Monday, April 8, 2019

Study Suggests Effective Next-Step Treatments for Treatment-Resistant Depression


A new study of predictors and moderators of remission for treatment-resistant major depressive disorder (MDD) found two subgroups of patients who may benefit from specific next-step treatments with aripiprazole or bupropion, according to a report in AJP in Advance.

The study by Sydney Zisook, M.D. (pictured left), a distinguished professor of psychiatry at the University of California, San Diego, and colleagues involved 1,500 mostly older white men with nonpsychotic MDD who were enrolled in the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study. To be included in VAST-D, participants had to have previously failed to respond to at least one course of antidepressant treatment.

VAST-D focused on the effectiveness and safety of three next-step treatment strategies over a 12-week trial: switching to sustained-release bupropion, combining the current medication with sustained-release bupropion, or augmenting the current medication with the antipsychotic aripiprazole. VAST-D participants took a battery of tests, including the Quick Inventory of Depressive Symptomatology—Clinician Rated (QIDS-C), the Clinical Global Impressions severity scale (CGI-S), and the Patient Health Questionnaire (PHQ-9) and had treatment visits at baseline and at weeks 1, 2, 4, 6, 8, 10, and 12.

The first report from the trial revealed that patients who took aripiprazole in addition to the antidepressant they were previously taking had the highest 12-week remission and response rates compared with patients who took bupropion in addition to antidepressants or switched to bupropion.

This latest study focused on helping clinicians predict the most effective treatment strategies for individual patients based on sociodemographic or clinical features, a subject on which Zisook told Psychiatric News there has been very little research to date. These features included age, ethnicity, and employment status; depressive symptom severity, chronicity, and subtype; level of anxiety; mixed hypomanic symptoms; childhood adversity; grief; co-occurring general medical and psychiatric conditions; positive mental health; and quality of life.

The analysis revealed that augmentation with aripiprazole was more effective for patients aged 65 years and older, compared with the bupropion regimens, whereas for patients with severe mixed hypomanic symptoms, augmentation with aripiprazole or combination of current treatment and bupropion was more effective than switching to bupropion.

The researchers also found that most patient demographic features did not predict overall remission at 12 weeks. However, remission was more likely for individuals who were employed, less severely and chronically depressed, less anxious, and not experiencing complicated grief symptoms and who had not experienced childhood adversity. Participants with longer durations of the initial antidepressant medication trial, better quality of life, and positive mental health were also more likely to achieve remission.

“Overall, it’s really a balancing act, and there’s no clear rule that’s going to apply to each patient,” Zisook said. “When considering what’s most likely to be effective versus potential side effects, you should always engage the patient when coming up with next-step treatments—because they’re the ones that need to be compliant in taking the medication. So they should be partners in making the decision.”

For more information, see the Psychiatric News article “Study to Answer What Comes Next When MDD Patients Don’t Respond.”

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