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Cited by 19Treatment of Major DepressionAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesBipolar Disorder and Treatment

Symptom Dimension of Interest-Activity Indicates Need for Aripiprazole Augmentation of Escitalopram in Major Depressive Disorder: A CAN-BIND-1 Report

Uher, Rudolf, Frey, Benicio N., Quilty, Lena C., Rotzinger, Susan, Blier, Pierre, Foster, Jane A., Müller, Daniel J., Ravindran, Arun V. +8 more·2020·The Journal of Clinical Psychiatry
DOI 10.4088/jcp.20m13229
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Abstract

OBJECTIVE: Differential predictors of response to alternative treatment options are needed to improve the outcomes in major depressive disorder. The symptom dimension comprising loss of interest and reduced activity has been reported as a predictor of poor outcome of treatment with antidepressants. We hypothesized that augmentation with partial dopamine agonist aripiprazole will be effective for individuals with pronounced interest-activity symptoms. METHODS: We tested the hypothesis in the 2-phase Canadian Biomarker Integration Network in Depression trial 1 (CAN-BIND-1). All participants had a primary diagnosis of major depressive disorder confirmed with the Mini-International Neuropsychiatric Interview. In phase 1, 188 individuals received escitalopram monotherapy 10-20 mg daily for 8 weeks. In phase 2, nonresponders received augmentation with aripiprazole 2-10 mg daily while responders continued escitalopram monotherapy for another 8 weeks. Outcomes were measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) every 2 weeks. Effects of baseline interest-activity symptoms on outcomes were tested in repeated-measures mixed-effects models. RESULTS: Higher baseline interest-activity score (indicative of more severe loss of interest and reduction in activity) predicted worse outcome of escitalopram monotherapy in phase 1 (b = 1.75; 95% CI, 0.45 to 3.05; P = .009), but the association disappeared with the augmentation option in phase 2 (b = -0.19; 95% CI, -1.30 to 0.92; P = .739). A significant interaction between the baseline interest-activity score and aripiprazole reflected the opposite direction of the relationship between baseline interest-activity score and degree of improvement with escitalopram monotherapy versus aripiprazole augmentation (b = -1.60; 95% CI, -2.35 to -0.84; P < .001). CONCLUSIONS: Individuals with prominent loss of interest and reduction in activity benefit less from escitalopram monotherapy and more from aripiprazole augmentation. Future trials may test the benefits of early prodopaminergic augmentation guided by interest-activity symptoms. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01655706.

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  1. [17]17. Jamerson BD, Krishnan KR, Roberts J, et al. Effect of bupropion SR on specific symptom clusters of depression: analysis of the 31-item Hamilton Rating Scale for depression. Psychopharmacol Bull . 2003;37(2):67-78. PubMed
  2. [21]21. Mohamed S, Johnson GR, Chen P, et al; VAST-D Investigators. Effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder unresponsive to antidepressant treatment: the VAST-D randomized clinical trial. JAMA . 2017;318(2):132-145. PubMed CrosRef
  3. [22]22. Kennedy SH, Lam RW, Rotzinger S, et al; CANBIND Investigator Team. Symptomatic and response to escitalopram monotherapy and sequential adjunctive aripiprazole therapy in patients with major depressive disorder: a CAN-BIND-1 report. J Clin Psychiatry . 2019;80(2):18m12202. PubMed CrosRef

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Authors
Uher, R., Frey, B. N., Quilty, L. C., Rotzinger, S., Blier, P., Foster, J. A., Müller, D. J., Ravindran, A. V., Soares, C. N., Turecki, G., Parikh, S. V., Milev, R., MacQueen, G., Lam, R. W., Kennedy, S. H., & on behalf of the CAN-BIND Investigator Team
Affiliations
  • Dalhousie University (CA)
  • St. Joseph’s Healthcare Hamilton (CA)
  • Centre for Addiction and Mental Health (CA)
  • St. Michael's Hospital (CA)
  • University of Ottawa (CA)
  • McGill University (CA)
  • University of Michigan (US)
  • Queen's University (CA)
  • University of Calgary (CA)
  • University of British Columbia (CA)
Corresponding author
Uher, Rudolf
ORCID
Venue
The Journal of Clinical Psychiatry
Publisher
Physicians Postgraduate Press, Inc
Published
2020-06-16
Volume
81
Issue
4
ISSN
  • 0160-6689 (ISSN-L)
  • 1555-2101
DOI
10.4088/jcp.20m13229
OpenAlex
W3035223437
Cited by
19
References
43
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 2
FWCI
1.65
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research (148394)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Keywords
major depressive disorder, aripiprazole, escitalopram, antidepressant augmentation, loss of interest, reduced activity, treatment response prediction, partial dopamine agonist
MeSH terms
Aripiprazole, Adolescent, Adult, Major Depressive Disorder, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Citalopram, Dopamine Agonists, Antidepressive Agents, Second-Generation, Lethargy, Young Adult

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