Early Symptom Trajectories as Predictors of Treatment Outcome for Citalopram Versus Placebo

Abstract

The high percentage of failed clinical trials for anti-depressant medications, especially in elderly populations, obscures the fact that some patients may benefit greatly from treatment. Early detection of patients who may benefit most from antidepressant medication may improve treatment decisions. We examined whether depressed patients in a large clinical trial exhibit distinct trajectories of early symptom change that predict differential response to medication or placebo. We reanalyzed data of 174 patients aged 75 years and older with unipolar depression who were randomly assigned to citalopram or placebo. We used growth mixture modeling to identify trajectories of early change (weeks 1-4) on the Hamilton Rating Scale for Depression in the citalopram and placebo conditions. In the citalopram condition, two distinct trajectories of early change were detected that were associated with significantly different symptom reduction, but only one trajectory was detected for the placebo condition. One of the early trajectories of patients receiving citalopram (N = 33) showed significantly better symptomatic change than placebo; the other trajectory (N = 51) did not differ significantly from placebo. Poor baseline functional scores predicted trajectory membership, so that individuals with a score below 4.5 on baseline instrumental activities of daily living showed a higher tendency to be in the trajectory that outperformed placebo. The subgroup of citalopram-treated patients exhibiting better symptom trajectory early in a trial are likely to have beneficial outcomes relative to placebo. Future research should focus on developing reliable pre-treatment clinical and biological measures to identify this subgroup.