{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:10:02Z","timestamp":1789693802499,"version":"4.0.1"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T00:00:00Z","timestamp":1608336000000},"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":["41895"],"award-info":[{"award-number":["41895"]}],"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":[[2021,2]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Tipepidine, a synthetic, non\u2010opioid expectorant, has been shown to improve depressive\u2010like behavior in animal models of depression. In this study, we assessed the efficacy and tolerability of tipepidine combination therapy with citalopram in treatment of major depressive disorder (MDD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a randomized, double\u2010blinded, placebo\u2010controlled clinical trial, 62 patients with MDD were assigned into two parallel groups to receive citalopram (up to 40 mg\/day) plus placebo or citalopram plus tipepidine (30 mg twice daily) for 6\u2009weeks. Participants were assessed with the Hamilton Rating Scale for Depression (HAM\u2010D) at baseline and Weeks 2, 4, and 6.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty\u2010six patients completed the trial. The tipepidine group showed greater improvement in HAM\u2010D scores from baseline to all three study time points (<jats:italic>P<\/jats:italic> =\u20090.048 for all). The remission and response\u2010to\u2010treatment rates were significantly higher in the tipepidine group (53.6% and 100%) compared to the placebo group (25.0% and 75%) at the study end\u2010point (<jats:italic>P<\/jats:italic> =\u20090.029 and 0.005, respectively). The remission and response times in patients in the tipepidine group were also shorter compared with the placebo group (log\u2013rank <jats:italic>P<\/jats:italic> =\u20090.020 and 0.004). There was no significant difference between the two groups in baseline parameters or frequency of side\u2010effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Tipepidine combination therapy with citalopram can effectively improve symptoms of patients with MDD in a shorter period of treatment. However, further studies with larger sample sizes and longer follow\u2010up treatment are needed to confirm our findings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pcn.13180","type":"journal-article","created":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T05:15:26Z","timestamp":1606540526000},"page":"57-62","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Efficacy and safety of tipepidine as adjunctive therapy in major depressive disorder: A randomized, double\u2010blind, placebo\u2010controlled clinical trial"],"prefix":"10.1111","volume":"75","author":[{"given":"Saba","family":"Hoobehfekr","sequence":"first","affiliation":[{"name":"Psychiatric Research Center, Roozbeh Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein Sanjari","family":"Moghaddam","sequence":"additional","affiliation":[{"name":"Psychiatric Research Center, Roozbeh Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadreza","family":"Shalbafan","sequence":"additional","affiliation":[{"name":"Mental Health Research Center, Department of Psychiatry, School of Medicine Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam Ghazizadeh","family":"Hashemi","sequence":"additional","affiliation":[{"name":"Mental Health Research Center, Department of Psychiatry, School of Medicine Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Mehdi","family":"Pirmoradi","sequence":"additional","affiliation":[{"name":"Psychiatric Research Center, Roozbeh Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirhossein","family":"Sakenian","sequence":"additional","affiliation":[{"name":"Psychiatric Research Center, Roozbeh Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirhossein","family":"Poopak","sequence":"additional","affiliation":[{"name":"Psychiatric Research Center, Roozbeh Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayan","family":"Kashefinejad","sequence":"additional","affiliation":[{"name":"Mental Health Research Center, Department of Psychiatry, School of Medicine Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoomeh","family":"Yarahmadi","sequence":"additional","affiliation":[{"name":"Department of Health Psychology, Khorramshahr \u2013 Persian Gulf International Branch Islamic Azad University  Khorramshahr Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2277-5101","authenticated-orcid":false,"given":"Shahin","family":"Akhondzadeh","sequence":"additional","affiliation":[{"name":"Psychiatric Research Center, Roozbeh Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.57.3.209"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.62.6.617"},{"key":"e_1_2_8_4_1","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","author":"American Psychiatric Association","year":"1994"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(02)01347-1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.4088\/PCC.v09n0606"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.56.10.897"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1017\/S003329170200586X"},{"key":"e_1_2_8_9_1","first-page":"50","article-title":"The WHO World Health Report 2001: New understanding\u2014new hope","volume":"39","author":"Levav I","year":"2002","journal-title":"Isr. 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