Loss of interest and reduction of activity reported among patients with major depressive disorder (MDD) are predictive of a poor response to antidepressant monotherapy with escitalopram and are indicative of the need for aripiprazole augmentation. These findings were reported in The Journal of Clinical Psychiatry.

Recognizing that the symptom dimension that comprises loss of interest and reduced activity has been shown to portend a poor response to treatment with antidepressants, the researched explored whether augmentation with the partial dopamine agonist aripiprazole would prove effective in this patient population.

The 2-phase, multisite, open-label, 16-week Canadian Biomarker Integration Network in Depression trial 1 (CAN-BIND-1; ClinicalTrials.gov identifier: NCT01655706) was conducted between August 2013 and September 2016. CAN-BIND-1 enrolled a total of 211 adults—78 men and 133 women—with MDD. Patients were from 6 study sites in 5 Canadian cities. Study inclusion criteria were age between 18 and 60 years, the ability to understand and speak English fluently, a diagnosis of MDD confirmed with the Mini-International Neuropsychiatric Interview, current depressive episode lasting for ≥3 months, and a minimum score of 24 on the Montgomery-Åsberg Depression Rating Scale (MADRS).

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In phase 1 (week 0 to week 8) of the trial, all of the participants were offered treatment with the antidepressant escitalopram for 8 weeks. Escitalopram monotherapy was initiated following the week 0 (baseline) evaluation and was adjusted during pharmacotherapy visits with a study psychiatrist every 2 weeks. Escitalopram therapy was started at 10 mg orally once daily, with the dose increased to 20 mg once daily at week 2, if tolerated. For the remainder of phase 1 of the trial, the maximum tolerated dose (10 mg to 20 mg) was continued. At week 8 (ie, the end of phase 1), participants’ outcomes were assessed as the proportion reduction in the primary outcome measure compared with the baseline measurement.

In phase 2 (week 8 to week 16) of the trial, participants were offered additional treatment based on their outcome in phase 1. Those individuals who attained response (which was defined as a 50% reduction in the primary outcome measure) by week 8 continued with escitalopram monotherapy for another 8 weeks, whereas those participants who did not meet response criteria at week 8 were offered augmentation with aripiprazole.

Results of the study indicated that in phase 1, higher baseline interest-activity score (which was indicative of more severe loss of interest and reduced activity) was predictive of a significantly worse outcome with escitalopram alone (95% CI, 0.45 to 3.05; P =.009). This significant association disappeared, however, with aripiprazole augmentation in phase 2 (95% CI, –1.30 to 0.92; P =.739).

A significant interaction was observed between the baseline interest-activity score and aripiprazole, with respect to their effect on reduction in MADRS score (95% CI, –2.35 to

–0.84; P <.001), with the standardized effect size of this interaction reported to be 0.15

(95% CI, 0.07 to 0.23). Additionally, higher baseline interest-activity symptoms were linked to less of an improvement during escitalopram monotherapy but to a greater improvement during aripiprazole augmentation.

Limitations of the study include the lack of random allocation, and as the study was open-label, there was no attempt to blind raters or participants to the treatment they were receiving.

The investigators concluded that future studies are warranted, which are designed to evaluate the accelerated use of augmentation with dopaminergic agents for depression that is characterized by prominent interest-activity symptoms, earlier in the treatment course


Uher R, Frey BN, Quilty LC, et al. Symptom dimension of interest-activity indicates need for aripiprazole augmentation of escitalopram in major depressive disorder: a CAN-BIND-1 report [published online June 16, 2020]. J Clin Psychiatry. doi: 10.4088/JCP.20m13229