Escitalopram combined with aripiprazole improves interest-activity reduction in MDD

Individuals with depression who experienced loss of interest and reduced activity appeared to benefit more from aripiprazole augmentation than escitalopram monotherapy, according to findings published in Journal of Clinical Psychiatry.

“Individuals with [major depressive disorder] who report profound loss of interest and severely reduced activity responded less well to both serotonergic (citalopram, escitalopram) and noradrenergic (nortriptyline) antidepressants,” Rudolf Uher, MD, PhD, of the department of psychiatry at Dalhousie University in Canada, and colleagues wrote. “In a separate study, the prodopaminergic antidepressant bupropion led to greater improvement in positive mood symptoms, including increases in interest and activity. The potential of other, more potent dopaminergic treatments, such as partial dopamine agonists aripiprazole and brexpiprazole, to improve interest and activity remains to be established.”

Prior studies have reported the symptom dimension that comprises reduced activity and loss of interest as a predictor of poor outcome of treatment with antidepressants. In the current study, Uher and colleagues sought to determine whether escitalopram augmentation with the partial dopamine agonist aripiprazole provided greater efficacy among individuals with prominent interest-activity symptoms.

The researchers analyzed data of participants with a primary diagnosis of MDD according to the Mini-International Neuropsychiatric Interview who were included in the two-phase Canadian Biomarker Integration Network in Depression trial 1. A total of 1,188 participants received 10-20 mg of escitalopram monotherapy daily for 8 weeks in phase 1. In phase 2, those who didn’t respond received augmentation with 2-10 mg of aripiprazole daily while those who responded maintained escitalopram monotherapy for 8 additional weeks. Uher and colleagues used the Montgomery-Åsberg Depression Rating Scale (MADRS) to measure outcomes every 2 weeks. They tested effects of baseline interest-activity symptoms on outcomes in repeated-measures mixed-effects models.

Results showed higher baseline interest-activity score, which was indicative of more severe reduction in activity and loss of interest, predicted worse escitalopram monotherapy outcome in phase 1 (beta = 1.75; 95% CI, 0.45-3.05); however, the association disappeared upon phase 2 augmentation (beta = 0.19; 95% CI, 1.30 to 0.92). The researchers observed that a significant interaction between aripiprazole and the baseline interest-activity score reflected the opposite direction of the relationship between degree of improvement with escitalopram monotherapy vs. aripiprazole augmentation and baseline interest-activity score (beta = 1.60; 95% CI, 2.35 to 0.84).

“Future studies may evaluate accelerated use of augmentation with dopaminergic agents for depression with prominent interest-activity symptoms earlier in the course of treatment,” Uher and colleagues wrote.