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Clonazepam for the management of sleep disorders

Neurological Sciences volume 44, pages 115–128 (2023)Cite this article

Abstract

Background

The objectives of this review and meta-analysis of polysomnographic data are those to focus on the clinical use of clonazepam for the management of sleep disorders by re-analyzing clinical trials and randomized clinical trials which have been published in peer-reviewed journals.

Methods

A review of the literature including clinical trials and randomized controlled trials was performed in PubMed®, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. A random effects model meta-analysis was then carried out for the four more frequently reported polysomnographic measures: total sleep time, sleep latency, sleep efficiency, and periodic leg movement during sleep (PLMS) index.

Results

A total of 33 articles were retrieved and screened in full text, of which 18 met the criteria for review; among the latter, nine met the criteria for meta-analysis. The studies included in the review involved patients with insomnia, REM sleep behavior disorder, sleep bruxism, and restless leg syndrome or PLMS which reported, most often, an increase in total sleep time with clonazepam. A clear sleep-promoting effect of clonazepam was found also by meta-analysis.

Discussion and conclusions

Our results indicate that the pharmacological treatment of sleep disorders with clonazepam must always be personalized according to the type of patient, the risk of addiction and the concomitant presence of respiratory disorders are key factors to take into account. However, in light of the clinical evidence of the few studies in the literature on the different types of disorders, more studies on the use of clonazepam (also in association with first choice treatments) are definitely needed.

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References

  1. Fazio C, Manfredi M, Piccinelli A (1975) Treatment of epileptic seizures with clonazepam. A reappraisal. Arch Neurol 32(5):304–307. https://doi.org/10.1001/archneur.1975.00490470048006

    Article  CAS  Google Scholar 

  2. Basit H, Kahwaji CI (2021) Clonazepam. In: StatPearls. Treasure Island (FL),

  3. Pinder RM, Brogden RN, Speight TM, Avery GS (1976) Clonazepam: a review of its pharmacological properties and therapeutic efficacy in epilepsy. Drugs 12(5):321–361. https://doi.org/10.2165/00003495-197612050-00001

    Article  CAS  Google Scholar 

  4. Marchesi C (2008) Pharmacological management of panic disorder. Neuropsychiatr Dis Treat 4(1):93–106. https://doi.org/10.2147/ndt.s1557

    Article  CAS  Google Scholar 

  5. Salem H, Nagpal C, Pigott T, Teixeira AL (2017) Revisiting antipsychotic-induced akathisia: current issues and prospective challenges. Curr Neuropharmacol 15(5):789–798. https://doi.org/10.2174/1570159X14666161208153644

    Article  CAS  Google Scholar 

  6. Griffin CE 3rd, Kaye AM, Bueno FR, Kaye AD (2013) Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J 13(2):214–223

    Google Scholar 

  7. Battistin L, Varotto M, Berlese G, Roman G (1984) Effects of some anticonvulsant drugs on brain GABA level and GAD and GABA-T activities. Neurochem Res 9(2):225–231. https://doi.org/10.1007/BF00964170

    Article  CAS  Google Scholar 

  8. Jenner P, Pratt JA, Marsden CD (1986) Mechanism of action of clonazepam in myoclonus in relation to effects on GABA and 5-HT. Adv Neurol 43:629–643

    CAS  Google Scholar 

  9. Petkov V, Georgiev VP, Getova D, Petkov VV (1982) Effects of some benzodiazepines on the acetylcholine release in the anterior horn of the lateral cerebral ventricle of the cat. Acta Physiol Pharmacol Bulg 8(3):59–66

    CAS  Google Scholar 

  10. Taft WC, DeLorenzo RJ (1984) Micromolar-affinity benzodiazepine receptors regulate voltage-sensitive calcium channels in nerve terminal preparations. Proc Natl Acad Sci USA 81(10):3118–3122. https://doi.org/10.1073/pnas.81.10.3118

    Article  CAS  Google Scholar 

  11. Paulson OB, Gyory A, Hertz MM (1982) Blood-brain barrier transfer and cerebral uptake of antiepileptic drugs. Clin Pharmacol Ther 32(4):466–477. https://doi.org/10.1038/clpt.1982.190

    Article  CAS  Google Scholar 

  12. Nelson J, Chouinard G (1999) Guidelines for the clinical use of benzodiazepines: pharmacokinetics, dependency, rebound and withdrawal. Canadian Society for Clinical Pharmacology. Can J Clin Pharmacol = J Can Pharmacol Clin 6(2):69–83

    CAS  Google Scholar 

  13. DeVane CL, Ware MR, Lydiard RB (1991) Pharmacokinetics, pharmacodynamics, and treatment issues of benzodiazepines: alprazolam, adinazolam, and clonazepam. Psychopharmacol Bull 27(4):463–473

