Symptom dimension of interest-activity indicates need for aripiprazole augmentation of escitalopram in major depressive disorder: A CAN-BIND-1 report

CAN-BIND Investigator Teamq

doi:10.4088/JCP.20m13229

Symptom dimension of interest-activity indicates need for aripiprazole augmentation of escitalopram in major depressive disorder: A CAN-BIND-1 report

CAN-BIND Investigator Teamq

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

14 Citas (Scopus)

Resumen

Objective: Differential predictors of response to alternative treatment options are needed to improve the outcomes in major depressive disorder. The symptom dimension comprising loss of interest and reduced activity has been reported as a predictor of poor outcome of treatment with antidepressants. We hypothesized that augmentation with partial dopamine agonist aripiprazole will be effective for individuals with pronounced interest-activity symptoms. Methods: We tested the hypothesis in the 2-phase Canadian Biomarker Integration Network in Depression trial 1 (CAN-BIND-1). All participants had a primary diagnosis of major depressive disorder confirmed with the Mini-International Neuropsychiatric Interview. In phase 1, 188 individuals received escitalopram monotherapy 10-20 mg daily for 8 weeks. In phase 2, nonresponders received augmentation with aripiprazole 2-10 mg daily while responders continued escitalopram monotherapy for another 8 weeks. Outcomes were measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) every 2 weeks. Effects of baseline interest-activity symptoms on outcomes were tested in repeated-measures mixed-effects models. Results: Higher baseline interest-activity score (indicative of more severe loss of interest and reduction in activity) predicted worse outcome of escitalopram monotherapy in phase 1 (b= 1.75; 95% CI, 0.45 to 3.05; P=.009), but the association disappeared with the augmentation option in phase 2 (b= −0.19; 95% CI, −1.30 to 0.92; P=.739). A significant interaction between the baseline interest-activity score and aripiprazole reflected the opposite direction of the relationship between baseline interest-activity score and degree of improvement with escitalopram monotherapy versus aripiprazole augmentation (b= −1.60; 95% CI, −2.35 to −0.84; P<.001). Conclusions: Individuals with prominent loss of interest and reduction in activity benefit less from escitalopram monotherapy and more from aripiprazole augmentation. Future trials may test the benefits of early prodopaminergic augmentation guided by interest-activity symptoms.

Idioma original	English
Número de artículo	20m13229
Publicación	Journal of Clinical Psychiatry
Volumen	81
N.º	4
DOI	https://doi.org/10.4088/JCP.20m13229
Estado	Published - ago. 2020

Nota bibliográfica

Funding Information:
Submitted: January 1, 2020; accepted April 27, 2020. Published online: June 16, 2020. Potential conflicts of interest: Dr Blier has received honoraria for advisory board participation, giving lectures, and/or scientific expertise from Allergan, Bristol-Myers Squibb, Janssen, Lundbeck, Otsuka, and Pierre Fabre Medicaments and research grants from Allergan, Canadian Biomarker Integration Network in Depression (CAN-BIND), Janssen, Lundbeck, and Otsuka. Dr Frey has received a research grant from Pfizer. Dr Kennedy has received research funding or honoraria from Abbott, Alkermes, Allergan, Bristol-Myers Squibb, Brain Canada, Canadian Institutes for Health Research (CIHR), Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute (OBI), Ontario Research Fund (ORF), Otsuka, Pfizer, Servier, Sunovion, and Xian-Janssen. Dr Lam has received honoraria for ad hoc speaking or advising/ consulting, or received research funds, from Akili, Allergan, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, CIHR, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, CME Institute, Hansoh, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, Medscape, Mind.Me, MITACS, Movember Foundation, OBI, Otsuka, Pfizer, St Jude Medical, University Health Network Foundation, and VGH-UBCH

Funding Information:
This research was conducted as part of the Canadian Biomarker Integration Network in Depression (CAN-BIND), an Integrated Discovery Program supported by the Ontario Brain Institute, which is an independent nonprofit corporation, funded partially by the Ontario Government. Additional funding was provided by the Canadian Institutes of Health Research (CIHR), Lundbeck, Bristol-Myers Squibb, and Servier. Funding and/or in-kind support was also provided by the investigators' universities and academic institutions. Dr Uher has received additional support from the Canada Research Chairs Program (award number 231397), the Canadian Institutes of Health Research (Grant reference number 148394), and the Dalhousie Medical Research Foundation.

