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https://www.readbyqxmd.com/read/29759268/prescription-drugs-used-in-insomnia
#1
REVIEW
Sylvie Dujardin, Angelique Pijpers, Dirk Pevernagie
The scope of this article is to review the effects on sleep of prescription drugs that are commonly prescribed for chronic insomnia in adults. The following groups are discussed: benzodiazepines and its receptor agonists, the dual orexin receptor antagonist suvorexant, melatonin and its receptor agonists, sedating antidepressants, and antipsychotics. Together with the neurobiologic and pharmacologic properties of these drugs, clinical effects are described, including subjective and objective effects on sleep duration, continuity, and architecture...
June 2018: Sleep Medicine Clinics
https://www.readbyqxmd.com/read/29739132/assessment-of-switching-to-suvorexant-versus-the-use-of-add-on-suvorexant-in-combination-with-benzodiazepine-receptor-agonists-in-insomnia-patients-a-retrospective-study
#2
Masakazu Hatano, Hiroyuki Kamei, Risa Inagaki, Haruna Matsuzaki, Manako Hanya, Shigeki Yamada, Nakao Iwata
Objective: Suvorexant is a novel hypnotic drug that does not interact with the conventional γ-aminobutyric acid (GABA)-A receptor. We investigated the method by which suvorexant was introduced in insomnia patients who were taking benzodiazepine receptor agonists (BzRA). Methods: This was a retrospective study. We extracted clinical data for patients who were prescribed suvorexant and were already using BzRA. The patients were assigned to two groups, the switching and add-on groups...
May 31, 2018: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29705869/safety-tolerability-and-pharmacokinetics-of-suvorexant-a-randomized-rising-dose-trial-in-healthy-men
#3
Ka Lai Yee, Jacqueline McCrea, Deborah Panebianco, Wen Liu, Nicole Lewis, Tamara Cabalu, Steven Ramael, Rebecca E Wrishko
BACKGROUND AND OBJECTIVES: Suvorexant (MK-4305) is an orexin receptor antagonist approved for the treatment of insomnia in the USA and other regions. This randomized, double-blind, placebo-controlled, sequential-panel, Phase 1 trial assessed the safety, tolerability, and pharmacokinetic data following single and multiple dosing of suvorexant in healthy men (aged 18-45 years). METHODS: Within allocated panels, subjects (n = 8) were randomized to receive nightly doses of suvorexant (10, 20, 40, 80, and 100 mg) administered orally for 14 days, or placebo...
April 28, 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29667471/cost-effectiveness-analysis-of-suvorexant-for-the-treatment-of-japanese-elderly-patients-with-chronic-insnomnia-in-a-virtual-cohort
#4
Shinichi Nishimura, Mutsuhiro Nakao
AIMS: We assessed the cost effectiveness of the orexin receptor antagonist suvorexant against zolpidem, the most widely used hypnotic benzodiazepine receptor agonist in Japan. To this end, a model was used that factored in insomnia and the risk for hip fractures, which have devastating effects on the elderly. METHODS: Data were derived from published papers. The target population was a virtual cohort of elderly patients (≥65 years) with insomnia residing in Japan...
April 18, 2018: Journal of Medical Economics
https://www.readbyqxmd.com/read/29650886/-usefulness-of-suvorexant-for-complicated-delirium-in-cancer-patients-who-experience-sleep-disturbance-during-hospitalization
#5
Takaomi Kessoku, Akihiko Kusakabe, Tetsuya Matsuura, Yasushi Honda, Asuka Yoshimi, Ayumu Goto, Haruhisa Yoshida, Akiko Sukegawa, Chiaki Hata, Yukie Saito, Yoko Miyashita, Ryoko Yashiro, Tomoya Komori, Sachiko Arai, Atsushi Nakajima, Yasushi Ichikawa
We investigated the usefulness of suvorexant for complicated delirium in patients with cancer who experience sleep disturbance during hospitalization. Nine patients with malignant tumors complicated with symptoms of delirium and insomnia were included in this study; their palliative care was managed by the palliative care team of our hospital for a period of one year from April 2016 to March 2017. A retrospective follow-up study was then conducted. The Japanese version of DRS-R98 was used to evaluate the severity of the patient's delirium...
