Body weight as a predictor of antidepressant efficacy in the GENDEP project

Rudolf Uher, Ole Mors, Joanna Hauser, Marcella Rietschel, Wolfgang Maier, Dejan Kozel, Neven Henigsberg, Daniel Souery, Anna Placentino, Nader Perroud, Moica Zvezdana Dernovsek, Jana Strohmaier, Erik Roj Larsen, Astrid Zobel, Anna Leszczynska-Rodziewicz, Petra Kalember, Laura Pedrini, Sylvie Linotte, Cerisse Gunasinghe, Katherine J. AitchisonPeter McGuffin, Anne Farmer

Research output: Contribution to journalArticle


Background: Being overweight or obese may be associated with poor response to antidepressants. The present report explores the moderation of antidepressant response by body weight to establish the specificity to antidepressant mode of action, type of depressive symptoms and gender. Methods: Height and weight were measured in 797 men and women with major depression treated with escitalopram or nortriptyline for twelve weeks as part of the Genome Based Therapeutic Drugs for Depression (GENDEP) project. Body mass index (BMI) and obesity (BMI > 30) were tested as predictors of change in depressive symptoms using mixed linear models. Results: Higher BMI and obesity predicted poor response to nortriptyline but did not significantly influence response to escitalopram. The moderation of response by body weight was due to differential improvement in neurovegetative symptoms, including sleep and appetite. The relationship between body weight and change in neurovegetative symptoms was moderated by gender with obese men responding less to nortriptyline and obese women having poorer response to both antidepressants. Limitations: As no placebo arm was included, the specificity of findings to antidepressants is relative. Lack of specific measures precluded accounting for differences in body fat distribution. Conclusions: Body weight should be considered in the assessment of depression as it may inform the selection of antidepressant treatment.

Original languageEnglish
Pages (from-to)147-154
Number of pages8
JournalJournal of Affective Disorders
Issue number1-3
Publication statusPublished - Nov 2009


  • Antidepressant medication
  • Body mass index
  • Body weight
  • Depression
  • Psychopharmacology
  • Psychosomatics

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

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    Uher, R., Mors, O., Hauser, J., Rietschel, M., Maier, W., Kozel, D., Henigsberg, N., Souery, D., Placentino, A., Perroud, N., Dernovsek, M. Z., Strohmaier, J., Larsen, E. R., Zobel, A., Leszczynska-Rodziewicz, A., Kalember, P., Pedrini, L., Linotte, S., Gunasinghe, C., ... Farmer, A. (2009). Body weight as a predictor of antidepressant efficacy in the GENDEP project. Journal of Affective Disorders, 118(1-3), 147-154.