Publisher Copyright:
© Copyright 2020 Physicians Postgraduate Press, Inc.

ASJC Scopus Subject Areas

Psychiatry and Mental health

PubMed: MeSH publication types

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

ODS de las Naciones Unidas

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@article{ab60ece6efa14a18a25350bbb0bc5ee9,

title = "Symptom dimension of interest-activity indicates need for aripiprazole augmentation of escitalopram in major depressive disorder: A CAN-BIND-1 report",

abstract = "Objective: Differential predictors of response to alternative treatment options are needed to improve the outcomes in major depressive disorder. The symptom dimension comprising loss of interest and reduced activity has been reported as a predictor of poor outcome of treatment with antidepressants. We hypothesized that augmentation with partial dopamine agonist aripiprazole will be effective for individuals with pronounced interest-activity symptoms. Methods: We tested the hypothesis in the 2-phase Canadian Biomarker Integration Network in Depression trial 1 (CAN-BIND-1). All participants had a primary diagnosis of major depressive disorder confirmed with the Mini-International Neuropsychiatric Interview. In phase 1, 188 individuals received escitalopram monotherapy 10-20 mg daily for 8 weeks. In phase 2, nonresponders received augmentation with aripiprazole 2-10 mg daily while responders continued escitalopram monotherapy for another 8 weeks. Outcomes were measured with the Montgomery-{\AA}sberg Depression Rating Scale (MADRS) every 2 weeks. Effects of baseline interest-activity symptoms on outcomes were tested in repeated-measures mixed-effects models. Results: Higher baseline interest-activity score (indicative of more severe loss of interest and reduction in activity) predicted worse outcome of escitalopram monotherapy in phase 1 (b= 1.75; 95% CI, 0.45 to 3.05; P=.009), but the association disappeared with the augmentation option in phase 2 (b= −0.19; 95% CI, −1.30 to 0.92; P=.739). A significant interaction between the baseline interest-activity score and aripiprazole reflected the opposite direction of the relationship between baseline interest-activity score and degree of improvement with escitalopram monotherapy versus aripiprazole augmentation (b= −1.60; 95% CI, −2.35 to −0.84; P<.001). Conclusions: Individuals with prominent loss of interest and reduction in activity benefit less from escitalopram monotherapy and more from aripiprazole augmentation. Future trials may test the benefits of early prodopaminergic augmentation guided by interest-activity symptoms.",

author = "{CAN-BIND Investigator Teamq} and Rudolf Uher and Frey, {Benicio N.} and Quilty, {Lena C.} and Susan Rotzinger and Pierre Blier and Foster, {Jane A.} and M{\"u}ller, {Daniel J.} and Ravindran, {Arun V.} and Soares, {Claudio N.} and Gustavo Turecki and Parikh, {Sagar V.} and Roumen Milev and Glenda MacQueen and Lam, {Raymond W.} and Kennedy, {Sidney H.}",

