Toss around the word preservative these days, and you’re sure to get a look of detestation from a fair number of people. The much-maligned molecules have come under intense scrutiny in recent years as contributing factors to a host of medical issues—often with scant scientific evidence to support even casual links. Yet now, researchers at the China Medical University in Taiwan may have just stumbled upon a new use for the common food preservative sodium benzoate in treating schizophrenia. Findings from the new study—published recently in Biological Psychiatry tin an article entitled “Sodium Benzoate, a D-amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial”—show that the preservative improves symptoms in clozapine-resistant schizophrenia patients.
“Clozapine is considered the last-line antipsychotic agent for patients with refractory schizophrenia,” explained senior study investigator Hsien-Yuan Lane, M.D., Ph.D., a research scientist at China Medical University, in reference to patients whose symptoms do not respond to available antipsychotics.
An estimated 40% to 70% of patients with refractory schizophrenia fail to improve, even with clozapine, and referred to as “clozapine-resistant,” exhausting all potential options for treatment. This new study is the first to demonstrate that sodium benzoate—which has been shown to enhance other antipsychotic drugs—works in clozapine-resistant patients.
“If the finding can be confirmed, this approach may bring hope for treating patients with the most refractory schizophrenia,” Dr. Lane remarked.
In this randomized, double-blind, placebo-controlled trial, the researchers examined 60 patients with schizophrenia that were all taking clozapine. Participants received either a placebo or sodium benzoate as an add-on treatment for six weeks. The investigators tested two different doses of sodium benzoate (1 or 2 grams per day) to find which offered the biggest impact on symptoms with minimal side effects.
“Both doses of sodium benzoate produced better improvement than placebo in the Scales for the Assessment of Negative Symptoms (SANS),” the authors reported, and “2-g/day sodium benzoate also produced better improvement than placebo in PANSS [Positive and Negative Syndrome Scale]-total score, PANSS-positive score, and Quality of Life Scale. Sodium benzoate was well tolerated without evident side effects. The changes of catalase, an antioxidant, were different among the three groups and correlated with the improvement of PANSS total and PANSS-positive score in the sodium benzoate group.”
Compared with the placebo, sodium benzoate improved negative symptoms, such as lack of emotion and motivation, which have a greater influence on a patient's functional outcome than the more prominent psychotic symptoms. The higher dose of sodium benzoate also improved ratings of overall symptoms and quality of life. Although sodium benzoate has improved cognitive function when combined with other antipsychotics in previous studies, the add-on treatment had no influence on cognitive function in this study. The authors hypothesized that a higher dose or longer duration of treatment might be needed to observe cognitive effects. Importantly, the patients taking sodium benzoate had no side effects, confirming the treatment is safe to use at the doses tested.
Sodium benzoate works by preventing the breakdown of D-serine, a brain chemical that plays an important role in signaling that is disrupted in the brains of people with schizophrenia.
“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,” noted editor-in-chief of Biological Psychiatry John Krystal, M.D., a professor at Yale University Medical School.
Although more studies are needed to learn how sodium benzoate enhances clozapine treatment in these patients, Dr. Krystal concluded that “this study highlights the importance for schizophrenia treatment of understanding the molecular switches that can be thrown to normalize brain circuit function.”