. 2020 Jun 2;20(1):268.

doi: 10.1186/s12888-020-02672-3.

A randomized, crossover comparison of ketamine and electroconvulsive therapy for treatment of major depressive episodes: a Canadian biomarker integration network in depression (CAN-BIND) study protocol

Jennifer L Phillips^{1

2}, Natalia Jaworska^{3

4}, Elizabeth Kamler³, Venkat Bhat^{5

6

7}, Jean Blier⁸, Jane A Foster^{5

9}, Stefanie Hassel¹⁰, Keith Ho^{5

6}, Lisa McMurray^{11

12}, Roumen Milev^{13

14}, Zahra Moazamigoudarzi^{5

6}, Franca M Placenza⁵, Stéphane Richard-Devantoy^{15

16}, Susan Rotzinger^{5

6

7}, Gustavo Turecki^{15

16}, Gustavo H Vazquez¹³, Sidney H Kennedy^{5

6

7}, Pierre Blier^{3

11

4}; CAN-BIND Investigator Team

Affiliations

¹ The Royal's Institute of Mental Health Research, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada. Jennifer.Phillips@theroyal.ca.
² Department of Psychiatry, University of Ottawa, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada. Jennifer.Phillips@theroyal.ca.
³ The Royal's Institute of Mental Health Research, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada.
⁴ Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
⁵ University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
⁶ Unity Health Toronto, St. Michael's Hospital, 193 Yonge Street, 6th floor, Toronto, ON, M5B 1M4, Canada.
⁷ Department of Psychiatry, University of Toronto, 250 College Street, 8th floor, Toronto, ON, M5T 1R8, Canada.
⁸ Montfort Hospital, 713 Montreal Rd, Ottawa, ON, K1K 0T2, Canada.
⁹ McMaster University, and St. Joseph's Healthcare, Hamilton, 1280 Main Street West, Hamilton, ON, L8S4L8, Canada.
¹⁰ Department of Psychiatry and Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada.
¹¹ Department of Psychiatry, University of Ottawa, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada.
¹² Royal Ottawa Mental Health Centre, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada.
¹³ Department of Psychiatry, Queen's University, Providence Care Hospital, 752 King Street West, Postal Bag 603, Kingston, ON, K7L 7X3, Canada.
¹⁴ Department of Psychology, Queens University, 62 Arch Street, Kingston, ON, K7L 3N6, Canada.
¹⁵ McGill University, 845 Rue Sherbrooke O, Montréal, QC, H3A 0G4, Canada.
¹⁶ Douglas Mental Health University Institute Frank B. Common (FBC) F-3145, 6875 LaSalle Boulevard, Montréal, QC, H4H 1R3, Canada.

PMID: 32487236
PMCID: PMC7265624
DOI: 10.1186/s12888-020-02672-3

A randomized, crossover comparison of ketamine and electroconvulsive therapy for treatment of major depressive episodes: a Canadian biomarker integration network in depression (CAN-BIND) study protocol

Jennifer L Phillips et al. BMC Psychiatry. 2020.

. 2020 Jun 2;20(1):268.

doi: 10.1186/s12888-020-02672-3.

Authors

Affiliations

¹ The Royal's Institute of Mental Health Research, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada. Jennifer.Phillips@theroyal.ca.
² Department of Psychiatry, University of Ottawa, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada. Jennifer.Phillips@theroyal.ca.
³ The Royal's Institute of Mental Health Research, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada.
⁴ Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
⁵ University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
⁶ Unity Health Toronto, St. Michael's Hospital, 193 Yonge Street, 6th floor, Toronto, ON, M5B 1M4, Canada.
⁷ Department of Psychiatry, University of Toronto, 250 College Street, 8th floor, Toronto, ON, M5T 1R8, Canada.
⁸ Montfort Hospital, 713 Montreal Rd, Ottawa, ON, K1K 0T2, Canada.
⁹ McMaster University, and St. Joseph's Healthcare, Hamilton, 1280 Main Street West, Hamilton, ON, L8S4L8, Canada.
¹⁰ Department of Psychiatry and Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada.
¹¹ Department of Psychiatry, University of Ottawa, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada.
¹² Royal Ottawa Mental Health Centre, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada.
¹³ Department of Psychiatry, Queen's University, Providence Care Hospital, 752 King Street West, Postal Bag 603, Kingston, ON, K7L 7X3, Canada.
¹⁴ Department of Psychology, Queens University, 62 Arch Street, Kingston, ON, K7L 3N6, Canada.
¹⁵ McGill University, 845 Rue Sherbrooke O, Montréal, QC, H3A 0G4, Canada.
¹⁶ Douglas Mental Health University Institute Frank B. Common (FBC) F-3145, 6875 LaSalle Boulevard, Montréal, QC, H4H 1R3, Canada.

