Global benefit-risk assessment of antidepressants: venlafaxine XR and fluoxetine.
BACKGROUND
Quantifying efficacy and safety differences between drugs is difficult because rigorous statistical methods to assess benefit and risk simultaneously are lacking.


METHODS
Global benefit-risk (GBR) analysis of clinical trial data was used retrospectively to compare venlafaxine extended release (XR) and fluoxetine. Of 301 outpatients with moderate to severe depression given venlafaxine XR 75-225 mg/day (n=100), fluoxetine 20-60 mg/day (n=103), or placebo (n=98) for up to 8 weeks, 295 qualified for analysis. Primary efficacy variables were Hamilton Rating Scale for Depression (HAM-D) remission (final on-therapy score <or=7) and Clinical Global Impressions (CGI) response (very much or much improved).


RESULTS
Using remission as outcome, the relative gain of venlafaxine XR was 1.78 vs. fluoxetine (P<0.01) and 2.04 vs. placebo (P<or=0.005). HAM-D remission benefit exceeded risk for significantly more patients given venlafaxine XR (34%) than with fluoxetine (19%, P=0.023) or placebo (19%, P=0.017). The odds ratios [95% confidence interval (CI)] that patients would be in the benefit > risk category were 2.1 (1.1-4.0) and 2.2 (1.1-4.3) for venlafaxine XR vs. fluoxetine and placebo, respectively. For CGI response, relative gains of venlafaxine XR were 1.39 (P<0.01) and 1.45 (P<0.01) vs. fluoxetine and placebo; benefit exceeded risk in 66, 53, and 52% of patients given venlafaxine XR, fluoxetine, and placebo (P=0.041 vs. venlafaxine XR), respectively.


CONCLUSIONS
GBR analysis can be applied to a wide array of efficacy and safety data to form statistical tests of clinically meaningful treatment comparisons. In this comparison, the GBR assessments on response and remission significantly favored venlafaxine XR.
Entsuah
Richard
R
Global Clinical Biostatistics, Wyeth-Ayerst Research, 500 Arcola Road, Collegeville, PA 19426, USA. entsuaa@war.wyeth.com
Gorman
Jack M
JM
D000284:Administration, Oral; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D003866:Depressive Disorder / Q000188:drug therapy*; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D005473:Fluoxetine; D000069470:Venlafaxine Hydrochloride