Is suvorexant a better choice than alternative hypnotics? [version 1; referees: 2 approved]

Suvorexant is a novel dual orexin receptor antagonist (DORA) newly introduced in the U.S. as a hypnotic, but no claim of superiority over other hypnotics has been offered. The manufacturer argued that the 5 and 10 mg starting doses recommended by the FDA might be ineffective. The manufacturer's main Phase III trials had not even included the 10 mg dosage, and the 5 mg dosage had not been tested at all in registered clinical trials at the time of approval. Popular alternative hypnotics may be similarly ineffective, since the FDA has also reduced the recommended doses for zolpidem and eszopiclone. The "not to exceed" suvorexant dosage of 20 mg does slightly increase sleep. Because of slow absorption, suvorexant has little effect on latency to sleep onset but some small effect in suppressing wakening after sleep onset and in improving sleep efficiency. The FDA would not approve the manufacturer's preferred 40 mg suvorexant dosage, because of concern with daytime somnolence, driving impairment, and possible narcolepsy-like symptoms. In its immediate benefits-to-risks ratio, suvorexant is unlikely to prove superior to currently available hypnotics—possibly worse—so there is little reason to prefer over the alternatives this likely more expensive hypnotic less-tested in practice. Associations are being increasingly documented relating hypnotic usage with incident cancer, with dementia risks, and with premature death. There is some basis to speculate that suvorexant might be safer than alternative hypnotics in terms of cancer, dementia, infections, and mortality. These safety considerations will remain unproven speculations unless adequate long-term trials can be done that demonstrate suvorexant advantages. Daniel F. Kripke ( ) Corresponding author: [email protected] Kripke DF. How to cite this article: Is suvorexant a better choice than alternative hypnotics? [version 1; referees: 2 approved] 2015, :456 (doi: ) F1000Research 4 10.12688/f1000research.6845.1 © 2015 Kripke DF. This is an open access article distributed under the terms of the , which Copyright: Creative Commons Attribution Licence permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The author(s) declared that no grants were involved in supporting this work. Grant information: Competing interests: Since 1979 publication of hypnotics epidemiology from the American Cancer Society CPSI study, the author has been a frequent critic of hypnotics risks and benefits, especially through his non-profit internet web site, , that provides www.DarkSideOfSleepingPills.com readers with more extensive information and references about risks of hypnotics. Dr. Kripke's family owns stock and options in a large conglomerate that in turn invested a tiny percentage of its capital in Sanofi-Aventis stock. The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, other stock ownership or options, expert testimony, grants or patents received or pending or royalties. No writing assistance was utilized in the production of this manuscript. 03 Aug 2015, :456 (doi: ) First published: 4 10.12688/f1000research.6845.1 Referee Status: