Major Depressive DisorderPhase 4CAN-BIND-17NCT05017311

Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D)

A Phase 4 study testing Escitalopram and Brexpiprazole in people with Major Depressive Disorder, run by Nova Scotia Health Authority at 10 sites in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

Search all trials

Trial summary

This is a study that will test a predictive biomarker algorithm based on results from a previous study. The goal of this study is to integrate clinical, imaging, EEG, and molecular data across 8 sites to predict treatment outcome for patients experiencing a major depressive episode (MDE). Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Major Depressive Disorder
What is being tested?: Escitalopram and Brexpiprazole
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 400 participants
Where: 10 sitesCanada
Study dates: 20 Jan 2023to 30 Apr 2029
Phase: Phase 4
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Outpatients 18 to 65 years of age.
Meet DSM-5 criteria for MDE in MDD as determined by SCID-5.
Free of psychotropic medications for at least 5 half-lives (e.g. 1 week for most antidepressants, 5 weeks for fluoxetine) before baseline Visit 1 (exceptions: stable use of hypnotics; stable use of stimulants for attention-deficit/hyperactive disorder).
MADRS score ≥ 24.
Fluency in English, sufficient to complete the interviews and self-report questionnaires.
18 to 65 years of age.
No history of psychiatric disorders (as determined by SCID-5) or significant physical conditions (e.g. arthritis, fibromyalgia).
Fluency in English, sufficient to complete the interviews and self-report questionnaires.

Who cannot join

Any diagnosis, other than MDD, that is considered the primary diagnosis.
Bipolar I or Bipolar-II diagnosis.
Presence of a significant Axis II diagnosis (borderline, antisocial).
High suicidal risk, defined by clinician judgment.
Substance dependence/abuse in the past 6 months.
Presence of significant neurological disorders, head trauma, or other unstable medical conditions.

Show all 11Show fewer

Pregnant or breastfeeding.
Failure of 4 or more adequate pharmacologic interventions (as determined by the Antidepressant Treatment History Form).
Started psychological treatment within the past 3 months with the intent of continuing treatment.
Patients who have previously failed escitalopram or showed intolerance to escitalopram or brexpiprazole, and patients at risk for hypomanic switch (i.e. with a history of antidepressant induced hypomania).
Healthy Comparison (HC) Participants

Trial locations and contacts

10 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Jessica B Toombs, MSc contact

