Summer 1996 Volume 5, Number 3
Improving schizophrenia treatment
Four decades ago, drugs that block dopamine D2 receptors
in the brain were found to reduce schizophrenia's psychotic symptoms
(hallucinations, delusions and disorganization) -- but with troubling
neurological side effects, including the potentially irreversible movement
disorder known as tardive dyskinesia. In a second major breakthrough, in 1988,
the drug, clozapine, was found to also ease "negative" symptoms (apathy,
isolation, decreased emotional expression) and cognitive deficits, without the
neurological side effects. Still, a one to two percent incidence of a
potentially fatal loss of white blood cells (agranulocytosis) limited use of
clozapine to severely treatment-resistant patients.
Most recently, evidence has linked an important neurotransmitter, glutamate, to
the underlying pathology of schizophrenia, opening a new line of attack on the
limitations of current treatments. Donald Goff and colleagues at the
Massachusetts General Hospital and Lindemann Mental Health Center have
demonstrated that an agent, d-cycloserine, acting at a specific nerve cell
receptor site for glutamate, substantially improves negative symptoms and
cognitive functioning when added to conventional antipsychotic agents. The
researchers, with new National Institutes of Health funding, are preparing
pursue this finding in an extended clinical trial.
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