Drug Combination Lessens Negative Symptoms of Schizophrenia

A combination of dextromethorphan and quinidine (DXQ) can help reduce the negative symptoms of schizophrenia, suggests a trial performed on 42 patients.

Paul J. Markovitz, MD, PhD, presented the findings of the trial at the American Psychiatric Association’s 2016 Annual Meeting this week.

“Every night I go to bed and I hope a little bit that this works. I think it would be great. I think there’s a lot of benefit to it,” he said.

Elevated glutamate levels are found in patients with schizophrenia, in areas such as the prefrontal cortex, anterior cingulate, and thalamus. Dextromethorphan is known to decrease glutamate levels in the central nervous system.

But dextromethorphan alone is almost completely and immediately metabolized by the liver to dextrorphan, which has many side effects, Markovitz said. Quinidine allows the majority of the dextromethorphan to bypass the liver, markedly lowering its conversion to dextrorphan.

The 42 patients in the study were all hospitalized at the Psychiatric Health Facility in Fresno, California from 2012 through 2014. They were between 18 and 62 years old.

Patients were started on an antipsychotic after entering the hospital, and remained on that alone until they reached optimal stabilization, which took 3 to 28 weeks.

Fourteen patients were on typical antipsychotics and 28 were on atypical antipsychotics, include 4 on clozapine. Twenty-nine were using long-acting injectables, both typical and atypical.

When patients were stabilized, researchers began to administer 20 mg of dextromethorphan and 10 mg of quinidine twice a day. Patients were assessed weekly using the Clinical Global Impression Clinician scale.

The group’s average CGI score dropped from the start of the study to when patients were on the neuroleptic alone, and dropped further while they were on the neuroleptic and DXQ.

Ten of the 42 patients also had the Positive and Negative Syndrome Scale (PANSS) done. Overall, the neuroleptic and DXQ together reduced negative symptoms scores on the scale.

No patients got worse after DXQ was added to their standard treatment, Markovitz said.

He said DXQ may work by stimulating sigma receptors. Too much glutamate could result in reduced neurotoxicity and cell firing, Markovitz said.

Controlled Phase II trials are being conducted by Avanir Pharmaceuticals to assess the efficacy of DXQ. Studies are also needed to determine optimal dosing, Markovitz said, and DXQ could be examined as a standalone treatment.

– Terri Airov

Reference

Treatment of negative symptoms of schizophrenia with dextromethorphan/quinidine augmentation of antipsychotics: An open trial in 42 patients. Presented at the American Psychiatric Association meeting. May 16, 2016.