
During the clinical trials, investigators assessed patients multiple times and used data from a patient's last visit for their analyses, even if the patient did not complete the study. This calculation, known as last observation carried forward (LOCF), is standard for medical studies.
None of the investigators or patients in either study (279 patients in the first and 272 patients in the second) knew whether the patients received venlafaxine XR or a placebo until the trials ended. The once-daily doses of venlafaxine ranged from 75 to 225 milligrams. Prior to the clinical trials, all participants received placebo for three to 10 days and after the trials, investigators tapered the patients' dosages for 14 days.
Patients in both studies met the Diagnostic and Statistical Manual of Mental Disorders-IV (criteria for generalized SAD for six or more months prior to their enrollment. The average duration of the patients' SAD was 22 years for study one and 26 years for study two. Baseline LSAS scores averaged 89 in both studies. The percentages of patients who had CGI-S scores of greater than four was 55 percent in study one and 47 percent in study two. Average age of the patients was 38 years; 44 percent were women.
Treatment-related adverse events reported by patients included nausea, insomnia, anorexia, dry mouth and sweating.
Wyeth Research supported the studies.
About Venlafaxine XR
Venlafaxine XR, a once-daily formulation of venlafaxine, is approved by the U.S. Food and Drug Administration (FDA) and 33 countries worldwide to treat patients with depression and generalized anxiety disorder (GAD). GAD, a very common anxiety disorder, is a long-term condition marked by overwhelming, chronic, and excessive worry, anxiety and tension that persist for at least six months. Venlafaxine extended-release is approved for both short- and long-term (six months) GAD treatment.
The most common adverse events reported in venlafaxine XR placebo-controlled depression trials (incidence greater than or equal to 10 percent or greater than or equal to twice that of placebo) were nausea, dizziness, somnolence, delayed ejaculation, sweating, dry mouth, and nervousness; and in generalized anxiety disorder (GAD) trials were nausea, dry mouth, insomnia, delayed ejaculation, anorexia, constipation, nervousness, and sweating. Venlafaxine XR is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs). Treatment with venlafaxine is associated with sustained increases in blood pressure (BP) in some patients. Regular BP monitoring is recommended. Patients should not be abruptly discontinued from antidepressant medication, including venlafaxine XR; see the Dosage and Administration section of the Prescribing Information.
Please see accompanying prescribing information.