Resveratrol Adjunct Therapy for Negative Symptoms in Patients With Stable Schizophrenia: A Double-Blind, Randomized Placebo-Controlled Trial

Abstract

Background Patients with schizophrenia can generally manifest a broad variety of primary negative symptoms. The current study aimed to assess the efficacy and tolerability of resveratrol add-on therapy in the treatment of negative symptoms in patients with stable schizophrenia. Methods In a randomized, double-blind, and placebo-controlled setting, schizophrenia patients were assigned to receive either 200 mg/d resveratrol or matched placebo in addition to a stable dose of risperidone for 8 weeks. Patients were assessed using the positive and negative syndrome scale, the extrapyramidal symptom rating scale, and Hamilton Depression Rating Scale over the trial period. The primary outcome was considered as the change in positive and negative subscale score from baseline to week 8 between the treatment arms. Results A total 52 patients completed the trial (26 in each arm). Baseline characteristics of both groups were statistically similar (P > .05). Despite the statistically similar behavior of positive symptoms between the groups across time (Greenhouse-Geisser corrected: F = 1.76, df = 1.88, P = .180), the resveratrol group demonstrated greater improvement in negative, general psychopathology, and total scores (Greenhouse-Geisser corrected: F = 12.25, df = 2.04, P < .001; F = 5.42, df = 1.56, P = .011; F = 7.64, df = 1.48, P = .003). HDRS scores and its changes, ESRS score, and frequency of other complications were not significantly different between resveratrol and placebo groups. Conclusion Adding resveratrol to risperidone can exhibit remarkable efficacy and safety in terms of management of schizophrenia-related negative symptoms.

Therapeutic potential of stilbenes in neuropsychiatric and neurological disorders: A comprehensive review of preclinical and clinical evidence

“…A total of 52 schizophrenia patients of both sexes assigned to receive either 200 mg of resveratrol per day or placebo in addition to risperidone completed the trial. Resveratrol as an adjunct therapy was well‐tolerated and importantly it improved negative symptoms of schizophrenia (Samaei et al, 2020).…”

“…Two clinical trials were performed on schizophrenia patients. In one study resveratrol reduced negative symptoms of schizophrenia (Samaei et al, 2020), whereas in the second one, it failed to improve cognitive symptoms and reduce cardiovascular risk factor (Zortea, Franco, Guimarães, & Belmonte‐de‐Abreu, 2016). The possible therapeutic efficacy of resveratrol in neurodegenerative disorders is also not sufficiently supported by clinical data (Yadav et al, 2022).…”

Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It?

“…In addition, negative symptoms such as verbal output, social communication, and loss of emotional and facial expressions developed in patients with schizophrenia and were found to be reduced when RSV was combined with risperidone in another study [ 92 ]. Additionally, RSV has been shown to have some beneficial effects on patients with muscular dystrophies, especially on motor function and muscular growth, and it has been shown to reduce ROS levels by inducing the expression of superoxide dismutase [ 93 ].…”

The interplay of dopamine metabolism abnormalities and mitochondrial defects in the pathogenesis of schizophrenia

“…In addition to vitamin C and NAC that have been used as antioxidant addition to antipsychotic treatment for schizophrenia, the others that have been tested in clinical trials with schizophrenia patients include ginkgo biloba [ 196 , 197 ], allopurinol [ 197 ], minocycline [ 198 ], resveratrol [ 199 ], essential polyunsaturated fatty acids (EPUFAs), particularly, omega-3 fatty acids [ 200 ], vitamin E [ 201 ], as well as a mixture of omega-3 and vitamin E/C [ 202 ]. Overall, there is preliminary data that suggests substances with antioxidant potential may be of use, although definitive studies are needed.…”