David Baxter PhD
Late Founder
FDA Warnings and Suicide Rates: Unintended Consequences
Norman Sussman, MD
Primary Psychiatry. 2008;15(10):22-23
In 2003, regulators in the United Kingdom and the United States became aware of clinical trial data suggesting that selective serotonin reuptake inhibitors increase the risk of thoughts of suicide and suicidal behavior in children and adults. There were no youths who committed suicide in these trials, but some did exhibit thoughts or acted in ways that were termed “suicidality.” In 2004, following highly publicized public hearings, the US Food and Drug Administration issued a general warning about the increased risk for youths taking antidepressants.
A new report,1 however, raises doubts about the wisdom of the warnings and suggests that the warnings may, in fact, have resulted in an increase in youth suicides. In a letter to the editor of the Journal of the American Medical Association in its September 3, 2008 issue, Bridge and colleagues1 wrote:
There have been numerous earlier indications that, following adverse publicity in 2003 and the subsequent FDA-initiated warning about suicide risk for antidepressants, there was a decrease in prescription of antidepressants.2-4 Parallelizing this drop in treatment have been various statistical findings of an increase in suicides among children and adolescents. The response to these apparently related phenomena has often been that we need to see if this trend persists over time before drawing any conclusions.
In 2007, for example, the US Centers for Disease Control and Prevention issued a report3 that showed the suicide rate for 10-to-24-year-olds increased by 8% from 2003–2004, after a drop totaling more than 28% from 1990 to 2003. The FDA responded to this finding by saying that no conclusions could be drawn from this information and that it was not necessarily the “beginning of a trend.” Bridge and colleagues1 concluded that this significant excess mortality due to youth suicide in 2004 and 2005 suggests that the marked increase in suicide rates from 2003–2004 is not likely to be a single-year anomaly and may reflect an emerging public health crisis.
It is also worth noting that an article published in 2008 in the Canadian Medical Association Journal5 looked at the possible impact of regulatory warnings about prescribing antidepressants to children and adolescents. The investigators looked at whether the Health Canada warning had the desired effects on prescribing patterns and outcomes and whether it had any unintended health consequences. They found that antidepressant presciptions had indeed declined for children, and that the number of completed suicides among children and adolescents (8–17 years of age) and young adults (19–24 years of age) had gone up. They concluded that...
I argue that the FDA overreacted to the publicity that followed the analysis of the pediatric antidepressant trials, including those that showed that any potential risk was limited to the child and adolescent population. The effect on young adults (>25 years of age) was neutral, and in the older population (>55 years of age) actually reduced suicidality. These findings are often overlooked.
Matters may get even more complicated. Earlier this year, the New York Times reported that the FDA is “now requiring drug makers to study closely whether patients become suicidal during clinical trials.”6 Not only psychotropic drugs are subject to this new policy.
References
Norman Sussman, MD
Primary Psychiatry. 2008;15(10):22-23
In 2003, regulators in the United Kingdom and the United States became aware of clinical trial data suggesting that selective serotonin reuptake inhibitors increase the risk of thoughts of suicide and suicidal behavior in children and adults. There were no youths who committed suicide in these trials, but some did exhibit thoughts or acted in ways that were termed “suicidality.” In 2004, following highly publicized public hearings, the US Food and Drug Administration issued a general warning about the increased risk for youths taking antidepressants.
A new report,1 however, raises doubts about the wisdom of the warnings and suggests that the warnings may, in fact, have resulted in an increase in youth suicides. In a letter to the editor of the Journal of the American Medical Association in its September 3, 2008 issue, Bridge and colleagues1 wrote:
“Following a decade of steady decline, the suicide rate among US youth younger than 20 years increased by 18% from 2003 to 2004, the largest single-year change in the pediatric suicide rate over the past 15 years. Federal health officials have urged caution in interpreting this 1-year apparent spike in youth suicide until data from additional years are available for comparison. We examined available national fatal injury data to assess whether the increase in suicide rates among US youth persisted from 2004 to 2005, the latest year for which data are available.”
