A retrospective clinical practice study comparing the usefulness of dual-orexin receptor antagonists and a melatonin receptor agonist in patients switching from long-term benzodiazepine receptor agonists
Open accessAbstract
Study objectives Although novel hypnotics have recently emerged, there are currently no data comparing the clinical potency of benzodiazepine receptor agonists (BZRAs) and novel hypnotics, or the effectiveness of different methods of switching between them. This study examined how novel hypnotics might help reduce BZRA use in real-world practice.Methods 289 patients with psychiatric disorders who took BZRAs for over 1 year before switching to either of 2 dual-orexin receptor antagonists (DORAs; suvorexant [SUV] or lemborexant [LEM]) or a melatonin receptor agonist (ramelteon [RMT]) were enrolled. We collected data on BZRAs at baseline and 3 months after commencement of SUV/LEM/RMT.Results Significant reductions in BZRAs were observed for all 3 agents: -4.10, -2.80, and -1.65 mg in diazepam-equivalent doses in the SUV, LEM, and RMT groups, respectively. Dose reduction was significantly greater in the DORA than the RMT group (F = 15.053, P < .001). Within the DORA group, dose reduction was significantly greater in patients taking SUV than those taking LEM (F = 4.337, P = .043). The switching success rate did not differ among the switching methods for any of the hypnotics.Conclusions The reduction rate of BZRAs achieved by the switch fell into their equivalent-potency range estimated from clinical trials. The results suggest that DORAs can replace approximately 1 tablet of a BZRA. The difference in dose reduction between DORAs and RMT reflected the greater sleeping potency of the DORAs, whereas that between SUV and LEM might have reflected patient backgrounds: patients taking LEM may have been more strongly dependent on BZRAs.Citation Tachibana M, Kanahara N, Oda Y, Hasegawa T, Kimura A, Iyo M. A retrospective clinical practice study comparing the usefulness of dual-orexin receptor antagonists and a melatonin receptor agonist in patients switching from long-term benzodiazepine receptor agonists. J Clin Sleep Med. 2024;20(4):603-613.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Suvorexant showed a significantly greater reduction than lemborexant.
“Suvorexant showed a significantly greater reduction than lemborexant. 83”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [83]
Dose reduction was significantly greater in patients receiving DORAs compared to those receiving ramelteon.
“Dose reduction was significantly greater in patients receiving DORAs compared to those receiving ramelteon.”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [83]
The introduction of lemborexant, suvorexant, or ramelteon was associated with significant reductions in BZD/Z-drug equivalent doses.
“The introduction of lemborexant, suvorexant, or ramelteon was associated with significant reductions in BZD/Z-drug equivalent doses.”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [83]
Cites
By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel (2015) · Journal of the American Geriatrics Society · doi:10.1111/jgs.13702 · Cited by 2,609 · see citing works
European guideline for the diagnosis and treatment of insomnia
Riemann, D., Baglioni, C., Bassetti, C., Bjorvatn, B., Dolenc Groselj, L., Ellis, J. G., Espie, C. A., Garcia‐Borreguero, D., Gjerstad, M., Gonçalves, M., et al. (2017) · Journal of Sleep Research · doi:10.1111/jsr.12594 · Cited by 2,049 · see citing works
Qaseem, A., Kansagara, D., Forciea, M. A., Cooke, M., Denberg, T. D., & for the Clinical Guidelines Committee of the American College of Physicians* (2016) · Annals of Internal Medicine · doi:10.7326/m15-2175 · Cited by 1,965 · see citing works
Sleep and mental disorders: a meta-analysis of polysomnographic research
Baglioni, C., Nanovska, S., Regen, W., Spiegelhalder, K., Feige, B., Nissen, C., Reynolds, C. F., & Riemann, D. (2016) · Psychological Bulletin · doi:10.1037/bul0000053 · Cited by 1,074 · see citing works
Benzodiazepines revisited—will we ever learn?
Lader, M. (2011) · Addiction · doi:10.1111/j.1360-0443.2011.03563.x · Cited by 573 · see citing works
De Crescenzo, F., D'Alò, G. L., Ostinelli, E. G., Ciabattini, M., Di Franco, V., Watanabe, N., Kurtulmus, A., Tomlinson, A., Mitrova, Z., Foti, F., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(22)00878-9 · Cited by 446 · see citing works
Benzodiazepine harm: how can it be reduced?
Lader, M. (2014) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2012.04418.x · Cited by 359 · see citing works
Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications
Cosci, F., & Chouinard, G. (2020) · Psychotherapy and Psychosomatics · doi:10.1159/000506868 · Cited by 265 · see citing works
Deprescribing benzodiazepine receptor agonists: Evidence-based clinical practice guideline.
