Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery

Pharmacological Reviews
Tobias AtkinGabriella Gobbi

Abstract

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. We analyzed the melatonergic agonist drugs, agomelatine, prolonged-release melatonin, ramelteon, and tasimelteon; the dual orexin receptor antagonist suvorexant; the modulators of the α2δ subunit of voltage-sensitive calcium channels, gabapentin and pregabalin; the H1 antagonist, low-dose doxepin; and the histamine and serotonin receptor antagonists, amitriptyline, mirtazapine, trazodone, olanzapine, and quetiapine. The pharmacology and mechanism of action of these treatments and the evidence-base for the use of these drugs in clinical practice is outlined along with novel pipelines. There is evidence to recommend suvorexant and low...Continue Reading

References

Oct 15, 1979·European Journal of Pharmacology·J FiggeE Richelson
Aug 1, 1992·Pharmacology & Toxicology·O G Nilsen, O Dale
Oct 1, 1991·Biological Psychiatry·J MendlewiczV de Maertelaer
Mar 1, 1986·Pharmacology, Biochemistry, and Behavior·J P Mäkelä, I T Hilakivi
Jan 1, 1988·Psychopharmacology·J MouretM Renardet
Aug 1, 1994·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Z LelkesG Benedek
Mar 1, 1995·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·A FoyJ Halliday
Mar 1, 1994·Neuropharmacology·A L SharpleyP J Cowen
Jul 1, 1994·The American Journal of Psychiatry·A A NierenbergM Rosenthal
Jan 1, 1994·Fundamental & Clinical Pharmacology·E SchlickerM Göthert
Apr 1, 1994·Brain Research. Molecular Brain Research·M PompeianoG Mengod
Apr 1, 1994·Journal of Clinical Psychopharmacology·L A CunninghamE Hearst
Apr 1, 1993·Pharmacology & Toxicology·O G NilsenB Husebø
Feb 1, 1996·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·F P BymasterD T Wong
Jul 2, 1997·JAMA : the Journal of the American Medical Association·B HemmelgarnG Pinard
Feb 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·L de LeceaJ G Sutcliffe
Jan 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·R L Jakab, P S Goldman-Rakic
Apr 16, 1998·European Journal of Pharmacology·M TatsumiE Richelson
Jun 13, 1998·Acta Psychiatrica Scandinavica·M Srisurapanont, N Jarusuraisin
Oct 10, 1998·Psychiatry and Clinical Neurosciences·H YamaderaS Endo
May 13, 1999·Cellular and Molecular Neurobiology·M V Rudorfer, W Z Potter
Jul 8, 1999·Biological Psychiatry·R J Salin-PascualM R Laurrabaquio
Aug 26, 1999·Neuropharmacology·N M Barnes, T Sharp
Sep 15, 1999·Proceedings of the National Academy of Sciences of the United States of America·J J HaganN Upton
Nov 26, 1999·European Psychiatry : the Journal of the Association of European Psychiatrists·P M Haffmans, M S Vos
Mar 30, 2000·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·L Camera PierrottiV A de Souza
Aug 21, 2001·Clinical Pharmacokinetics·C L DeVane, C B Nemeroff
Oct 19, 2001·CNS Drug Reviews·S A Anttila, E V Leinonen
Nov 24, 2001·Trends in Neurosciences·C B SaperT E Scammell

❮ Previous
Next ❯

Citations

Dec 27, 2018·Journal of Pineal Research·Gabriella Gobbi, Stefano Comai
Mar 6, 2019·European Journal of Clinical Pharmacology·Raquel MerinoRosa Terré
Feb 23, 2019·Expert Opinion on Pharmacotherapy·Morohunfolu Akinnusi, Ali A El Solh
Jun 18, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Monika HaackJanet Mullington
Jun 20, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Barbara E Jones
Oct 28, 2019·Biomolecules & Therapeutics·Tae-Ho KimYi-Sook Jung
Jan 31, 2020·Clinical Journal of Sport Medicine : Official Journal of the Canadian Academy of Sport Medicine·Cindy J ChangAndrew T Wolanin
Feb 8, 2020·Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine·Yash D ShahSanjeev V Kothare
Sep 20, 2020·Journal of Autism and Developmental Disorders·Bárbara Virginia Vitti-RuelaMonica Levy Andersen
Mar 17, 2020·Child and Adolescent Psychiatry and Mental Health·Addo BoafoRébecca Robillard
Jul 21, 2020·Neural Plasticity·Kunkun WangShan Sun
Sep 29, 2018·Substance Abuse : Research and Treatment·Alyssa M PeckhamJordan R Covvey
Jan 24, 2020·Frontiers in Aging Neuroscience·Miren EttchetoAntonio Camins
Aug 2, 2020·Pain and Therapy·Heath McAnallyAlan D Kaye
Mar 19, 2019·Frontiers in Endocrinology·Gabriella Gobbi, Stefano Comai
Jul 19, 2019·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·E Z YakupovD V Artemieva
Jul 19, 2019·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·A Yu Melnikov
Dec 21, 2018·Frontiers in Endocrinology·Kari A MäkeläKarl-Heinz Herzig
Feb 14, 2020·Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer·Deborah P SaundersUNKNOWN Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (
Oct 23, 2019·Expert Opinion on Pharmacotherapy·Oliviero BruniRaffaele Ferri
Jul 17, 2019·Bioorganic & Medicinal Chemistry Letters·Younggi Choi, Brian K Raymer
Mar 13, 2021·Translational Research : the Journal of Laboratory and Clinical Medicine·Mark K GreenwaldTimothy A Roehrs
Jul 12, 2020·Current Opinion in Psychology·Irene BraithwaiteGiles Newton-Howes

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