title: Suicidal ideation during treatment of depression with escitalopram and nortriptyline in genome-based therapeutic drugs for depression (GENDEP): a clinical trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  EudraCT (No.2004-001723-38) and ISRCTN (No. 03693000).
authors.affiliation: MRC SGDP Centre, Institute of Psychiatry at King's College London, UK. nader.perroud@hcuge.ch
authors.forename: Nader
authors.initials: N
authors.lastname: Perroud
authors.forename: Rudolf
authors.initials: R
authors.lastname: Uher
authors.forename: Andrej
authors.initials: A
authors.lastname: Marusic
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.forename: Neven
authors.initials: N
authors.lastname: Henigsberg
authors.forename: Joanna
authors.initials: J
authors.lastname: Hauser
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Daniel
authors.initials: D
authors.lastname: Souery
authors.forename: Anna
authors.initials: A
authors.lastname: Placentino
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szczepankiewicz
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Jorgensen
authors.forename: Jana
authors.initials: J
authors.lastname: Strohmaier
authors.forename: Astrid
authors.initials: A
authors.lastname: Zobel
authors.forename: Caterina
authors.initials: C
authors.lastname: Giovannini
authors.forename: Amanda
authors.initials: A
authors.lastname: Elkin
authors.forename: Cerisse
authors.initials: C
authors.lastname: Gunasinghe
authors.forename: Joanna
authors.initials: J
authors.lastname: Gray
authors.forename: Desmond
authors.initials: D
authors.lastname: Campbell
authors.forename: Bhanu
authors.initials: B
authors.lastname: Gupta
authors.forename: Anne E
authors.initials: AE
authors.lastname: Farmer
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Aitchison
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects* / Q000627:therapeutic use; D015283:Citalopram / Q000009:adverse effects* / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009661:Nortriptyline / Q000009:adverse effects* / Q000627:therapeutic use; D010555:Personality Inventory; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D013405:Suicide / Q000706:statistics & numerical data*; D055815:Young Adult
chemical_list: D000929:Antidepressive Agents, Tricyclic; D015283:Citalopram; D009661:Nortriptyline; D017367:Selective Serotonin Reuptake Inhibitors