Antidepressants and Suicide Risk* - 11/19/2008

Among suicidal patients who had taken antidepressants, fluoxetine (Prosac) was associated with the lowest risk for causing suicidal tendencies and venlafaxine (Effexor) with the highest risk, according to the results of a cohort study published in the December 2006 issue of the Archives of General Psychiatry. The aim of this important 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. The results were compelling and will be discussed in this report.

Study Methodology
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. 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.

Results
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.

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 (Paxil) use (ARR, 5.44; 95% CI, 2.15 - 13.70; P < .001).

Discussion
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. Lower mortality was attributable to a decrease in cardiovascular- and cerebrovascular- related deaths during selective serotonin reuptake inhibitor use.

They go on to say that their 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. Possible mechanisms underlying decreased cardiovascular-related mortality may be associated with improvement in heart rate variability or platelet function.

Medical-Legal Considerations
This large study shows that antidepressants may increase the risk of attempting suicide, but also shows that antidepressants decrease the lethality of suicide attempts. Other randomized controlled trials to date 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. The conclusion is that the use of antidepressants should be carefully monitored in those patients who have had prior suicide attempts. A smaller quantity of pills should be prescribed and the patient's suicide risk should be carefully assessed by the patient's physician, and documented as such. Any evidence of suicide ideation should be taken seriously and dealt with immediately.

* Medscape Medical News