Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine.
BACKGROUND
The US Food and Drug Administration issued a black box warning for antidepressants and suicidal thoughts and behavior in children and young adults.


OBJECTIVE
To determine the short-term safety of antidepressants by standard assessments of suicidal thoughts and behavior in youth, adult, and geriatric populations and the mediating effect of changes in depressive symptoms.


METHODS
All intent-to-treat person-level longitudinal data of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride.


METHODS
All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine.


METHODS
The suicide items from the Children's Depression Rating Scale-Revised and the Hamilton Depression Rating Scale as well as adverse event reports of suicide attempts and suicide during active treatment were analyzed in 9185 patients (fluoxetine: 2635 adults, 960 geriatric patients, 708 youths; venlafaxine: 2421 adults with immediate-release venlafaxine and 2461 adults with extended-release venlafaxine) for a total of 53 260 person-week observations.


RESULTS
Suicidal thoughts and behavior decreased over time for adult and geriatric patients randomized to fluoxetine or venlafaxine compared with placebo, but no differences were found for youths. In adults, reduction in suicide ideation and attempts occurred through a reduction in depressive symptoms. In all age groups, severity of depression improved with medication and was significantly related to suicide ideation or behavior.


CONCLUSIONS
Fluoxetine and venlafaxine decreased suicidal thoughts and behavior for adult and geriatric patients. This protective effect is mediated by decreases in depressive symptoms with treatment. For youths, no significant effects of treatment on suicidal thoughts and behavior were found, although depression responded to treatment. No evidence of increased suicide risk was observed in youths receiving active medication. To our knowledge, this is the first research synthesis of suicidal thoughts and behavior in depressed patients treated with antidepressants that examined the mediating role of depressive symptoms using complete longitudinal person-level data from a large set of published and unpublished studies.
Department of Medicine, University of Chicago, Chicago, IL 60637, USA. rdg@uchicago.edu
Robert D
RD
Gibbons
C Hendricks
CH
Brown
Kwan
K
Hur
John
J
Davis
J John
JJ
Mann
D003511:Cyclohexanols / Q000009:adverse effects*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005473:Fluoxetine / Q000009:adverse effects*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D013405:Suicide; D000069470:Venlafaxine Hydrochloride
D003511:Cyclohexanols; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride