TY - JOUR

T1 - Efficacy of resveratrol in the treatment of unipolar depression

T2 - 33rd Congress of the European-College-of-Neuropsychopharmacology (ECNP)

AU - Aftanas, L. I.

AU - Markov, A. A.

AU - Rikita, M. V.

AU - Danilenko, K. V.

PY - 2020/11

Y1 - 2020/11

N2 - Background: SIRT1 gene was found to be involved in the prevalence of depression in the Chinese population [1] and some SIRT1 alleles were met with greater frequency in depressed patients in Russia [2]. This gene mediates the activity of the sirtuin-1 protein, which is an antioxidant/cytoprotective enzyme [3]. For the SIRT1 enzyme, a known activator is natural phytoalexin, flavonoid-polyphenol resveratrol. The two-third of people in the USA who consume dietary supplements consume resveratrol [4]. The clinical effects of resveratrol are being studied in diabetes and obesity, oncological and cardiovascular diseases (www.clinicaltrials.gov). One study showed an alleviation of depressive symptoms in menopausal women after 12-week intake of 10 mg of equol and 25 mg of resveratrol [5]. However, studies in depression have not been performed. Method(s): Criteria for participation in the study included: major depressive disorder (MDD) or dysthymia, with melancholic features (DSM-5 criteria); HDRS-17 (Hamilton Depression Rating Scale 17 items) score at least 16; no antidepressant intake; absence of serious or unstable disease(s). The target number of patients to complete the study was 60. The study was approved by local Ethics Committee and was registered at clinicaltrials.gov (# NCT03384329). Patients visited the clinic 5 times: on days -5 (selection), 0 (inclusion), 15, 30 (during and after medication intake), and 45 (follow-up). The patients were administered to take randomly (1:1) resveratrol pill (Biotivia, USA) 500 mg daily in the morning or placebo pill, for 28 days. The masking was quadruple: participant, care provider, investigator and outcomes assessor were blind to the treatment type. Primary outcome measures were a change of HDRS-17 score and a change of SIRT1 enzymatic activity in serum from day 0 to day 30. Unblinding was planned in the middle of the study to make an intermediate analysis. Result(s): Twenty-two patients completed the study (age+/-SD 37.4+/-9.7 years, range 23-59 years, 10 males), HDRS-17 scored from 16 to 31. Eleven patients received resveratrol, 11 - placebo. The study was stopped with these 22 patients due to a similar (p=0.32, Student t-test) decrease of total HDRS-17 score in resveratrol group (from 22.4+/-4.3 to 15.2+/-5.0) and placebo group (from 21.9+/-3.6 to 12.0+/-7.7). Conclusion(s): The preliminary conclusion from this study is that antidepressant action of resveratrol (in a dose of 500 mg daily) did not significantly differ from the placebo effect in the treatment of unipolar depression. The further steps will include analysis of resveratrol-induced SIRT1 activity in serum, a change of HDRS-17 separate items scores, and accounting for independent variables (age, gender, body mass index, diagnosis type [MDD or dysthymia], expectation towards the treatment, daily hours of sunshine, single nucleotide polymorphism of SIRT1 gene, SIRT1 expression levels). Disclosure statement: Supported by the Russian Science Foundation (grant no. 16-15-00128, 2016-2018 data acquisition) and budgetary funding for basic scientific research (theme No. AAAA-A16-116021010228-0 data analysis).Copyright © 2020

AB - Background: SIRT1 gene was found to be involved in the prevalence of depression in the Chinese population [1] and some SIRT1 alleles were met with greater frequency in depressed patients in Russia [2]. This gene mediates the activity of the sirtuin-1 protein, which is an antioxidant/cytoprotective enzyme [3]. For the SIRT1 enzyme, a known activator is natural phytoalexin, flavonoid-polyphenol resveratrol. The two-third of people in the USA who consume dietary supplements consume resveratrol [4]. The clinical effects of resveratrol are being studied in diabetes and obesity, oncological and cardiovascular diseases (www.clinicaltrials.gov). One study showed an alleviation of depressive symptoms in menopausal women after 12-week intake of 10 mg of equol and 25 mg of resveratrol [5]. However, studies in depression have not been performed. Method(s): Criteria for participation in the study included: major depressive disorder (MDD) or dysthymia, with melancholic features (DSM-5 criteria); HDRS-17 (Hamilton Depression Rating Scale 17 items) score at least 16; no antidepressant intake; absence of serious or unstable disease(s). The target number of patients to complete the study was 60. The study was approved by local Ethics Committee and was registered at clinicaltrials.gov (# NCT03384329). Patients visited the clinic 5 times: on days -5 (selection), 0 (inclusion), 15, 30 (during and after medication intake), and 45 (follow-up). The patients were administered to take randomly (1:1) resveratrol pill (Biotivia, USA) 500 mg daily in the morning or placebo pill, for 28 days. The masking was quadruple: participant, care provider, investigator and outcomes assessor were blind to the treatment type. Primary outcome measures were a change of HDRS-17 score and a change of SIRT1 enzymatic activity in serum from day 0 to day 30. Unblinding was planned in the middle of the study to make an intermediate analysis. Result(s): Twenty-two patients completed the study (age+/-SD 37.4+/-9.7 years, range 23-59 years, 10 males), HDRS-17 scored from 16 to 31. Eleven patients received resveratrol, 11 - placebo. The study was stopped with these 22 patients due to a similar (p=0.32, Student t-test) decrease of total HDRS-17 score in resveratrol group (from 22.4+/-4.3 to 15.2+/-5.0) and placebo group (from 21.9+/-3.6 to 12.0+/-7.7). Conclusion(s): The preliminary conclusion from this study is that antidepressant action of resveratrol (in a dose of 500 mg daily) did not significantly differ from the placebo effect in the treatment of unipolar depression. The further steps will include analysis of resveratrol-induced SIRT1 activity in serum, a change of HDRS-17 separate items scores, and accounting for independent variables (age, gender, body mass index, diagnosis type [MDD or dysthymia], expectation towards the treatment, daily hours of sunshine, single nucleotide polymorphism of SIRT1 gene, SIRT1 expression levels). Disclosure statement: Supported by the Russian Science Foundation (grant no. 16-15-00128, 2016-2018 data acquisition) and budgetary funding for basic scientific research (theme No. AAAA-A16-116021010228-0 data analysis).Copyright © 2020

UR - https://www.mendeley.com/catalogue/596fd82b-aaef-3800-a396-24136b9824b1/

U2 - 10.1016/j.euroneuro.2020.09.248

DO - 10.1016/j.euroneuro.2020.09.248

M3 - Meeting Abstract

VL - 40

SP - S189-S189

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

Y2 - 12 September 2020 through 15 September 2020

ER -