Best News in 50 Years for Schizophrenics

An entirely different approach could provide safer and better medicines.

By Dr Robert W LashOct 18, 2007 5:00 AM


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If you had to pick one disease not to get, schizophrenia would have to be at or near the top of your list. Schizophrenia typically affects young adults, who are suddenly plunged into a world of delusions, hallucinations, and paranoia. Fifty years ago, neuroscientists and psychiatrists identified dopamine, one of the many molecules that brain cells use to communicate, as the bad actor in this story. A half century later, drugs that block dopamine action in the brain continue to be the mainstay of schizophrenia treatment. However, these drugs often control only the most dramatic symptoms, and they leave many patients with highly unpleasant side effects, like tremors and uncontrollable lip smacking. Now a new study suggests that researchers may have found a new class of drugs that could revolutionize the treatment of schizophrenia.

Numerous medicines we use today were discovered by accident, and this new drug likewise received a nudge by an unlikely source: the street drug PCP, or angel dust. Many years ago, researchers observed that people who take PCP often experience symptoms similar to those of schizophrenia. It was also known that PCP affects the action of glutamate, an important brain-signaling peptide. Even more intriguing, glutamate modulates how dopamine works. Once they saw this set of connections, researchers began hunting for a glutamate-related drug to treat schizophrenia.

This research finally paid off with a report in Nature Medicine by scientists at Eli Lilly showing that a glutamate-related drug (named LY2140023, for now) appears to be a safe and effective treatment for schizophrenia—at least in short-term trials with a small number of patients. Patients who received the drug experienced improvement in most of their symptoms when compared with placebo, with none of the side effects associated with more traditional dopamine medications.

Schizophrenia is a devastating disease with lifelong consequences for those diagnosed and their families and friends. With this discovery, our understanding of schizophrenia has undergone one its biggest shifts in the past half century, and we may now be on the verge of having a new class of treatments. The jury is still out on its long-term effects, but I am very heartened to know that neuroscientists have a new and very promising approach to battle this most debilitating of disorders.

Robert W. Lash, M.D. is an associate professor of internal medicine at the University of Michigan Medical School. His clinical interests include thyroid disease, diabetes, endocrine disorders in pregnancy, osteoporosis and metabolic bone disease, and medical education. A member of the LLuminari team of experts, a board certified internist and endocrinologist, Dr. Lash has an active clinical practice and is a hospitalist at the University of Michigan.

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