{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:40:44Z","timestamp":1791294044246,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Inflammatory processes play a role in the etiopathogenesis of bipolar disorder type 1. Full therapeutic responses are seldom seen and the ongoing inflammatory processes in the brain could lead to neuronal loss. Curcumin, a relatively safe herbal compound, has been shown to have anti-inflammatory effects. The present randomized double-blind clinical trial study aimed to investigate the effect of adding curcumin to the treatment regimen of BID.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>This randomized double-blind clinical trial was conducted on 78 patients diagnosed with BID according to the Diagnostic and Statistical Manual of Mental Disorders (DSM 5) criteria. The sample were divided into two groups. Patients in both groups received sodium valproate starting at a dose of 600 milligrams per day and administered up to 20 milligrams per kilogram per day or the highest dosage of the patient\u2019s tolerance. Patients in the intervention group also received curcumin as nanomicelle in soft gelatin capsules 40 milligrams per day. The control group received placebo tablets with the same characteristics as the curcumin tablets. They were assessed by a psychiatrist using the Young Mania Rating Scale (YMRS), Mini-Mental State Examination (MMSE), Clinical Global Impression (CGI), and a medication side effect questionnaire at the beginning of the study, as well as in the first, second, and fourth weeks of the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 78 patients chosen to participate in the project, 54 people completed the trial. No specific side effect was observed in the two groups. Both groups showed an increase in their MMSE scores compared to the beginning of the study (value of <jats:italic>p<\/jats:italic> &amp;lt; 0.001). Although this increase was not statistically different between the two groups (value of <jats:italic>p<\/jats:italic> =\u20090.68). The YMRS score of both groups decreased significantly by the end of the study (value of <jats:italic>p<\/jats:italic> &amp;lt; 0.001); however, this decrease was not significantly different between the two groups (value of <jats:italic>p<\/jats:italic> =\u20090.64). In addition, the two groups experienced a significant increase in their CGI scores throughout the study (value of <jats:italic>p<\/jats:italic> &amp;lt; 0.001), this increase however was not statistically different between the two groups (value of <jats:italic>p<\/jats:italic> =\u20090.88).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present study suggested that curcumin may not be a useful adjuvant agent in the management of patients with BID receiving sodium valproate as treatment.<\/jats:p><jats:p>Clinical trial registration: Iranian Registry of Clinical Trials (IRCT), identifier IRCT2016102530504N1.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpsyt.2023.1068277","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T11:38:24Z","timestamp":1675337904000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["The effect of adding curcumin to sodium valproate in treatment of patients with bipolar disorder in the acute phase of mania: A randomized double-blind clinical trial"],"prefix":"10.3389","volume":"14","author":[{"given":"Farzad","family":"Akbarzadeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabahat","family":"Niksun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghazal","family":"Behravan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Behdani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Hooshang","family":"Mohammadpour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoudreza","family":"Jaafari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayebeh","family":"Hosseini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Rajai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Ebrahimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboubeh","family":"Eslamzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref1","first-page":"78","article-title":"Kaplan and Sadock\u2019s synopsis of psychiatry","volume":"58","author":"Kaplan","year":"2016","journal-title":"Behav Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1016\/j.jpsychires.2011.03.002","article-title":"Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis","volume":"45","author":"Fernandes","year":"2011","journal-title":"J Psychiatr Res"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1097\/YCT.0b013e3181c18bbf","article-title":"The level of serum brain-derived neurotrophic factor is associated with the therapeutic efficacy of modified electroconvulsive therapy in Chinese patients with depression","volume":"26","author":"Hu","year":"2010","journal-title":"J ECT"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.neulet.2011.02.054","article-title":"Lithium increases plasma brain-derived neurotrophic factor in acute bipolar mania: a preliminary 4-week study","volume":"494","author":"de Sousa","year":"2011","journal-title":"Neurosci Lett"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.brainres.2006.08.129","article-title":"Brain-derived