ACNP Issues Final Report on SSRIs and Suicidal Behavior in Youth
NASHVILLE, Tenn., Nov. 23 /PRNewswire/ -- The benefits of treating youth with depression with one antidepressant medication outweigh the increase in risk of suicidal thoughts and nonfatal suicidal behavior found in an analysis of a Food and Drug Administration (FDA) database of adverse event reports, according to the findings of the American College of Neuropsychopharmacology (ACNP) Task Force Report on SSRIs and Suicidal Behavior in Youth. The report was published today in the journal Neuropsychopharmacology, and updates a preliminary report that ACNP released in January 2004.
"Given that untreated major depression is the main cause of suicide in children and adolescents, and that suicide is the third leading cause of death among 15-to-24 year-olds, there is an urgent need for effective antidepressant treatments," explained John Mann, MD, Task Force Co-Chair and lead author, Professor of Translational Neuroscience in Psychiatry and Radiology, and Chief of the Department of Neuroscience, New York State Psychiatric Institute at Columbia University Medical Center. "Although many medications have been tested, only one has proven effective in testing done to date."
The ACNP Task Force evaluated the safety and efficacy of selective serotonin reuptake inhibitor (SSRI) antidepressant medication for depressed youth under 18 years of age. Antidepressant medications, including SSRIs, have been proven effective for treating depression in adults, and while this effect may also generalize to youth, it has received less study.
According to the ACNP Task Force Report, fluoxetine is the only medication that has been presently documented to effectively treat depression in youth. No other SSRI, non-SSRI new generation antidepressant, or tricyclic antidepressant has demonstrated efficacy according to the standard of the report, which required two placebo-controlled clinical trials to find such an effect. Cognitive behavioral therapy, a form of psychotherapy, was found to be effective if combined with fluoxetine use, but used alone has not been shown to be more effective than placebo.
The Report was undertaken by the ACNP after regulatory agencies in the United States and United Kingdom raised concerns in 2003 about the possibility that treatment of depression with SSRIs in that age group might increase the risk of suicide. In September 2004, the FDA decided to require a black box warning regarding suicide risk for all antidepressants, continuing the debate on the efficacy and relative risk of antidepressant use in youth with depression.
The ACNP Task Force Report urges clinicians treating depressed youth to ask about suicide, suicidal thinking, and plans for suicide, and noted that ongoing monitoring of suicidal thoughts in patients treated with antidepressants is necessary. "Our concern is that the FDA warning may be misinterpreted, and clinicians may choose not to treat youth with major depression," noted Mann.
The ACNP Task Force concluded that the available data from clinical trials of SSRIs and other new generation antidepressant medications indicate a small increase in the risk of adverse event reports of suicidal thinking or suicide attempts in youth (2% vs. 4% on average). However, no suicides have occurred in the FDA database of trials of antidepressants in youth. Furthermore, the FDA analysis of systematic ratings of suicidal ideation and behavior in these antidepressant studies of depressed youth did not find an increased risk of a worsening of those thoughts or behaviors among those taking SSRIs vs. placebo.
"The adverse event data found no suicides among youth receiving SSRIs in these studies and only a small increase in suicidal thoughts and attempts," explained Dr. Mann. "Other studies also systematically asked youth about their suicidal thoughts and behavior, and found no increase in suicide attempts or thoughts among those taking SSRIs." The ACNP Task Force members found that this inconsistency raised questions about the reliability of adverse event reports compared with systematic questioning.
The report calculated that there was a substantial risk-benefit ratio for the use of fluoxetine in those under 18. Using the FDA's meta-analyses of adverse event data, the ACNP Task Force members determined a "number needed to treat" (NNT) and a "number needed to harm," (NNH) using a very low threshold that included suicidal thoughts (not just suicide attempts). The NNH average for all the antidepressants tested and reviewed by the FDA was 28 times that of NNT (mean of 402 for NNH vs. 17.4 for NNT).
"Psychiatric disorders, such as depression, are the major causes of suicide," said Mann. "Our Task Force concluded that the benefits of treating this serious illness far exceed the risk associated with the use of fluoxetine."
The report concluded that there is additional evidence that does not support the hypothesis that SSRIs increase the risk of fatal suicide attempts. Epidemiology studies show that the rates of suicide among youth decrease in nations in proportion to the increase in use of antidepressants, a finding not related to the national rates of drug use or firearms policy. In the United States, those regions prescribing the most SSRIs have experienced the biggest falls in youth suicide rates. Also, autopsy studies among youth who have died by suicide showed that few or none tested positive for SSRIs at the time of their death.
The ACNP Task Force Report findings are based on the full range of publicly available data on the use of antidepressants in depressed youth under 18 years of age, including the data used by the FDA in 2004 to review the use of SSRIs in depressed youth and the data reported to the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA). Additionally, the authors reviewed new studies published since the preliminary report, including the 2004 findings of the Treatment for Adolescents with Depression Study (TADS). However, the ACNP Task Force did not have access to some unpublished data, including detailed findings held by drug companies.
The ACNP Task Force called for all data held by the FDA or pharmaceutical companies to be made rapidly available to ACNP and other research organizations to conduct further independent evaluations of the risks and benefits of SSRIs. The report also noted the need for clinical trials and other research studies to include better measures for evaluating suicidal behavior, including asking study participants about suicidal thoughts and behavior, and not excluding patients at high risk for suicidal behavior. "Adverse event reports of antidepressants are a poor way to determine suicide risk," explained Dr. Mann, "We need studies using other, better systematically collected measures."
The full report of the article, found in the journal Neuropsychopharmacology, is available online at http://www.nature.com/npp/index.html
The ACNP, a non-profit organization, receives revenues from a variety of sources including membership dues, publication sales, registration fees and pharmaceutical industry grants. The ACNP Task Force on SSRIs and Suicidal Behavior in Youth received no fees or industry grants. The cost of the report was supported solely by the ACNP.
ACNP, founded in 1961, is a professional organization of more than 700 leading scientists, including four Nobel Laureates. The mission of ACNP is to further research and education in neuropsychopharmacology and related fields in the following ways: promoting the interaction of a broad range of scientific disciplines of brain and behavior in order to advance the understanding of prevention and treatment of disease of the nervous system including psychiatric, neurological, behavioral and addictive disorders; encouraging scientists to enter research careers in fields related to these disorders and their treatment; and ensuring the dissemination of relevant scientific advances.
SOURCE American College of Neuropsychopharmacology