Review
Biochemistry & Molecular Biology
Wojciech Ziemichod, Karolina Grabowska, Antonina Kurowska, Grazyna Biala
Summary: This article provides a comprehensive review of daridorexant, including its pharmacodynamics, animal and human research, pharmacokinetics, and safety. Daridorexant is considered a safe hypnotic drug with potential therapeutic effects for insomnia.
Review
Clinical Neurology
Maria P. Mogavero, Alessandro Silvani, Giuseppe Lanza, Lourdes M. DelRosso, Luigi Ferini-Strambi, Raffaele Ferri
Summary: After describing orexins and their roles in sleep and medical disorders, the article discusses the clinical evidence on the effects of DORAs and SORAs on insomnia to provide recommendations for further assessment in personalized and precision medicine. Trials with orexin receptor antagonists have shown potential as a valid therapeutic option for insomnia in various medical conditions, but more studies are needed to determine the most suitable options for different patient populations.
NATURE AND SCIENCE OF SLEEP
(2023)
Review
Clinical Neurology
Laura Palagini, Pierre A. Geoffroy, Matteo Balestrieri, Mario Miniati, Giovanni Biggio, Claudio Liguori, Danilo Menicucci, Luigi Ferini-Strambi, Lino Nobili, Dieter Riemann, Angelo Gemignani
Summary: Insomnia disorder is associated with hyperarousal, stress, and emotion dysregulation. The orexinergic system plays a key role in sleep, arousal, and stress modulation, making it of interest for insomnia treatment. Research suggests that overactivation of the orexinergic system may contribute to disrupted sleep and insomnia in response to stress. Dual orexin receptor antagonists (DORAs) may rebalance orexins and regulate sleep and stress-related systems, potentially reducing hyperarousal in insomnia. However, further research is needed to fully understand the role of the orexin system in insomnia and assess the effects of DORAs on sleep and stress regulation.
JOURNAL OF SLEEP RESEARCH
(2023)
Article
Psychology, Developmental
Aaron D. Besterman, Shafali S. Jeste
Summary: Insomnia is a common and difficult-to-treat comorbidity in children with neurodevelopmental disorders. The use of dual orexin receptor antagonists (DORAs) as a treatment option for insomnia in these children has little safety or efficacy data. Research shows diverse responses to DORA suvorexant, with some patients experiencing significant improvement in sleep while others had mild or no benefit.
EUROPEAN CHILD & ADOLESCENT PSYCHIATRY
(2023)
Article
Medicine, General & Internal
Craig Chepke, Rakesh Jain, Russell Rosenberg, Margaret Moline, Jane Yardley, Kate Pinner, Dinesh Kumar, Carlos Perdomo, Gleb Filippov, Norman Atkins, Manoj Malhotra
Summary: This analysis evaluated the effects of lemborexant, a dual orexin receptor antagonist, on reducing fatigue in patients with insomnia. The results showed that lemborexant significantly reduced subject-reported fatigue over a 6-month treatment period, and this reduction was sustained over 12 months. Improvements in fatigue were positively correlated with improvements in sleep onset and maintenance parameters.
POSTGRADUATE MEDICINE
(2022)
Review
Clinical Neurology
Tao Xue, Xin Wu, Shujun Chen, Yanbo Yang, Zeya Yan, Zhaoming Song, Wei Zhang, Jianguo Zhang, Zhouqing Chen, Zhong Wang
Summary: Multiple large randomized controlled trials have confirmed the efficacy and safety of dual orexin receptor antagonists (DORAs) for primary insomnia. Although there have been few systematic comparisons of different DORAs, it is generally believed that DORAs are superior to placebos in terms of efficacy and safety.
SLEEP MEDICINE REVIEWS
(2022)
Review
Pharmacology & Pharmacy
Jessica Barreto Ribeiro dos Santos, Michael Ruberson Ribeiro da Silva
Summary: Daridorexant is an effective and safe medication for the treatment of insomnia disorder. Further studies are needed to evaluate its long-term safety and compare it with other medications.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Review
Neurosciences
Catherine Roch, Giorgio Bergamini, Michel A. Steiner, Martine Clozel
Summary: Dual orexin receptor antagonists (DORAs), such as daridorexant, offer a novel type of sleep medication with benefits in insomnia treatment and improvement in daytime functioning, without the risk of tolerance or physical dependence. This new DORA inhibits the wake-promoting orexin neuropeptides specifically, avoiding widespread inhibition of neuronal pathways and associated side effects typical of positive allosteric GABA-A receptor modulators.
