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Symptom Dimension of Interest-Activity Indicates Need for Aripiprazole Augmentation of Escitalopram in Major Depressive Disorder: A CAN-BIND-1 Report.
J Clin Psychiatry. 2020 Jun 16; 81(4)JC

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.

Authors+Show Affiliations

Dalhousie University, 5909 Veterans Memorial Lane, Halifax, NS, B3H 2E2, NS, Canada. uher@dal.ca. Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. Nova Scotia Health Authority, Halifax, Nova Scotia, Canada.Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada. St Joseph's Healthcare, Hamilton, Ontario, Canada.Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Department of Psychiatry, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.Royal's Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada.Department of Psychiatry & Behavioural Neurosciences, St Joseph's Healthcare, Hamilton, Ontario, Canada.Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.Departments of Psychiatry and Psychology, Queen's University, Providence Care Hospital, Kingston, Ontario, Canada.Douglas Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA.Departments of Psychiatry and Psychology, Queen's University, Providence Care Hospital, Kingston, Ontario, Canada.University of Calgary, Hotchkiss Brain Institute, Calgary, Alberta, Canada.Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Department of Psychiatry, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. Department of Psychiatry, University Health Network, Toronto, Ontario, Canada. Krembil Research Centre, University Health Network, University of Toronto, Canada.Members of the CAN-BIND Investigator Team are listed at www.canbind.ca/about-can-bind/our-team/.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32558407

Citation

Uher, Rudolf, et al. "Symptom Dimension of Interest-Activity Indicates Need for Aripiprazole Augmentation of Escitalopram in Major Depressive Disorder: a CAN-BIND-1 Report." The Journal of Clinical Psychiatry, vol. 81, no. 4, 2020.
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. J Clin Psychiatry. 2020;81(4).
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. (2020). Symptom Dimension of Interest-Activity Indicates Need for Aripiprazole Augmentation of Escitalopram in Major Depressive Disorder: A CAN-BIND-1 Report. The Journal of Clinical Psychiatry, 81(4). https://doi.org/10.4088/JCP.20m13229
Uher R, et al. Symptom Dimension of Interest-Activity Indicates Need for Aripiprazole Augmentation of Escitalopram in Major Depressive Disorder: a CAN-BIND-1 Report. J Clin Psychiatry. 2020 Jun 16;81(4) PubMed PMID: 32558407.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Symptom Dimension of Interest-Activity Indicates Need for Aripiprazole Augmentation of Escitalopram in Major Depressive Disorder: A CAN-BIND-1 Report. AU - Uher,Rudolf, AU - Frey,Benicio N, AU - Quilty,Lena C, AU - Rotzinger,Susan, AU - Blier,Pierre, AU - Foster,Jane A, AU - Müller,Daniel J, AU - Ravindran,Arun V, AU - Soares,Claudio N, AU - Turecki,Gustavo, AU - Parikh,Sagar V, AU - Milev,Roumen, AU - MacQueen,Glenda, AU - Lam,Raymond W, AU - Kennedy,Sidney H, AU - ,, Y1 - 2020/06/16/ PY - 2020/01/01/received PY - 2020/04/27/accepted PY - 2020/6/20/entrez JF - The Journal of clinical psychiatry JO - J Clin Psychiatry VL - 81 IS - 4 N2 - 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. SN - 1555-2101 UR - https://www.unboundmedicine.com/medline/citation/32558407/Symptom_Dimension_of_Interest-Activity_Indicates_Need_for_Aripiprazole_Augmentation_of_Escitalopram_in_Major_Depressive_Disorder:_A_CAN-BIND-1_Report L2 - http://www.psychiatrist.com/JCP/article/Pages/2020/v81/20m13229.aspx DB - PRIME DP - Unbound Medicine ER -
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