Predicting Response to Fluoxetine in Geriatric Patients With Major Depression

Abstract

No consensus exists regarding whether early response to an antidepressant strongly predicts a good outcome, what is the criterion for early response, or when to measure it. We hypothesized that early response (> or = 20% decrease in HAM-d21) after any of weeks 1, 2, or 3 of fluoxetine treatment of major depression in geriatric outpatients would predict a favorable outcome by week 6 or an earlier endpoint accurately enough for clinical use. We also hypothesized that the week 1, 2, and 3 percent changes in 21-item Hamilton Rating Scale for Depression (HAM-D21) 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-blind, placebo-controlled trial of fluoxetine, 20 mg/day. For analysis, fluoxetine-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 responders at weeks 1, 2, and 3 were statistically significantly more likely to experience marked improvement or remission than those lacking early response. However, at week 3, this criterion correctly classified only about three-fourths of patients with regard to marked improvement and only about two-thirds with regard to remission. Moreover, about one-third of patients predicted to experience marked improvement and about three-fifths of those predicted to remit did not. The continuous variable, percent change in HAM-D21, did not produce predictive results of any greater clinical utility. We believe that the sensitivity, specificity, false-positive rate, false-negative rate, and kappa of outcome predictions all should be reported in future studies. Without a full set of descriptive statistics, clinicians can be misled by statistically significant results.

Early response as predictor of final remission in elderly depressed patients

“…Only one geriatric study (Mulsant et al, 2006) compared different cut offs within the same patient group and found that final remission can be predicted after 4 weeks of treatment, although this study did not present confidence intervals. Koran et al (1995) found that their criterion to predict final remission, at least 20% reduction in week 1, 2 or 3, was not a clinically useful predictor because only 64.4% of their patients were correctly classified with regard to remission. This is in accordance with our findings in week 1, where only 54.5% of patients and in week 3 only 64.1% of patients were correctly classified using at least 20% reduction as cut-off.…”

“…We are aware of only one other study in elderly patients using data from one RCT (n ¼ 671), but this study compared prediction using only one cut off ( 20% reduction) in week 1, 2 and 3 (Koran et al, 1995). Both other geriatric studies compared data from two RCTs (n ¼ 446; Sackeim et al, 2005) or three RCTs (n ¼ 472; Mulsant et al, 2006) thus improving the power but at the cost of loosing internal validity.…”

“…In the first, a 20% decrease in HAM-D score at week 3 correctly classified two-third of elderly depressed patients in remission at 6 weeks (Koran et al, 1995). The second study found that only 16.5% of elderly patients with < 30% reduction in baseline HAM-D 24 score by week 4, achieved remission after 12 weeks (final HAM-D 6) (Sackeim et al, 2005).…”

Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression

“…It was suggested that time to remission of patients demonstrating depression of late life is about 2 weeks longer compared with younger patients. 182 On the whole, the results of the larger ALCAR studies support a role for ALCAR in depression even when compared with the results obtained with other antidepressants including fluoxetine (eg, Koran et al 183 ).…”

Initial Rate of Improvement in Relation to Remission of Major Depressive Disorder in Primary Care

“…3 As a consequence, it may be pertinent to reexamine a commonly quoted recommendation, that an antidepressant trial must last at least 6 weeks before considering a change in treatment. 4 Another reason to reexamine the relation between initial symptom change and outcome is that earlier studies [5][6][7][8] recommended treatment change based on analyses in which the treatment objective was defined as response, i.e., a reduction of at least 50% from pretreatment depression severity. The ultimate treatment goal, however, is remission.…”