Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration.
OBJECTIVE
To examine the risk of suicidal behaviour within clinical trials of antidepressants in adults.


METHODS
Meta-analysis of 372 double blind randomised placebo controlled trials.


METHODS
Drug development programmes for any indication in adults.


METHODS
99 231 adults assigned to antidepressants or placebo. Median age was 42 and 63.1% were women. Indications for treatment were major depression (45.6%), other depression (4.6%), other psychiatric disorders (27.6%), and non-psychiatric disorders (22.2%).


METHODS
Suicidal behaviour (completed suicide, attempted suicide, or preparatory acts) and ideation.


RESULTS
For participants with non-psychiatric indications, suicidal behaviour and ideation were extremely rare. For those with psychiatric indications, risk was associated with age. For suicidal behaviour or ideation and for suicidal behaviour only, the respective odds ratios were 1.62 (95% confidence interval 0.97 to 2.71) and 2.30 (1.04 to 5.09) for participants aged <25, 0.79 (0.64 to 0.98) and 0.87 (0.58 to 1.29) for those aged 25-64, and 0.37 (0.18 to 0.76) and 0.06 (0.01 to 0.58) for those aged >or=65. When age was modelled as a continuous variable, the odds ratio for suicidal behaviour or ideation declined at a rate of 2.6% per year of age (-3.9% to -1.3%, P=0.0001) and the odds ratio for suicidal behaviour declined at a rate of 4.6% per year of age (-7.4% to -1.8%, P=0.001).


CONCLUSIONS
Risk of suicidality associated with use of antidepressants is strongly age dependent. Compared with placebo, the increased risk for suicidality and suicidal behaviour among adults under 25 approaches that seen in children and adolescents. The net effect seems to be neutral on suicidal behaviour but possibly protective for suicidal ideation in adults aged 25-64 and to reduce the risk of both suicidality and suicidal behaviour in those aged >or=65.
Stone
Marc
M
Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002, USA. marc.stone@fda.hhs.gov
Laughren
Thomas
T
Jones
M Lisa
ML
Levenson
Mark
M
Holland
P Chris
PC
Hughes
Alice
A
Hammad
Tarek A
TA
Temple
Robert
R
Rochester
George
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000009:adverse effects*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013405:Suicide / Q000523:psychology / Q000706:statistics & numerical data*; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult
D000928:Antidepressive Agents