Predictors of Quality of Life Improvement with Escitalopram and Adjunctive Aripiprazole in Patients with Major Depressive Disorder: A CAN-BIND Study Report



Non-response to first-line treatment for major depressive disorder (MDD) is common; for such individuals, quality of life (QoL) impairments can be severe. Identifying predictors of QoL changes may support the management of cases with persistent depressive symptoms despite adequate initial pharmacological/psychological treatment.


The present study aimed to explore predictors of domain-specific QoL improvement following adjunctive aripiprazole treatment for inadequate response to initial antidepressant therapy.


We evaluated secondary QoL outcomes from a CAN-BIND (Canadian Biomarker Integration Network in Depression) study in patients with MDD who did not respond to an initial 8 weeks of escitalopram and received a further 8 weeks of adjunctive aripiprazole (n = 96). Physical, psychological, social, and environmental QoL domains were assessed using the World Health Organization QoL Scale Brief Version (WHOQOL-BREF). Clinician-rated depressive symptoms were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS). Functioning was measured with the Sheehan Disability Scale (SDS). Satisfaction with medication was assessed with a single item from the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Exploratory t-tests were used to describe domain score changes. A hierarchical linear regression was used to explore demographic, clinical, and treatment-related predictors of improvement.


Across domains, QoL improved with adjunctive aripiprazole treatment. Satisfaction with medication and MADRS and SDS scores similarly improved. Symptom reduction was a predictor for positive change to physical and psychological QoL; functioning improvements were predictive of increases to all QoL domains. Satisfaction with medication predicted improvements to physical and psychological domains, whereas number of medication trials was a predictor of worsening QoL in the physical domain.


The final model explained the most variance in psychological (68%) and physical (67%) QoL. Less variance was explained for environmental (43%) and social QoL (33%), highlighting a need for further exploration of predictors in these domains. Strategies such as functional remediation may have potential to support QoL for individuals with persistent depressive symptoms.

Clinical Trials Registry identifier: NCT016557.

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Correspondence to Emma Morton.

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Author contributions

EM conceptualized and conducted the statistical analysis and drafted the manuscript. SHK, RWL, RVM, SR, PG, SM, BNF, SVP, DJM, VB, WL, EEM, and TC made substantial contributions to overall study conception and design and to ongoing data collection and analysis. All authors provided critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.


CAN-BIND is an Integrated Discovery Programme that is carried out in partnership with, and receives financial support from, the Ontario Brain Institute, an independent non-profit corporation funded partially by the Ontario government. The opinions, results and conclusions are those of the authors, and no endorsement by the Ontario Brain Institute is intended or should be inferred. Additional funding was provided by the Canadian Institutes of Health Research, Lundbeck, Bristol Myers Squibb, and Servier. Funding and/or in-kind support was also provided by the investigators’ academic institutions. Emma Morton was supported by a postdoctoral award from the Marshall Scholars and Fellows Programme in Mental Health, Institute of Mental Health, University of British Columbia, Canada. Venkat Bhat was supported by an Academic Scholar Award from the Department of Psychiatry at the University of Toronto.

Conflict of interest

Emma Morton, Venkat Bhat, Wendy Lou, Trisha Chakrabarty, and Daniel J. Müller have no conflicts of interest that are directly relevant to the content of this article. Peter Giacobbe has received research support from the Academic Scholar’s Award, University of Toronto Department of Psychiatry, CIHR, PSI, and Veteran's Affairs Canada; served on an advisory board for Janssen; and been an unpaid consultant for St. Jude Medical. Erin E. Michalak has received funding from Otsuka to support patient education initiatives. Shane McInerney has received advisory panel income from Janssen and research grant funding through the Healthy Minds Canada/Pfizer Canada Workplace Depression Awards. Benicio N. Frey has received a research grant from Pfizer outside of this work. Roumen V. Milev has received consulting and speaking honoraria from AbbVie, Allergan, Janssen, KYE, Lundbeck, Otsuka, and Sunovion and research grants from CAN-BIND, CIHR, Janssen, Lallemand, Lundbeck, Nubiyota, OBI, and OMHF. Sagar V. Parikh has received honoraria or research funds from Assurex, Takeda, Janssen, Mensante, Aifred, and Sage. Susan Rotzinger holds a patent ‘Teneurin C-Terminal Associated Peptides (TCAP) and methods and uses thereof.’ (inventors: David Lovejoy, R.B. Chewpoy, Dalia Barsyte, and Susan Rotzinger). Sidney H. Kennedy has received honoraria or research funds from Abbott, Alkermes, Allergan, Boehringer Ingelheim, Brain Canada, CIHR, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion, and Sun Pharmaceuticals and holds stock in Field Trip Health. Raymond W. Lam has received honoraria or research funds from Allergan, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, CIHR, CANMAT, Canadian Psychiatric Association, Hansoh, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, MITACS, Myriad Neuroscience, Ontario Brain Institute, Otsuka, Pfizer, St. Jude Medical, University Health Network Foundation, and the VGH-UBC Hospital Foundation.

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Morton, E., Bhat, V., Giacobbe, P. et al. Predictors of Quality of Life Improvement with Escitalopram and Adjunctive Aripiprazole in Patients with Major Depressive Disorder: A CAN-BIND Study Report. CNS Drugs 35, 439–450 (2021).

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