9024735313

Jessica.Toombs@NSHealth.ca

Nicole M Stinson, BSc contact

9024735313

Nicole.Stinson@NSHealth.ca

City, postcode or hospital

Sites recruiting now only

10 sites in 1 country

Canada10 sites, 10 recruiting

University of Calgary
Calgary, Alberta, T2N 2T9
Maddie Kelly, 403-210-7445, Madison.Kelly@ucalgary.ca
Alex Du, 403-220-6533, mi.du@ucalgary.ca
Recruiting
Nova Scotia Health Authority
Halifax, Nova Scotia, B3H 2E2
Jessica Toombs, MSc, 902-473-5313, Jessica.Toombs@NSHealth.ca
Nicole Stinson, BSc, 902-473-5313, Nicole.Stinson@NSHealth.ca
Recruiting
McMaster University
Hamilton, Ontario, L8P3B6
Elizabeth Hewitson, 905-522-1155 ext. 39178, ehewitso@stjoes.ca
Saba Khoshroo, 905-522-1155 ext. 36462, skhoshro@stjoes.ca
Recruiting
Queen's University
Kingston, Ontario, K7L4X3
Caroline Côté, 613-544-4900 ext. 52212, c.cote@queensu.ca
Rida Khan, 613-544-4900 ext. 53354, khanr@providencecare.ca
Recruiting
The Royal Ottawa Mental Health Centre
Ottawa, Ontario, K1Z 7K4
Dikshpreet Kaur, 613-722-6521 ext. 6856, Dikshpreet.Kaur@theroyal.ca
Yamini Singh, 613-722-6521 ext. 6405, Yamini.Singh@theroyal.ca
Recruiting
University of Saskatchewan
Saskatoon, Saskatchewan, S7N 0W8
Quentin Greba, 306-371-7987, qmg131@usask.ca
AG (Adekunle Garba) Ahmed, MBBS, MSc
Recruiting
University Health Network
Toronto, Ontario, M5T2S8
Yudi Kang, 416-603-5800 ext. 6094, Yudi.Kang@uhn.ca
Franca Placenza, PhD, 416-603-5800 ext. 8839, Franca.Placenza@uhn.ca
Recruiting
Centre for Addiction and Mental Health
Toronto, Ontario, M6J1H4
Victoria Herbert, 416-535-8501 ext. 30186, Victoria.Herbert@camh.ca
Dima Alkaed, 416-535-8501 ext. 39019, Dima.Alkaed@camh.ca
Recruiting
University of British Columbia
Vancouver, British Columbia, V6T2A1
Sara Lee, 604-822-0332, Sara.Lee@ubc.ca
Jennifer Tong, 604-822-8012, Jennifer.Tong@ubc.ca
Recruiting
Ontario Shores Centre for Mental Health Sciences
Whitby, Ontario, L1N 0H7
Houra Parsinejad, 905-430-4055 ext. 6134, parsinejadh@ontarioshores.ca
Emily Vernum, 905-430-4055 ext. 6081, vernume@ontarioshores.ca
Recruiting

Other trials in Canada

About this study

Read the detailed description

This is a multi-site, randomized study with two treatment phases: a double-blind primary treatment phase of 8 weeks, and an open-label secondary extension phase of 4 weeks. This study aims to test a predictive biomarker algorithm to select medication treatment for patients with major depressive disorder (MDD) based on results from the recently completed Canadian Biomarker Integration Network in Depression (CAN-BIND)-1 study. This will be accomplished through collection of clinical, neurophysiological, and molecular measures from both MDD patients and healthy controls. This is not a study to evaluate efficacy of medications; medications in this study have been approved by Health Canada and are widely used for the treatment of MDD.

In this study, individuals diagnosed with MDD in a current major depressive episode (MDE) will be randomly assigned to one of the two treatment groups: Personalized Assignment group or Random Assignment group. Patients in the Random Assignment group will randomly receive open-label escitalopram with the addition of either blinded placebo or brexpiprazole for 8 weeks. Patients in the Personalized Assignment group will receive open-label escitalopram with the addition of either placebo or blinded brexpiprazole for 8 weeks depending on what the predictive biomarker algorithm suggests.

At Week 8, participants will be assessed for treatment response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale score). All patients who initially received both open-label escitalopram and blinded brexpiprazole (regardless of treatment group) will continue to receive these medications for another 4 weeks but the brexpiprazole will no longer be blinded. For those patients who initially received open-label escitalopram and blinded placebo (regardless of treatment group), nonresponders will receive open-label escitalopram and open-label brexpiprazole for another 4 weeks and responders will receive open-label escitalopram only for another 4 weeks.

Over the 12 weeks, participants will attend 7 study visits where they will complete clinical assessments (clinician administered and self-report) and cognitive tests; provide blood, urine, and stool samples; undergo neuroimaging procedures (MRI and EEG); and provide speech samples. At the end of the study, modeling methods will be used to integrate data from these measures to determine the features that best predict treatment outcome.

Conditions: Major Depressive Disorder
Being tested: Escitalopram, Brexpiprazole
Keywords: major depression, major depressive disorder, MDD, escitalopram, brexpiprazole, neuroimaging, genomics, proteomics, metabolomics
Medical subject headings: Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EscitalopramDrug
Also called Cipralex
All patients will receive open-label escitalopram (10-20 mg/d) for the entire study duration (12 weeks).
BrexpiprazoleDrug
Also called Rexulti
Depending on the initial randomization process, patients will either receive blinded brexpiprazole (0.5-2 mg/d) for the entire study duration (12 weeks) or for the last 4 weeks of the study if they received the placebo during the first 8 weeks of the study and were non-responders.