    CAS  Google Scholar 

  14. Dokkedal-Silva V, Berro LF, Galduroz JCF, Tufik S, Andersen ML (2019) Clonazepam: indications, side effects, and potential for nonmedical use. Harv Rev Psychiatry 27(5):279–289. https://doi.org/10.1097/HRP.0000000000000227

    Article  Google Scholar 

  15. Preuss CV, Kalava A, King KC (2020) Prescription of controlled substances: benefits and risks. In: StatPearls. Treasure Island (FL),

  16. Freeman S (1997) The realities of clonazepam discontinuation. Psychiatr Serv 48(7):881–882. https://doi.org/10.1176/ps.48.7.881

    Article  CAS  Google Scholar 

  17. Kales A, Manfredi RL, Vgontzas AN, Baldassano CF, Kostakos K, Kales JD (1991) Clonazepam: sleep laboratory study of efficacy and withdrawal. J Clin Psychopharmacol 11(3):189–193

    Article  CAS  Google Scholar 

  18. Brown M, Freeman S (2009) Clonazepam withdrawal-induced catatonia. Psychosomatics 50(3):289–292. https://doi.org/10.1176/appi.psy.50.3.289

    Article  Google Scholar 

  19. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8(5):336–341. https://doi.org/10.1016/j.ijsu.2010.02.007

    Article  Google Scholar 

  20. Hedges LV, Olkin I (1985) Statistical methods in meta-analysis. J Educ Stat 13(1):75–78

    Google Scholar 

  21. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. https://doi.org/10.1002/sim.1186

    Article  Google Scholar 

  22. Kontopantelis E, Reeves D (2012) Performance of statistical methods for meta-analysis when true study effects are non-normally distributed: a comparison between DerSimonian-Laird and restricted maximum likelihood. Stat Methods Med Res 21(6):657–659. https://doi.org/10.1177/0962280211413451

    Article  Google Scholar 

  23. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (2019) Cochrane Handbook for Systematic Reviews of Interventions, 2nd edn. John Wiley & Sons, Chichester (UK)

    Book  Google Scholar 

  24. Mowla A, Ahmadzadeh L, Razeghian Jahromi L, Dastgheib SA (2015) Comparing gabapentin with clonazepam for residual sleeping problems following antidepressant therapy in patients with major depressive disorder: a randomized clinical trial. Clin Drug Investig 35(8):513–517. https://doi.org/10.1007/s40261-015-0304-8

    Article  CAS  Google Scholar 

  25. Ferri R, Marelli S, Ferini-Strambi L, Oldani A, Colli F, Schenck CH, Zucconi M (2013) An observational clinical and video-polysomnographic study of the effects of clonazepam in REM sleep behavior disorder. Sleep Med 14(1):24–29. https://doi.org/10.1016/j.sleep.2012.09.009

    Article  Google Scholar 

  26. Shin C, Park H, Lee WW, Kim HJ, Kim HJ, Jeon B (2019) Clonazepam for probable REM sleep behavior disorder in Parkinson’s disease: a randomized placebo-controlled trial. J Neurol Sci 401:81–86. https://doi.org/10.1016/j.jns.2019.04.029

    Article  CAS  Google Scholar 

  27. Saletu A, Parapatics S, Saletu B, Anderer P, Prause W, Putz H, Adelbauer J, Saletu-Zyhlarz GM (2005) On the pharmacotherapy of sleep bruxism: placebo-controlled polysomnographic and psychometric studies with clonazepam. Neuropsychobiology 51(4):214–225. https://doi.org/10.1159/000085917

    Article  CAS  Google Scholar 

  28. Saletu A, Parapatics S, Anderer P, Matejka M, Saletu B (2010) Controlled clinical, polysomnographic and psychometric studies on differences between sleep bruxers and controls and acute effects of clonazepam as compared with placebo. Eur Arch Psychiatry Clin Neurosci 260(2):163–174. https://doi.org/10.1007/s00406-009-0034-0

    Article  Google Scholar 

  29. Boghen D, Lamothe L, Elie R, Godbout R, Montplaisir J (1986) The treatment of the restless legs syndrome with clonazepam: a prospective controlled study. CanJNeurolSci 13(3):245–247

    CAS  Google Scholar 

  30. Edinger JD, Fins AI, Sullivan RJ, Marsh GR, Dailey DS, Young M (1996) Comparison of cognitive-behavioral therapy and clonazepam for treating periodic limb movement disorder. Sleep 19(5):442–444

    CAS  Google Scholar 

  31. Manconi M, Ferri R, Zucconi M, Bassetti C, Fulda S, Arico D, Ferini-Strambi L (2012) Dissociation of periodic leg movements from arousals in restless legs syndrome. AnnNeurol 71:834–844