PMID: 32487236
PMCID: PMC7265624
DOI: 10.1186/s12888-020-02672-3

Abstract

Background: Recent evidence underscores the utility of rapid-acting antidepressant interventions, such as ketamine, in alleviating symptoms of major depressive episodes (MDE). However, to date, there have been limited head-to-head comparisons of intravenous (IV) ketamine infusions with other antidepressant treatment strategies in large randomized trials. This study protocol describes an ongoing multi-centre, prospective, randomized, crossover, non-inferiority trial comparing acute treatment of individuals meeting diagnostic criteria for a major depressive episode (MDE) with ketamine and electroconvulsive therapy (ECT) on efficacy, speed of therapeutic effects, side effects, and health care resource utilization. A secondary aim is to compare a 6-month maintenance strategy for ketamine responders to standard of care ECT maintenance. Finally, through the measurement of clinical, cognitive, neuroimaging, and molecular markers we aim to establish predictors and moderators of treatment response as well as treatment-elicited effects on these outcomes.

Methods: Across four participating Canadian institutions, 240 patients with major depressive disorder or bipolar disorder experiencing a MDE are randomized (1:1) to a course of ECT or racemic IV ketamine (0.5 mg/kg) administered 3 times/week for 3 or 4 weeks. Non-responders (< 50% improvement in Montgomery-Åsberg Depression Rating Scale [MADRS] scores) crossover to receive the alternate treatment. Responders during the randomization or crossover phases then enter the 6-month maintenance phase during which time they receive clinical assessments at identical intervals regardless of treatment arm. ECT maintenance follows standard of care while ketamine maintenance involves: weekly infusions for 1 month, then bi-weekly infusions for 2 months, and finally monthly infusions for 3 months (returning to bi-weekly in case of relapse). The primary outcome measure is change in MADRS scores after randomized treatment as assessed by raters blind to treatment modality.

Discussion: This multi-centre study will help identify molecular, imaging, and clinical characteristics of patients with treatment-resistant and/or severe MDEs who would benefit most from either type of therapeutic strategy. In addition to informing clinical practice and influencing health care delivery, this trial will add to the robust platform and database of CAN-BIND studies for future research and biomarker discovery.

Trial registration: ClinicalTrials.gov identifier NCT03674671. Registered September 17, 2018.

Keywords: Biomarkers; Bipolar disorder; Clinical trial; Depression; Electroconvulsive therapy; Genomics; Intravenous ketamine; Major depressive disorder; Neuroimaging.

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Conflict of interest statement

RM has received consulting and speaking honoraria from Allergan, Janssen, KYE, Lundbeck, Otsuka, Pfizer and Sunovion, and research grants from Janssen, Lallemand, Lundbeck, Nubiyota, and Pfizer.

GT has received an Investigator-initiated grant from Pfizer Canada, and honoraria from Bristol-Meyers Squibb Canada and Janssen Canada.

GHV has received honoraria for participation in advisory boards, giving lectures, and/or expert consultation from Allergan, Gador, Janssen, Lundbeck/Otsuka, Raffo and Sunovion.

SHK has received research funding or honoraria from Abbott, Alkermes, Allergan, BMS, Janssen, Lundbeck, Lundbeck Institute, Otsuka, Pfizer, Servier, Sunovion and Xian-Janssen.

PB received honoraria for participation in advisory boards, giving lectures, and/or expert consultation from Allergan, Bristol Myers Squibb, Janssen, Lundbeck, Otsuka, Pierre Fabre Medicaments, Pfizer and Sunovion; he received grants from Allergan, Janssen, and Lundbeck/Otsuka.

JLP, NJ, EK, VB, JB, JAF, SH, KH, LM, ZM, FMP, SRD, SR list no competing interests.

Figures

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References

1. World Health Organization . The global burden of diseases. 2004 Update. WHO Press. 2008. pp. 40–51.
1. Judd LL, Akiskal HS, Schettler PJ, Endicott J, Maser J, Solomon DA, Leon AC, Rice JA, Keller MB. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59(6):530–537. - PubMed
1. Judd LL, Akiskal HS, Schettler PJ, Coryell W, Endicott J, Maser JD, Solomon DA, Leon AC, Keller MB. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003;60:261–269. - PubMed
1. Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M. STAR*D study team. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163(1):28–40. - PubMed
1. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–4. - PubMed

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A randomized, crossover comparison of ketamine and electroconvulsive therapy for treatment of major depressive episodes: a Canadian biomarker integration network in depression (CAN-BIND) study protocol

Affiliations

A randomized, crossover comparison of ketamine and electroconvulsive therapy for treatment of major depressive episodes: a Canadian biomarker integration network in depression (CAN-BIND) study protocol

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical