Patient Response Trajectories in Major Depressive Disorder

Objective

To investigate whether the efficacy of antidepressants can be understood in terms of patient response-trajectory classes.

Experimental Design

Patient-level data were analysed from 1357 adults with MDD randomised to either escitalopram 20 mg/day ( n = 676) or placebo ( n = 681) in five 8-week randomised placebo-controlled trials. Growth mixture models (GMMs) were used to identify the response trajectories; longitudinal latent class analysis (LLCA) was used to corroborate the findings.

Principal Observations

Three classes of response were identified for escitalopram and placebo based on the trajectory of the patients’ Montgomery-Åsberg Depression Rating Scale (MADRS) total scores during treatment. All three classes had similar mean baseline MADRS scores, but the change from baseline after 8 weeks differed: –4.2 MADRS points for non-responders, –18.4 MADRS points for slow responders, and –26.7 points for fast responders. The proportions of non-responders, slow responders and fast responders were 53%, 38% and 9%, respectively, with placebo and 27%, 58% and 14%, respectively, with escitalopram. Receiver operating curve analysis showed that a cut-off of ≥43% improvement from baseline to week 2 predicted fast responders, and a cut-off of ≥28% improvement from baseline to week 4 predicted responders (fast or slow). There were no clinically useful differences at baseline that predicted the trajectory class to which a patient would belong.

Conclusions

The presence of fast-, slow- and non-responder classes has a clear clinical relevance for guiding treatment decisions; individual patients can be classified by the change in their MADRS score from baseline at 2 or 4 weeks.