Diane K. Wysowski, Ph.D. Office of Drug Safety FDA

1. Recent Observational Studies of Antidepressants (ADs) and Suicidal Behavior (Slides shown on Sept. 14, 2004) Diane K. Wysowski, Ph.D. Office of Drug Safety FDA

2. BACKUP SLIDES—Wysowski—RE: Jick’s supplemental analyses

3. RRs (95% CIs) with dothiepin as reference: Amitriptyline 0.83 (0.61-1.13) Fluoxetine 1.16 (0.90-1.50) Paroxetine 1.29 (0.97-1.70) RRs (95% CIs) with amitriptyline as reference: Dothiepin 1.21 (0.89-1.64) Fluoxetine 1.40 (1.03-1.91) Paroxetine 1.55 (1.11-2.16) Jick’s Case-Control Study--Supplemental Analyses

4. Jick’s Case-Control Study—Supplemental Analyses Statement of investigators: “We advise that these post hoc analyses be interpreted with caution. They were not the pre-planned primary analysis, and the P-value and confidence intervals are not adjusted for multiple hypothesis testing. We think conservative interpretation requires that P-values lower than 0.05 or confidence intervals with coverage greater than 95% would be necessary to assert that these results are ‘statistically significant’ with overall 5% type I error.”

5. Jick’s Case-Control Study—Supplemental Analyses Statement of investigators (cont.):“These results are consistent with the interpretation in our report that the risk of suicidal behavior after starting antidepressant treatment is ‘similar among users of amitriptyline, fluoxetine, and paroxetine compared with the risk among users of dothiepin’ and that a ‘possible small increase in risk (bordering statistical significance) among those starting the newest antidepressant, paroxetine, is of a magnitude that could readily be due to uncontrolled confounding by severity of depression.’ Moreover, we did not observe an increased risk of suicide itself for the users of amitriptyline, fluoxetine, or paroxetine compared to users of dothiepin.”