Adjunctive use of sodium benzoate (BZ), a common food preservative that has previously shown promise in the treatment of chronic refractory psychosis, appears to be ineffective in the early stages of the disorder, new research suggests.
Results of a randomized controlled trial show the agent was no more effective than placebo in reducing early psychosis symptoms, although it was safe and well tolerated.
“Both groups of patients improved over the 12 weeks of the study, [suggesting] that most people with early psychosis will get well with antipsychotic medication and psychosocial interventions and adding sodium benzoate to their treatment does not add any additional benefits,” the study’s lead author, James Scott, MBBS, PhD, head of mental health research, QIMR Berghofer Medical Research Institute, Herston, Australia, told Medscape Medical News.
The paper was published online November 10 in JAMA Network Open.
Positive outcomes in chronic disease
Despite treatment with antipsychotics, many patients with psychosis experience persistent impairment, the investigators note.
Most antipsychotics are dopaminergic in action, but it is now recognized that the pathophysiology underlying psychosis extends beyond dopaminergic dysregulation with hypofunction of the N-methyl-D-aspartate (NMDA) receptors also implicated but not addressed by standard antipsychotics, they add.
NMDA receptors consist of two main subunits – the glutamate and glycine-binding sites. D-amino acids (DAAs) are agonists of the glycine subunit and have shown promise as adjunctive therapies for the treatment of schizophrenia, the investigators note.
DAAs are subject to oxidation by the flavoenzyme D-amino acid oxidase (DAAO). The oxidation limits their bioavailability and can cause nephrotoxic side effects. The food preservative BZ, which is not related to the benzodiazepine class of medications, inhibits DAAO and therefore may make DAAs safer and more effective.
Scott noted that two previous trials of BZ – a 2013 study and a 2017 investigation – in chronic, treatment-refractory schizophrenia have “reported excellent outcomes with significant improvement in clinical symptoms.”
“We saw that sodium benzoate was a safe and well-tolerated agent, and we thought it was important to conduct a trial of this medication in people in the early stages of psychotic illness,” he said.
To investigate, the researchers randomly assigned 100 individuals who were experiencing early psychosis, which was defined as illness onset within the last 2 years, to receive either 500 mg of BZ twice daily or placebo for 12 weeks.
Participants (mean [SD] age 21.4 [4.1] years, 73% male) were required to be taking antipsychotic medications for at least 1 continuous month during the previous 2 years and to be free of comorbid physical illnesses requiring additional treatment or hospitalization.
Most participants (84%) had schizophrenia and the remainder had affective psychoses. Most participants (88%) lived independently.
The BZ and the placebo groups were similar with respect to baseline characteristics, except that the mean waist circumference was higher in the placebo group than in the BZ group.
The majority of patients were being treated with antipsychotics alone (83%), followed by antipsychotics in combination with mood stabilizers (13%) and a small number were taking mood stabilizers alone (4%). The most commonly used antipsychotics were olanzapine and aripiprazole.