https://immattersacp.org/weekly/archives/2017/07/18/2.htm

Adding aripiprazole to antidepressant therapy may help treat patients with resistant major depressive disorder

A study group that added aripiprazole to current therapy significantly exceeded remission rates compared to a group that switched antidepressants.


For patients with major depressive disorder that is inadequately controlled with antidepressant therapy, adding an atypical antipsychotic may help more than switching to or adding another antidepressant, according to a recent trial.

At 35 VA medical centers, researchers randomized 1,522 participants diagnosed with major depressive disorder unresponsive to at least one antidepressant to receive one of three treatment options: switching to a different antidepressant, bupropion (n=511); adding bupropion to the current treatment (n=506); or adding aripiprazole to the current treatment (n=505).

The primary outcome was remission of depression after 12 weeks of acute treatment (defined as a score of ≤5 on the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] questionnaire at two consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale).

Results were published online on July 11 by JAMA.

At 12 weeks, remission rates were 22.3% (n=114) for the switch group, 26.9% (n=136) for the add-bupropion group, and 28.9% (n=146) for the add-aripiprazole group. The aripiprazole group significantly exceeded the switch group in remission (relative risk, 1.30 [95% CI, 1.05 to 1.60]; P=0.02), but other remission rate comparisons did not reach significance.

The aripiprazole group also saw greater response at 12 weeks (74.3%) than both the switch group (62.4%; RR, 1.19 [95% CI, 1.09 to 1.29]; P<0.001) and the add-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04 to 1.23]; P=0.003). In the two bupropion groups, anxiety was a more frequent adverse effect, whereas somnolence, akathisia, and weight gain occurred more frequently in the aripiprazole group.

The authors noted limitations to their study, such as how only one antidepressant and one antipsychotic were evaluated. They added that differences in between-group outcomes were small in magnitude and that only 1,137 participants (74.7%) completed the acute treatment phase.

An accompanying editorial noted that the study population was predominantly male (85.2%) and that up to 48% of participants in the study had posttraumatic stress disorder, which may have influenced the modest yet significant advantage of adding aripiprazole to major depressive disorder treatment. With this in mind, the study “offers an important perspective on the role of treatment using augmentation with atypical antipsychotic agents in this population commonly seen in VA clinics,” the editorialist wrote.

In another study related to antidepressants, published online on July 12 by JAMA Psychiatry, researchers used national registry data of nearly 180,000 children to explore the association of maternal antidepressant use during pregnancy and intellectual disability in offspring. After adjusting for confounders (e.g., parental age, mother's psychiatric disorder), they found no such association.