Attempted Suicide Risk Increased with Antidepressants

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.

Learning Objectives for This Educational Activity

Upon completion of this activity, participants will be able to:

• Describe previous research regarding antidepressants and the risk for suicide.
• Compare antidepressant agents with regard to their associated risk for suicide.

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

• The study population included all patients admitted with a diagnosis of attempted suicide in Finland between 1997 and 2003. Patients younger than 10 years and those with a past history of psychosis were excluded from study analysis.
• Prescription records were reviewed from a national database. The researchers particularly examined the 10 most commonly used antidepressants in Finland: amitryptyline, doxepin, fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, mianserin, mirtazapine, and venlafaxine.
• The main study outcome was the ARR for completed suicides, suicide attempts, and overall mortality associated with particular classes of antidepressants vs no antidepressant therapy. Participants were followed up for a mean of 3.4 years after the index admission for suicide attempt, and the authors adjusted outcomes for potential confounders, including age and previous suicide attempts.
• The study cohort included 15,390 patients, and this group was evenly divided between males and females. The mean age of subjects was 38 years old.
• During the follow-up period, the researchers recorded 602 suicides, 7136 suicide attempts leading to hospital admission, and 1583 deaths. The number of previous suicide attempts was the strongest predictor of suicide attempt.
• The ARR of completed suicide attempt in comparing the cohort of patients who purchased an antidepressant vs those who did not was 0.91, a nonsignificant difference. There were no significant differences between antidepressant classes in the outcome of suicide, and antidepressant use did not significantly increase the risk for suicide among the subgroup of patients between the ages of 10 and 19 years. Examining individual medications, only fluoxetine (ARR, 0.52) and venlafaxine (ARR, 1.61) had a significant effect on the risk for suicide.
• The use of any antidepressant increased the risk for suicide attempt (ARR, 1.64). This result was similar when examining the subgroup of patients between the ages of 10 and 19 years.
• Total mortality was reduced with the use of any antidepressant (ARR, 0.64), and this benefit was mostly derived from a significant reduction in the risk for circulatory death associated with antidepressants vs no antidepressant therapy. Specific medications associated with a reduced risk for mortality included fluoxetine, citalopram, sertraline, mianserin, and mirtazapine. Paroxetine was associated with an increased risk for death (ARR, 5.44) among patients between the ages of 10 and 19 years.

Pearls for Practice

• Antidepressants may increase the risk of attempting suicide, but some research suggests that antidepressants decrease the lethality of suicide attempts. Randomized controlled trials have not significantly contributed to the controversy surrounding antidepressants and the risk for suicide.
• In the current study of patients with a prior history of suicide attempt, the use of antidepressants was linked with a significant increase in the risk for suicide attempt. However, antidepressants significantly decreased the risk for completed suicide, death due to circulatory disease, and overall mortality.

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Target Audience

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

Goal

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.