Suicidal ideation during treatment of depression with escitalopram and nortriptyline in genome-based therapeutic drugs for depression (GENDEP): a clinical trial.
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).
Perroud
Nader
N
MRC SGDP Centre, Institute of Psychiatry at King's College London, UK. nader.perroud@hcuge.ch
Uher
Rudolf
R
Marusic
Andrej
A
Rietschel
Marcella
M
Mors
Ole
O
Henigsberg
Neven
N
Hauser
Joanna
J
Maier
Wolfgang
W
Souery
Daniel
D
Placentino
Anna
A
Szczepankiewicz
Aleksandra
A
Jorgensen
Lisbeth
L
Strohmaier
Jana
J
Zobel
Astrid
A
Giovannini
Caterina
C
Elkin
Amanda
A
Gunasinghe
Cerisse
C
Gray
Joanna
J
Campbell
Desmond
D
Gupta
Bhanu
B
Farmer
Anne E
AE
McGuffin
Peter
P
Aitchison
Katherine J
KJ
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
D000929:Antidepressive Agents, Tricyclic; D015283:Citalopram; D009661:Nortriptyline; D017367:Selective Serotonin Reuptake Inhibitors