Open Access Research article

Suicidal ideation during treatment of depression with escitalopram and nortriptyline in Genome-Based Therapeutic Drugs for Depression (GENDEP): a clinical trial

Nader Perroud1*, Rudolf Uher1, Andrej Marusic2, Marcella Rietschel3, Ole Mors4, Neven Henigsberg5, Joanna Hauser6, Wolfgang Maier7, Daniel Souery8, Anna Placentino9, Aleksandra Szczepankiewicz6, Lisbeth Jorgensen10, Jana Strohmaier3, Astrid Zobel7, Caterina Giovannini9, Amanda Elkin1, Cerisse Gunasinghe1, Joanna Gray1, Desmond Campbell1, Bhanu Gupta1, Anne E Farmer1, Peter McGuffin1 and Katherine J Aitchison1

Author Affiliations

1 MRC SGDP Centre, Institute of Psychiatry at King's College London, UK

2 Institute of Public Health, Ljubljana, Slovenia

3 Central Institute of Mental Health, Division of Genetic Epidemiology in Psychiatry, Mannheim, Germany

4 Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark

5 Croatian Institute for Brain Research, Medical School, University of Zagreb, Zagreb, Croatia

6 Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland

7 Department of Psychiatry, University of Bonn, Bonn, Germany

8 Université Libre de Bruxelles, Erasme Academic Hospital, Department of Psychiatry, Brussels, Belgium

9 Biological Psychiatry Unit and Dual Diagnosis Ward IRCCS, Centro San Giovanni di Dio, Brescia, Italy

10 Mood Disorders Research Unit, Aarhus University Hospital, Risskov, Denmark

For all author emails, please log on.

BMC Medicine 2009, 7:60  doi:10.1186/1741-7015-7-60

Published: 15 October 2009



Suicidal thoughts and behaviours during antidepressant treatment, especially during the first weeks of treatment, have prompted warnings by regulatory bodies. The aim of the present study is to investigate the course and predictors of emergence and worsening of suicidal ideation during tricyclic antidepressant and serotonin reuptake inhibitor treatment.


In a multicentre part-randomised open-label study, 811 adult patients with moderate to severe unipolar depression were allocated to flexible dosage of escitalopram or nortriptyline for 12 weeks. The suicidality items of three standard measures were integrated in a suicidal ideation score. Increases in this score were classified as treatment emergent suicidal ideation (TESI) or treatment worsening suicidal ideation (TWOSI) according to the absence or presence of suicidal ideation at baseline.


Suicidal ideation decreased during antidepressant treatment. Rates of TESI and TWOSI peaked in the fifth week. Severity of depression predicted TESI and TWOSI. In men, nortriptyline was associated with a 9.8-fold and 2.4-fold increase in TESI and TWOSI compared to escitalopram, respectively. Retirement and history of suicide attempts predicted TWOSI.


Increases in suicidal ideation were associated with depression severity and decreased during antidepressant treatment. In men, treatment with escitalopram is associated with lower risk of suicidal ideation compared to nortriptyline. Clinicians should remain alert to suicidal ideation beyond the initial weeks of antidepressant treatment.

Trial registration

EudraCT (No.2004-001723-38) and ISRCTN (No. 03693000).