{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T05:11:00Z","timestamp":1770268260994,"version":"3.49.0"},"reference-count":47,"publisher":"Cambridge University Press (CUP)","issue":"4","license":[{"start":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T00:00:00Z","timestamp":1589241600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Spectr."],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S1092852920001376_sec1\"><jats:title>Background<\/jats:title><jats:p>Combination olanzapine and samidorphan (OLZ\/SAM), in development for schizophrenia and bipolar I disorder, is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. OLZ\/SAM safety, tolerability, and efficacy from a 52-week open-label extension study in patients with schizophrenia are reported.<\/jats:p><\/jats:sec><jats:sec id=\"S1092852920001376_sec2\" sec-type=\"methods\"><jats:title>Methods<\/jats:title><jats:p>Patients previously completing the 4-week, double-blind ENLIGHTEN-1 study switched from OLZ\/SAM, olanzapine, or placebo to OLZ\/SAM. Assessments included adverse events (AEs), weight, vital signs, Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression-Severity (CGI-S) scores. Baseline was prior to first dose of OLZ\/SAM in the extension study.<\/jats:p><\/jats:sec><jats:sec id=\"S1092852920001376_sec3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>In total, 281 patients enrolled, 277 received \u22651 OLZ\/SAM dose, and 183 (66.1%) completed 52 weeks. Reasons for discontinuation included patient withdrawal (15.5%), loss to follow-up (6.9%), AEs (5.8%), and lack of efficacy (1.8%). AEs were reported in 136 (49.1%) patients; increased weight (13%) and somnolence (8%) were most common. Ten serious AEs were reported in eight patients (2.9%); none were considered treatment related. There were no deaths. Mean (SD) baseline weight was 79.1 (17.8) kg. Mean weight change from baseline to week 52 was 1.86 kg (2.79% increase). PANSS total and CGI-S scores continued to decline over 52 weeks (mean [95% CI] changes from baseline to week 52: \u221216.2 [\u221218.5, \u221214.0] and \u22120.9 [\u22121.0, \u22120.8], respectively).<\/jats:p><\/jats:sec><jats:sec id=\"S1092852920001376_sec4\" sec-type=\"conclusions\"><jats:title>Conclusion<\/jats:title><jats:p>OLZ\/SAM was generally well tolerated in this extension study; most patients completed the 52-week treatment period with sustained improvement in schizophrenia symptoms. Mean increases in weight stabilized by week 6 with limited subsequent change through end of treatment.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s1092852920001376","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T05:13:47Z","timestamp":1589260427000},"page":"383-392","source":"Crossref","is-referenced-by-count":17,"title":["Long-term safety and durability of effect with a combination of olanzapine and samidorphan in patients with schizophrenia: results from a 1-year open-label extension study"],"prefix":"10.1017","volume":"26","author":[{"given":"Sergey","family":"Yagoda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Graham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Arevalo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"McDonnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2020,5,12]]},"reference":[{"key":"S1092852920001376_r27","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1958.10501452"},{"key":"S1092852920001376_r12","doi-asserted-by":"publisher","DOI":"10.1097\/01.jcp.0000245563.06660.0f"},{"key":"S1092852920001376_r2","unstructured":"2. Lehman, AF , Lieberman, JA , Dixon, LB , et al. Practice guideline for the treatment of patients with schizophrenia. 2nd ed. 2010. https:\/\/psychiatryonline.org\/pb\/assets\/raw\/sitewide\/practice_guidelines\/guidelines\/schizophrenia.pdf. Accessed January 28, 2019."},{"key":"S1092852920001376_r18","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.19m12769"},{"key":"S1092852920001376_r11","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2008.11.007"},{"key":"S1092852920001376_r42","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-9-88"},{"key":"S1092852920001376_r41","first-page":"5","article-title":"Physical and psychological consequences of weight gain","volume":"60","author":"Kawachi","year":"1999","journal-title":"J Clin Psychiatry"},{"key":"S1092852920001376_r17","doi-asserted-by":"publisher","DOI":"10.1185\/030079906X148616"},{"key":"S1092852920001376_r20","first-page":"534","volume-title":"ECDEU Assessment Manual for Psychopharmacology","author":"Guy","year":"1976"},{"key":"S1092852920001376_r29","unstructured":"29. US Food and Drug Administration. Guidance document. drug-induced liver injury: premarketing clinical evaluation. 2009. https:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/UCM174090.pdf. Accessed June 4, 2019."