Reducing Inflammation May Improve Cognition in Schizophrenia

Cognition may improve significantly in schizophrenia patients when they are given anti-inflammatory treatment along with standard schizophrenia therapy, according to researchers at the Medical College of Georgia at Augusta University.

The new findings add to the growing body of evidence that at least some symptoms of schizophrenia are closely tied to the immune system and inflammatory reactions.

After only two intravenous doses of tocilizumab, an immune-suppressing drug typically prescribed for people with rheumatoid and juvenile arthritis, all five study participants with schizophrenia experienced improved cognitive ability.

“This adds to the growing evidence that inflammation plays a role in patients with schizophrenia and again suggests that targeting inflammation may be a viable therapeutic target, at least for cognitive impairment, which is a huge area of unmet need,” said researcher Dr. Brian J. Miller, a psychiatrist at the university.

Difficulties with cognition are a major source of dysfunction and disability in many schizophrenia patients and can be among its earliest symptoms, said Miller, corresponding author of the report in the Journal of Clinical Psychiatry.

Anywhere from 25 to 50 percent of patients may have inflammation in the brain contributing to cognitive dysfunction. Problems range from having trouble remembering important numbers to impairment of executive function leaving affected patients unable to analyze, organize, and generally manage their lives.

For the study, Miller administered tocilizumab, a drug that targets the receptor for IL-6, a protein which helps regulate inflammation. Higher IL-6 levels also have been connected to having a smaller hippocampus, a center for learning and memory in the brain, as well as experiencing more psychiatric symptoms.

Targeting inflammation did not appear to improve any of the “positive” symptoms of schizophrenia, such as hallucinations and delusions, but these were already well-controlled with antipsychotics, Miller said.

Nonsteroidal anti-inflammatory drugs, including aspirin, have been tried in these patients, but tend to be less potent and have multiple mechanisms of action, Miller said. “If we see improvements with this drug, then we know it’s not due to other effects.”

With the growing evidence of inflammation’s role in schizophrenia, Miller routinely tests his patients’ blood level of C-reactive protein, an indicator of inflammation and IL-6 levels. Based on those lab results, he may try a variety of anti-inflammatory drugs in addition to an antipsychotic.

While he did not pretest in the study patients, Miller later learned that while all appeared to benefit from the targeted anti-inflammatory therapy, only half had elevated C-reactive protein level. That finding is another reason a larger, double-blind study is needed, he said.

While the patients in this study received tocilizumab intravenously, a newer injectable version of the drug is now available. Furthermore, drugs that directly target IL-6, rather than its receptor, are also now available.

Miller recently received a grant from the nonprofit Stanley Medical Research Institute to examine the effectiveness of one of these drugs, siltuximab, in patients with blood evidence of inflammation.

Source: Medical College of Georgia at Augusta University