The suicidality risk for active drug relative to placebo was most prominent in adults younger than 25 years, while there was a negative association of suicidality with antidepressant treatment in older adults. "There appears to be a further distinction between a modest protective effect in subjects age 25 to 64 . . . and a stronger protective effect in subjects aged 65 and older," Stone and Jones observed.
Suicidality was found in 0.26% of subjects whose depression symptoms had responded to antidepressant treatment, according to the criteria of the respective trial, and in 1.18% of nonresponding subjects. Although there were too few patients manifesting suicidality for this distinction to be statistically significant, the analysts found it intriguing. "The results are consistent with the idea that an increased risk of suicidal behavior in young adults associated with antidepressant treatment may be limited to subjects who do not show a clinical response to treatment," they suggested.
The meta-analysis was characterized as "exploratory" by Thomas Laughren, MD, director of psychiatry products at the FDA, because suicidality had not been a primary effect for assessment in any of the trial designs. The new NIMH-sponsored studies, however, are expected to provide more detail on the risk of and emergence of antidepressant-linked suicidality.
The new studies
A study by Kelly Kelleher, MD, MPH, of Ohio State University and Joel Greenhouse, PhD, of Carnegie Mellon University will use much of the same data gathered by the FDA. However, Kelleher and Greenhouse have proposed innovative statistical approaches to integrate data from numerous other studies, and they anticipate revealing a "more complete picture of the relationship between antidepressant medication use and suicidal thoughts or actions," according to the NIMH announcement.
The NIMH grant to Marcia Valenstein, MD, of the University of Michigan, will enable analysis of the records of almost 1 million persons from the US Department of Veterans Affairs National Registry for Depression, Medicare records, and the National Drug Index to ascertain relationships between antidepressant use, suicide attempts and/or deaths, and use of concurrent medications or treatments. The NIMH indicated that the study will "help determine the relative effectiveness of different depression treatments in reducing suicidal thoughts and actions."
Wayne Goodman, MD, of the University of Florida, will study pediatric patients with obsessive-compulsive disorder to determine whether their SSRI treatment can induce an "activation syndrome" that may lead to suicidal thoughts or actions. "By focusing on patients with a disorder that is less likely to be associated with suicidality, he will be able to better assess whether SSRIs are related to an actual activation syndrome, and whether suicidality is a component of the syndrome," the NIMH announcement explains.
Several large datasets of SSRI users will be examined by Sebastian Schneeweiss, MD, ScD, of Brigham and Women's Hospital in Boston, to measure rates of suicidality and identify social and demographic factors that may be associated with SSRI use and suicidality. Schneeweiss will also examine the impact of the FDA warnings on the use of SSRIs. "The study aims to develop and better target prescribing and risk management strategies," the NIMH announced.
A fifth NIMH-funded study will be conducted by Prudence Fisher, PhD, of the New York State Psychiatric Institute. The investigator intends to construct a standardized computer tool for adolescents and parents that can be used to screen for antidepressant-linked suicidality. Fisher expects the study to yield "better and more reliable ways of monitoring for adverse reactions."