},{"key":"S1092852920001376_r31","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852915000917"},{"key":"S1092852920001376_r1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01121-6"},{"key":"S1092852920001376_r32","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyy002"},{"key":"S1092852920001376_r7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60486-9"},{"key":"S1092852920001376_r25","first-page":"217","volume-title":"ECDEU Assessment Manual for Psychopharmacology","author":"Guy","year":"1976"},{"key":"S1092852920001376_r19","unstructured":"19. Correll, CU , Kahn, R , Silverman, B , et al. A combination of olanzapine and samidorphan mitigates the weight gain observed with olanzapine alone: results from the phase 3 ENLIGHTEN-2 schizophrenia study [poster]. Presented at: Annual Congress of the Schizophrenia International Research Society; April 10-14, 2019; Orlando, FL."},{"key":"S1092852920001376_r45","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.59.11.1021"},{"key":"S1092852920001376_r44","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/hup.1225","article-title":"Comparison of metabolic changes in patients with schizophrenia during randomized treatment with intramuscular olanzapine long-acting injection versus oral olanzapine","volume":"26","author":"McDonnell","year":"2011","journal-title":"Hum Psychopharmacol"},{"key":"S1092852920001376_r34","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-017-1459-z"},{"key":"S1092852920001376_r10","doi-asserted-by":"publisher","DOI":"10.2147\/POR.S64973"},{"key":"S1092852920001376_r24","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/13.2.261"},{"key":"S1092852920001376_r14","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1176\/ajp.156.11.1686","article-title":"Antipsychotic-induced weight gain: a comprehensive research synthesis","volume":"156","author":"Allison","year":"1999","journal-title":"Am J Psychiatry"},{"key":"S1092852920001376_r22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1970.tb02066.x"},{"key":"S1092852920001376_r30","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2016.04.013"},{"key":"S1092852920001376_r28","doi-asserted-by":"crossref","first-page":"274","DOI":"10.4103\/0974-7788.76794","article-title":"Understanding survival analysis: Kaplan-Meier estimate","volume":"1","author":"Goel","year":"2010","journal-title":"Int J Ayurveda Res"},{"key":"S1092852920001376_r33","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852917000220"},{"key":"S1092852920001376_r15","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60733-3"},{"key":"S1092852920001376_r38","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1248313"},{"key":"S1092852920001376_r13","doi-asserted-by":"publisher","DOI":"10.1002\/wps.20632"},{"key":"S1092852920001376_r5","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbp116"},{"key":"S1092852920001376_r40","unstructured":"40. Zyprexa [package insert]. Indianapolis, IN: Eli Lilly and Company; 2018."},{"key":"S1092852920001376_r36","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v60n0602"},{"key":"S1092852920001376_r37","doi-asserted-by":"publisher","DOI":"10.2165\/11589060-000000000-00000"},{"key":"S1092852920001376_r21","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.154.5.672"},{"key":"S1092852920001376_r43","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0564-3"},{"key":"S1092852920001376_r23","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.10111704"},{"key":"S1092852920001376_r26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-11-113"},{"key":"S1092852920001376_r39","doi-asserted-by":"publisher","DOI":"10.1177\/0269881112473789"},{"key":"S1092852920001376_r16","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.10m06497"},{"key":"S1092852920001376_r8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051688"},{"key":"S1092852920001376_r9","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2006.09.005"},{"key":"S1092852920001376_r4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024597"},{"key":"S1092852920001376_r6","doi-asserted-by":"publisher","DOI":"10.3109\/15622975.2012.739708"},{"key":"S1092852920001376_r35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094112"},{"key":"S1092852920001376_r3","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.156"},{"key":"S1092852920001376_r47","unstructured":"47. World Health Organization. Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus: Abbreviated Report of a WHO Consultation. 2011. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK304267\/pdf\/Bookshelf_NBK304267.pdf. Accessed May 25, 2020."},{"key":"S1092852920001376_r46","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.325.7358.243"}],"container-title":["CNS Spectrums"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1092852920001376","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T23:19:52Z","timestamp":1696115992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1092852920001376\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,12]]},"references-count":47,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["S1092852920001376"],"URL":"https:\/\/doi.org\/10.1017\/s1092852920001376","relation":{},"ISSN":["1092-8529","2165-6509"],"issn-type":[{"value":"1092-8529","type":"print"},{"value":"2165-6509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,12]]}}}