Study groups in NCT05017311
Study group	Role	What they receive
Allocation by Predictive Biomarker Algorithm; Escitalopram + Brexpiprazole	Active comparator	Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted as non-responders to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded. Receives: Drug: Escitalopram; Drug: Brexpiprazole
Allocation by Predictive Biomarker Algorithm; Placebo	Placebo comparator	Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted to respond to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole. Receives: Drug: Escitalopram
Random Allocation; Escitalopram + Brexpiprazole	Active comparator	Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded. Receives: Drug: Escitalopram; Drug: Brexpiprazole
Random Allocation; Placebo	Placebo comparator	Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole. Receives: Drug: Escitalopram

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline
Measured as clinical response, defined as a decrease in Montgomery Asberg Depression Rating Scale (MADRS) score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit (i.e., lower MADRS scores = better outcome)
Measured: Baseline to Week 8

Secondary outcomes (3)

Clinical response
Defined as a decrease in MADRS score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit
Measured: Baseline to Week 8
Time to clinical response
Defined as time (i.e., number of weeks) to achieve clinical response (i.e., decrease in MADRS score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit)
Measured: Baseline to Week 8
Remission at Week 8
Defined as MADRS score ≤10 at Week 8
Measured: Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Jan 202330 Apr 2029

First posted23 Aug 2021
Study start20 Jan 2023
Primary completion31 Dec 2028 (estimated)
Study completion30 Apr 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (17)Papers the sponsor has linked to this study.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
More trials run by Nova Scotia Health AuthorityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Double blind
Who is masked: Participant, Care provider
Enrolment: 400 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05017311
Sponsor's protocol ID: 1027397
Acronym: CAN-BIND-17
Status last verified: Jun 2026
First submitted: 16 Aug 2021
Last updated: 11 Jun 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: This study is funded by the Ontario Brain Institute (OBI). Data collected from this study is entered into a research database called "Brain-CODE", deployed at a High Performance Computer Virtual Lab (HPCVL). The HPCVL supports the regulatory-compliant (e.g. 21 CRF Part 11, HIPPA, PIPEDA) processes for securing privacy of healthcare data.

