Suicidal thoughts and behavior with antidepressant treatment: Reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine

Robert D. Gibbons, C. Hendricks Brown, Kwan Hur, John M. Davis, J. John Mann

Research output: Contribution to journalArticle

163 Citations (Scopus)

Abstract

Context: 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 anti-depressants by standard assessments of suicidal thoughts and behavior in youth, adult, and geriatric populations and the mediating effect of changes in depressive symptoms. Data Sources: 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. Study Selection: All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine. Data Extraction: 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. Data Synthesis: 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.

Original languageEnglish
Pages (from-to)580-587
Number of pages8
JournalArchives of General Psychiatry
Volume69
Issue number6
DOIs
StatePublished - Jun 1 2012

Fingerprint

Fluoxetine
Antidepressive Agents
Placebos
Depression
Suicide
Geriatrics
Therapeutics
Randomized Controlled Trials
Drug Labeling
Venlafaxine Hydrochloride
Reanalysis
Placebo
Antidepressants
Controlled
Information Storage and Retrieval
Major Depressive Disorder
Child Behavior
United States Food and Drug Administration
Young Adult
Age Groups

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Arts and Humanities (miscellaneous)

Cite this

Suicidal thoughts and behavior with antidepressant treatment : Reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. / Gibbons, Robert D.; Brown, C. Hendricks; Hur, Kwan; Davis, John M.; Mann, J. John.

In: Archives of General Psychiatry, Vol. 69, No. 6, 01.06.2012, p. 580-587.

Research output: Contribution to journalArticle

Gibbons, Robert D. ; Brown, C. Hendricks ; Hur, Kwan ; Davis, John M. ; Mann, J. John. / Suicidal thoughts and behavior with antidepressant treatment : Reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. In: Archives of General Psychiatry. 2012 ; Vol. 69, No. 6. pp. 580-587.
@article{432f7c197dce4e9a8ba78de5e3ab8fa9,
title = "Suicidal thoughts and behavior with antidepressant treatment: Reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine",
abstract = "Context: 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 anti-depressants by standard assessments of suicidal thoughts and behavior in youth, adult, and geriatric populations and the mediating effect of changes in depressive symptoms. Data Sources: 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. Study Selection: All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine. Data Extraction: 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. Data Synthesis: 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.",
author = "Gibbons, {Robert D.} and Brown, {C. Hendricks} and Kwan Hur and Davis, {John M.} and Mann, {J. John}",
year = "2012",
month = "6",
day = "1",
doi = "10.1001/archgenpsychiatry.2011.2048",
language = "English",
volume = "69",
pages = "580--587",
journal = "JAMA Psychiatry",
issn = "2168-622X",
publisher = "American Medical Association",
number = "6",

}

TY - JOUR

T1 - Suicidal thoughts and behavior with antidepressant treatment

T2 - Reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine

AU - Gibbons, Robert D.

AU - Brown, C. Hendricks

AU - Hur, Kwan

AU - Davis, John M.

AU - Mann, J. John

PY - 2012/6/1

Y1 - 2012/6/1

N2 - Context: 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 anti-depressants by standard assessments of suicidal thoughts and behavior in youth, adult, and geriatric populations and the mediating effect of changes in depressive symptoms. Data Sources: 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. Study Selection: All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine. Data Extraction: 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. Data Synthesis: 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.

AB - Context: 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 anti-depressants by standard assessments of suicidal thoughts and behavior in youth, adult, and geriatric populations and the mediating effect of changes in depressive symptoms. Data Sources: 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. Study Selection: All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine. Data Extraction: 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. Data Synthesis: 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.

UR - http://www.scopus.com/inward/record.url?scp=84862001724&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862001724&partnerID=8YFLogxK

U2 - 10.1001/archgenpsychiatry.2011.2048

DO - 10.1001/archgenpsychiatry.2011.2048

M3 - Article

C2 - 22309973

AN - SCOPUS:84862001724

VL - 69

SP - 580

EP - 587

JO - JAMA Psychiatry

JF - JAMA Psychiatry

SN - 2168-622X

IS - 6

ER -