Department News
UIC Researchers to Study New Drug for Schizophrenic
Patients

Researchers at the University of Illinois Psychiatric Clinic research Center are beginning clinical trials of a new oral drug that could offer life-saving hope for some schizophrenia patients.

The drug, Conivaptan, prevents water intoxication in schizophrenia patients. "Water intoxication is a serious danger to many schizophrenia patients," said Morris Goldman, M.D., director of the clinical research program at UIC's Psychiatric Institute and lead researcher in the 24-month FDA-sponsored study.

Many schizophrenic patients have dangerously high levels of the antidiuretic hormone arginine vasopressin, which is secreted from the hypothalamus into the blood stream. When combined with excessive water intake, which also occurs frequently in the illness, it can cause patients to retain up an extra 20 to 30 pounds of water. The extra water swells brain tissue, compressing it against the skull and creating pressure that can cause seizures and death.

The new drug blocks vasopressin receptors in the kidney. That blocking function prevents the key, triggering biochemical event that would otherwise result in water intoxication, Goldman said.

"I am very excited about this," said Goldman. "Guarding schizophrenic patients against water intoxication has always been a thorny problem," he said. The only available treatments for water intoxication are ongoing water restriction, which means patients must be kept in a water-free environment; targeted fluid restriction, which requires patient hospitalization; or use of the drug clozapine, which can have life-threatening side effects, Dr. Goldman said.

Scientists still don't clearly understand what causes excessive levels of vasopressin in schizophrenic patients. But Dr. Goldman, who has conducted federally-funded research on the problem of water intoxication in schizophrenia for more than 10 years, believes it is a consequence of structural brain changes associated with schizophrenia.
In normal brains, the hippocampal region in the middle of the brain at the base of the skull controls emotional, behavioral and hormonal responses to stress. Schizophrenic patients who become water intoxicated show signs of structural damage to the hippocampal formation and they produce more vasopressin as they become more psychotic, Dr. Goldman said. Closely matched schizophrenic patients who never become water intoxicated show no signs of structural damage to the hippocampal formation and do not produce vasopressin when they become psychotic, he said.

The link between the mental illness and abnormally high vasopressin levels is funded by a $1.2 million grant awarded to Dr. Goldman by the National Institute of Health.

Of 18 U.S. centers testing the new drug, UIC is the only site studying the drug's effect in psychiatric patients. The drug will be studied in four to 10 patients in UIC's Psychiatry Department. Nationwide, 90 patients will participate in the study.

In addition to Dr. Goldman, others in the UIC Psychiatry Department involved in the new study are Beth Winans, Ph.D.; Unit Administrator Jane Strong, RNC, MS; Unit Nurse Dolly Metts, RN; and research coordinator Tallat Tayyaba, MD.

At any given time, about 2 million U.S. citizens suffer from schizophrenia. Symptoms, which usually begin in early adulthood, include loss of interest in other people and the outside world, delusions and hallucinations, and preoccupation with one's own mental life.