Efficacy of venlafaxine in patients with major depressive disorder who have unsustained or no response to selective serotonin reuptake inhibitors: an open-label, uncontrolled study.

BACKGROUND: Approximately half of patients who are prescribed selective serotonin re-uptake inhibitors (SSRIs) either do not respond to treatment or do not experience a sustained response.

OBJECTIVE: The purpose of this study was to assess the efficacy of venlafaxine immediate-release (IR) and extended-release (XR) in outpatients who either did not respond to SSRI treatment or did not maintain a sustained response.

METHODS: Outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depressive disorder who were previously treated with an SSRI (fluoxetine > or = 20 mg/d; sertraline > or = 50 mg/d; paroxetine > or = 20 mg/d) for > or = 6 weeks, but demonstrated an inadequate or unsustained response, were switched to venlafaxine (IR or XR formulation, 50-400 mg/d, titrated from 37.5 mg/d) for > or = 6 weeks. Response at 6 to 8 weeks was defined as total score < or = 10 on the modified 25-item Hamilton Depression (HAM-D25) rating scale or total score > or = 5 on the 21-item Patient Global Improvement (PGI-21) scale. Remission was defined as a HAM-D25 total score < or = 8 or PGI-21 score > or = 7. Tests were administered by an unblinded, board-certified psychiatrist.

RESULTS: A total of 73 patients (54 women, 19 men; mean age, 38.6 years) were enrolled and treated with venlafaxine IR (n = 63) or venlafaxine XR (n = 10); 33 were SSRI nonresponders and 36 had an unsustained response to SSRI treatment. Four patients receiving venlafaxine IR discontinued due to drug-related adverse events (agitation, sedation, or nausea). Data from these patients were excluded from the analysis. After 6 to 8 weeks of treatment, 94.2% (65/69) of patients were considered responders (HAM-D25 or PGI-21 criteria); 91.3% (63/69) of patients responded to treatment as assessed by both measures. Eighty-seven percent (60/69) and 85.5% (59/69) of patients achieved remission based on HAM-D,5 and PGI-21 criteria, respectively. Response/remission rates were comparable among patients treated with SSRIs, regardless of whether patients had failed to respond to treatment with 1 or 2 SSRIs.

CONCLUSION: Venlafaxine IR/venlafaxine XR may be effective in outpatients with major depressive disorder who do not respond or have an unsustained response to SSRIs. However, randomized, controlled trials are needed before any conclusions can be drawn about the efficacy of this agent in this population.