The National Institute of Mental Health (NIMH), part of the National Institutes of Health, is funding five new research projects that will shed light on antidepressant medications, notably selective serotonin reuptake inhibitors (SSRIs), and their association with suicidal thoughts and actions (suicidality).

Studies have shown that most individuals suffering from moderate and severe depression, even those with suicidal thoughts, can substantially benefit from antidepressant medication treatment. However, use of SSRIs in children and adolescents has become controversial. In 2005, the U.S. Food and Drug Administration (FDA) adopted a “black box” warning — the most serious type of warning in prescription drug labeling — for all SSRIs. The notice alerts doctors and patients of the potential for SSRIs to prompt suicidal thinking in children and adolescents, and urges diligent clinical monitoring of individuals of all ages taking the medications. This can be particularly challenging because it is difficult for patients, their family members and practitioners to determine whether suicidal thoughts may be related to the depression, the medication, or both.

“These new, multi-year projects will clarify the connection between SSRI use and suicidality,” said NIMH Director Thomas Insel, M.D. “They will help determine why and how SSRIs may trigger suicidal thinking and behavior in some people but not others, and may lead to new tools that will help us screen for those who are most vulnerable,” he added.

The projects are listed below.

• Kelly Kelleher, M.D., of the Columbus Children’s Hospital and the Ohio State University, and Joel Greenhouse, PhD., of Carnegie Mellon University, will build on data initially collected by the FDA to analyze antidepressant medication use and suicidal behavior among youth, adults and older adults. Dr. Kelleher will use new and more sensitive statistical approaches to integrate data from numerous other studies — both randomized and non-experimental — to paint a more complete picture of the relationship between antidepressant medication use and suicidal thoughts or actions.

• Marcia Valenstein, M.D., of the University of Michigan, will examine the records of 994,000 individuals from the U.S. Department of Veterans Affairs National Registry for Depression, Medicare records and the National Death Index to determine what relationships exist between the use of antidepressants and suicide attempts and/or deaths, and use of any concurrent medications or treatments. The study will help determine the relative effectiveness of different depression treatments in reducing suicidal thoughts and actions.

• Wayne Goodman, M.D., of the University of Florida, will investigate if and how SSRIs may induce in some young people an “activation syndrome” — a set of symptoms such as irritability, agitation and mood swings that may lead to suicidal thoughts or actions. He will study this potential syndrome among pediatric patients diagnosed with obsessive compulsive disorder. 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 study will improve recognition and understanding of the syndrome, and help identify interventions that will reduce the risk of suicide.

• Sebastian Schneeweiss, M.D., of Brigham and Women’s Hospital, will assess critical issues surrounding the safety of antidepressant medication use by comparing several large datasets of SSRI users. He will measure rates of suicidality; identify social and demographic factors that may be associated with SSRI use and suicidality; and examine the impact of FDA actions on use of SSRIs. The study aims to develop and better target prescribing and risk management strategies.

• Prudence Winslow Fisher, PhD., of the New York State Psychiatric Institute, will develop better and more reliable ways of monitoring for adverse reactions to the use of antidepressant medication. The study’s long-term goal is to construct a standardized computer tool for adolescents and parents that could be used to screen for suicidality associated with the use of antidepressant medications.

In addition to these new projects, NIMH is currently funding other studies that aim to find the best treatments for individuals suffering from depression, and reduce or prevent suicidal behavior. Studies focused on youth depression and suicidal behavior include the Treatment for Adolescents with Depression study, the Treatment of SSRI-Resistant Depression in Adolescents, and the Treatment of Adolescent Suicide Attempters.

The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior. More information is available at the NIMH website, http://www.nimh.nih.gov.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.