note = "Funding Information: Submitted: January 1, 2020; accepted April 27, 2020. Published online: June 16, 2020. Potential conflicts of interest: Dr Blier has received honoraria for advisory board participation, giving lectures, and/or scientific expertise from Allergan, Bristol-Myers Squibb, Janssen, Lundbeck, Otsuka, and Pierre Fabre Medicaments and research grants from Allergan, Canadian Biomarker Integration Network in Depression (CAN-BIND), Janssen, Lundbeck, and Otsuka. Dr Frey has received a research grant from Pfizer. Dr Kennedy has received research funding or honoraria from Abbott, Alkermes, Allergan, Bristol-Myers Squibb, Brain Canada, Canadian Institutes for Health Research (CIHR), Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute (OBI), Ontario Research Fund (ORF), Otsuka, Pfizer, Servier, Sunovion, and Xian-Janssen. Dr Lam has received honoraria for ad hoc speaking or advising/ consulting, or received research funds, from Akili, Allergan, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, CIHR, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, CME Institute, Hansoh, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, Medscape, Mind.Me, MITACS, Movember Foundation, OBI, Otsuka, Pfizer, St Jude Medical, University Health Network Foundation, and VGH-UBCH Funding Information: This research was conducted as part of the Canadian Biomarker Integration Network in Depression (CAN-BIND), an Integrated Discovery Program supported by the Ontario Brain Institute, which is an independent nonprofit corporation, funded partially by the Ontario Government. Additional funding was provided by the Canadian Institutes of Health Research (CIHR), Lundbeck, Bristol-Myers Squibb, and Servier. Funding and/or in-kind support was also provided by the investigators' universities and academic institutions. Dr Uher has received additional support from the Canada Research Chairs Program (award number 231397), the Canadian Institutes of Health Research (Grant reference number 148394), and the Dalhousie Medical Research Foundation. Publisher Copyright: {\textcopyright} Copyright 2020 Physicians Postgraduate Press, Inc.",

year = "2020",

month = aug,

doi = "10.4088/JCP.20m13229",

language = "English",

volume = "81",

journal = "Journal of Clinical Psychiatry",

issn = "0160-6689",

publisher = "Physicians Postgraduate Press Inc.",

number = "4",

}

TY - JOUR

T1 - Symptom dimension of interest-activity indicates need for aripiprazole augmentation of escitalopram in major depressive disorder

T2 - A CAN-BIND-1 report

AU - CAN-BIND Investigator Teamq

AU - Uher, Rudolf

AU - Frey, Benicio N.

AU - Quilty, Lena C.

AU - Rotzinger, Susan

AU - Blier, Pierre

AU - Foster, Jane A.

AU - Müller, Daniel J.

AU - Ravindran, Arun V.

AU - Soares, Claudio N.

AU - Turecki, Gustavo

AU - Parikh, Sagar V.

AU - Milev, Roumen

AU - MacQueen, Glenda

AU - Lam, Raymond W.

AU - Kennedy, Sidney H.

N1 - Funding Information: Submitted: January 1, 2020; accepted April 27, 2020. Published online: June 16, 2020. Potential conflicts of interest: Dr Blier has received honoraria for advisory board participation, giving lectures, and/or scientific expertise from Allergan, Bristol-Myers Squibb, Janssen, Lundbeck, Otsuka, and Pierre Fabre Medicaments and research grants from Allergan, Canadian Biomarker Integration Network in Depression (CAN-BIND), Janssen, Lundbeck, and Otsuka. Dr Frey has received a research grant from Pfizer. Dr Kennedy has received research funding or honoraria from Abbott, Alkermes, Allergan, Bristol-Myers Squibb, Brain Canada, Canadian Institutes for Health Research (CIHR), Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute (OBI), Ontario Research Fund (ORF), Otsuka, Pfizer, Servier, Sunovion, and Xian-Janssen. Dr Lam has received honoraria for ad hoc speaking or advising/ consulting, or received research funds, from Akili, Allergan, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, CIHR, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, CME Institute, Hansoh, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, Medscape, Mind.Me, MITACS, Movember Foundation, OBI, Otsuka, Pfizer, St Jude Medical, University Health Network Foundation, and VGH-UBCH Funding Information: This research was conducted as part of the Canadian Biomarker Integration Network in Depression (CAN-BIND), an Integrated Discovery Program supported by the Ontario Brain Institute, which is an independent nonprofit corporation, funded partially by the Ontario Government. Additional funding was provided by the Canadian Institutes of Health Research (CIHR), Lundbeck, Bristol-Myers Squibb, and Servier. Funding and/or in-kind support was also provided by the investigators' universities and academic institutions. Dr Uher has received additional support from the Canada Research Chairs Program (award number 231397), the Canadian Institutes of Health Research (Grant reference number 148394), and the Dalhousie Medical Research Foundation. Publisher Copyright: © Copyright 2020 Physicians Postgraduate Press, Inc.

PY - 2020/8

Y1 - 2020/8

N2 - Objective: Differential predictors of response to alternative treatment options are needed to improve the outcomes in major depressive disorder. The symptom dimension comprising loss of interest and reduced activity has been reported as a predictor of poor outcome of treatment with antidepressants. We hypothesized that augmentation with partial dopamine agonist aripiprazole will be effective for individuals with pronounced interest-activity symptoms. Methods: We tested the hypothesis in the 2-phase Canadian Biomarker Integration Network in Depression trial 1 (CAN-BIND-1). All participants had a primary diagnosis of major depressive disorder confirmed with the Mini-International Neuropsychiatric Interview. In phase 1, 188 individuals received escitalopram monotherapy 10-20 mg daily for 8 weeks. In phase 2, nonresponders received augmentation with aripiprazole 2-10 mg daily while responders continued escitalopram monotherapy for another 8 weeks. Outcomes were measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) every 2 weeks. Effects of baseline interest-activity symptoms on outcomes were tested in repeated-measures mixed-effects models. Results: Higher baseline interest-activity score (indicative of more severe loss of interest and reduction in activity) predicted worse outcome of escitalopram monotherapy in phase 1 (b= 1.75; 95% CI, 0.45 to 3.05; P=.009), but the association disappeared with the augmentation option in phase 2 (b= −0.19; 95% CI, −1.30 to 0.92; P=.739). A significant interaction between the baseline interest-activity score and aripiprazole reflected the opposite direction of the relationship between baseline interest-activity score and degree of improvement with escitalopram monotherapy versus aripiprazole augmentation (b= −1.60; 95% CI, −2.35 to −0.84; P<.001). Conclusions: Individuals with prominent loss of interest and reduction in activity benefit less from escitalopram monotherapy and more from aripiprazole augmentation. Future trials may test the benefits of early prodopaminergic augmentation guided by interest-activity symptoms.

AB - Objective: Differential predictors of response to alternative treatment options are needed to improve the outcomes in major depressive disorder. The symptom dimension comprising loss of interest and reduced activity has been reported as a predictor of poor outcome of treatment with antidepressants. We hypothesized that augmentation with partial dopamine agonist aripiprazole will be effective for individuals with pronounced interest-activity symptoms. Methods: We tested the hypothesis in the 2-phase Canadian Biomarker Integration Network in Depression trial 1 (CAN-BIND-1). All participants had a primary diagnosis of major depressive disorder confirmed with the Mini-International Neuropsychiatric Interview. In phase 1, 188 individuals received escitalopram monotherapy 10-20 mg daily for 8 weeks. In phase 2, nonresponders received augmentation with aripiprazole 2-10 mg daily while responders continued escitalopram monotherapy for another 8 weeks. Outcomes were measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) every 2 weeks. Effects of baseline interest-activity symptoms on outcomes were tested in repeated-measures mixed-effects models. Results: Higher baseline interest-activity score (indicative of more severe loss of interest and reduction in activity) predicted worse outcome of escitalopram monotherapy in phase 1 (b= 1.75; 95% CI, 0.45 to 3.05; P=.009), but the association disappeared with the augmentation option in phase 2 (b= −0.19; 95% CI, −1.30 to 0.92; P=.739). A significant interaction between the baseline interest-activity score and aripiprazole reflected the opposite direction of the relationship between baseline interest-activity score and degree of improvement with escitalopram monotherapy versus aripiprazole augmentation (b= −1.60; 95% CI, −2.35 to −0.84; P<.001). Conclusions: Individuals with prominent loss of interest and reduction in activity benefit less from escitalopram monotherapy and more from aripiprazole augmentation. Future trials may test the benefits of early prodopaminergic augmentation guided by interest-activity symptoms.

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Symptom dimension of interest-activity indicates need for aripiprazole augmentation of escitalopram in major depressive disorder: A CAN-BIND-1 report

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PubMed: MeSH publication types

ODS de las Naciones Unidas

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