neurotrophic factor rapidly increases NMDA receptor channel activity through Fyn-mediated phosphorylation","volume":"1121","author":"Xu","year":"2006","journal-title":"Brain Res"},{"key":"ref6","first-page":"189","article-title":"Downregulation in components of the mitochondrial electron transport chain in the postmortem frontal cortex of subjects with bipolar disorder","volume":"31","author":"Sun","year":"2006","journal-title":"J Psychiatry Neurosci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.jad.2008.04.013","article-title":"Oxidative stress markers in bipolar disorder: a meta-analysis","volume":"111","author":"Andreazza","year":"2008","journal-title":"J Affect Disord"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1111\/j.1365-2184.1991.tb01150.x","article-title":"Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli","volume":"24","author":"Lennon","year":"1991","journal-title":"Cell Prolif"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1016\/j.neubiorev.2010.10.001","article-title":"Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors","volume":"35","author":"Berk","year":"2011","journal-title":"Neurosci Biobehav Rev"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.pnpbp.2012.11.007","article-title":"Putative neuroprotective agents in neuropsychiatric disorders","volume":"42","author":"Dodd","year":"2013","journal-title":"Prog Neurol Psychopharmacol Biol Psychiatry"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.ijdevneu.2010.08.007","article-title":"Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia","volume":"29","author":"Clay","year":"2011","journal-title":"Int J Dev Neurosci"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1126\/science.1213099","article-title":"Neuroimmune communication","volume":"334","author":"Trakhtenberg","year":"2011","journal-title":"Science"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.bbi.2010.10.015","article-title":"Immune modulation of learning, memory, neural plasticity and neurogenesis","volume":"25","author":"Yirmiya","year":"2011","journal-title":"Brain Behav Immun"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1017\/S1461145710001410","article-title":"Understanding the role of inflammatory-related pathways in the pathophysiology and treatment of psychiatric disorders: evidence from human peripheral studies and CNS studies","volume":"14","author":"Dean","year":"2011","journal-title":"Int J Neuropsychopharmacol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.4088\/JCP.08r04505","article-title":"Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder: a systematic review of the literature","volume":"70","author":"Goldstein","year":"2009","journal-title":"J Clin Psychiatry"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cbi.2008.05.003","article-title":"Antioxidant and radical scavenging properties of curcumin","volume":"174","author":"Ak","year":"2008","journal-title":"Chem Biol Interact"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1021\/jf9805348","article-title":"Chemical studies on antioxidant mechanism of curcuminoid: analysis of radical reaction products from curcumin","volume":"47","author":"Masuda","year":"1999","journal-title":"J Agric Food Chem"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.neulet.2012.01.019","article-title":"Therapeutic role of curcumin in prevention of biochemical and behavioral aberration induced by alcoholic neuropathy in laboratory animals","volume":"511","author":"Kandhare","year":"2012","journal-title":"Neurosci Lett"},{"key":"ref19","first-page":"3293","article-title":"Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines","volume":"25","author":"Ramachandran","year":"2005","journal-title":"Anticancer Res"},{"key":"ref20","first-page":"150","article-title":"Standardization, reliability, and validity of the Young mania rating scale","volume":"11","author":"Barekatain","year":"2007","journal-title":"Psychology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1080\/17425255.2019.1650914","article-title":"Is curcumin bioavailability a problem in humans: lessons from clinical trials","volume":"15","author":"Kunnumakkara","year":"2019","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"282","DOI":"10.22038\/ijbms.2019.32873.7852","article-title":"Novel nanomicelle formulation to enhance bioavailability and stability of curcuminoids","volume":"22","author":"Hatamipour","year":"2019","journal-title":"Iran J Basic Med Sci"},{"key":"ref23","first-page":"217","article-title":"Reliability and validity of the bipolar depression rating scale on an Iranian sample","volume":"13","author":"Amir","year":"2010","journal-title":"Arch Iran Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-244X-11-83","article-title":"The clinical global impression scale and the influence of patient or staff perspective on outcome","volume":"11","author":"Forkmann","year":"2011","journal-title":"BMC Psychiatry"},{"key":"ref25","first-page":"29","article-title":"Validation of mini-mental state examination (MMSE) in the elderly population of Tehran","volume":"10","author":"Foroughan","year":"2008","journal-title":"Adv Cogn Sci"},{"key":"ref26","first-page":"28","article-title":"The