Dimensions of temperament and character as predictors of antidepressant discontinuation, response and adverse reactions during treatment with nortriptyline and escitalopram

Ole Köhler-Forsberg; Robert Keers; Rudolf Uher; Joanna Hauser; Wolfgang Maier; Marcella Rietschel; Peter McGuffin; Anne E. Farmer; Katherine J. Aitchison; Ole Mors

doi:10.1017/S003329172100444X

Dimensions of temperament and character as predictors of antidepressant discontinuation, response and adverse reactions during treatment with nortriptyline and escitalopram

Ole Köhler-Forsberg^*, Robert Keers, Rudolf Uher, Joanna Hauser, Wolfgang Maier, Marcella Rietschel, Peter McGuffin, Anne E. Farmer, Katherine J. Aitchison, Ole Mors

^*Corresponding author for this work

Social Genetic & Developmental Psychiatry

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Background Personality traits may predict antidepressant discontinuation and response. However, previous studies were rather small, only explored a few personality traits and did not include adverse drug effects nor the interdependency between antidepressant discontinuation patterns and response. Methods GENDEP included 589 patients with unipolar moderate-severe depression treated with escitalopram or nortriptyline for 12 weeks. Seven personality dimensions were measured using the self-reported 240-item Temperament and Character Inventory-Revised (TCI-R). We applied Cox proportional models to study discontinuation patterns, logistic and linear regression to investigate response and remission after 8 and 12 weeks, and mixed-effects linear models regarding time-varying treatment response and adverse drug reactions. Results Low harm avoidance, low cooperativeness, high self-transcendence and high novelty seeking were associated with higher risks for antidepressant discontinuation, independent of depressed mood, adverse drug reactions, drug, sex and age. Regression analyses showed that higher novelty seeking and cooperativeness scores were associated with a greater likelihood of response and remission after 8 and 12 weeks, respectively, but we found no correlations with response in the mixed-effects models. Only high harm avoidance was associated with more self-reported adverse effects. Conclusions This study, representing the largest investigation between several personality traits and response to two different antidepressants, suggests that correlations between personality traits and antidepressant treatment response may be confounded by differential rates of discontinuation. Future trials on personality in the treatment of depression need to consider this interdependency and study whether interventions aiming at improving compliance for some personality types may improve response to antidepressants.

Original language	English
Pages (from-to)	1-9
Journal	Psychological Medicine
Early online date	12 Nov 2021
DOIs	https://doi.org/10.1017/S003329172100444X
Publication status	E-pub ahead of print - 12 Nov 2021

Keywords

Antidepressant
depression
discontinuation
major depressive disorder (MDD)
personality
response

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1017/S003329172100444X

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Köhler-Forsberg, O., Keers, R., Uher, R., Hauser, J., Maier, W., Rietschel, M., McGuffin, P., Farmer, A. E., Aitchison, K. J., & Mors, O. (2021). Dimensions of temperament and character as predictors of antidepressant discontinuation, response and adverse reactions during treatment with nortriptyline and escitalopram. Psychological Medicine, 1-9. https://doi.org/10.1017/S003329172100444X

@article{ead569018db14ec7bb9d2a177843e8a3,

title = "Dimensions of temperament and character as predictors of antidepressant discontinuation, response and adverse reactions during treatment with nortriptyline and escitalopram",

abstract = "Background Personality traits may predict antidepressant discontinuation and response. However, previous studies were rather small, only explored a few personality traits and did not include adverse drug effects nor the interdependency between antidepressant discontinuation patterns and response. Methods GENDEP included 589 patients with unipolar moderate-severe depression treated with escitalopram or nortriptyline for 12 weeks. Seven personality dimensions were measured using the self-reported 240-item Temperament and Character Inventory-Revised (TCI-R). We applied Cox proportional models to study discontinuation patterns, logistic and linear regression to investigate response and remission after 8 and 12 weeks, and mixed-effects linear models regarding time-varying treatment response and adverse drug reactions. Results Low harm avoidance, low cooperativeness, high self-transcendence and high novelty seeking were associated with higher risks for antidepressant discontinuation, independent of depressed mood, adverse drug reactions, drug, sex and age. Regression analyses showed that higher novelty seeking and cooperativeness scores were associated with a greater likelihood of response and remission after 8 and 12 weeks, respectively, but we found no correlations with response in the mixed-effects models. Only high harm avoidance was associated with more self-reported adverse effects. Conclusions This study, representing the largest investigation between several personality traits and response to two different antidepressants, suggests that correlations between personality traits and antidepressant treatment response may be confounded by differential rates of discontinuation. Future trials on personality in the treatment of depression need to consider this interdependency and study whether interventions aiming at improving compliance for some personality types may improve response to antidepressants. ",