March 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29509180/cns-drug-development-lessons-learned-part-5-how-preclinical-and-human-safety-studies-inform-the-approval-and-subsequent-use-of-a-new-drug-suvorexant-as-an-example
#6
Sheldon H Preskorn
This column is the fifth in a series examining the advances being made in central nervous system drug development because of advances in molecular pharmacology and an improved understanding of the neurobiology underlying disturbances in brain function including psychiatric illnesses. This column covers the special animal and human studies conducted as part of the development of suvorexant, which is the first in the class of dual orexin 1 and 2 receptor antagonists to be approved; it has an indication for the treatment of disturbances in sleep onset and maintenance...
March 2018: Journal of Psychiatric Practice
https://www.readbyqxmd.com/read/29488104/identification-of-ortho-substituted-benzoic-acid-ester-derivatives-via-the-gas-phase-neighboring-group-participation-effect-in-esi-high-resolution-mass-spectrometry
#7
William D Blincoe, Agustina Rodriguez-Granillo, Josep Saurí, Nicholas A Pierson, Leo A Joyce, Ian Mangion, Huaming Sheng
Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighboring group participation (NGP) effect to differentiate ortho-substituted benzoic acid/ester derivatives with high resolution mass spectrometry (HRMS1 ). Significant water/alcohol loss (>30% abundance in MS1 spectra) was observed for ortho-substituted nucleophilic groups; these fragment peaks are not observable for the corresponding para and meta-substituted analogs...
April 2018: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/29487083/drugs-for-insomnia-beyond-benzodiazepines-pharmacology-clinical-applications-and-discovery
#8
REVIEW
Tobias Atkin, Stefano Comai, Gabriella Gobbi
Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon discontinuation, car accidents/falls, abuse, and dependence liability. Consequently, the clinical use of off-label drugs and novel drugs that do not target the GABAergic system is increasing. The purpose of this review is to analyze the neurobiological and clinical evidence of pharmacological treatments of insomnia, excluding the BZDs and Z-drugs...
April 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29450984/computational-studies-on-horseshoe-shape-pocket-of-human-orexin-receptor-type-2-and-boat-conformation-of-suvorexant-by-molecular-dynamics-simulations
#9
Qifeng Bai, Horacio Pérez-Sánchez, Zhuoyu Shi, Lanlan Li, Danfeng Shi, Huanxiang Liu, Xiaojun Yao
The FDA approved drug suvorexant binds to the horseshoe shape pocket of OX2 R with the boat conformation. The horseshoe shape pocket plays an important role on the biological activity of OX2 R in the cell membrane. To study the binding mechanism between the horseshoe shape pocket of OX2 R and boat conformation of suvorexant, the crystal structures of wild type and N324A mutant of OX2 R in complex with antagonist suvorexant are chosen to perform molecular dynamics (MD) simulations, QM/MM and MMGBSA calculations...
February 16, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29445409/suvorexant-for-insomnia-in-older-adults-a-perspective-review
#10
REVIEW
Rajesh R Tampi, Geetha Manikkara, Silpa Balachandran, Piyush Taparia, Stephanie Hrisko, Shilpa Srinivasan, Deena J Tampi
The aim of this review was to identify published randomized control trials (RCTs) that evaluated the efficacy and tolerability of suvorexant for the treatment of insomnia among older adults (≥65 years). A literature search was conducted of PubMed, MEDLINE, EMBASE, PsycINFO and Cochrane collaboration databases for RCTs in any language evaluating suvorexant for the treatment of insomnia in older adults. Additionally, references of full-text articles that were included in this review were searched for further studies...