Publications

Lam RW, Milev R, Rotzinger S, Andreazza AC, Blier P, Brenner C, Daskalakis ZJ, Dharsee M, Downar J, Evans KR, Farzan F, Foster JA, Frey BN, Geraci J, Giacobbe P, Feilotter HE, Hall GB, Harkness KL, Hassel S, Ismail Z, Leri F, Liotti M, MacQueen GM, McAndrews MP, Minuzzi L, Muller DJ, Parikh SV, Placenza FM, Quilty LC, Ravindran AV, Salomons TV, Soares CN, Strother SC, Turecki G, Vaccarino AL, Vila-Rodriguez F, Kennedy SH; CAN-BIND Investigator Team. Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort. BMC Psychiatry. 2016 Apr 16;16:105. doi: 10.1186/s12888-016-0785-x.
PubMed 27084692
Kennedy SH, Lam RW, Rotzinger S, Milev RV, Blier P, Downar J, Evans KR, Farzan F, Foster JA, Frey BN, Giacobbe P, Hall GB, Harkness KL, Hassel S, Ismail Z, Leri F, McInerney S, MacQueen GM, Minuzzi L, Muller DJ, Parikh SV, Placenza FM, Quilty LC, Ravindran AV, Sassi RB, Soares CN, Strother SC, Turecki G, Vaccarino AL, Vila-Rodriguez F, Yu J, Uher R; CAN-BIND Investigator Team. Symptomatic and Functional Outcomes and Early Prediction of Response to Escitalopram Monotherapy and Sequential Adjunctive Aripiprazole Therapy in Patients With Major Depressive Disorder: A CAN-BIND-1 Report. J Clin Psychiatry. 2019 Feb 5;80(2):18m12202. doi: 10.4088/JCP.18m12202.
PubMed 30840787
Farzan F, Atluri S, Frehlich M, Dhami P, Kleffner K, Price R, Lam RW, Frey BN, Milev R, Ravindran A, McAndrews MP, Wong W, Blumberger D, Daskalakis ZJ, Vila-Rodriguez F, Alonso E, Brenner CA, Liotti M, Dharsee M, Arnott SR, Evans KR, Rotzinger S, Kennedy SH. Standardization of electroencephalography for multi-site, multi-platform and multi-investigator studies: insights from the canadian biomarker integration network in depression. Sci Rep. 2017 Aug 7;7(1):7473. doi: 10.1038/s41598-017-07613-x.
PubMed 28785082
Lopez JP, Fiori LM, Cruceanu C, Lin R, Labonte B, Cates HM, Heller EA, Vialou V, Ku SM, Gerald C, Han MH, Foster J, Frey BN, Soares CN, Muller DJ, Farzan F, Leri F, MacQueen GM, Feilotter H, Tyryshkin K, Evans KR, Giacobbe P, Blier P, Lam RW, Milev R, Parikh SV, Rotzinger S, Strother SC, Lewis CM, Aitchison KJ, Wittenberg GM, Mechawar N, Nestler EJ, Uher R, Kennedy SH, Turecki G. MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes. Nat Commun. 2017 May 22;8:15497. doi: 10.1038/ncomms15497.
PubMed 28530238
Uher R, Frey BN, Quilty LC, Rotzinger S, Blier P, Foster JA, Muller DJ, Ravindran AV, Soares CN, Turecki G, Parikh SV, Milev R, MacQueen G, Lam RW, Kennedy SH; CAN-BIND Investigator Team. 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):20m13229. doi: 10.4088/JCP.20m13229.
PubMed 32558407
Allen TA, Harkness KL, Lam RW, Milev R, Frey BN, Mueller DJ, Uher R, Kennedy SH, Quilty LC. Interactions between neuroticism and stressful life events predict response to pharmacotherapy for major depression: A CAN-BIND 1 report. Personal Ment Health. 2021 Nov;15(4):273-282. doi: 10.1002/pmh.1514. Epub 2021 May 18.
PubMed 34008342
Nogovitsyn N, Muller M, Souza R, Hassel S, Arnott SR, Davis AD, Hall GB, Harris JK, Zamyadi M, Metzak PD, Ismail Z, Downar J, Parikh SV, Soares CN, Addington JM, Milev R, Harkness KL, Frey BN, Lam RW, Strother SC, Rotzinger S, Kennedy SH, MacQueen GM. Hippocampal tail volume as a predictive biomarker of antidepressant treatment outcomes in patients with major depressive disorder: a CAN-BIND report. Neuropsychopharmacology. 2020 Jan;45(2):283-291. doi: 10.1038/s41386-019-0542-1. Epub 2019 Oct 14.
