Update on Antidepressants and Suicidality

Major public events during that time included the FDA Public Health Advisory (October 2003) on the occurrence of suicidality in clinical trials examining antidepressants in the treatment of children and adolescents with major depression; the FDA hearing (February 2004) to review data regarding suicidality from these trials; and the FDA Public Health Advisory (March 2004) that asked antidepressant manufacturers to include a warning on the potential for suicidality and the importance of monitoring pediatric patients for suicidality.

Information on antidepressant prescriptions was obtained from Verispan, a company that uses retail pharmacy physician data and physician audit data that capture nearly half of US prescriptions. There was a significant decrease found in the prescription of antidepressants for children and adolescents. In particular, there was a decrease of 4% per month from February 2004 through July 2004. In addition, the prescription of antidepressants for patients younger than 18 years shifted from general physicians to psychiatrists. For example, 44% of antidepressants were prescribed by psychiatrists from December 2003 to February 2004, which increased to 63% from December 2004 to February 2005.

It is particularly noteworthy that there was a change in the type of antidepressants that were prescribed for children and adolescents. Prescriptions of SSRIs decreased from 74.5% in February 2004 to 57.9% in February 2005. There was a significant increase in the prescription of bupropion, from 10.7% to 20.8%, during this period. This is striking since there have been no published double-blind, placebo-controlled trials regarding the effica- cy of bupropion in the treatment of major depression in children and adolescents. Similarly, the prescription of tricyclic antidepressants increased from 2.8% to 6.1% for children and adolescents.

Are there clinical implications regarding the decreased use of antidepressants in pediatric patients with depression? Recently, it was reported that there was an increase of 18.2% in the death rate from suicide in youth between 2003 and 2004.² The authors noted that the death rate increased significantly only for suicidality and not for any other causes. There has been some speculation that this increase may be attributable to the decreased use of antidepressants in youth.

A number of recent publications, both in the United States and Europe, have examined antidepressant use in children and adolescents to determine any association with suicidality. Computerized health plan records of adolescents who received antidepressants from 1992 to 2003 were examined by Simon and colleagues.³ They found that the highest risk for suicide was in the month before starting treatment, and that there was a sharp decrease in suicide risk immediately after initiation of antidepressant treatment, which continued to decline over the next 6 months.

In a nationwide Danish pharmacoepidemiological study⁴ of youths aged 10 to 17 years, the use of SSRIs increased from 1995 to 1999, yet suicide rates remained stable. Of the 42 suicides in the age group, none were treated with SSRIs within 2 weeks before the suicide. The authors concluded that there was no association between SSRI treatment and suicide in this populaton.

In a follow-up study of patients who were hospitalized for suicide attempts, researchers found that in those who had ever used antidepressants, the current use of an antidepressant was associated with an increased risk of suicide attempts but a decreased risk of completed suicide.⁵ A potential confounder of this study was that the clinical condition of the persons for whom antidepressants were currently prescribed may have differed from that of those persons for whom antidepressants were not prescribed.

Data on completed suicides from Multiple Causes of Death Public Use Files, provided by the CDC, were examined with regard to antidepressant use.⁶ Antidepressant prescription data were obtained from a nationally representative sample of office-based physicians in US private practices. No relationship was found between suicide and antidepressant use in youths aged 10 to 19 years. Moreover, the use of SSRIs or serotonin and norepinephrine reuptake inhibitors was associated with a lower number of suicides in youths aged 15 to 19 years.

National county-level suicide rate data for children aged 5 to 14 years and antidepressant use from 1996 to 1998 were examined by Gibbons and associates.⁷ Higher SSRI prescription rates were associated with lower suicide rates in children and adolescents. Based on their findings, these investigators estimated that there would be 253 more youth suicides per year if children were not given antidepressants.

Most recent publications that have examined antidepressant use have not demonstrated a relationship between antidepressant use in pediatric populations and suicide. Since antidepressant prescription rates for depressed youths have decreased following warnings about potential suicidality, it is imperative that prospective studies with appropriate scientific rigor be conducted to determine whether there is any causal link between antidepressant use and suicidal ideation, suicide attempts, and completed suicides.

References:

References

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Nemeroff CB, Kalali A, Keller MB, et al. Impact of publicity concerning pediatric suicidality data on physician practice patterns in the United States.

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Hamilton BE, Minino AM, Martin JA, et al. Annual summary of vital statistics: 2005.

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Simon GE, Savarino J, Operskalski B, Wang PS. Suicide risk during antidepressant treatment.

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Sondergard L, Kvist K, Andersen PK, Kessing LV. Do antidepressants precipitate youth suicide? A nationwide pharmacoepidemiological study.

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Tiihonen J, Lonnqvist J, Wahlbeck K, et al. Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort.

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Markowitz S, Cuellar A. Antidepressants and youth: healing or harmful?

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Gibbons RD, Hur K, Bhaumik DK, Mann JJ. The relationship between antidepressant prescription rates and rate of early adolescent suicide.

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