The Darkness of Depression

This week's cover story on depression vividly illustrates the centrality of chemistry to biomedicine today. Chemistry is one of the tools being used to understand the molecular basis of this complex and dangerous disease. And chemistry, of course, is the basis of efforts to develop treatments to alleviate the debilitating and life-threatening symptoms of depression.

Senior Editor Sophie Rovner has tackled complex biomedical topics previously for C&EN, including major reports on the biochemical basis of violent behavior (C&EN, June 2, 2003, page 33) and the causes of and potential treatments for Alzheimer's disease (C&EN, March 11, 2002, page 45).

"Each time I research one of these stories," Rovner says, "I'm awed by the marvelous complexity and delicately balanced interdependence of the biochemical systems within the human organism. And I become more and more convinced that we owe much of our personality to our biochemistry."

Depression casts its pall widely, Rovner observes. More than 12 million women and 6 million men in the U.S. are affected by depression in any given year, according to the National Institute of Mental Health. Another 2.5 million suffer from bipolar disorder. As many as 20% of those with bipolar disorder who aren't treated commit suicide, according to NIMH.

Rovner paints a picture of a bewilderingly complex condition. In fact, she writes, "the term 'depression' encompasses several different conditions with a range of causes. What unites them is an interaction between genetics and environmental factors such as stress and substance abuse."

Researchers know that depression interferes with the balance of neurotransmitters such as serotonin, norepinephrine, and dopamine. And they have determined that the medications used to treat depression either increase the availability of such neurotransmitters or change the sensitivity of receptors for them.

Pharmaceutical companies have taken major strides in the past 20 years in developing drugs that selectively modulate brain chemistry to alleviate depression. The selective serotonin reuptake inhibitors (SSRIs) such as Prozac, in particular, have revolutionized the treatment of depression and offered hope to millions of people. And Rovner points to numerous other classes of compounds that have been developed that give physicians a broad set of tools to alleviate depression's symptoms.

Use of SSRIs and a few other new medications for treating depression in children and adolescents was very much in the news last week. On Feb. 2, the Food & Drug Administration convened a panel of experts to review clinical trials of drugs used to treat pediatric depression, specifically to determine whether the drugs caused an increase in suicidal thoughts or behavior or other forms of violence.

FDA's action caps several months of building anxiety about prescribing SSRIs to children. On Oct. 27, 2003, FDA released a public health advisory alerting health professionals to its concern over eight drugs. Also last year, British regulators recommended that doctors stop prescribing six SSRIs to children and adolescents.

The FDA panel that met last week recommended that the agency issue stronger warnings about the risks of prescribing SSRIs to children while continuing to evaluate the clinical data developed by drug companies on the use of the drugs to treat pediatric depression. That's probably prudent. But this is an extraordinarily complex issue. Childhood and adolescent depression is a very real phenomenon, and SSRIs may be useful for treating it.

Depression itself often leads to suicidal thoughts and behavior. Drugs that alleviate depression can, conceivably, combat suicide among some individuals and increase the risk of suicide among others.

What is needed to sort out the conflicting claims are data and dispassionate analysis, which is the course FDA is pursuing. If the data from clinical trials conducted by drug companies are inconclusive, a major clinical trial conducted under NIH auspices should be carried out.

Patience is a hard course to advocate when the subject is as gut-wrenching as childhood suicide, but it is the only course available to us.

Thanks for reading.