PubMed 31610545
Chakrabarty T, McInerney SJ, Torres IJ, Frey BN, Milev RV, Muller DJ, Rotzinger S, Kennedy SH, Lam RW; CAN-BIND Investigator Team. Cognitive Outcomes with Sequential Escitalopram Monotherapy and Adjunctive Aripiprazole Treatment in Major Depressive Disorder: A Canadian Biomarker Integration Network in Depression (CAN-BIND-1) Report. CNS Drugs. 2021 Mar;35(3):291-304. doi: 10.1007/s40263-021-00793-1. Epub 2021 Mar 8.
PubMed 33683582
Morton E, Bhat V, Giacobbe P, Lou W, Michalak EE, McInerney S, Chakrabarty T, Frey BN, Milev RV, Muller DJ, Parikh SV, Rotzinger S, Kennedy SH, Lam RW; CAN-BIND Investigator Team. Predictors of Quality of Life Improvement with Escitalopram and Adjunctive Aripiprazole in Patients with Major Depressive Disorder: A CAN-BIND Study Report. CNS Drugs. 2021 Apr;35(4):439-450. doi: 10.1007/s40263-021-00803-2. Epub 2021 Apr 16.
PubMed 33860922
Ayyash S, Davis AD, Alders GL, MacQueen G, Strother SC, Hassel S, Zamyadi M, Arnott SR, Harris JK, Lam RW, Milev R, Muller DJ, Kennedy SH, Rotzinger S, Frey BN, Minuzzi L, Hall GB; CAN-BIND Investigator Team. Exploring brain connectivity changes in major depressive disorder using functional-structural data fusion: A CAN-BIND-1 study. Hum Brain Mapp. 2021 Oct 15;42(15):4940-4957. doi: 10.1002/hbm.25590. Epub 2021 Jul 23.
PubMed 34296501
Caspani G, Turecki G, Lam RW, Milev RV, Frey BN, MacQueen GM, Muller DJ, Rotzinger S, Kennedy SH, Foster JA, Swann JR. Metabolomic signatures associated with depression and predictors of antidepressant response in humans: A CAN-BIND-1 report. Commun Biol. 2021 Jul 22;4(1):903. doi: 10.1038/s42003-021-02421-6.
PubMed 34294869
Allen TA, Lam RW, Milev R, Rizvi SJ, Frey BN, MacQueen GM, Muller DJ, Uher R, Kennedy SH, Quilty LC. Early change in reward and punishment sensitivity as a predictor of response to antidepressant treatment for major depressive disorder: a CAN-BIND-1 report. Psychol Med. 2019 Jul;49(10):1629-1638. doi: 10.1017/S0033291718002441. Epub 2018 Sep 17.
PubMed 30220263
Alders GL, Davis AD, MacQueen G, Strother SC, Hassel S, Zamyadi M, Sharma GB, Arnott SR, Downar J, Harris JK, Lam RW, Milev R, Muller DJ, Ravindran A, Kennedy SH, Frey BN, Minuzzi L, Hall GB; CAN-BIND Investigator Team. Escitalopram ameliorates differences in neural activity between healthy comparison and major depressive disorder groups on an fMRI Emotional conflict task: A CAN-BIND-1 study. J Affect Disord. 2020 Mar 1;264:414-424. doi: 10.1016/j.jad.2019.11.068. Epub 2019 Nov 13.
PubMed 31757619
Chakrabarty T, Harkness KL, McInerney SJ, Quilty LC, Milev RV, Kennedy SH, Frey BN, MacQueen GM, Muller DJ, Rotzinger S, Uher R, Lam RW. Childhood maltreatment and cognitive functioning in patients with major depressive disorder: a CAN-BIND-1 report. Psychol Med. 2020 Nov;50(15):2536-2547. doi: 10.1017/S003329171900268X. Epub 2019 Oct 4.
PubMed 31583989
Dunlop K, Rizvi SJ, Kennedy SH, Hassel S, Strother SC, Harris JK, Zamyadi M, Arnott SR, Davis AD, Mansouri F, Schulze L, Ceniti AK, Lam RW, Milev R, Rotzinger S, Foster JA, Frey BN, Parikh SV, Soares CN, Uher R, Turecki G, MacQueen GM, Downar J. Clinical, behavioral, and neural measures of reward processing correlate with escitalopram response in depression: a Canadian Biomarker Integration Network in Depression (CAN-BIND-1) Report. Neuropsychopharmacology. 2020 Jul;45(8):1390-1397. doi: 10.1038/s41386-020-0688-x.
PubMed 32349119