(2018) · Europe PMC (PubMed Central) · Cited by 250 · see citing works
Effectiveness of current treatment approaches for benzodiazepine discontinuation: a meta‐analysis
Parr, J. M., Kavanagh, D. J., Cahill, L., Mitchell, G., & Young, R. M. (2009) · Addiction · doi:10.1111/j.1360-0443.2008.02364.x · Cited by 212 · see citing works
Alcohol use disorders and current pharmacological therapies: the role of GABAA receptors
Liang, J., & Olsen, R. W. (2014) · Acta Pharmacologica Sinica · doi:10.1038/aps.2014.50 · Cited by 155 · see citing works
Campbell, A., Axon, D. R., Martin, J. R., Slack, M. K., Mollon, L. E., & Lee, J. K. (2019) · BMC Geriatrics · doi:10.1186/s12877-019-1297-6 · Cited by 119 · see citing works
Muehlan, C., Vaillant, C., Zenklusen, I., Kraehenbuehl, S., & Dingemanse, J. (2020) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2020.1817380 · Cited by 102 · see citing works
Xue, T., Wu, X., Chen, S., Yang, Y., Yan, Z., Song, Z., Zhang, W., Zhang, J., Chen, Z., & Wang, Z. (2021) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2021.101573 · Cited by 98 · see citing works
Lemborexant vs suvorexant for insomnia: A systematic review and network meta-analysis
Kishi, T., Nomura, I., Matsuda, Y., Sakuma, K., Okuya, M., Ikuta, T., & Iwata, N. (2020) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2020.05.025 · Cited by 96 · see citing works
Time course for development of benzodiazepine tolerance and physical dependence
Rosenberg, H. C., & Chiu, T. H. (1985) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(85)90038-7 · Cited by 90 · see citing works
Landry, I. S., Nakai, K., Ferry, J., Aluri, J., Hall, N., Lalovic, B. B., & Moline, M. L. (2020) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.817 · Cited by 71 · see citing works
Withdrawing Benzodiazepines in Patients With Anxiety Disorders
Lader, M., & Kyriacou, A. (2016) · Current Psychiatry Reports · doi:10.1007/s11920-015-0642-5 · Cited by 67 · see citing works
Hatta, K., Kishi, Y., Wada, K., et al. (2019) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.19m12865 · Cited by 64 · see citing works
Watson, N. F., Benca, R. M., Krystal, A. D., McCall, W. V., & Neubauer, D. N. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12072493 · Cited by 59 · see citing works
Cloos, J.-M., Bocquet, V., Rolland-Portal, I., Koch, P., & Chouinard, G. (2015) · Psychotherapy and Psychosomatics · doi:10.1159/000434755 · Cited by 57 · see citing works
Comparative efficacy of lemborexant and other insomnia treatments: a network meta-analysis
McElroy, H. J., O’Leary, B., ADENA, M. A., Campbell, R., Monfared, A. A. T., & Meier, G. (2021) · Journal of Managed Care & Specialty Pharmacy · doi:10.18553/jmcp.2021.21011 · Cited by 43 · see citing works
Mini, L. J., Wang‐Weigand, S., & Zhang, J. (2007) · The American Journal of Geriatric Pharmacotherapy · doi:10.1016/j.amjopharm.2007.09.004 · Cited by 40 · see citing works
Interventions to improve benzodiazepine tapering success in the elderly: a systematic review
Dou, C., Rebane, J., & Bardal, S. K. (2018) · Aging & Mental Health · doi:10.1080/13607863.2017.1423030 · Cited by 38 · see citing works
Melatonin and melatonergic drugs in sleep disorders
Kim, H. K., & Yang, K. I. (2022) · Translational and Clinical Pharmacology · doi:10.12793/tcp.2022.30.e21 · Cited by 35 · see citing works
Lee, J. Y., Farrell, B., & Holbrook, A. M. (2018) · Polish Archives of Internal Medicine · doi:10.20452/pamw.4391 · Cited by 32 · see citing works
Evidence‐based insomnia treatment strategy using novel orexin antagonists: A review
Kishi, T., Nishida, M., Koebis, M., Taninaga, T., Muramoto, K., Kubota, N., Moline, M. L., Sakuma, K., Okuya, M., Nomura, I., et al. (2021) · Neuropsychopharmacology Reports · doi:10.1002/npr2.12205 · Cited by 31 · see citing works
Assessment of Patterns of Potentially Unsafe Use of Zolpidem
Moore, T. J., & Mattison, D. R. (2018) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2018.3031 · Cited by 29 · see citing works
Inada, K., Enomoto, M., Yamato, K., & Mishima, K. (2021) · Drugs - Real World Outcomes · doi:10.1007/s40801-021-00244-9 · Cited by 29 · see citing works
Lemborexant for the Treatment of Insomnia
Citrome, L., Juday, T. R., Ferch, F., & Atkins, N. (2021) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.20m13795 · Cited by 23 · see citing works
Okino, K., Suzuki, H., Tomioka, H., Sanada, K., Kawai, K., Iwanami, A., & Inamoto, A. (2023) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2868 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Stelzer, F. G., Bacelar, A., Éckeli, A. L., Negrão, A. B., Almeida, C. M. O., Franco, C. M. R., Pires, G. N., Gitaí, L. L. G., Sobreira-Neto, M. A., Assis, M., et al. (2025) · Arquivos de Neuro-Psiquiatria · doi:10.1055/s-0045-1812323 · Cited by 1 · see citing works
- Authors
- Tachibana, M., Kanahara, N., Oda, Y., Hasegawa, T., Kimura, A., & Iyo, M.
- Affiliations
- Chiba University (JP)
- Corresponding author
- Kanahara, Nobuhisa
- Venue
- Journal of Clinical Sleep Medicine
- Published
- 2024-04
- Volume
- 20
- Issue
- 4
- Pages
- 603-613
- ISSN
- 1550-9389 (ISSN-L)
- 1550-9397
- PMC
- PMC10985311
- OpenAlex
- W4389474925
- Cited by
- 17
- References
- 31
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 2
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Sleep Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (21K07476)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- benzodiazepine receptor agonists, dual orexin receptor antagonists, suvorexant, lemborexant, ramelteon, melatonin receptor agonists, benzodiazepine dependence, dose reduction, mental illness, sleep disorders
- MeSH terms
- Orexin Receptor Antagonists, Humans, Hypnotics and Sedatives, Indenes, Sleep Initiation and Maintenance Disorders, Receptors, GABA-A, Retrospective Studies, Sleep, Receptors, Melatonin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
