Age, Hypomanic Symptoms May Predict Response to Next-Step Treatment for Depression

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If replicated, preliminary findings could help clinicians determine whether patients who require next-step treatment will benefit most from a switching, augmentation, or combination strategy.

Age and the presence of hypomanic symptoms may predict differential response to next-step depression treatments, according to study data published in the American Journal of Psychiatry.

Investigators abstracted data from the US Department of Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, a multisite, randomized, single-blind trial of 1522 Veterans Health Administration patients who did not achieve adequate response to at least 1 course of antidepressant treatment. Per VAST-D protocol, participants received 1 of 3 possible next-step treatments for 12 weeks: switch to another antidepressant (in this case, sustained-release bupropion), receive a combination of the present drug with another antidepressant (sustained-release bupropion), or augmentation with an antipsychotic (aripiprazole). The primary outcome measure was remission, defined as a Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C) score ≤5 at 2 consecutive follow-up visits during the 12-week acute treatment phase. Basic demographic and clinical features of participants were obtained at baseline; life table regression models were used to identify baseline characteristics associated with remission overall, as well as remission in each treatment group.

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The mean (standard deviation) age of participants was 54.4 years (standard deviation, 12.2 years), and 85% were men. The majority of participants (69%) were white, 26% were black, and 10% were Hispanic. Worse baseline scores on the QIDS-C, Patient Health Questionnaire-9, and Clinical Global Impression-Severity (all P <.0001) were negatively associated with remission, as was greater duration of depression symptoms (P <.005). All 3 clusters of the QIDS-C (sleep, core emotional, and atypical) were negatively associated with remission (all P <.0001). In addition, greater anxiety per the Beck Anxiety Inventory (P <.001), greater childhood adversity (P =.02), and complicated grief symptoms (P <.0001) were also inversely associated with remission. Participants with longer duration of the index medication trial, better quality of life, and positive mental health were more likely to achieve remission (all P <.001).

Two promising potential moderators of treatment effect were identified: age group (P =.10) and mixed hypomanic symptoms (P =.01). In participants aged 65 years or older, higher remission rates were observed among those who received aripiprazole augmentation than those who switched to bupropion (37.6% vs 20.5%; hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.18-3.28). In addition, in participants with severe mixed hypomanic symptoms, switching to bupropion was associated with lower remission rates compared with augmentation with aripiprazole (13.9% vs 30.1%; HR, 2.19; 95% CI, 1.29-3.72) and combination with bupropion (13.9% vs 29.0%; HR, 2.21; 95% CI, 1.30-3.77).

Depression chronicity and severity were predictors of remission likelihood in participants. In addition, the efficacy of next-step treatments may be predicted in part by age and experience with mixed hypomanic symptoms. Additional research is necessary to confirm these preliminary findings.

“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,” the researchers concluded.

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Zisook S, Johnson GR, Tal I, et al. General predictors and moderators of depression remission: a VAST-D report [published online April 5, 2019]. Am J Psychiatry. doi:10.1176/appi.ajp.2018.18091079