Interested in taking part?

Jessica B Toombs, MSc

9024735313

Jessica.Toombs@NSHealth.ca

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D)
ClinicalTrials.gov ID: NCT05017311
Acronym / sponsor ID: CAN-BIND-17 / 1027397
Conditions: Major Depressive Disorder
Keywords: major depression, major depressive disorder, MDD, escitalopram, brexpiprazole, neuroimaging, genomics, proteomics
Phase: Phase 4
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 400 participants (estimated)
Lead sponsor: Nova Scotia Health AuthorityUniversity, hospital or other
Collaborators: Unity Health Toronto, Centre for Addiction and Mental Health, McMaster University, Queen's University, University of Ottawa, University of British Columbia, University of Calgary, McGill University, Dalhousie University, University of Michigan, Simon Fraser University, Ontario Shores Centre for Mental Health Sciences, University of Saskatchewan
Study start: 20 Jan 2023 (actual)
Primary completion: 31 Dec 2028 (estimated)
Study completion: 30 Apr 2029 (estimated)
First posted: 23 Aug 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Double blind (participant, care provider)
Number of arms: 4

Arm	Type	Receives
Allocation by Predictive Biomarker Algorithm; Escitalopram + Brexpiprazole	Active comparator	Drug: Escitalopram, Drug: BrexpiprazolePatients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted as non-responders to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.
Allocation by Predictive Biomarker Algorithm; Placebo	Placebo comparator	Drug: EscitalopramPatients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted to respond to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole.
Random Allocation; Escitalopram + Brexpiprazole	Active comparator	Drug: Escitalopram, Drug: BrexpiprazolePatients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.
Random Allocation; Placebo	Placebo comparator	Drug: EscitalopramPatients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Outpatients 18 to 65 years of age.
Meet DSM-5 criteria for MDE in MDD as determined by SCID-5.
Free of psychotropic medications for at least 5 half-lives (e.g. 1 week for most antidepressants, 5 weeks for fluoxetine) before baseline Visit 1 (exceptions: stable use of hypnotics; stable use of stimulants for attention-deficit/hyperactive disorder).
MADRS score ≥ 24.
Fluency in English, sufficient to complete the interviews and self-report questionnaires.

Key exclusion criteria (11 listed)

Any diagnosis, other than MDD, that is considered the primary diagnosis.
Bipolar I or Bipolar-II diagnosis.
Presence of a significant Axis II diagnosis (borderline, antisocial).
High suicidal risk, defined by clinician judgment.
Substance dependence/abuse in the past 6 months.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EscitalopramAlso: CipralexAll patients will receive open-label escitalopram (10-20 mg/d) for the entire study duration (12 weeks).	Drug	Allocation by Predictive Biomarker Algorithm; Escitalopram + Brexpiprazole, Allocation by Predictive Biomarker Algorithm; Placebo, Random Allocation; Escitalopram + Brexpiprazole, Random Allocation; Placebo
BrexpiprazoleAlso: RexultiDepending on the initial randomization process, patients will either receive blinded brexpiprazole (0.5-2 mg/d) for the entire study duration (12 weeks) or for the last 4 weeks of the study if they received the placebo during the first 8 weeks of the study and were non-responders.	Drug	Allocation by Predictive Biomarker Algorithm; Escitalopram + Brexpiprazole, Random Allocation; Escitalopram + Brexpiprazole

Primary outcome

Change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline
Time frame: Baseline to Week 8
Measured as clinical response, defined as a decrease in Montgomery Asberg Depression Rating Scale (MADRS) score at the Week 8 visit, by 50% or greater, from MADRS score at Baseline visit (i.e., lower MADRS scores = better outcome)

3 secondary outcomes

Clinical response
Time frame: Baseline to Week 8
Time to clinical response
Time frame: Baseline to Week 8
Remission at Week 8
Time frame: Week 8

