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Older age, mixed hypomanic symptoms may moderate depression remission

Although an exploratory analysis indicated several general, nonspecific predictors of depression remission, only two possible moderators — older age and mixed hypomanic symptoms — were identified that might help clinicians decide next-step treatment.

Many patients with major depression do not achieve remission, even after receiving optimally dosed antidepressant medication, Sidney Zisook, MD, from the VA San Diego Healthcare System and the department of psychiatry, University of California, San Diego, and colleagues wrote in American Journal of Psychiatry.

“Thus, providing effective, feasible and safe ‘next-step’ treatments aimed at increasing remission rates is a clinical imperative,” they wrote. “Finding specific moderators of outcomes to alternative subsequent treatments could help clinicians tailor treatment to individual patients with more precision, thereby minimizing exposure to inefficacious trial-and-error pharmacotherapy.”

The researchers analyzed data from the VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, a randomized trial of 1,522 Veterans Health Administration patients with major depressive disorder who did not respond to at least one course of antidepressant treatment.

Participants received one of three next-step treatment strategies for 12 weeks: switching to sustained-release bupropion; combining their current medication with sustained-release bupropion; or augmenting current medication with aripiprazole. Researchers examined which baseline characteristics were associated with remission overall (general predictors) and their interaction with remission in each treatment group (moderators).

Although the researchers found that most demographic features were not predictive of remission at 12 week, patients who were unemployed were less likely to achieve remission.

Certain baseline measures of severity and chronic depression were significantly negatively linked to remission, including worse scores on the Patient Health Questionnaire–9, Quick Inventory of Depressive Symptomatology–Clinician Rated and Clinical Global Impressions severity scale, and longer duration of depressive symptoms, Zisook and colleagues found.

Patients with greater anxiety, childhood adversity and complicated grief symptoms were less likely to achieve remission, but those with longer durations of the index medication trial, better general quality of life and positive mental health were more likely to achieve remission, according to the results.

The researchers found that only age group (P = .1) and mixed hypomanic symptoms (P = .01), were potential moderators of treatment effect.

Post hoc analysis of age indicated that augmentation with aripiprazole was more effective at inducing remission vs. switching to bupropion among those aged 65 years and older (37.6% vs. 20.5%; HR = 1.97; 95% CI, 1.18-3.28). For mixed hypomanic symptoms, analysis indicated that the interaction was driven by lower remission rates among participants who switched to bupropion compared with both augmentation with aripiprazole (13.9% vs. 30.1%; HR = 2.19; 95% CI, 1.29-3.72) and combination with bupropion (13.9% vs. 29%; HR = 2.21; 95% CI, 1.3-3.77).

“These preliminary findings begin to offer clinicians tentative evidence for tailoring next-step medication treatment,” Zisook and colleagues wrote. “If replicated, these findings should enhance clinicians’ ability to determine which depressed outpatients requiring next-step treatment are most effectively treated with specific augmentation, combination, or switching strategies.” – by Savannah Demko

Disclosure: Zisook reports no relevant financial disclosures. Please see the study for other authors’ relevant financial disclosures.