    Google Scholar 

  32. Mitler MM, Browman CP, Menn SJ, Gujavarty K, Timms RM (1986) Nocturnal myoclonus: treatment efficacy of clonazepam and temazepam. Sleep 9(3):385–392. https://doi.org/10.1093/sleep/9.3.385

    Article  CAS  Google Scholar 

  33. Montagna P, Sassoli DB, Zucconi M, Cirignotta F, Lugaresi E (1984) Clonazepam and vibration in restless legs syndrome. Acta NeurolScand 69(6):428–430

    Article  CAS  Google Scholar 

  34. Inami Y, Horiguchi J, Nishimatsu O, Sasaki A, Sukegawa T, Katagiri H, Yamawaki S (1997) A polysomnographic study on periodic limb movements in patients with restless legs syndrome and neuroleptic-induced akathisia. Hiroshima JMedSci 46(4):133–141

    CAS  Google Scholar 

  35. Noseda A, Nouvelle M, Lanquart JR, Kempenaers C, De MV, Linkowski R, Kerkhofs M (2002) High leg motor activity in sleep apnea hypopnea patients: efficacy of clonazepam combined with nasal CPAP on polysomnographic variables. RespirMed 96(9):693–699

    CAS  Google Scholar 

  36. Peled R, Lavie P (1987) Double-blind evaluation of clonazepam on periodic leg movements in sleep. J Neurol Neurosurg Psychiatry 50(12):1679–1681. https://doi.org/10.1136/jnnp.50.12.1679

    Article  CAS  Google Scholar 

  37. Saletu M, Anderer P, Saletu-Zyhlarz G, Prause W, Semler B, Zoghlami A, Gruber G, Hauer C, Saletu B (2001) Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam. Eur Neuropsychopharmacol: J Eur Coll Neuropsychopharmacol 11(2):153–161

    Article  CAS  Google Scholar 

  38. Schenck CH, Mahowald MW (1996) Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am J Med 100(3):333–337. https://doi.org/10.1016/S0002-9343(97)89493-4

    Article  CAS  Google Scholar 

  39. Shinno H, Oka Y, Otsuki M, Tsuchiya S, Mizuno S, Kawada S, Innami T, Sasaki A, Hineno T, Sakamoto T, Inami Y, Nakamura Y, Horiguchi J (2010) Proposed dose equivalence between clonazepam and pramipexole in patients with restless legs syndrome. Prog Neuropsychopharmacol Biol Psychiatry 34(3):522–526. https://doi.org/10.1016/j.pnpbp.2010.02.011

    Article  CAS  Google Scholar 

  40. Nishimatsu O, Horiguchi J, Inami Y, Sukegawa T, Sasaki A (1997) Periodic limb movement disorder in neuroleptic-induced akathisia. Kobe J Med Sci 43(5):169–177

    CAS  Google Scholar 

  41. Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Erlbaum, Hillsdale, NJ

    Google Scholar 

  42. Schenck CH, Bundlie SR, Ettinger MG, Mahowald MW (1986) Chronic behavioral disorders of human REM sleep: a new category of parasomnia. Sleep 9(2):293–308. https://doi.org/10.1093/sleep/9.2.293

    Article  CAS  Google Scholar 

  43. Raggi A, Ferri R (2010) Sleep disorders in neurodegenerative diseases. Eur J Neurol 17(11):1326–1338. https://doi.org/10.1111/j.1468-1331.2010.03034.x

    Article  CAS  Google Scholar 

  44. Mahowald MW, Schenck CH, Cramer Bornemann MA (2005) Sleep-related violence. CurrNeurolNeurosciRep 5(2):153–158

    Google Scholar 

  45. Schenck CH, Lee SA, Bornemann MA, Mahowald MW (2009) Potentially lethal behaviors associated with rapid eye movement sleep behavior disorder: review of the literature and forensic implications. J Forensic Sci 54(6):1475–1484. https://doi.org/10.1111/j.1556-4029.2009.01163.x

    Article  Google Scholar 

  46. Hendricks JC, Morrison AR, Mann GL (1982) Different behaviors during paradoxical sleep without atonia depend on pontine lesion site. Brain Res 239(1):81–105

    Article  CAS  Google Scholar 

  47. Fuller PM, Saper CB, Lu J (2007) The pontine REM switch: past and present. J Physiol 584(Pt 3):735–741. https://doi.org/10.1113/jphysiol.2007.140160

    Article  CAS  Google Scholar 

  48. Lu J, Sherman D, Devor M, Saper CB (2006) A putative flip-flop switch for control of REM sleep. Nature 441(7093):589–594. https://doi.org/10.1038/nature04767

    Article  CAS  Google Scholar 

  49. Figorilli M, Lanza G, Congiu P, Lecca R, Casaglia E, Mogavero MP, Puligheddu M, Ferri R (2021) Neurophysiological aspects of REM sleep behavior disorder (RBD): a narrative review. Brain Sciences 11(12). https://doi.org/10.3390/brainsci11121588

