San Diego, CA—Using medications to treat schizophrenia can be a delicate balance, according to a new report. Too little, and physical- and mental-health symptoms are uncontrolled; too much and the drugs could have a cumulative effect of worsening cognitive function.

The article in The American Journal of Psychiatry explains that psychotropic medications, which are often used to control schizophrenia symptoms in the about 1.5 million Americans with the condition, also have anticholinergic properties and inhibit acetylcholine, a neurotransmitter critical for brain signaling.

“Many medications have anticholinergic effects, and we are becoming increasingly aware about their potential long-term risks,” said lead study author Yash Joshi, MD, assistant professor in the Department of Psychiatry at University of California San Diego School of Medicine.

Dr. Joshi and colleagues sought to elucidate the effect of cognitive impairment attributable to anticholinergic-medication use, noting that might help optimize cognitive outcomes in schizophrenia.

To do that, they analyzed cross-sectional data to determine the relationship between anticholinergic-medication burden and cognition. The focus was on 1,120 patients with a diagnosis of schizophrenia or schizoaffective disorder who were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia.

Prescribed medications were assessed according to a modified Anticholinergic Cognitive Burden (ACB) scale for each participant. Researchers determined that ACB score was significantly associated with cognitive performance; higher ACB groups scoring worse than lower ACB groups on all domains tested on the Penn Computerized Neurocognitive Battery.

The authors advise that, not only were similar effects revealed on other cognitive tests, but effects remained notable even after controlling for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage.

“This is striking because previous studies have shown that an ACB score of 3 in a healthy, older adult is associated with cognitive dysfunction and a 50 percent increased risk for developing dementia,” Dr. Joshi said, yet about one-quarter of the schizophrenia patients in the study had ACB scores of 6 or more.

The study describes how a patient prescribed daily olanzapine for symptoms of psychosis already starts with an ACB score of 3. If hydroxyzine is added for anxiety and insomnia in the same patient, the ACB score doubles. “Brain health in schizophrenia is a game of inches, and even small negative effects on cognitive functioning through anticholinergic medication burden may have large impacts on patients’ lives,” according to Dr. Joshi, especially for schizophrenia patients treated with multiple psychotropic drugs.

The study team points out that schizophrenia patients often struggle with learning, memory, executive function, and social cognition. “We wanted to better understand how anticholinergic medication burden impacted cognitive functioning in individuals who may have already some cognitive difficulties due to schizophrenia,” Dr. Joshi explained.

Researchers found that anticholinergic medication burden in schizophrenia “is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes—including psychotropics used in usual care—should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.”

“It is easy even for well-meaning clinicians to inadvertently contribute to anticholinergic medication burden through routine and appropriate care,” added Gregory Light, PhD, professor of psychiatry and senior author. “The unique finding here is that this burden comes from medications we don’t usually think of as typical anticholinergic agents.”

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