clinical global impressions scale: applying a research tool in clinical practice","volume":"4","author":"Busner","year":"2007","journal-title":"Psychiatry (Edgmont)"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1034\/j.1600-0447.107.s416.5.x","article-title":"The clinical global impression\u2013schizophrenia scale: a simple instrument to measure the diversity of symptoms present in schizophrenia","volume":"107","author":"Haro","year":"2003","journal-title":"Acta Psychiatr Scand"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.biopsych.2009.09.033","article-title":"A meta-analysis of cytokines in major depression","volume":"67","author":"Dowlati","year":"2010","journal-title":"Biol Psychiatry"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1016\/j.ejca.2005.05.009","article-title":"Curcumin: the story so far","volume":"41","author":"Sharma","year":"2005","journal-title":"Eur J Cancer"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"497","DOI":"10.2147\/JPR.S48432","article-title":"Safety and efficacy of an add-on therapy with curcumin phytosome and piperine and\/or lipoic acid in subjects with a diagnosis of peripheral neuropathy treated with dexibuprofen","volume":"6","author":"Di Pierro","year":"2013","journal-title":"J Pain Res"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1177\/014860710603000145","article-title":"Curcumin, an atoxic antioxidant and natural NF\u03baB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases","volume":"30","author":"Bengmark","year":"2006","journal-title":"J Parenter Enter Nutr"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.mehy.2013.02.001","article-title":"Is there a role for curcumin in the treatment of bipolar disorder?","volume":"80","author":"Brietzke","year":"2013","journal-title":"Med Hypotheses"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1016\/j.psyneuen.2011.04.012","article-title":"Curcumin ameliorates reserpine-induced pain\u2013depression dyad: Behavioral, biochemical, neurochemical and molecular evidences","volume":"36","author":"Arora","year":"2011","journal-title":"Psychoneuroendocrinology"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.ejphar.2013.02.012","article-title":"Ameliorative effect of Curcumin on seizure severity, depression like behavior, learning and memory deficit in post-pentylenetetrazole-kindled mice","volume":"704","author":"Choudhary","year":"2013","journal-title":"Eur J Pharmacol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1177\/0269881116686883","article-title":"Curcumin for neuropsychiatric disorders: a review of in vitro, animal and human studies","volume":"31","author":"Lopresti","year":"2017","journal-title":"J Psychopharmacol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1097\/JCP.0000000000000352","article-title":"Chronic supplementation of curcumin enhances the efficacy of antidepressants in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study","volume":"35","author":"Yu","year":"2015","journal-title":"J Clin Psychopharmacol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.ejphar.2013.12.028","article-title":"Neuroprotective and antioxidant effects of curcumin in a ketamine-induced model of mania in rats","volume":"724","author":"Gazal","year":"2014","journal-title":"Eur J Pharmacol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.brainres.2008.01.104","article-title":"Curcumin protects against glutamate excitotoxicity in rat cerebral cortical neurons by increasing brain-derived neurotrophic factor level and activating TrkB","volume":"1210","author":"Wang","year":"2008","journal-title":"Brain Res"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1016\/S0891-5849(00)00294-X","article-title":"Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress","volume":"28","author":"Motterlini","year":"2000","journal-title":"Free Radic Biol Med"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.pnpbp.2009.10.016","article-title":"Curcumin produces neuroprotective effects via activating brain-derived neurotrophic factor\/TrkB-dependent MAPK and PI-3K cascades in rodent cortical neurons","volume":"34","author":"Wang","year":"2010","journal-title":"Prog Neurol Psychopharmacol Biol Psychiatry"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/j.lfs.2003.06.042","article-title":"Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats","volume":"74","author":"Thiyagarajan","year":"2004","journal-title":"Life Sci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/s00213-008-1300-y","article-title":"Antidepressant activity of curcumin: involvement of serotonin and dopamine system","volume":"201","author":"Kulkarni","year":"2008","journal-title":"Psychopharmacology"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2023.1068277\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T11:38:34Z","timestamp":1675337914000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2023.1068277\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,2]]},"references-count":42,"alternative-id":["10.3389\/fpsyt.2023.1068277"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2023.1068277","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,2]]},"article-number":"1068277"}}