NCDEU Poster Session 2012

Trajectories of Symptom Changes in Depression Clinical Trials

Craig Mallinckrodt, PhD; Ralitza Gueorguieva, PhD; and John H. Krystal, MD
From Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana (Dr Mallinckrodt); School of Public Health and Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut (Dr Gueorguieva); and VA National Center for PTSD, VA Healthcare System, West Haven, Connecticut (Dr Krystal).

This poster presentation did not receive funding.

Heterogeneous responses to antidepressant medications and placebo have plagued antidepressant drug development.1 The goal of the current study was to use growth mixture models to gain insights into the nature of response to drug and placebo. We reanalyzed data from seven randomized, double-blind, placebo and SSRI-controlled clinical trials of duloxetine (N=2517) to identify distinct trajectories of Hamilton Depression Rating Scale (HAMD) scores during treatment.2 In the entire sample and in the antidepressant-treated subsample, we identified trajectories of “responders” (76% of the sample) and “non-responders” (24% of the sample) while placebo-treated subjects were characterized by a single response trajectory. Duloxetine and SSRI did not differ in efficacy and they significantly decreased the odds of following the “non-responder” trajectory compared to placebo. Antidepressant “responders” had significantly better HAMD scores over time than placebo-treated patients, but antidepressant “non-responders” had significantly worse HAMD scores over time than placebo-treated group. This analysis confirmed that the majority of patients treated with serotonergic antidepressants show a clinical trajectory over time that is superior to placebo but it also indicated that a sizable minority of patients do more poorly on these medications than placebo. Medication risks and benefits during serotonergic antidepressant treatment should be carefully controlled. These results should further stimulate the search for biomarkers or other predictors of responder status in guiding antidepressant treatment.

Learning Objectives:
Appreciate the applicability of growth mixture models in understanding patient heterogeneity

Understand the differential trajectories for drug- and placebo-treated patients

1.  Turner EH, Matthews AM, Linardatos E, et al. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 358:(3);252–260. PubMed

2.  Gueorguieva R, Mallinckrodt C, Krystal JH. Trajectories of depression severity in clinical trials of duloxetine: insights into antidepressant and placebo responses. Arch Gen Psychiatry. 2011:68(12);1227–1237. PubMed

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