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,Sidney H Kennedy,Geoffrey B Hall,Sagar V Parikh,Lena C Quilty,Kate L Harkness,Luciano Minuzzi,Pierre Blier,Susan Rotzinger,Kenneth R Evans,Peter Giacobbe,Roumen Milev,Daniel J Müller,Faranak Farzan,Moyez Dharsee,Joseph Geraci,Mario Liotti,Gustavo Turecki,Stefanie Hassel,Stephen C Strother,Mary Pat Mcandrews,Jonathan Downar,Zahinoor Ismail,Zafiris J Daskalakis,Tim V Salomons,Jane A Foster,Francesco Leri,Anthony L Vaccarino,Harriet Feilotter ,Fidel Vila‐Rodriguez ,Ana Cristina Andreazza ,Arun Ravindran ,Glenda Macqueen ,Colleen A Brenner ,Cláudio N Soares ,Franca Placenza ,Benício N Frey

doi:10.1186/s12888-016-0785-x

Abstract

BackgroundMajor Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD.MethodsCAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response.DiscussionFrom June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.Trial registrationClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.

Highlights

Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide
Treatment of depressive disorders is based on empirical data and evidence-based guidelines, but treatment selection remains more of an art than a science
Clinical, neuroimaging and molecular assessments are conducted at Baseline (Week 0) and Weeks 2 and 8; clinical and molecular assessments are conducted at Weeks 4, 10, and 16; and additional brief clinical evaluations are completed at Weeks 6, 12, and 14

Summary

Methods

Overview of protocol Patients with MDD are treated with open-label escitalopram 10–20 mg/d for 8 weeks. Specific data-collection platforms with Brain-CODE include: 1) Brain-CODE Subject Registry, a secure portal used by study centres in Ontario to link encrypted personal health information from study participants to provincial health/administrative databases; 2) OpenClinica Enterprise, a regulatory-compliant, web-based electronic data capture (EDC) system and database for demographic and historical data, diagnostic information, and clinician-rated assessments and scales (OpenClinica, Waltham, MA, USA); 3) LimeSurvey e-PRO Questionnaires, an open-source survey tool used by participants for direct entry of the 20 self-reported measures using a laptop or tablet while attending clinic visits (LimeSurvey, Hamburg, Germany); 4) SPReD (originally the Stroke Patient Recovery Research Database), a comprehensive online repository powered by the open-source Extensible Neuroimaging Archiving Toolkit (XNAT) imaging informatics platform [61]. Neuropsychiatric Interview cPercentages may not add up to 100 % because patients may have more than 1 comorbid condition MDD Major depressive disorder, SD Standard deviation, MADRS Montgomery Åsberg Depression Rating Scale, YMRS Young Mania Rating Scale, CGI Clinical Global Impression, QIDS-SR Quick Inventory of Depressive Symptomatology, Self-Report, SDS Sheehan Disability Scale, LEAPS Lam Employment Absence and Productivity Scale by MADRS, QIDS-SR, and CGI-S mean scores, as well as moderately impaired as assessed by psychosocial (SDS) and work (LEAPS) functioning scales

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