Efficacy and Safety of Sulforaphane Added to Antipsychotics for the Treatment of Negative Symptoms of Schizophrenia: A Randomized Controlled Trial.

Objective: There are few established treatments for negative symptoms in schizophrenia, which persist in many patients after positive symptoms are reduced. Oxidative stress, inflammation, and epigenetic modifications involving histone deacetylase (HDAC) have been implicated in the pathophysiology of schizophrenia. Sulforaphane has antioxidant properties and is an HDAC inhibitor. We conducted a 24-week, double-blind, placebo-controlled study, in Hunan, China, to assess the effect of high-dose sulforaphane (Nutramax extra strength sulforaphane tablets glucoraphanin content 30 mg/ tablet) on reducing negative symptoms in antipsychotic-treated patients with schizophrenia.

Methods: Participants were recruited from August 2020 to August 2022 and met DSM-5 criteria for schizophrenia. Participants were randomly assigned (2:1) to receive antipsychotics plus sulforaphane (1,700 mg Avmacol Extra Strength sulforaphane daily) or antipsychotics plus placebo for 24 weeks. Fifty-three patients treated with sulforaphane and 24 patients treated with placebo who had at least 1 postintervention clinical scale evaluation were analyzed. The primary outcome measure was change in the Positive and Negative Syndrome Scale (PANSS) negative symptoms.

Results: Sulforaphane-treated patients showed a significantly greater decrease in PANSS negative symptom total score (P = .01) and PANSS negative factor score (P = .02) than placebo-treated patients, with the most prominent difference occurring at 24 weeks (P ≤ .001) with a large effect size at this time point (d = 0.8). Sulforaphane's effect on decreasing negative symptoms was not mediated by changes in scores of depression or cognitive factors on the PANSS.

Conclusions: The results of this study suggest that add-on high-dose sulforaphane may reduce negative symptoms in patients with schizophrenia. The clinical significance of this reduction in negative symptoms needs further evaluation.

Trial Registration: ClinicalTrials.gov identifier: NCT04521868.