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A comprehensive meta-analysis was performed to address the possible association of fluoxetine with violence or aggression. Data from the United States Investigational New Drug Clinical Trial Databases for approved and potential indications (depression, obesity, bulimia nervosa, obsessive-compulsive disorder, smoking cessation, alcoholism; n = 3992) were evaluated. Statistically significantly fewer fluoxetine-treated patients (0.15%) than placebo-treated patients (0.65%) experienced events suggestive of aggression (hostility, personality disorder, antisocial reaction). A relative risk analysis indicated that aggression events were four times more likely to occur in placebo-treated patients than in fluoxetine-treated patients. Although the possibility that some rare phenomenon was not detected cannot be excluded, this meta-analysis did not show fluoxetine to be associated with an increased risk of emergence of violent or aggressive behaviour.

OBJECTIVE--A comprehensive meta-analysis of clinical trial data was performed to assess the possible association of fluoxetine and suicidality (suicidal acts and ideation). DESIGN--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. MAIN OUTCOME MEASURES--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.

As part of a study in which reduced rapid eye movement latency was used to predict treatment response, fluoxetine and placebo were compared in 89 outpatients with major depression with (n = 52) and without (n = 37) DSM-III-R melancholia, to determine whether the presence or absence of melancholia predicted antidepressant and/or placebo response. Following a 2-week, single-blind placebo lead-in, men and women were assigned by random allocation to double-blind fluoxetine, 20 mg/day, or placebo for 8 weeks. Fluoxetine was statistically significantly superior to placebo in patients with melancholia (endpoint change in the Montgomery-Asberg Depression Rating Scale [MADRS] score, response rates and remission rates). A weekly analysis demonstrated statistical superiority of fluoxetine compared with placebo at week 3 and continuing for the remainder of the study. Fluoxetine was statistically significantly more likely to reduce suicidal ideation compared with placebo, using the MADRS item 10 (suicidal ideation question).