keywords = "Antidepressant, depression, discontinuation, major depressive disorder (MDD), personality, response",

author = "Ole K{\"o}hler-Forsberg and Robert Keers and Rudolf Uher and Joanna Hauser and Wolfgang Maier and Marcella Rietschel and Peter McGuffin and Farmer, {Anne E.} and Aitchison, {Katherine J.} and Ole Mors",

note = "Funding Information: Dr Aitchison holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. Dr Aitchison has been a member of various advisory boards, received consultancy fees and honoraria, and has received research grants from various companies including Johnson and Johnson Pharmaceuticals Research and Development and Bristol-Myers Squibb Pharmaceuticals Limited. Dr K{\"o}hler-Forsberg reports honoraria for lectures for Lundbeck Pharma A/S. Drs Farmer and McGuffin have received honoraria for participating in expert panels for Lundbeck and GlaxoSmithKline. The other authors report no financial relationships with commercial interests. Funding Information: The GENDEP study was funded by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. Lundbeck provided both nortriptyline and escitalopram free of charge for the GENDEP study. GlaxoSmithKline and the Medical Research Council contributed by funding add-on projects in the London centre. The project also received additional funding at the London centre from the Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London and South London and Maudsley NHS Foundation Trust [grant from the National Institute for Health Research (NIHR), Department of Health, UK]. None of the above had any role in the design and conduct of the study, in data collection, analysis, interpretation nor writing or submission of the paper. Publisher Copyright: {\textcopyright} The Author(s), 2021. Published by Cambridge University Press.",

year = "2021",

month = nov,

day = "12",

doi = "10.1017/S003329172100444X",

language = "English",

pages = "1--9",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

}

Köhler-Forsberg, O, Keers, R , Uher, R, Hauser, J, Maier, W, Rietschel, M, McGuffin, P , Farmer, AE , Aitchison, KJ & Mors, O 2021, 'Dimensions of temperament and character as predictors of antidepressant discontinuation, response and adverse reactions during treatment with nortriptyline and escitalopram', Psychological Medicine, pp. 1-9. https://doi.org/10.1017/S003329172100444X

TY - JOUR

T1 - Dimensions of temperament and character as predictors of antidepressant discontinuation, response and adverse reactions during treatment with nortriptyline and escitalopram

AU - Köhler-Forsberg, Ole

AU - Keers, Robert

AU - Uher, Rudolf

AU - Hauser, Joanna

AU - Maier, Wolfgang

AU - Rietschel, Marcella

AU - McGuffin, Peter

AU - Farmer, Anne E.

AU - Aitchison, Katherine J.

AU - Mors, Ole

N1 - Funding Information: Dr Aitchison holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. Dr Aitchison has been a member of various advisory boards, received consultancy fees and honoraria, and has received research grants from various companies including Johnson and Johnson Pharmaceuticals Research and Development and Bristol-Myers Squibb Pharmaceuticals Limited. Dr Köhler-Forsberg reports honoraria for lectures for Lundbeck Pharma A/S. Drs Farmer and McGuffin have received honoraria for participating in expert panels for Lundbeck and GlaxoSmithKline. The other authors report no financial relationships with commercial interests. Funding Information: The GENDEP study was funded by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. Lundbeck provided both nortriptyline and escitalopram free of charge for the GENDEP study. GlaxoSmithKline and the Medical Research Council contributed by funding add-on projects in the London centre. The project also received additional funding at the London centre from the Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London and South London and Maudsley NHS Foundation Trust [grant from the National Institute for Health Research (NIHR), Department of Health, UK]. None of the above had any role in the design and conduct of the study, in data collection, analysis, interpretation nor writing or submission of the paper. Publisher Copyright: © The Author(s), 2021. Published by Cambridge University Press.

