OMH Advisory on Antidepressants and the Risk of Suicide

June 26, 2007

Antidepressants and the Risk of Suicide

In October 2003, the U.S. Food and Drug Administration (FDA) issued a public health advisory about the risk of suicidality in pediatric patients taking selective serotonin reuptake inhibitors (SSRIs). A year later, the FDA required all antidepressants (ADs) carry a black–box warning stating that ADs are associated with an increased risk of suicidal thinking, feeling, and behavior in children and adolescents.

Notably, since the 2003 advisory the use of ADs for the treatment of pediatric depression has reduced significantly, without a concomitant increase in alternative treatments. The diagnosis of depression has likewise decreased during this period while the rate of adolescent suicide has increased (Libby et al 2007). This latter finding furthers the belief among many experts that although antidepressant therapy may entail some risk, the risk of not receiving appropriate AD treatment may be greater. (Friedman and Leon 2007).

On May 2, 2007, the FDA ordered that all antidepressant medications carry an expanded black–box warning, including stating that there is an increased risk of suicidal symptoms in adults 18 to 24 years of age. This expansion of the FDA warning was based on a meta–analysis of short term efficacy studies of many different classes of antidepressants, which also revealed (Friedman and Leon 2007):

• no increase in the risk of suicidal behavior or ideation across all age groups or in persons 24–64 years of age
• the risk for suicidal thinking and behavior, although not for actual suicide, was slightly numerically elevated for patients 18 to 24 years of age (although this did not attain statistical significance)
• risk was decreased for persons 65 years of age and older

Friedman and Leon write that this series of warnings, especially the most recent, in light of the limits of the evidence for suicidal risk, may discourage depressed patients and their families from seeking and their physicians from prescribing antidepressants.

The NYS Office of Mental Health (OMH) shares this concern, particularly since we already observe a reduction in AD treatment for children and adolescents suffering from depression. Since the most recent evidence suggests that antidepressants confer either no risk or are actually protective against suicidality in adults ages 25 and older, it is critical that depressed patients in this population receive antidepressants when clinically appropriate.

It is well known, though rare, that a patient experiences an increase in suicidal ideation when started on antidepressants in general and SSRIs in particular (Hamilton and Opler, 1992). Whether this is actually caused by the medication or is simply a consequence of the illness itself is unknown. This effect, usually seen in the first 4–6 weeks following the start of treatment, should be managed by careful clinical monitoring, counseling about risks and benefits, and joint decision making by patients and physicians.

Compared to the risk of suicide in patients taking antidepressants in the FDA analysis of the clinical trials (0.01%), the risk of suicide in untreated depression ranges from 2.2 to 15%. Thus, the risk of untreated depression is several orders of magnitude greater than that of antidepressant treatment (Friedman and Leon 2007). In fact, in one study of adolescents who had committed suicide, antidepressants were rarely detected in postmortem reports (Leon et al., 2006), suggesting that is untreated depression, not antidepressants, that is the "real killer." Under–detection and under–treatment of depression, in adults and seniors, is a significant cause of morbidity and mortality and has become a public health crisis (Sederer et al, 2006).

Thus, OMH issues this advisory to inform the public and professional community about recent evidence about the potential risks of antidepressant treatment (very small) and those of untreated depression (very large). We hope to contain a medically ill–advised overreaction to FDA warnings. OMH encourages depressed patients to seek treatment and encourages medical professionals to detect and treat depression in their patients, in pediatric, adult, and geriatric primary care settings as well as in mental health settings.

Furthermore, in order to improve the lives of those with depression and their families and communities we support:

1. Standardized screening for depression in adolescent, adult, and senior settings such as primary care, colleges and universities, and senior centers.
2. Evidence–based treatments for depression that include pharmacotherapy, psychotherapy and patient self–management.
   
3. Monitoring and counseling of persons with depression for suicidal thoughts and intent, particularly in the early phases of treatment.
   
4. Research into the causes, prevention, treatments, and means of reducing disparities in access and quality of care and improving the dissemination of evidence–based interventions for depression.

References

Friedman RA, Leon AC. Expanding the black box—depression, antidepressants, and the risk of suicide. N Engl J Med 2007;356:2343–2346

Hamilton MS, Opler LA. Akathisia, suicidality, and fluoxetine. J Clin Psychiatry 1992;53:401–406

Leon AC, Marzuk PM, Tardiff K, et al. Antidepressants and youth suicide in new york city: 1999–2002. J Am Acad Child Adolesc Psychiatry 2006;45:1054–1058

Libby AM, Brent DA, Morrato EH, et al. Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with ssris. Am J Psychiatry 2007;164:884–891

Sederer, LI, Silver, L, McVeigh, KH, Levy, J: Integrating Care for Medical and Mental Illnesses. April 2006, Preventing Chronic Disease, http://www.cdc.gov/pcd/issues/2006/apr/05_0214.htm