Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression.
OBJECTIVE
A comprehensive meta-analysis of clinical trial data was performed to assess the possible association of fluoxetine and suicidality (suicidal acts and ideation).


METHODS
Retrospective analysis of pooled data from 17 double blind clinical trials in patients with major depressive disorder comparing fluoxetine (n = 1765) with a tricyclic antidepressant (n = 731) or placebo (n = 569), or both.


METHODS
Multiple data sources were searched to identify patients with suicidal acts. Suicidal ideation was assessed with item 3 of the Hamilton depression rating scale, which systematically rates suicidality. Emergence of substantial suicidal ideation was defined as a change in the rating of this item from 0 or 1 at baseline to 3 or 4 during double blind treatment; worsening was defined as any increase from baseline; improvement was defined as a decrease from baseline at the last visit during the treatment.


RESULTS
Suicidal acts did not differ significantly in comparisons of fluoxetine with placebo (0.2% v 0.2%, p = 0.494, Mantel-Haenszel adjusted incidence difference) and with tricyclic antidepressants (0.7% v 0.4%, p = 0.419). The pooled incidence of suicidal acts was 0.3% for fluoxetine, 0.2% for placebo, and 0.4% for tricyclic antidepressants, and fluoxetine did not differ significantly from either placebo (p = 0.533, Pearson's chi 2) or tricyclic antidepressants (p = 0.789). Suicidal ideation emerged marginally significantly less often with fluoxetine than with placebo (0.9% v 2.6%, p = 0.094) and numerically less often than with tricyclic antidepressants (1.7% v 3.6%, p = 0.102). The pooled incidence of emergence of substantial suicidal ideation was 1.2% for fluoxetine, 2.6% for placebo, and 3.6% for tricyclic antidepressants. The incidence was significantly lower with fluoxetine than with placebo (p = 0.042) and tricyclic antidepressants (p = 0.001). Any degree of worsening of suicidal ideation was similar with fluoxetine and placebo (15.4% v 17.9%, p = 0.196) and with fluoxetine and tricyclic antidepressants (15.6% v 16.3%, p = 0.793). The pooled incidence of worsening of suicidal ideation was 15.3% for fluoxetine, 17.9% for placebo, and 16.3% for tricyclic antidepressants. The incidence did not differ significantly with fluoxetine and placebo (p = 0.141) or tricyclic antidepressants (p = 0.542). Suicidal ideation improved significantly more with fluoxetine than with placebo (72.0% v 54.8%, p less than 0.001) and was similar to the improvement with tricyclic antidepressants (72.5% v 69.8%, p = 0.294). The pooled incidence of improvement of suicidal ideation was 72.2% for fluoxetine, 54.8% for placebo, and 69.8% for tricyclic antidepressants. The incidence with fluoxetine was significantly greater than with placebo (p less than 0.001) and did not differ from that with tricyclic antidepressants (p = 0.296).


CONCLUSIONS
Data from these trials do not show that fluoxetine is associated with an increased risk of suicidal acts or emergence of substantial suicidal thoughts among depressed patients.
Beasley
C M
CM
Division of Clinical Neurosciences, Eli Lilly and Company, Indianapolis, Indiana 46285.
Dornseif
B E
BE
Bosomworth
J C
JC
Sayler
M E
ME
Rampey
A H
AH
Heiligenstein
J H
JH
Thompson
V L
VL
Murphy
D J
DJ
Masica
D N
DN
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects; D002648:Child; D003866:Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013405:Suicide / Q000523:psychology
D000929:Antidepressive Agents, Tricyclic; D005473:Fluoxetine