Antidepressant Response Trajectories and Associated Clinical Prognostic Factors Among Older Adults

Abstract

Importance: More than 50% of older adults with late-life major depressive disorder fail to respond to initial treatment with first-line pharmacological therapy.

Objectives: To assess typical patterns of response to an open-label trial of extended-release venlafaxine hydrochloride (venlafaxine XR) for late-life depression and to evaluate which clinical factors are associated with the identified longitudinal response patterns.

Design, setting, and participants: Group-based trajectory modeling was applied to data from a 12-week open-label pharmacological trial conducted in specialty care as part of the Incomplete Response in Late Life: Getting to Remission Study. Clinical prognostic factors, including domain-specific cognitive performance and individual depression symptoms, were examined in relation to response trajectories. Participants included 453 adults aged 60 years or older with current major depressive disorder. The study was conducted between August 2009 and August 2014.

Intervention: Open-label venlafaxine XR (titrated up to 300 mg/d) for 12 weeks.

Main outcomes and measures: Subgroups exhibiting similar response patterns were derived from repeated measures of overall depression severity obtained using the Montgomery-Asberg Depression Rating Scale.

Results: Among the 453 study participants, 3 subgroups with differing baseline depression severity clearly responded to treatment: one group with the lowest baseline severity had a rapid response (n = 69 [15.23%]), and distinct responses were also apparent among groups starting at moderate (n = 108 [23.84%]) and higher (n = 25 [5.52%]) baseline symptom levels. Three subgroups had nonresponding trajectories: 2 with high baseline symptom levels (totaling 35.98%: high, nonresponse 1, n = 110 [24.28%]; high, nonresponse 2, n = 53 [11.70%]) and 1 with moderate baseline symptom levels (n = 88 [19.43%]). Several factors were independently associated with having a nonresponsive trajectory, including greater baseline depression severity, longer episode duration, less subjective sleep loss, more guilt, and more work/activity impairment (P < .05). Higher delayed memory (list recognition) performance was independently associated with having a rapid response (adjusted odds ratio = 2.22; 95% CI, 1.18-4.20).

Conclusions and relevance: Based on the observed trajectory patterns, patients who have late-life depression with high baseline depression severity are unlikely to respond after 12 weeks of treatment with venlafaxine XR. However, high baseline depression severity alone may be neither a necessary nor sufficient predictor of treatment nonresponse.

Trial registration: clinicaltrials.gov Identifier: NCT00892047.

Figures

Figure 1

Mean depressive symptom severity over 12-weeks of open-label treatment by data-derived trajectory group (Abbreviation: MADRS – Montgomery Asberg Depression Rating Scale)