Updates in Insomnia: New Developments for an Often-Forgotten Symptom

{"title":"Updates in Insomnia: New Developments for an Often-Forgotten Symptom","authors":"Tyler Luonuansuu MD,&nbsp;Claudia Chou MD,&nbsp;Leslie Siegel PharmD,&nbsp;Erin Taylor LICSW MSW","doi":"10.1016/j.jpainsymman.2025.02.042","DOIUrl":null,"url":null,"abstract":"<div><h3>Outcomes</h3><div>1. Participants will be able to describe the neurotransmitter-based mechanisms governing consciousness and sleep and recognize how they can be applied to rationally treat common scenarios in palliative care.</div><div>2. Participants will be able to describe recent developments in the treatment of insomnia such as ongoing use of orexin antagonists to reduce incidence of delirium, mechanisms and effects of medical marijuana and psychedelics on sleep, and efficacy of virtual cognitive behavioral therapy for insomnia.</div></div><div><h3>Key Message</h3><div>Insomnia is a highly prevalent yet often forgotten symptom in palliative care. Due to limited understanding of the mechanistic basis of the symptom, effective treatments were often limited to medication classes with high adverse effect burden (ex. benzodiazepines). This is rapidly changing with new medication classes such as DORAs and cannabinoids and a new, organized approach to treatment is needed.</div></div><div><h3>Abstract</h3><div>Insomnia is a highly prevalent symptom in the palliative care population, with an estimated median prevalence of 49.5% (1). Etiology is often polyfactorial with physical disease, medication adverse effects, psychological and social factors all playing a role. Historic treatment of insomnia utilized agents such as melatonin agonists, benzodiazepines, non-benzodiazepine GABA receptor modulators, histamine receptor antagonists, and antipsychotics. These carry risk of adverse effects, limited efficacy, and in some situations, both. These obstacles can contribute to a sense of therapeutic nihilism for both patient and provider. While, at first, this may seem like an almost impossibly complex symptom with limited treatment options, research has progressed in recent years, from longstanding knowledge of sleep cycles (N1-REM sleep) to a relatively complete understanding of the mechanisms behind consciousness and sleep regulation at the level of cerebral structures and neurotransmitters (2). This has paved the way for discussions of a mechanistic approach to treating insomnia rationally by neurotransmitter target. This has led to significant milestones in the treatment of insomnia such as the development of dual orexin antagonists (DORAs) and increasing understanding of the hypnotic effects of complementary treatments such as cannabinoids and serotonergic psychedelics (3-4). DORAs have been found to prolong REM sleep by blunting the effects of the excitatory neuropeptide orexin (5). Significant research shows that DORAs may be the first hypnotics which reduce incident delirium which could represent a major milestone in palliative care treatment of insomnia (6). Further, the nonpharmacologic treatment of insomnia has been undergoing significant changes through the increasing uptake and validation of cognitive behavioral therapy for insomnia (CBT-I) delivered electronically which could significantly democratize access to CBT-I for medically underserved populations (7). Using an interdisciplinary approach, with a physician, pharmacist and palliative social worker, this presentation will summarize and present these developments and applications for current practice.</div></div><div><h3>References</h3><div>1. Nzwalo I, Aboim MA, Joaquim N, Marreiros A, Nzwalo H. Systematic Review of the Prevalence, Predictors, and Treatment of Insomnia in Palliative Care. American Journal of Hospice and Palliative Medicine. 2020;37(11):957-969. 2. Porkka-Heiskanen, T., Zitting, K.-.-M. and Wigren, H.-.-K. (2013), Sleep, its regulation and possible mechanisms of sleep disturbances. Acta Physiol, 208: 311-328.  3. Allen, N., Jeremiah, A., Murphy, R. et al. LSD increases sleep duration the night after microdosing. Transl Psychiatry 14, 191 (2024). 4. Kolla BP, Hayes L, Cox C, Eatwell L, Deyo-Svendsen M, Mansukhani MP. The Effects of Cannabinoids on Sleep. J Prim Care Community Health. 2022 Jan-Dec;13:21501319221081277. 5. Mengzhen Zhou, Rujia Liu, Zhengqi Xie,The effects of different dosages of dual orexin receptor antagonists and zolpidem on sleep and cognitive function: A meta-analysis and systematic review, Sleep Epidemiology, Volume 3, 2023. 6. Tian Y, Qin Z, Han Y. Suvorexant with or without ramelteon to prevent delirium: a systematic review and meta-analysis. Psychogeriatrics. 2022 Mar;22(2):259-268. doi: 10.1111/psyg.12792. Epub 2021 Dec 8. 7. Erten Uyumaz B, Feijs L, Hu J. A Review of Digital Cognitive Behavioral Therapy for Insomnia (CBT-I Apps): Are They Designed for Engagement? Int J Environ Res Public Health. 2021 Mar 12;18(6):2929.</div></div>","PeriodicalId":16634,"journal":{"name":"Journal of pain and symptom management","volume":"69 5","pages":"Pages e433-e434"},"PeriodicalIF":3.2000,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pain and symptom management","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0885392425001022","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}