A new randomized trial from Taiwan shows that a common food preservative could enhance the effect of a schizophrenia drug, even in the case of people normally resistant to treatment.

Schizophrenia is a chronic, sometimes disabling mental disorder characterized by delusions, flat affect, agitated movements, and a difficulty in sustaining activities.

Treatments include antipsychotic medication—such as brexpiprazole, clozapine, or risperidone—and psychosocial treatments.

Studies have shown that "one fifth to one half of [people with schizophrenia] are classified as refractory to pharmacological treatment," meaning that they do not respond to antipsychotics.

Researchers from China Medical University in Taiwan may now have found a way of boosting the effectiveness of certain drugs, which may help some people living with schizophrenia to respond better to treatment.

The answer, says the study's lead investigator Dr. Hsien-Yuan Lane, may be found in a common food preservative: sodium benzoate. Dr. Lane and team conducted a randomized, double-blind, placebo-controlled trial showing that this preservative could enhance the effects of the antipsychotic drug clozapine.

"Clozapine," he explains, "is considered the last-line antipsychotic agent for patients with refractory schizophrenia." Despite this, a significant number of people living with schizophrenia are resistant to this drug.

The new trial seems to confirm for the first time that sodium benzoate—which has successfully been used as an add-on to other antipsychotics—can be added to clozapine to improve the symptoms of drug-resistant patients.

Dr. Lane and colleagues' findings were recently published in the journal Biological Psychiatry. "If the finding can be confirmed, this approach may bring hope for treating patients with the most refractory schizophrenia," he suggests.

Sodium benzoate helps with symptoms

The study involved 60 individuals receiving clozapine as a treatment for schizophrenia. As part of the trial, the participants were split into three groups: the control group, who were given a placebo alongside clozapine, and the study groups, who received sodium benzoate in addition to the usual dose of clozapine.

In order to gain a better understanding about the impact of dosage, Dr. Lane and colleagues tested the sodium benzoate add-on in two different quantities—1 or 2 grams of the substance per day—hence the two separate study groups.

The researchers administered the treatments to the subjects in the three groups over a period of 6 weeks.

At the end of the trial, Dr. Lane and team found that the people who took sodium benzoate alongside clozapine experienced an improvement in negative symptoms, which include flat affect (emotionless facial expressions), anhedonia (lack of enjoyment of usually pleasurable activities), and difficulty in pursuing normal activities.

Moreover, a higher sodium benzoate dosage was more efficient in boosting the effectiveness of the treatment. Still, the researchers note that the add-on did not influence cognitive symptoms—such as difficulty in maintaining focus, or memory issues—and they hypothesize that still larger doses of sodium benzoate may be needed to observe an effect in this respect.

Dr. Lane and colleagues were also happy to observe that participants taking the sodium benzoate add-on registered no side effects, which offers reassurance that the doses tested so far can be administered safely.

The team explains that the reason why sodium benzoate is such an effective aid in the treatment of schizophrenia is because it stops D-serine, a brain amino acid, from breaking down. D-serine is also a neuromodulator, meaning that it helps to regulate electrical signals transmitted between the brain cells.

These signals don't function normally in the brains of people with schizophrenia, so it is important to maintain the regulatory effect of D-serine in order to counteract some of the negative impact of this disorder.

"Receptors for D-serine are long-standing targets for medication development in schizophrenia, and sodium benzoate is probably the first meaningful tool that we have had to influence this target," notes Dr. John Krystal, the editor of the journal Biological Psychiatry.

He adds that "this study highlights the importance for schizophrenia treatment of understanding the molecular switches that can be thrown to normalize brain circuit function."