PREDICTING RESPONSE TO FLUOXETINE IN GERIATRIC-PATIENTS WITH MAJOR DEPRESSION

No consensus exists regarding whether early response to an antidepress ant strongly predicts a good outcome, what is the criterion for early response, or when to measure it. We hypothesized that early response ( greater than or equal to 20% decrease in HAM-D-21) after any of weeks 1, 2, or 3 of fluoxetine treatment of major depression in geriatric ou tpatients would predict a favorable outcome by week 6 or an earlier en dpoint accurately enough for clinical use. We also hypothesized that t he meek 1, 2, an 3 percent changes in 21-item Hamilton Rating Scale fo r Depression (HAM-D-21) would predict the percent change at week 6 (or endpoint) accurately enough for clinical use. We enrolled 671 elderly outpatients with unipolar DSM-III-R major depression in a double-blin d, placebo-controlled trial of fluoxetine, 20 mg/day. For analysis, fl uoxetine-treated patients were randomly divided into a development set (N = 154) for a preliminary test of our criteria and a validation set (N = 181) to validate the development data set's results. Early respo nders gt weeks 1, 2, and 3 were statistically significantly more likel y to experience marked improvement or remission than those lacking ear ly response. However, at week 3, this criterion correctly classified o nly about three-fourths of patients with regard to marked improvement and only about two-thirds with regard to remission. Moreover, about on e-third of patients predicted to experience marked improvement and abo ut three-fifths of those predicted to remit did not. The continuous va riable, percent change in HAM-D-21, did not produce predictive results of any greater clinical utility. We believe that the sensitivity, spe cificity, false-positive rate, false-negative rate, and kappa of outco me predictions all should be reported in future studies. Without a ful l set of descriptive statistics, clinicians can be misled by statistic ally significant results.