The group looked at data, obtained from the National Vital Statistics Systems, on deaths for which suicide was listed as the underlying cause among youths between 10–19 years of age. Information was extracted regarding number of suicide deaths per year, age, and sex. They found that the overall observed rate of suicide among youths decreased by 5.3% between 2004 and 2005. Both the 2004 and 2005 rates were still significantly greater than the expected rates based on the 1996–2003 trend. In absolute numbers, data showed that “in 2004 there were an estimated 326 excess suicide deaths among youth aged 10 to 19 years (167 females, 159 males) compared with the number of deaths predicted by the regression model. In 2005, the overall number of excess suicide deaths was 292 (105 females, 187 males).”1There have been numerous earlier indications that, following adverse publicity in 2003 and the subsequent FDA-initiated warning about suicide risk for antidepressants, there was a decrease in prescription of antidepressants.2-4 Parallelizing this drop in treatment have been various statistical findings of an increase in suicides among children and adolescents. The response to these apparently related phenomena has often been that we need to see if this trend persists over time before drawing any conclusions.
In 2007, for example, the US Centers for Disease Control and Prevention issued a report3 that showed the suicide rate for 10-to-24-year-olds increased by 8% from 2003–2004, after a drop totaling more than 28% from 1990 to 2003. The FDA responded to this finding by saying that no conclusions could be drawn from this information and that it was not necessarily the “beginning of a trend.” Bridge and colleagues1 concluded that this significant excess mortality due to youth suicide in 2004 and 2005 suggests that the marked increase in suicide rates from 2003–2004 is not likely to be a single-year anomaly and may reflect an emerging public health crisis.
It is also worth noting that an article published in 2008 in the Canadian Medical Association Journal5 looked at the possible impact of regulatory warnings about prescribing antidepressants to children and adolescents. The investigators looked at whether the Health Canada warning had the desired effects on prescribing patterns and outcomes and whether it had any unintended health consequences. They found that antidepressant presciptions had indeed declined for children, and that the number of completed suicides among children and adolescents (8–17 years of age) and young adults (19–24 years of age) had gone up. They concluded that...
“...health advisories and warnings issued by regulatory bodies may have unintended consequences on the provision of care, delivery of health services, and clinical outcomes. Further efforts are required to ensure that health warnings do not result in unexpected harm.”5
I argue that the FDA overreacted to the publicity that followed the analysis of the pediatric antidepressant trials, including those that showed that any potential risk was limited to the child and adolescent population. The effect on young adults (>25 years of age) was neutral, and in the older population (>55 years of age) actually reduced suicidality. These findings are often overlooked.
Matters may get even more complicated. Earlier this year, the New York Times reported that the FDA is “now requiring drug makers to study closely whether patients become suicidal during clinical trials.”6 Not only psychotropic drugs are subject to this new policy.
References
- Bridge JA, Greenhouse JB, Weldon AH, Campo JV, Kelleher KJ. Suicide trends among youths aged 10 to 19 years in the United States, 1996–2005. JAMA. 2008:300(9);1025-1026.
- Gibbons RD, Brown CH, Hur K, et al. Early evidence on the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry. 2007;164(9):1356-1363.
- Centers for Disease Control and Prevention. Suicide trends among youths and young adults aged 10–24 years: United States, 1990–2004. MMWR Morb Mortal Wkly Rep. 2007;56(35):905-908.
- Libby AM, Brent DA, Morrato EH, Orton HD, Allen R, Valuck RJ. Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with SSRIs. Am J Psychiatry. 2007;164(6):884-891.
- Katz LY, Kozyrskyj AL, Prior HJ, Enns MW, Cox BJ, Sareen J. Effect of regulatory warnings on antidepressant prescription rates, use of health services and outcomes among children, adolescents and young adults. CMAJ. 2008;178(8):1005-1011. Erratum in: CMAJ. 2008;178(11):1466.
- Harris G. F.D.A. Requiring Suicide Studies in Drug Trials. Available at: F.D.A. Requiring Suicide Studies in Drug Trials - New York Times . Accessed September 17, 2008.