PY - 2021/11/12

Y1 - 2021/11/12

N2 - Background Personality traits may predict antidepressant discontinuation and response. However, previous studies were rather small, only explored a few personality traits and did not include adverse drug effects nor the interdependency between antidepressant discontinuation patterns and response. Methods GENDEP included 589 patients with unipolar moderate-severe depression treated with escitalopram or nortriptyline for 12 weeks. Seven personality dimensions were measured using the self-reported 240-item Temperament and Character Inventory-Revised (TCI-R). We applied Cox proportional models to study discontinuation patterns, logistic and linear regression to investigate response and remission after 8 and 12 weeks, and mixed-effects linear models regarding time-varying treatment response and adverse drug reactions. Results Low harm avoidance, low cooperativeness, high self-transcendence and high novelty seeking were associated with higher risks for antidepressant discontinuation, independent of depressed mood, adverse drug reactions, drug, sex and age. Regression analyses showed that higher novelty seeking and cooperativeness scores were associated with a greater likelihood of response and remission after 8 and 12 weeks, respectively, but we found no correlations with response in the mixed-effects models. Only high harm avoidance was associated with more self-reported adverse effects. Conclusions This study, representing the largest investigation between several personality traits and response to two different antidepressants, suggests that correlations between personality traits and antidepressant treatment response may be confounded by differential rates of discontinuation. Future trials on personality in the treatment of depression need to consider this interdependency and study whether interventions aiming at improving compliance for some personality types may improve response to antidepressants.

AB - Background Personality traits may predict antidepressant discontinuation and response. However, previous studies were rather small, only explored a few personality traits and did not include adverse drug effects nor the interdependency between antidepressant discontinuation patterns and response. Methods GENDEP included 589 patients with unipolar moderate-severe depression treated with escitalopram or nortriptyline for 12 weeks. Seven personality dimensions were measured using the self-reported 240-item Temperament and Character Inventory-Revised (TCI-R). We applied Cox proportional models to study discontinuation patterns, logistic and linear regression to investigate response and remission after 8 and 12 weeks, and mixed-effects linear models regarding time-varying treatment response and adverse drug reactions. Results Low harm avoidance, low cooperativeness, high self-transcendence and high novelty seeking were associated with higher risks for antidepressant discontinuation, independent of depressed mood, adverse drug reactions, drug, sex and age. Regression analyses showed that higher novelty seeking and cooperativeness scores were associated with a greater likelihood of response and remission after 8 and 12 weeks, respectively, but we found no correlations with response in the mixed-effects models. Only high harm avoidance was associated with more self-reported adverse effects. Conclusions This study, representing the largest investigation between several personality traits and response to two different antidepressants, suggests that correlations between personality traits and antidepressant treatment response may be confounded by differential rates of discontinuation. Future trials on personality in the treatment of depression need to consider this interdependency and study whether interventions aiming at improving compliance for some personality types may improve response to antidepressants.

KW - Antidepressant

KW - depression

KW - discontinuation

KW - major depressive disorder (MDD)

KW - personality

KW - response

UR - http://www.scopus.com/inward/record.url?scp=85119282000&partnerID=8YFLogxK

U2 - 10.1017/S003329172100444X

DO - 10.1017/S003329172100444X

M3 - Article

AN - SCOPUS:85119282000

SN - 0033-2917

SP - 1

EP - 9

JO - Psychological Medicine

JF - Psychological Medicine

ER -

Dimensions of temperament and character as predictors of antidepressant discontinuation, response and adverse reactions during treatment with nortriptyline and escitalopram

Abstract

Keywords

UN SDGs

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