New Hope for Patients with Treatment-Resistant Schizophrenia

Researchers at Northwestern University Feinberg School of Medicine have discovered a genetic biomarker that could help identify schizophrenia patients who are resistant to antipsychotic drugs (about 30 percent of all schizophrenia patients).

“Many treatment-resistant patients are not identified as such and are treated with mixtures of ineffective antipsychotic and other drugs, accruing little benefit and serious side effects,” said Herbert Meltzer, M.D., professor in psychiatry and behavioral sciences, pharmacology, and physiology.

By definition, treatment-resistant schizophrenia patients are those who continue to have psychotic symptoms, such as delusions and hallucinations, after they have completed at least two rounds of conventional antipsychotic medications.

For the research, Meltzer and Jiang Li, Ph.D., a research assistant professor in Psychiatry and Behavioral Sciences, conducted a genome-wide association study on a group of Caucasian schizophrenia patients — a combination of both treatment-responsive and treatment-resistant patients.

In the treatment-resistant group, the researchers found a mutation in the dopa decarboxylase gene, which is involved in the production of dopamine and serotonin. Certain variations of this gene have been linked to psychosis in previous studies.

Many patients who were once treatment-resistant do eventually respond to a drug called clozapine. However, it’s usually not administered in early treatment stages due to potentially severe side effects and required weekly blood monitoring.

“This biomarker can be used to easily identify patients who should be treated with clozapine, avoiding the use of drugs that are not able to help them. This can be life-saving,” said Meltzer, who has dedicated years to developing atypical antipsychotic drugs to help these patients.

He was the lead researcher in the landmark clinical trial that led to the FDA’s approval of clozapine in 1989.

Not every patient who benefits from clozapine, however, has the specific dopa decarboxylase genetic mutation. The researchers will work with a greater variety of schizophrenia patients in the future — particularly patients from other ethnic groups — to look for other biomarkers and treatment options for those who don’t get better with conventional treatments.

“In a broader sense, this work defines treatment-resistant schizophrenia as a distinct subtype of the illness,” said Meltzer.

Schizophrenia is one of the most severe and rarest of the mental health disorders, occurring in about one in 100 people. It is characterized by symptoms such as hallucinations, delusions, paranoia, cognitive impairment, social withdrawal, self-neglect, and loss of motivation and initiative.

The findings were published in the journal Schizophrenia Research.

Source: Northwestern Medicine