PSYCHOPHARMACOLOGY
(2021)
Review
Clinical Neurology
Russell Rosenberg, Leslie Citrome, Christopher L. Drake
Summary: Chronic insomnia affects 6-10% of the population and is characterized by difficulties with sleep initiation or maintenance at least three times per week for at least 3 months, along with daytime impairment. Despite misconceptions about treatment options, this complex disorder may not be remedied simply by getting more sleep, necessitating consideration of nonpharmacologic and pharmacologic treatments for efficacious outcomes. Recent advancements in treatment, including cognitive behavioral therapy (CBT-I) and dual orexin receptor antagonist (DORA) pharmacologics, offer promising new approaches for improving outcomes in patients with chronic insomnia.
NEUROPSYCHIATRIC DISEASE AND TREATMENT
(2021)
Article
Psychiatry
Yoshikazu Takaesu, Hitoshi Sakurai, Yumi Aoki, Masahiro Takeshima, Kenya Ie, Kentaro Matsui, Tomohiro Utsumi, Akiyoshi Shimura, Isa Okajima, Nozomu Kotorii, Hidehisa Yamashita, Masahiro Suzuki, Kenichi Kuriyama, Eiji Shimizu, Kazuo Mishima, Koichiro Watanabe, Ken Inada
Summary: This study investigated the answers to clinical questions about treating insomnia disorder, finding that the use of hypnotic and non-pharmacological treatments varies depending on clinical situations, and alternative treatments can help reduce or stop benzodiazepine hypnotics. Expert consensus suggests that orexin receptor antagonists and sleep hygiene education are recommended as first-line treatments in most clinical situations.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Behavioral Sciences
Lu Wang, Yundan Pan, Chunyan Ye, Lizhe Guo, Sumei Luo, Sisi Dai, Na Chen, E. Wang
Summary: Orexin receptor antagonists can be widely used in adults and the elderly, with both short-term and long-term use being effective for primary insomnia. H1 antagonists are more effective in adults than in the elderly. Although benzodiazepines have a more obvious effect on sleep maintenance, it is best to reduce their use due to their side effects, especially for the elderly. As a food supplement, melatonin has little effect on adults, but it still has a certain effect on the elderly.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Neurosciences
Jessica M. Illenberger, Francisco J. Flores-Ramirez, Glenn Pascasio, Alessandra Matzeu, Remi Martin-Fardon
Summary: Chronic opioid use disrupts circadian rhythm and sleep, which can lead to increased opioid use and relapse. Dual orexin receptor antagonists (DORAs), developed for insomnia treatment, are found to alleviate withdrawal-associated sleep disturbances. This study aimed to investigate the effect of DORA-12, a newly developed DORA, on physiological activity disturbances during oxycodone abstinence and its potential role in preventing oxycodone-seeking behavior.
Article
Clinical Neurology
Ajna Hamidovic
Summary: Smoking is a major cause of chronic diseases, but quitting smoking is difficult due to limited effectiveness of current medications. Sleep problems worsen during smoking abstinence and are associated with poor cessation outcomes. Dual orexin receptor antagonists (DORAs) that target the sleep-wake cycle show promise in addressing these sleep problems and improving smoking cessation rates.
Review
Psychiatry
Habibolah Khazaie, Masoud Sadeghi, Sepideh Khazaie, Max Hirshkowitz, Amir Sharafkhaneh
Summary: The study conducted a systematic review and meta-analysis on the treatment of insomnia with suvorexant and lemborexant, showing that both drugs are effective and safe for patients with insomnia.
FRONTIERS IN PSYCHIATRY
(2022)
Review
Psychiatry
Xin Wu, Tao Xue, Zhouqing Chen, Zhong Wang, Gang Chen
Summary: This review examines the use of orexin receptor antagonists (ORAs) in treating insomnia. Recent research focuses on comorbid insomnia with suvorexant, while lemborexant and daridorexant are still being studied for primary insomnia. Almorexant is mainly used in animal studies due to safety concerns. There is limited research on the sleep-promoting effects of filorexant. Seltorexant, a selective ORA, has not reached phase 3 yet. High-quality clinical trials are needed to compare authorized ORAs, investigate non-approved ORAs, and explore the pathophysiology of the orexin signaling system in insomnia.
CURRENT PSYCHIATRY REPORTS
(2022)