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
Background: PubMed 27084692Lam RW, Milev R, Rotzinger S, Andreazza AC, Blier P, Brenner C, Daskalakis ZJ, Dharsee M, Downar J, Evans KR, Farzan F, Foster JA, Frey BN, Geraci J, Giacobbe P, Feilotter HE, Hall GB, Harkness KL, Hassel S, Ismail Z, Leri F, Liotti M, MacQueen GM, McAndrews MP, Minuzzi L, Muller DJ, Parikh SV, Placenza FM, Quilty LC, Ravindran AV, Salomons TV, Soares CN, Strother SC, Turecki G, Vaccarino AL, Vila-Rodriguez F, Kennedy SH; CAN-BIND Investigator Team. Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort. BMC Psychiatry. 2016 Apr 16;16:105. doi: 10.1186/s12888-016-0785-x.
Background: PubMed 30840787Kennedy SH, Lam RW, Rotzinger S, Milev RV, Blier P, Downar J, Evans KR, Farzan F, Foster JA, Frey BN, Giacobbe P, Hall GB, Harkness KL, Hassel S, Ismail Z, Leri F, McInerney S, MacQueen GM, Minuzzi L, Muller DJ, Parikh SV, Placenza FM, Quilty LC, Ravindran AV, Sassi RB, Soares CN, Strother SC, Turecki G, Vaccarino AL, Vila-Rodriguez F, Yu J, Uher R; CAN-BIND Investigator Team. Symptomatic and Functional Outcomes and Early Prediction of Response to Escitalopram Monotherapy and Sequential Adjunctive Aripiprazole Therapy in Patients With Major Depressive Disorder: A CAN-BIND-1 Report. J Clin Psychiatry. 2019 Feb 5;80(2):18m12202. doi: 10.4088/JCP.18m12202.
Background: PubMed 28785082Farzan F, Atluri S, Frehlich M, Dhami P, Kleffner K, Price R, Lam RW, Frey BN, Milev R, Ravindran A, McAndrews MP, Wong W, Blumberger D, Daskalakis ZJ, Vila-Rodriguez F, Alonso E, Brenner CA, Liotti M, Dharsee M, Arnott SR, Evans KR, Rotzinger S, Kennedy SH. Standardization of electroencephalography for multi-site, multi-platform and multi-investigator studies: insights from the canadian biomarker integration network in depression. Sci Rep. 2017 Aug 7;7(1):7473. doi: 10.1038/s41598-017-07613-x.
Background: PubMed 28530238Lopez JP, Fiori LM, Cruceanu C, Lin R, Labonte B, Cates HM, Heller EA, Vialou V, Ku SM, Gerald C, Han MH, Foster J, Frey BN, Soares CN, Muller DJ, Farzan F, Leri F, MacQueen GM, Feilotter H, Tyryshkin K, Evans KR, Giacobbe P, Blier P, Lam RW, Milev R, Parikh SV, Rotzinger S, Strother SC, Lewis CM, Aitchison KJ, Wittenberg GM, Mechawar N, Nestler EJ, Uher R, Kennedy SH, Turecki G. MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes. Nat Commun. 2017 May 22;8:15497. doi: 10.1038/ncomms15497.
Background: PubMed 32558407Uher R, Frey BN, Quilty LC, Rotzinger S, Blier P, Foster JA, Muller DJ, Ravindran AV, Soares CN, Turecki G, Parikh SV, Milev R, MacQueen G, Lam RW, Kennedy SH; CAN-BIND Investigator Team. 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):20m13229. doi: 10.4088/JCP.20m13229.
Background: PubMed 34008342Allen TA, Harkness KL, Lam RW, Milev R, Frey BN, Mueller DJ, Uher R, Kennedy SH, Quilty LC. Interactions between neuroticism and stressful life events predict response to pharmacotherapy for major depression: A CAN-BIND 1 report. Personal Ment Health. 2021 Nov;15(4):273-282. doi: 10.1002/pmh.1514. Epub 2021 May 18.
Background: PubMed 31610545Nogovitsyn N, Muller M, Souza R, Hassel S, Arnott SR, Davis AD, Hall GB, Harris JK, Zamyadi M, Metzak PD, Ismail Z, Downar J, Parikh SV, Soares CN, Addington JM, Milev R, Harkness KL, Frey BN, Lam RW, Strother SC, Rotzinger S, Kennedy SH, MacQueen GM. Hippocampal tail volume as a predictive biomarker of antidepressant treatment outcomes in patients with major depressive disorder: a CAN-BIND report. Neuropsychopharmacology. 2020 Jan;45(2):283-291. doi: 10.1038/s41386-019-0542-1. Epub 2019 Oct 14.
