A growing body of evidence suggests that progressive changes in brain structure and function occur with the unfolding of schizophrenia.1 Oxidative stress may be one of the mediators of neurodegeneration, grey matter loss, and subsequent cognitive and functional impairment. Antioxidants are “exogenous or endogenous molecules and mitigate any form of oxidative stress or its consequences.”1 Their role is to protect cells from the damage caused by unstable molecules called free radicals, which cause oxidative stress—a condition that occurs either from overproduction of free radicals or from a deficiency in antioxidant defenses.2 The mechanism of antioxidants may be to directly scavenge free radicals or to increase anti-oxidative defenses. The brain is particularly vulnerable to the impact of oxidative damage, which has been implicated in many psychiatric disorders, most notably schizophrenia.3

Some evidence suggests that current therapies may affect oxidative pathways and, to some extent, reverse oxidative states in schizophrenia.1 However, these treatments may not fully restore oxidative balance. Interventions specifically aimed at addressing mitigating oxidative stress have garnered attention as potential tools in the schizophrenia armamentarium and the investigation of the potential use of antioxidants in schizophrenia has “increased exponentially in the past decade.”1

A recent review article1 evaluated the effect of antioxidants as add-on treatments to standard antipsychotic medication to improve acute psychotic episodes and core symptoms, and prevent relapse in patients with schizophrenia.

Review Design

The researchers analyzed 22 randomized controlled trials (RCTs), consisting of a total of 2041 adult participants (over age 18 years) with schizophrenia or other types of schizophrenia-like psychosis (eg, schizophreniform and schizoaffective disorders), regardless of the diagnostic criteria used in each trial. Of the studies that reported the patients’ gender, men outnumbered women by approximately two to one.

The Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS) were most commonly used for measuring psychopathology, functioning, and adverse events. Other scales included the Schedule for the Assessment of Positive Symptoms (SANS), the Global Assessment of Functioning (GAF), the Global Assessment Scale (GAS), and the Treatment Emergent Symptoms Scale (TESS).

The primary outcome was change in global state. Secondary outcomes are listed in Table 1.

The studies included several different adjunctive antioxidants, including Ginkgo biloba extract, selegiline, allopurinol, vitamin E, N-acetyl cysteine (NAC) dehydroepiandrosterone (DHEA), and vitamin C. In all studies, the comparison group utilized an adjunctive placebo. Median follow-up was eight weeks.