Steven P. Cuffe, M.D.
Director, Division of Child and Adolescent Psychiatry
William S. Hall Psychiatric Institute, SC Department of Mental Health
Department of Neuropsychiatry and Behavioral Science
University of South Carolina School of Medicine

DevelopMentor, Summer 2007

In the Summer, 2004 issue of the DevelopMentor I wrote an article on the suicide risk posed by serotonin reuptake inhibitor medications (this article is available in the DevelopMentor archive under the topic “SSRIs”). At that time I outlined in detail the issues prompting the FDA to place a black box warning on all antidepressants. It has now been almost three years since the FDA issued the black box warning for all antidepressants due to elevation of suicide ideation and behavior. The data showed a small increase in suicidal thought and behaviors, from 2% in the placebo groups to 4% in the medication groups, when data from all trials for all indications were combined. There were no completed suicides in any of the studies conducted on antidepressant medications. The FDA issued the warning despite evidence that increasing prescriptions for SSRI antidepressant medications was clearly correlated with decreasing rates of actual suicide, and use of antidepressant medications was not associated with suicide in any prior studies.

Due to the conflicting data, in October, 2004, the Assembly of Regional Organizations of the American Academy of Child and Adolescent Psychiatry discussed the issue. The primary concern was that the black box warning for antidepressant medications may cause more harm than good. Granted, the risk of suicidal ideation or behavior, even for 1-2 children out of 100, is important to understand and be careful to observe. And parents and children deserve to know and provide informed consent for treatment with antidepressants. However, if the correlation between increasing SSRI prescription rates and decreasing suicide rates is real, and there is a backlash against antidepressant use, then AACAP members of the Assembly worried the suicide rate may actually increase due to the FDA action. They worried that pediatricians and family physicians, the groups prescribing the majority of prescriptions for antidepressant medications, would be uncomfortable prescribing to children and adolescents, and that parents would likewise be fearful and not allow their child to be treated. The Assembly expressed their concern over this possibility, and asked the President to write a letter to the FDA asking them to be carefully study the impact of the black box warning for antidepressants on prescription rates and suicide trends.

This article reviews the research on suicide and antidepressants for the past three years, and ends with the first new suicide data available since the black box warning, for the year 2004.

In the November 2005 American Journal of Psychiatry (AJP), Bridge et al., reported emergent suicidality in a psychotherapy trial similar to the antidepressant trials. In the January 2006 AJP issue, Simon et al., studied suicide rates before and after an initial prescription of antidepressant medication. They found the risk of suicide attempt was highest in the month preceding initiation of antidepressant treatment, and the risk declined progressively after starting antidepressant medication.

In August 2006, the first, and only, study associating suicide with antidepressant treatment was published. Olfson et al., studied children admitted to psychiatric inpatient settings with a diagnosis of depression. When comparing depressed patients treated with antidepressants to those not treated with antidepressants, the treated group was at significantly higher risk for suicide attempts and suicide deaths. This study was, however, flawed. The assumption that the two groups are at equal risk for suicide is not viable. It is highly likely that the group treated with antidepressants was a more severely depressed group, and thus at significantly higher risk of suicide on that basis.

In September 2006, Leon found only one of 36 suicides from New York City had antidepressants detectable in their blood at autopsy. In April 2007, Bridge et al., published a new meta-analysis of antidepressant drug trials including more data than the prior study, and found only a 1% difference in suicide thought and behaviors between placebo (2%) and antidepressant treated (3%) groups. They further concluded that antidepressants were efficacious for depression, OCD and other anxiety disorders in children and adolescents, although effects are more modest in depression.

Finally, Nemeroff et al., in April 2007 reported on the impact of the black box warning on prescription rates of antidepressant medication. They found prescription rates decreased 18-20% in the aftermath of the FDA actions. They also found a shift in care from “generalists” to psychiatric specialists. Family medicine physicians and pediatricians were less likely to prescribe antidepressant medications. The fears of the Assembly appear to have been justified. But what happened to the suicide rate in 2004? The rate of suicide in children and adolescents up to age 19 increased 18%, from 2.2 to 2.6 per 100,000 (Hamilton et al., 2007). This is the first increase in over 10 years. This does not necessarily mean the decrease in antidepressant prescriptions caused the increase, but it is suggestive there is a problem, and further research is necessary. Hopefully, this trend can be reversed. Anecdotally, I see primary care physicians feeling more comfortable again prescribing medications for children. We should use the new research to fully educate physicians and the public about the risks and benefits of antidepressants for children and adolescents.

References

Bridge JA, Barbe RP, Birmaher B, Kolko DJ, Brent DA (2005).
Emergent suicidality in a clinical psychotherapy trial for adolescent depression. Am J Psychiatry 162: 2173-2175
Bridge JA, Iyengar S, Salary CB, Barbe RP, Birmaher B, Pincus HA, Ren L, Brent DA,(2007).
Clinical response and risk for reported suicidal ideation and suicideattempts in pediatric antidepressant treatment. A meta-analysis of randomized controlled trials. JAMA, 297:1683-1696

Hamilton BE, Miniño AM, Martin JA, Kochanek KD, Strobino DM, Guyer B (2007).
Annual summary of vital statistics: 2005. Pediatrics 119:345-360

Leon AC, Marzuk PM, Tardiff K, Bucciarelli A, Piper TM, Galea S (2006).
Antidepressants and youth suicide in New York City, 1999-2002. J Am Acad Child Adolesc Psychiatry 45(9):1054-1058

Nemeroff CB, Kalali A, Keller MB, Charney DS, Lenderts SE, Cascade EF, Stephenson H, Schatzberg AF (2007).
Impact of publicity concerning pediatric suicidality data on physician practice patterns in the United States. Arch Gen Psychiatry 64:466-472

Olfson M, Marcus SC, Shaffer D (2006).
Antidepressant drug therapy and suicide in severely depressed children and adults. Arch Gen Psychiatry 63:865-872

Simon GE, Savarino J, Operskalski B, Wang PS (2006).
Suicide risk during anti-depressant treatment. Am J Psychiatry 163:41-47