A benefit-risk analysis of once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression

The traditional analysis of clinical trial data for antidepressants separately evaluates the results of efficacy and tolerability. The present analysis simultaneously evaluated these outcome criteria in a double-blind, placebo-controlled study of outpatients with major depression. Patients received either once-daily extended release (XR) venlafaxine or immediate release (IR) venlafaxine. Individual patient data on efficacy and treatment-emergent study events (TESE) for venlafaxine XR and venlafaxine IR were grouped into five categories. Efficacy was defined as a final on-therapy Clinical Global Impressions improvement score of 1 (very much improved) or 2 (much improved). A TESE was defined as any new adverse event or any adverse event that existed at baseline and increased in severity during treatment. Benefit/risk was evaluated using a linear measure and a ratio measure for dizziness, Insomnia, nausea, nervousness, somnolence, and a composite of anticholinergic events. This analysis demonstrated a superior benefit/risk ratio for the once-daily venlafaxine XR compared with venlafaxine IR, and a statistically significant benefit-to-risk ratio of at least 2:1 for venlafaxine XR over venlafaxine IR was demonstrated for nausea and dizziness. This approach to the statistical analysis of clinical trial data represents an advancement in addressing treatment outcome by incorporating clinically relevant measures of both efficacy and safety.