Four Decades Later, Meltzer's Work on Schizophrenia Still Breaking New Ground
What happens when the atypical becomes common?
For Herbert Meltzer, MD, professor in psychiatry and behavioral sciences and physiology, whose science has revolutionized the field of antipsychotic drugs, the topic has helped focus part of his lab on the way physicians care for treatment-resistant schizophrenia.
Atypical antipsychotic drugs differ from typical agents in that they produce significantly fewer movement disorders at a dose that produces comparable control of psychosis.
“The atypicals have displaced the typicals as the most widely used drugs for schizophrenia,” said Meltzer, director of the Translational Neuropharmacology Program. “They have also become invaluable tools for basic research to better understand the biology of schizophrenia and bipolar disorder.”
Meltzer credits atypical drugs with changing the field from exclusively looking at the role of dopamine as a key neurotransmitter involved in schizophrenia, to a broader perspective, especially the neurotransmitter serotonin.
Meltzer was principle investigator of the critical clinical trial, published in 1988 and now cited more than 2,400 times, that led to the FDA approval of clozapine for patients who have not responded to or who had intolerable motor side effects with other antipsychotic drugs. He then proposed the pharmacologic theory for these effects, which led to the development of a half-dozen other atypical antipsychotic drugs that are safer than clozapine itself.
In the next decade, he identified the unique efficacy of clozapine, not shared by any other drug, to reduce the risk for suicide attempts and completion by up to 75 percent in schizophrenia and related psychoses. This indication was approved by the FDA in 2003. Despite its recommendation for this purpose in all major guidelines, he believes it is significantly underutilized for this purpose.
Earlier this year, Meltzer published an “Update on Typical and Atypical Antipsychotic Drugs” in the high-impact journal the Annual Review of Medicine.
“My review focused on the controversies as well as the non-controversial issues like the greater tolerability and safety of the atypicals with regard to motor or extrapyramidal side effects,” Meltzer said. “At the same time, there are important controversies about their advantages for cognition and negative symptoms in schizophrenia and my lab is engaged in a host of clinical and basic science research with the latest drugs.”
In the midst of a key study testing a substitute for clozapine for patients who fail to respond to other antipsychotics, Meltzer is also leading an educational program to inform practitioners about the great value of clozapine to reduce the risk for suicide in schizophrenia.
“The use of clozapine for suicide prevention is entirely non-controversial; it is universally accepted as effective,” he said. “With funding from the National Institute of Mental Health, industry, and private donations, we will embark on new clinical trials and basic research to resolve the remaining controversies surrounding atypical drugs.”