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Suicidal Tendencies and Behavior Risk of Antidepressants

Depression is usually treated with either medication or psychotherapy, or both. Often, from a biological perspective, the causes of psychiatric disorders are called "chemical imbalances" because it is believed that abnormal amounts or functions of chemicals in the brain produce the symptoms and changes in behavior usually observed. The sources of these imbalances can be either genetic or environmental. It is likely that in most cases, the causes are multiple, including both genes and situational changes. For example, especially for depressed individuals who have several blood relatives with depression, genes are likely to be playing an important role in the source of the depression and even in the types of medications most likely to be beneficial. Other factors, such as stress-related environmental effects and learned changes in thought and behavior, are very frequently involved. Accumulating evidence indicates not only that genes can affect environmental responses, but also that environmental factors and behaviors can modulate gene action.

In 2001, Americans spent $12.5 billion on antidepressants to treat the debilitating symptoms of depression. Scientists know that antidepressants work by restoring the normal balance of hormones and neurotransmitters in the brain. But no one knows exactly how they do it. Robert Thompson, Ph.D., an assistant professor of psychiatry in the Medical School, is trying to find out.

As director of the U-M Child/Adolescent Depression Program, Cheryl King, Ph.D., works with some of depression’s most vulnerable victims. Adolescents with serious depression are difficult to treat and often struggle with suicidal thoughts. Other than hospitalization, psychiatrists have few options; no outpatient intervention has been shown to be effective at preventing these teens from attempting suicide.

“These are extremely ill young people,” says King, an associate professor and chief psychologist in the Medical School’s Department of Psychiatry. “They have serious social impairment and often feel out of control. Many of these youth either have no close relationships or constant conflict in their relationships.”

Using antidepressants increases the risk of suicidal thoughts and behavior among young adults but lessens it for seniors, the Food and Drug Administration said recently.

The effects of antidepressants on adults from 25 to 64 were mixed, so much so that the FDA would only conclude the drug had a neutral effect on suicidal behavior for them but possibly lowers the risk of suicidal thoughts.

The information came from a mass review of 372 studies involving roughly 100,000 patients and 11 drugs, including Lexapro, Zoloft, Prozac and Paxil. The FDA analysis will be incorporated in future changes to antidepressant labels, but the agency wants to first discuss its plans with outside advisers.

In 2004, the FDA ordered strong warnings about the pediatric risk of suicidal tendencies put on antidepressant labels, and began analyzing whether adults face a similar risk, in part by requesting data from drug companies.

It now appears there is an increased risk among adults between the ages of 18 and 25.

"When results are analyzed by age, it becomes clear that there is an elevated risk for suicidality and suicidal behavior among adults younger than 25 years of age that approaches that seen in the pediatric population," the FDA said in documents that were released ahead of the Dec. 13 meeting of its psychopharmacologic drugs advisory committee.

The FDA's analysis of the multiple studies suggests an age-related shift in the risk of suicidal thoughts and behavior associated with treatment with the drugs. That means the risk appears to decline with age, even if the numbers don't explain why, the FDA said. The issue is complex to sort out because depression itself can lead to suicide.

All antidepressants now bear a so-called "black-box" warning about the increased risk of suicidal thinking and behavior in children and adolescents.

In May, GlaxoSmithKline and the FDA warned Paxil may raise the risk of suicidal behavior in young adults, too, and changed the drug's label to reflect that risk.