2018: Drugs in Context
https://www.readbyqxmd.com/read/29423967/suvorexant-is-associated-with-a-low-incidence-of-delirium-in-critically-ill-patients-a-retrospective-cohort-study
#11
Tomoyuki Masuyama, Masamitsu Sanui, Naoto Yoshida, Yusuke Iizuka, Kunio Ogi, Satoko Yagihashi, Kanae Nagatomo, Yusuke Sasabuchi, Alan K Lefor
BACKGROUND: Benzodiazepine use is a risk factor for the development of delirium in adult intensive care unit (ICU) patients. Suvorexant is an alternative to benzodiazepines to induce sleep, but the incidence of delirium in critically ill patients is unknown. We undertook this retrospective study to investigate the incidence of delirium in patients who receive suvorexant in the ICU. METHODS: This retrospective cohort study was conducted in a closed 12-bed ICU at a tertiary teaching hospital...
February 8, 2018: Psychogeriatrics: the Official Journal of the Japanese Psychogeriatric Society
https://www.readbyqxmd.com/read/29303950/cns-drug-development-lessons-learned-part-4-the-role-of-brain-circuitry-and-genes-tasimelteon-as-an-example
#12
Sheldon H Preskorn
This is the fourth in a series of columns discussing the rational and targeted development of drugs to affect specific central nervous system (CNS) circuits in specific ways based on knowledge gained by molecular biology and the human genome project. The first column in this series described 6 CNS drugs with novel mechanisms of action developed over the last 25 years. The second column discussed differences between syndromic diagnoses as exemplified by the third through the fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM III through DSM-5) and the new approach to psychiatric diagnoses championed by the National Institute of Mental Health in their Research Domain Criteria Initiative...
November 2017: Journal of Psychiatric Practice
https://www.readbyqxmd.com/read/29300899/tissue-distribution-of-suvorexant-in-three-forensic-autopsy-cases
#13
Brian Waters, Kenji Hara, Natsuki Ikematsu, Mio Takayama, Aya Matsusue, Masayuki Kashiwagi, Shin-Ichi Kubo
Suvorexant (Belsomra®) is a relatively new insomnia medication that has been available in USA and Japan since 2014. It is a dual orexin receptor antagonist that promotes sleep by inhibiting the binding of orexin neurons to the OX1R and OX2R receptors. In this report, we describe the detection and quantitation of suvorexant from the postmortem specimens of three separate autopsy cases handled by our department. Suvorexant was identified by fast gas chromatography/mass spectrometry during routine screening, and quantitated by a fully validated liquid chromatography-tandem mass spectroscopy method...
December 28, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/29289556/chronopathophysiological-implications-of-orexin-in-sleep-disturbances-and-lifestyle-related-disorders
#14
REVIEW
Hiroshi Tsuneki, Tsutomu Wada, Toshiyasu Sasaoka
Sleep, a mysterious behavior, has recently been recognized as a crucial factor for health and longevity. The daily sleep/wake cycle provides the basis of biorhythms controlling whole-body homeostasis and homeodynamics; therefore, disruption of sleep causes several physical and psychological disorders, including cardiovascular disease, obesity, diabetes, cancer, anxiety, depression, and cognitive dysfunction. However, the mechanism linking sleep disturbances and sleep-related disorders remains unknown. Orexin (also known as hypocretin) is a neuropeptide produced in the hypothalamus...
December 29, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29237271/suvorexant-for-the-treatment-of-insomnia-in-patients-with-alzheimer-s-disease
#15
Atsushi Hamuro, Minoru Honda, Yuya Wakaura
No abstract text is available yet for this article.
