{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:43:06Z","timestamp":1787013786192,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007605","name":"Aarhus Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007605","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010078","name":"Region Midtjylland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010078","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Psychiatr Scand"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A wide range of drugs is used to alleviate insomnia symptoms in individuals with severe mental illness (SMI), including licensed drugs and sedating drugs prescribed off\u2010label. Yet, no review has gathered the evidence on illness\u2010specific or transdiagnostic outcomes of pharmacological interventions for insomnia. We aimed to perform a systematic review and meta\u2010analysis of randomised controlled trials (RCTs) studying the efficacy and acceptability of pharmacological interventions for insomnia among individuals with SMI, defined as schizophrenia, bipolar disorder (BD) or major depressive disorder (MDD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched for RCTs of pharmacological interventions for insomnia that used either placebo or another medication as inactive control or active comparator. Two independent reviewers performed the literature screening, data extraction and risk of bias assessment (RoB2). We performed random effects meta\u2010analyses on the co\u2010primary outcomes total sleep time (TST), sleep quality and acceptability (all\u2010cause discontinuation) and the secondary outcomes safety and tolerability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The search identified 3331 hits, of which 25 RCTs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092476 individuals) were included, with 18 RCTs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092199) in MDD, 4 RCTs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009162) in BD and 3 RCTs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009115) in schizophrenia. Of 25 RCTs, 22 had a high risk of bias. The most frequently studied drugs were agomelatine (RCTs\u2009=\u20093,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009686), eszopiclone (RCTs\u2009=\u20093,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009599) and zolpidem (RCTs\u2009=\u20093,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009601). Compared to placebo, pharmacological interventions for insomnia were associated with improved sleep quality by a small effect size (RCTs\u2009=\u20098,\n                      <jats:italic>g<\/jats:italic>\n                      \u2009=\u20090.24, 95% CI\u2009=\u20090.05\u20130.43) and improved TST (RCTs\u2009=\u200910, MD\u2009=\u200930.82\u2009min, 95% CI\u2009=\u200919.13\u201342.50), with similar acceptability (RCTs\u2009=\u200910, RR\u2009=\u20091.06, 95% CI\u2009=\u20090.90\u20131.25).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Despite their frequent use, many licensed and off\u2010label pharmacological interventions for insomnia have never been investigated in patients with SMI. The studies that provided sufficient data for meta\u2010analysis showed better efficacy with similar acceptability compared to placebo, but the generalizability of these results is limited by the high heterogeneity and low quality of the included studies. This underscores the need for high\u2010quality RCTs to provide a better scientific basis for the pharmacological treatment of insomnia in SMI.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      CRD42023413787\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acps.70032","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T05:03:42Z","timestamp":1756875822000},"page":"405-421","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and Acceptability of Licensed and Off\u2010Label Pharmacological Interventions for Insomnia in Patients With Severe Mental Illness: A Systematic Review and Meta\u2010Analysis of Randomised Trials"],"prefix":"10.1111","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9714-0063","authenticated-orcid":false,"given":"Nina Friis Bak","family":"Fuglsang","sequence":"first","affiliation":[{"name":"Psychosis Research Unit, Aarhus University Hospital\u2014Psychiatry  Aarhus Denmark"},{"name":"Department of Clinical Medicine, Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanna Marker","family":"Madsen","sequence":"additional","affiliation":[{"name":"Psychosis Research Unit, Aarhus University Hospital\u2014Psychiatry  Aarhus Denmark"},{"name":"Department of Clinical Medicine, Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren Lundorff","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Psychosis Research Unit, Aarhus University Hospital\u2014Psychiatry  Aarhus Denmark"},{"name":"Department of Clinical Medicine, Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie Eg","family":"Fr\u00f8kj\u00e6r","sequence":"additional","affiliation":[{"name":"Psychosis Research Unit, Aarhus University Hospital\u2014Psychiatry  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Ladegaard","sequence":"additional","affiliation":[{"name":"Department of Affective Disorders, Aarhus University Hospital\u2014Psychiatry  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc Alberg","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Psychosis Research Unit, Aarhus University Hospital\u2014Psychiatry  Aarhus Denmark"},{"name":"Department of Clinical Medicine, Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph U.","family":"Correll","sequence":"additional","affiliation":[{"name":"DZPG, German Center for Mental Health, Partner Site Berlin  Berlin Germany"},{"name":"Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra\/Northwell  Hempstead New York USA"},{"name":"Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research  Manhasset New York USA"},{"name":"Department of Child and Adolescent Psychiatry, Charit\u00e9 Universit\u00e4tsmedizin  Berlin Germany"},{"name":"Department of Psychiatry, Zucker Hillside Hospital, Northwell Health  Glen Oaks New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Otte","sequence":"additional","affiliation":[{"name":"DZPG, German Center for Mental Health, Partner Site Berlin  Berlin Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Department of Psychiatry and Neuroscience  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikkel","family":"H\u00f8jlund","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark  Odense 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