Friday, June 13, 2003

By Byron Spice, Post-Gazette Science Editor

Two decades ago, psychiatric researchers thought they had found an effective treatment for manic-depressives -- a drug called lithium carbonate -- and then many of them turned their attention to other mental illnesses that seemed more compelling.

But the victory declaration was premature. It has since become clear that more people suffer from the disease, now known as bipolar disorder, than doctors once thought, and that only about 30 percent of patients can be successfully treated with lithium.

"It's not quite 'The Emperor's New Clothes,'" said Dr. David Kupfer, chairman of psychiatry at the University of Pittsburgh School of Medicine. "But it's close."

Dr. Thomas Insel, who became director of the National Institute of Mental Health last fall, now calls the search for new treatments for bipolar disorder "an urgent issue."

Insel said scientists still need to find the root cause of the disorder, an insight that would help them design drugs specifically for the disease.

In the meantime, Insel said, there is an urgent need for research into what combination of existing drugs might help, because bipolar disorder afflicts between 1 million and 2 million Americans and is a leading cause of disability.

"That [research] can't wait until we work out the neurobiology of this disorder," he said yesterday between presentations at the Fifth International Conference on Bipolar Disorder.

One measure of the urgency is reflected in attendance at the conference, which continues through Saturday at the Sheraton Station Square.

When the international meetings began in 1994, between 300 and 400 researchers showed up; this week, more than 1,000 researchers from 30 countries are attending and Kupfer predicted that the next meeting, in 2005, will probably be so large it will have to be moved to the new David L. Lawrence Convention Center.

As a mood stabilizer, lithium often works wonders at controlling mania -- episodes marked by high energy, lack of self-control and inflated self-esteem.

"Everybody was always worried about mania -- the spending sprees, the public embarrassment," said Kupfer, the immediate past president of the International Society for Bipolar Disorders.

But it's the other side of the disease -- depression -- that has proven more disabling and difficult to treat. People with bipolar disorder might spend 50 percent to 60 percent of their lives in a low-grade depression. "They're not bothering anybody," as they might during a manic episode, Kupfer said, "but they're not functioning very well, either."

The NIMH's Insel noted that relapses of the disease involve depression more than mania. "That may be where we're losing people," he added.

People with bipolar disorder don't respond to anti-depressive therapy in the same way as other people with depression and are more difficult to treat, Kupfer said. And there's always the risk that getting the patient out of depression will trigger a manic episode.

New techniques for imaging the brain and for identifying genes that are activated during disease episodes may eventually give scientists a better understanding of what causes bipolar disorder. "A lot is going to happen in the next four or five years," Insel predicted.

"I think we're underfunding bipolar disorder," he added. Of roughly $800 million the NIMH spends each year to sponsor researchers outside the institute -- the bulk of its spending -- no more than 10 percent goes to studies of bipolar disorder.

That's partly because it is a notoriously difficult disease to study -- many patients are suicidal, have multiple disorders or are substance abusers. Many researchers hesitate to submit grant applications because patient selection is so difficult and because the researchers themselves often can't agree on the best way to design the studies, he said.

Because of that, grant applications for bipolar disorder studies often don't do well when reviewed by peers, which in turn further discourages researchers from applying.

Because of these problems, the NIMH has tried a different approach -- contracting with a network of researchers to test treatments on patients who may not be considered ideal research subjects, but who nevertheless are representative of the population of bipolar patients.

Called the Systematic Treatment Enhancement Program, the effort is headed by Dr. Gary Sachs of Massachusetts General Hospital. Western Psychiatric Institute and Clinic is one of the sites for the program, with Dr. Michael Thase as the local investigator. About 3,000 patients are now enrolled in the program. The goal is to reach 5,000 patients.

Byron Spice can be reached at bspice@post-gazette.com or 412-263-1578.