{"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":1791294044253,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004484","name":"Tehran University of Medical Sciences and Health Services","doi-asserted-by":"publisher","award":["50780"],"award-info":[{"award-number":["50780"]}],"id":[{"id":"10.13039\/501100004484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychiatry Clin Neurosci"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Palmitoylethanolamide is an endogenous fatty acid amide with neuroprotective and anti\u2010inflammatory actions. We performed a randomized, double\u2010blind, placebo\u2010controlled clinical trial to investigate the efficacy and safety of palmitoylethanolamide combination therapy in acute mania.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients in the acute phase of mania were assigned into two parallel groups given either lithium (blood level of 0.8\u20131.1 mEq\/L) and risperidone 3 mg plus palmitoylethanolamide 600 mg or placebo twice per day for 6\u2009weeks. All participants were assessed with the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), and Extrapyramidal Symptom Rating Scale (ESRS) at baseline and at weeks 1, 2, 4, and 6.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 63 patients (32 in palmitoylethanolamide and 31 in placebo groups) completed the trial. We found a significant effect for time\u00d7treatment interaction on the YMRS score (<jats:italic>F<\/jats:italic>\u00a0=\u00a05.22, d.f.\u00a0=\u00a02.34, <jats:italic>P<\/jats:italic>=\u20090.004) from baseline to study end point. Results from independent <jats:italic>t<\/jats:italic> test showed a significantly greater decrease in YMRS scores in the palmitoylethanolamide group, compared with the placebo group, from baseline to weeks 4 and 6 (<jats:italic>P<\/jats:italic>=\u20090.018 and <jats:italic>P<\/jats:italic>=\u20090.002, respectively). There was no significant difference between palmitoylethanolamide and placebo groups based on ESRS scores or ESRS changes in scores (<jats:italic>P<\/jats:italic>&gt;0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings provide preliminary evidence that palmitoylethanolamide is an effective adjunctive medication that improves manic symptoms and overall clinical status in acute episodes of mania. However, larger sample sizes and more extended follow\u2010up therapy are needed in future studies to confirm our findings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pcn.13441","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T17:13:01Z","timestamp":1656004381000},"page":"505-511","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Efficacy and safety of palmitoylethanolamide as an adjunctive treatment for acute mania: A randomized, double\u2010blind, placebo\u2010controlled trial"],"prefix":"10.1111","volume":"76","author":[{"given":"Talieh","family":"Abedini","sequence":"first","affiliation":[{"name":"Psychiatric Research Center, Roozbeh Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reyhaneh","family":"Hosseyni","sequence":"additional","affiliation":[{"name":"Psychiatric Research Center, Roozbeh Hospital 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