Canadian Biomarker Integration Network for Depression Study

Conditions

Major Depressive Disorder

Keywords

major depression, major depressive disorder, biomarkers, escitalopram, aripiprazole, MDD, neuroimaging, proteomic, genomics

Brief summary

This study is a pilot to assess feasibility of the protocol in patients and controls across six participating sites. The goal is to identify biological markers (biomarkers)that can be measured at baseline or early in treatment to predict treatment outcome in individual patients with Major Depressive Disorder (MDD). Biomarkers of interest will be clinical (using interview and self-report measures), molecular (from blood samples) and neurobiological (using neuroimaging and EEG).

Detailed description

This is a study to collect clinical and biomarker data which will be used to build models to predict treatment response. This is not a study to evaluate efficacy of medications, as medications in this study have been approved by Health Canada and are widely used for the treatment of MDD. This is an open label study involving MDD patients and healthy controls.Patients with a diagnosis of MDD and a current major depressive episode (MDE) will receive open-label standard of care treatment with escitalopram (10-20mg). Healthy controls will not receive medication; however, they will go through clinical assessments, blood collection and neuroimaging procedures. At week 8, patients will be assessed for medication response (response is defined as ≥ 50% reduction in MADRS scores from baseline). Responders will continue medication at their effective dose until study endpoint while non-responders will receive open label add-on treatment with aripiprazole (2-10mg). There are approximately 7 clinic visits over a 16 week period during which patients and healthy controls will undergo clinician administered scales and self reports, provide blood and urine samples (which will undergo proteomic and genomic analyses) as well as neuroimaging (fMRI and EEG). At the end of the study, mathematical modeling methods will be used to integrate the data from the various modalities to see which features best predict treatment outcome.

Mazurka R, Cunningham S, Hassel S, Foster JA, Nogovitsyn N, Fiori LM, Strother SC, Arnott SR, Frey BN, Lam RW, MacQueen GM, Milev RV, Rotzinger S, Turecki G, Kennedy SH, Harkness KL.

2023-12-202 citations

10.1016/j.euroneuro.2023.12.003

Machine Learning Prediction of Quality of Life Improvement During Antidepressant Treatment of Patients With Major Depressive Disorder

Tejas Phaterpekar, John-Jose Nuñez, Emma Morton, Yang S. Liu, Bo Cao et al. (14 authors)

The Journal of Clinical Psychiatry2023-11-102 citations

10.4088/jcp.23m14864

Influence of CYP2C19, CYP2D6, and ABCB1 Gene Variants and Serum Levels of Escitalopram and Aripiprazole on Treatment-Emergent Sexual Dysfunction: A Canadian Biomarker Integration Network in Depression 1 (CAN-BIND 1) Study

Farhana Islam, Leen Magarbeh, Samar S. M. Elsheikh, Stefan Kloiber, Caroline Wanderley Espinola et al. (23 authors)

The Canadian Journal of Psychiatry2023-10-054 citations

10.1177/07067437231203433

Rasch analyses of the Quick Inventory of Depressive Symptomatology Self-Report in neurodegenerative and major depressive disorders

Anthony L. Vaccarino, Sandra E. Black, Susan Gilbert Evans, Benício N. Frey, Mojib Javadi et al. (19 authors)

Frontiers in Psychiatry2023-06-022 citations

10.3389/fpsyt.2023.1154519

Males and females differ in reported sexual functioning with escitalopram treatment for major depressive disorder: A CAN-BIND-1 study report

Caroline Wanderley Espinola, Yuelee Khoo, Roohie Parmar, Ilya Demchenko, Benício N. Frey et al. (14 authors)

Journal of Psychopharmacology2022-05-013 citations

10.1177/02698811221095832

Cerebello-cerebral Functional Connectivity Networks in Major Depressive Disorder: a CAN-BIND-1 Study Report.

Anteraper SA, Guell X, Lee YJ, Raya J, Demchenko I, Churchill NW, Frey BN, Hassel S, Lam RW, MacQueen GM, Milev R, Schweizer TA, Strother SC, Whitfield-Gabrieli S, Kennedy SH, Bhat V, CAN-BIND Investigator Team.

2022-01-133 citations

10.1007/s12311-021-01353-5

Baseline Functional Connectivity in Resting State Networks Associated with Depression and Remission Status after 16 Weeks of Pharmacotherapy: A CAN-BIND Report

Gwen van der Wijk, Jacqueline K. Harris, Stefanie Hassel, Andrew D. Davis, Mojdeh Zamyadi et al. (16 authors)

Cerebral Cortex2021-07-2618 citations

10.1093/cercor/bhab286

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.

Chakrabarty T, McInerney SJ, Torres IJ, Frey BN, Milev RV, Müller DJ, Rotzinger S, Kennedy SH, Lam RW, CAN-BIND Investigator Team.

2021-03-085 citations

10.1007/s40263-021-00793-1

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.

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.

2020-07-0135 citations

10.1038/s41386-020-0688-x

Symptom Dimension of Interest-Activity Indicates Need for Aripiprazole Augmentation of Escitalopram in Major Depressive Disorder

Rudolf Uher, Benício N. Frey, Lena C. Quilty, Susan Rotzinger, Pierre Blier et al. (16 authors)

The Journal of Clinical Psychiatry2020-06-1517 citations

10.4088/jcp.20m13229

Symptomatic and Functional Outcomes and Early Prediction of Response to Escitalopram Monotherapy and Sequential Adjunctive Aripiprazole Therapy in Patients With Major Depressive Disorder

Sidney H. Kennedy, Raymond W. Lam, Susan Rotzinger, Roumen Milev, Pierre Blier et al. (33 authors)

The Journal of Clinical Psychiatry2019-02-0486 citations

10.4088/jcp.18m12202

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Raymond W. Lam, Roumen Milev, Susan Rotzinger, Ana C. Andreazza, Pierre Blier et al. (38 authors)

BMC Psychiatry2016-04-15144 citations

10.1186/s12888-016-0785-x

Interventions

DRUGescitalopram

Patients will be given escitalopram for the first 8 weeks of the trial. At week 8, patients who are assessed as 'responders' will continue on escitalopram until study endpoint.

DRUGaripiprazole

At Week 8, patients assessed as 'non-responders' will be given aripiprazole as an add-on treatment to escitalopram.

Study design

Allocation

NON_RANDOMIZED

Intervention model

FACTORIAL

Primary purpose

DIAGNOSTIC

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Yes

Inclusion criteria

For Depressed patients: Inclusion Criteria: * Outpatients who are 18-60 years of age * Meet DSM-IV-TR criteria for Major Depressive Episode in Major Depressive Disorder by the MINI * Episode duration ≥ 3 months * Free of psychotropic medications for at least 5 half-lives (i.e. 1 week for most antidepressants, 5 weeks for fluoxetine) before baseline Visit 1 * MADRS ≥ 24 * Fluency in English, sufficient to complete the interviews and self-report questionnaires

Exclusion criteria

* Any Axis I 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 * Pregnant or breastfeeding * Failure of 3 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 and patients at risk for hypomanic switch (i.e. with a history of antidepressant hypomania) Inclusion criteria for Healthy Controls: * 18 to 60 years of age * No history of Axis I or Axis II disorders, as determined by the MINI. * Fluency in English, sufficient to complete the interviews and self-report questionnaires.

Design outcomes

Primary

Measure	Time frame	Description
Change in MADRS (Montgomery-Asberg Depression Rating Scale) scores from baseline	Week 8, Week 16	Clinical response (≥ 50% reduction in MADRS scores from baseline)

Countries

Canada

Outcome results

None listed