{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:41:31Z","timestamp":1791110491404,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,2,18]],"date-time":"2014-02-18T00:00:00Z","timestamp":1392681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Psychiatry Clin Neurosci"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Management of recent\u2010onset schizophrenia (<jats:styled-content style=\"fixed-case\">SZ<\/jats:styled-content>) and schizoaffective disorder (<jats:styled-content style=\"fixed-case\">SA<\/jats:styled-content>) is challenging owing to frequent insufficient response to antipsychotic agents. This study aimed to test the efficacy and safety of the neurosteroid pregnenolone in patients with recent\u2010onset <jats:styled-content style=\"fixed-case\">SZ<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">SA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty out\u2010 and inpatients who met <jats:styled-content style=\"fixed-case\">DSM\u2010IV<\/jats:styled-content> criteria for <jats:styled-content style=\"fixed-case\">SZ<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">SA<\/jats:styled-content>, with suboptimal response to antipsychotics were recruited for an 8\u2010week, double\u2010blind, randomized, placebo\u2010controlled, two\u2010center add\u2010on trial, that was conducted between 2008 and 2011. Participants were randomized to receive either pregnenolone (50\u2009mg\/day) or placebo added on to antipsychotic medications. The primary outcome measures were the Positive and Negative Symptoms Scale and the Assessment of Negative Symptoms scores. Secondary outcomes included assessments of functioning, and side\u2010effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Analysis was by linear mixed model. Fifty\u2010two participants (86.7%) completed the trial. Compared to placebo, adjunctive pregnenolone significantly reduced Positive and Negative Symptoms Scale negative symptom scores with moderate effect sizes (<jats:italic>d<\/jats:italic>\u2009=\u20090.79). Significant improvement was observed in weeks 6 and 8 of pregnenolone therapy among patients who were not treated with concomitant mood stabilizers (arms\u2009\u00d7\u2009visit\u2009\u00d7\u2009mood stabilizers; <jats:italic>P<\/jats:italic>\u2009=\u20090.010). Likewise, pregnenolone significantly reduced Assessment of Negative Symptoms scores compared to placebo (<jats:italic>d<\/jats:italic>\u2009=\u20090.57), especially on blunted affect, avolition and anhedonia domain scores. Other symptoms, functioning, and side\u2010effects were not significantly affected by adjunctive pregnenolone. Antipsychotic agents, benzodiazepines and sex did not associate with pregnenolone augmentation. Pregnenolone was well tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Thus, add\u2010on pregnenolone reduces the severity of negative symptoms in recent\u2010onset schizophrenia and schizoaffective disorder, especially among patients who are not treated with concomitant mood stabilizers. Further studies are warranted.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pcn.12150","type":"journal-article","created":{"date-parts":[[2014,2,19]],"date-time":"2014-02-19T04:03:28Z","timestamp":1392782608000},"page":"432-440","source":"Crossref","is-referenced-by-count":57,"title":["Pregnenolone treatment reduces severity of negative symptoms in recent\u2010onset schizophrenia: An 8\u2010week, double\u2010blind, randomized add\u2010on two\u2010center trial"],"prefix":"10.1111","volume":"68","author":[{"given":"Michael S.","family":"Ritsner","sequence":"first","affiliation":[{"name":"Sha'ar Menashe Mental Health Center  Hadera Israel"},{"name":"The Rappaport Faculty of Medicine Technion  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisham","family":"Bawakny","sequence":"additional","affiliation":[{"name":"The Rappaport Faculty of Medicine Technion  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoly","family":"Kreinin","sequence":"additional","affiliation":[{"name":"The Rappaport Faculty of Medicine Technion  Haifa Israel"},{"name":"Tirat Carmel Mental Health Center  Tirat Carmel Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,18]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1","article-title":"Neurosteroids: Of the nervous system, by the nervous system, for the nervous system","volume":"52","author":"Baulieu E","year":"1997","journal-title":"Recent Prog. 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