Background: PubMed 33683582Chakrabarty T, McInerney SJ, Torres IJ, Frey BN, Milev RV, Muller DJ, Rotzinger S, Kennedy SH, Lam RW; CAN-BIND Investigator Team. Cognitive Outcomes with Sequential Escitalopram Monotherapy and Adjunctive Aripiprazole Treatment in Major Depressive Disorder: A Canadian Biomarker Integration Network in Depression (CAN-BIND-1) Report. CNS Drugs. 2021 Mar;35(3):291-304. doi: 10.1007/s40263-021-00793-1. Epub 2021 Mar 8.
Background: PubMed 33860922Morton E, Bhat V, Giacobbe P, Lou W, Michalak EE, McInerney S, Chakrabarty T, Frey BN, Milev RV, Muller DJ, Parikh SV, Rotzinger S, Kennedy SH, Lam RW; CAN-BIND Investigator Team. Predictors of Quality of Life Improvement with Escitalopram and Adjunctive Aripiprazole in Patients with Major Depressive Disorder: A CAN-BIND Study Report. CNS Drugs. 2021 Apr;35(4):439-450. doi: 10.1007/s40263-021-00803-2. Epub 2021 Apr 16.
Background: PubMed 34296501Ayyash S, Davis AD, Alders GL, MacQueen G, Strother SC, Hassel S, Zamyadi M, Arnott SR, Harris JK, Lam RW, Milev R, Muller DJ, Kennedy SH, Rotzinger S, Frey BN, Minuzzi L, Hall GB; CAN-BIND Investigator Team. Exploring brain connectivity changes in major depressive disorder using functional-structural data fusion: A CAN-BIND-1 study. Hum Brain Mapp. 2021 Oct 15;42(15):4940-4957. doi: 10.1002/hbm.25590. Epub 2021 Jul 23.
Background: PubMed 34294869Caspani G, Turecki G, Lam RW, Milev RV, Frey BN, MacQueen GM, Muller DJ, Rotzinger S, Kennedy SH, Foster JA, Swann JR. Metabolomic signatures associated with depression and predictors of antidepressant response in humans: A CAN-BIND-1 report. Commun Biol. 2021 Jul 22;4(1):903. doi: 10.1038/s42003-021-02421-6.
Background: PubMed 30220263Allen TA, Lam RW, Milev R, Rizvi SJ, Frey BN, MacQueen GM, Muller DJ, Uher R, Kennedy SH, Quilty LC. Early change in reward and punishment sensitivity as a predictor of response to antidepressant treatment for major depressive disorder: a CAN-BIND-1 report. Psychol Med. 2019 Jul;49(10):1629-1638. doi: 10.1017/S0033291718002441. Epub 2018 Sep 17.
Individual participant dataSharing planned: Yes. This study is funded by the Ontario Brain Institute (OBI). Data collected from this study is entered into a research database called "Brain-CODE", deployed at a High Performance Computer Virtual Lab (HPCVL). The HPCVL supports the regulatory-compliant (e.g. 21 CRF Part 11, HIPPA, PIPEDA) processes for securing privacy of healthcare data.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Jessica B Toombs, MSc contact

9024735313

Jessica.Toombs@NSHealth.ca

Nicole M Stinson, BSc contact

9024735313

Nicole.Stinson@NSHealth.ca

Rudolf Uher, MD, PhD principal investigator

Nova Scotia Health Authority

10 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Escitalopram and Brexpiprazole in people with Major Depressive Disorder, run by Nova Scotia Health Authority at 10 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jessica B Toombs, MSc (9024735313, Jessica.Toombs@NSHealth.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline (time frame: Baseline to Week 8). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05017311, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.