Schizophrenia can affect all aspects of a person — thinking, feeling and behaving — and is associated with tremendous personal suffering, disability, family burden, premature death and societal cost. Getting people into treatment quickly is important for recovery.

Randomized trials have shown that intervention close to psychosis onset improves symptoms and functioning more than traditional care and can reduce hospital admission. These studies also show that inclusion of psychological interventions as part of early intervention may improve outcomes, and a comprehensive treatment plan may benefit individuals with established psychosis.

In the early 1990s, a new class of drugs, atypical antipsychotics, was developed to treat the psychotic symptoms of schizophrenia. These drugs were proven as effective as earlier generation typical antipsychotics but with far fewer extrapyramidal side effects. Clozaril (clozapine), the gold standard medication for treatment-resistant schizophrenia, was the first atypical antipsychotic to receive FDA approval in 1990 and remains a mainstay of care.

However, about 40 percent of patients treated with clozapine do not show an adequate response at least a 20 percent reduction in their Positive and Negative Syndrome Score (PANSS) or similar assessment. Given that 1 in 3 people with psychosis fails to respond to initial antipsychotic therapies before being prescribed clozapine, this means that 1 in 8 psychosis patients will have a refractory illness that will fail to respond to first-line treatments and clozapine.

A randomized, double-blind, placebo-controlled study showed that the common food preservative sodium benzoate which has been shown to enhance other antipsychotic drugs improves symptoms in clozapine-resistant schizophrenia patients, providing a new option for the hardest-to-treat patients. 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.

In this new study, 60 schizophrenia inpatients who had been stabilized with clozapine were allocated into three groups for six weeks of add-on treatment of 1 g/day sodium benzoate, 2 g/day sodium benzoate or placebo. The primary outcome measures were PANSS total score, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, and Global Assessment of Functioning. Side effects and cognitive functions were also measured.

Both doses of sodium benzoate produced better improvement than placebo in the Scale for the Assessment of Negative Symptoms. The 2 g/day sodium benzoate also produced better improvement than placebo in PANSS-total score, PANSS-positive score and Quality of Life Scale. The changes of catalase, an antioxidant, were different among the three groups and correlated with the improvement of PANSS-total score and PANSS-positive score in the sodium benzoate group.

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. According to lead researcher Hsien-Yuan Lane, M.D., Ph.D., of China Medical University, Taiwan, a higher dose or longer duration of treatment may be needed for these effects.

Importantly, the patients taking sodium benzoate had no side effects, which confirms that the treatment is safe to use at the doses tested. Lane stressed that further studies are needed to identify the optimal dose and treatment duration as well as the mechanisms of sodium benzoate for clozapine-resistant schizophrenia.