February 2018: Australian and New Zealand Journal of Psychiatry
https://www.readbyqxmd.com/read/29225076/crystal-structures-of-human-orexin-2-receptor-bound-to-the-subtype-selective-antagonist-empa
#16
Ryoji Suno, Kanako Terakado Kimura, Takanori Nakane, Keitaro Yamashita, Junmei Wang, Takaaki Fujiwara, Yasuaki Yamanaka, Dohyun Im, Shoichiro Horita, Hirokazu Tsujimoto, Maki S Tawaramoto, Takatsugu Hirokawa, Eriko Nango, Kensuke Tono, Takashi Kameshima, Takaki Hatsui, Yasumasa Joti, Makina Yabashi, Keiko Shimamoto, Masaki Yamamoto, Daniel M Rosenbaum, So Iwata, Tatsuro Shimamura, Takuya Kobayashi
Orexin peptides in the brain regulate physiological functions such as the sleep-wake cycle, and are thus drug targets for the treatment of insomnia. Using serial femtosecond crystallography and multi-crystal data collection with a synchrotron light source, we determined structures of human orexin 2 receptor in complex with the subtype-selective antagonist EMPA (N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl-acetamide) at 2.30-Å and 1.96-Å resolution. In comparison with the non-subtype-selective antagonist suvorexant, EMPA contacted fewer residues through hydrogen bonds at the orthosteric site, explaining the faster dissociation rate...
January 2, 2018: Structure
https://www.readbyqxmd.com/read/29112763/insight-into-reduction-of-wakefulness-by-suvorexant-in-patients-with-insomnia-analysis-of-wake-bouts
#17
Vladimir Svetnik, Ellen S Snyder, Peining Tao, Thomas E Scammell, Thomas Roth, Christopher Lines, W Joseph Herring
Study Objectives: To examine the duration and frequency of wake bouts underlying the wakefulness-after-sleep-onset (WASO) reduction with suvorexant. Methods: We analyzed polysomnogram recordings from clinical trials involving 1518 insomnia patients receiving suvorexant (40/30, 20/15 mg) or placebo to determine the following: (1) the number of, and time spent in, long or short wake bouts and (2) the association between sleep quality and bout characteristics. We also compared wake and sleep bout characteristics of suvorexant in insomnia patients versus zolpidem in healthy subjects undergoing experimentally induced transient insomnia...
January 1, 2018: Sleep
https://www.readbyqxmd.com/read/29066641/adverse-reaction-with-suvorexant-for-insomnia-acute-worsening-of-depression-with-emergence-of-suicidal-thoughts
#18
Jeremy Petrous, Kevin Furmaga
A 59-year-old woman on daily peritoneal dialysis for end-stage renal failure received care at an outpatient psychiatric clinic for her diagnoses that include major depressive disorder, generalised anxiety disorder and insomnia disorder. Although there was partial improvement in the patient's mood and anxiety symptoms with antidepressant treatment, insomnia remained a persistent complaint despite adequate trials of different sleep medications. The novel hypnotic, suvorexant (Belsomra, Merck & Co.) was then initiated at the recommended bedtime dose of 10 mg and was followed by a 15 mg dose the following night...
October 23, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28994603/suvorexant-scientifically-interesting-utility-uncertain
#19
Nicholas A Keks, Judy Hope, Simone Keogh
OBJECTIVE: Suvorexant, a new hypnotic, is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance, and is used long-term. This paper will briefly review suvorexant. RESULTS: Orexin is a hypothalamic peptide which promotes wakefulness. By blocking orexin receptors, suvorexant induces sleep. Peaking 2 h after ingestion, it has a half-life of 12 h and is hepatically metabolized mainly by CYP3A. Kinetics are not affected by age but concentrations are higher in females and obese patients...
December 2017: Australasian Psychiatry: Bulletin of Royal Australian and New Zealand College of Psychiatrists
https://www.readbyqxmd.com/read/28992822/therapy-update-for-insomnia-in-the-elderly
#20
REVIEW
Sum Lam, Lucy O Macina
OBJECTIVE: To offer an update on insomnia in older adults and treatment options. DATA SOURCES: A search of PubMed using the terms "insomnia" and "older adults" was performed. Current guidelines, review articles, and drug database and manufacturer package inserts were utilized to provide relevant information. STUDY SELECTION: All English-language articles from 2012 to February 2017 and their bibliographies were reviewed for relevance...
October 1, 2017: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
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