December 7, 2006 — Among suicidal patients who had taken antidepressants, fluoxetine was associated with the lowest risk for causing suicidal tendencies and venlafaxine with the highest risk, according to the results of a cohort study published in the December issue of the Archives of General Psychiatry.

"It is not known if antidepressant treatment is associated with either an increased or a decreased risk of suicide," write Jari Tiihonen, MD, PhD, of Kuopio University Hospital in Finland, and colleagues. "The aim of this study was to investigate, with high statistical power in a nationwide cohort of suicidal subjects, how the risk of suicide, severe suicide attempts, and mortality differs between subjects receiving selective serotonin reuptake inhibitor (SSRIs), tricyclic antidepressants (TCAs), or serotonergic-noradrenergic antidepressants (SNAs) vs. no antidepressant treatment."

In this study, 15,390 patients without psychosis who were hospitalized for a suicide attempt between January 1, 1997, and December 31, 2003, were followed up through a nationwide computerized database, with a mean follow-up of 3.4 years. The primary endpoints were the propensity score–adjusted relative risks (ARRs) during monotherapy with the most frequently used antidepressants vs no antidepressant treatment.

Risk for suicide was lowest with fluoxetine (ARR, 0.52; 95% confidence interval [CI], 0.30 - 0.93), and venlafaxine hydrochloride use with the highest risk (ARR, 1.61; 95% CI, 1.01 - 2.57). Mortality was substantially lower during SSRI use (ARR, 0.59; 95% CI, 0.49 - 0.71; P < .001), which was attributed to decreased cardiovascular- and cerebrovascular-related deaths (ARR, 0.42; 95% CI, 0.24 - 0.71; P = .001).

For subjects who had ever used any antidepressant, current medication use was associated with a markedly increased risk for attempted suicide (39%; P < .001), but also with a markedly decreased risk for completed suicide (-32%; P = .002) and mortality (-49%; P < .001) when compared with no current medication use. For subjects aged 10 to 19 years, the findings were essentially the same as those in the total population, except for an increased risk for death with paroxetine hydrochloride use (ARR, 5.44; 95% CI, 2.15 - 13.70; P < .001).

"Among suicidal subjects who had ever used antidepressants, the current use of any antidepressant was associated with a markedly increased risk of attempted suicide and, at the same time, with a markedly decreased risk of completed suicide and death," the authors write. "Lower mortality was attributable to a decrease in cardiovascular- and cerebrovascular-related deaths during selective serotonin reuptake inhibitor use."

Study limitations include possible confounding factors, lack of information on psychiatric diagnoses beyond exclusion of psychosis, and residual selection bias.

"Our results on suicidal behavior from a cohort of suicidal patients may not be representative of the whole patient population with depression, but the effect of SSRIs on cardiovascular- and cerebrovascular-related mortality might apply to all patients receiving antidepressant medication," the authors conclude. "Possible mechanisms underlying decreased cardiovascular-related mortality may be associated with improvement in heart rate variability or platelet function."

Annual EVO financing (special government subsidies) from Niuvanniemi Hospital supported this study. The authors have disclosed no relevant financial relationships.

Arch Gen Psychiatry. 2006;63:1358-1367.

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Clinical Context

Both the medical literature and popular media have devoted significant attention to the issue of antidepressants and the risk for suicide. While some research has suggested an inverse relationship between the use of antidepressants and the lethality of suicide attempts, other studies have demonstrated an increased risk for suicidal behavior associated with antidepressant use. In particular, paroxetine and venlafaxine have recently received attention for a possible increased risk for suicide.

The precise relationship between antidepressants and suicide has been difficult to document, as suicide is a relatively rare event. Randomized controlled trials of antidepressants have generally not helped to distinguish the risk for suicide associated with their interventions. Therefore, the authors of the current study examine a national database of inpatient admissions to determine the risk for suicidal behavior and completed suicide associated with the use of antidepressants.

Study Highlights

Pearls for Practice

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This article is intended for primary care clinicians, psychiatrists, and other specialists who care for patients with depression.


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