  50. Boeve BF, Silber MH, Saper CB, Ferman TJ, Dickson DW, Parisi JE, Benarroch EE, Ahlskog JE, Smith GE, Caselli RC, Tippman-Peikert M, Olson EJ, Lin SC, Young T, Wszolek Z, Schenck CH, Mahowald MW, Castillo PR, Del TK, Braak H (2007) Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 130(Pt 11):2770–2788

    Article  CAS  Google Scholar 

  51. Ferini-Strambi L, Zucconi M (2000) REM sleep behavior disorder. Clin Neurophysiol: Off J Int Fed Clin Neurophysiol 111(Suppl 2):S136-140

    Article  Google Scholar 

  52. Ferini-Strambi L, Fantini ML, Zucconi M, Castronovo V, Marelli S, Oldani A, Cappa S (2005) REM sleep behaviour disorder. Neurol Sci: Off J Italian Neurol Soc Italian Soc Clin Neurophysiol 26(Suppl 3):s186-192. https://doi.org/10.1007/s10072-005-0485-7

    Article  Google Scholar 

  53. Dauvilliers Y, Schenck CH, Postuma RB, Iranzo A, Luppi PH, Plazzi G, Montplaisir J, Boeve B (2018) REM sleep behaviour disorder. Nat Rev Dis Primers 4(1):19. https://doi.org/10.1038/s41572-018-0016-5

    Article  Google Scholar 

  54. Miglis MG, Adler CH, Antelmi E, Arnaldi D, Baldelli L, Boeve BF, Cesari M, Dall’Antonia I, Diederich NJ, Doppler K, Dusek P, Ferri R, Gagnon JF, Gan-Or Z, Hermann W, Hogl B, Hu MT, Iranzo A, Janzen A, Kuzkina A, Lee JY, Leenders KL, Lewis SJG, Liguori C, Liu J, Lo C, Ehgoetz Martens KA, Nepozitek J, Plazzi G, Provini F, Puligheddu M, Rolinski M, Rusz J, Stefani A, Summers RLS, Yoo D, Zitser J, Oertel WH (2021) Biomarkers of conversion to alpha-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder. Lancet Neurol 20(8):671–684. https://doi.org/10.1016/S1474-4422(21)00176-9

    Article  CAS  Google Scholar 

  55. Raggi A, Bella R, Pennisi G, Neri W, Ferri R (2013) Sleep disorders in Parkinson’s disease: a narrative review of the literature. Rev Neurosci 24(3):279–291. https://doi.org/10.1515/revneuro-2013-0002

    Article  Google Scholar 

  56. Giannini G, Provini F, Cortelli P, Calandra-Buonaura G (2021) REM sleep behaviour disorder in multiple system atrophy: from prodromal to progression of disease. Front Neurol 12:677213. https://doi.org/10.3389/fneur.2021.677213

    Article  Google Scholar 

  57. Raggi A, Neri W, Ferri R (2015) Sleep-related behaviors in Alzheimer’s disease and dementia with Lewy bodies. Rev Neurosci 26(1):31–38. https://doi.org/10.1515/revneuro-2014-0050

    Article  Google Scholar 

  58. Antelmi E, Pizza F, Franceschini C, Ferri R, Plazzi G (2020) REM sleep behavior disorder in narcolepsy: a secondary form or an intrinsic feature? Sleep Med Rev 50:101254. https://doi.org/10.1016/j.smrv.2019.101254

    Article  Google Scholar 

  59. Schenck CH, Hurwitz TD, Mahowald MW (1993) Symposium: normal and abnormal REM sleep regulation: REM sleep behaviour disorder: an update on a series of 96 patients and a review of the world literature. J Sleep Res 2(4):224–231

    Article  CAS  Google Scholar 

  60. McCarter SJ, St Louis EK, Boswell CL, Dueffert LG, Slocumb N, Boeve BF, Silber MH, Olson EJ, Morgenthaler TI, Tippmann-Peikert M (2014) Factors associated with injury in REM sleep behavior disorder. Sleep Med 15(11):1332–1338. https://doi.org/10.1016/j.sleep.2014.06.002

    Article  Google Scholar 

  61. Antelmi E, Lippolis M, Biscarini F, Tinazzi M, Plazzi G (2021) REM sleep behavior disorder: Mimics and variants. Sleep Med Rev 60:101515. https://doi.org/10.1016/j.smrv.2021.101515

    Article  Google Scholar 

  62. Schaefer C, Kunz D, Bes F (2017) Melatonin effects in REM sleep behavior disorder associated with obstructive sleep apnea syndrome: a case series. Curr Alzheimer Res 14(10):1084–1089. https://doi.org/10.2174/1567205014666170523094938

    Article  CAS  Google Scholar 

  63. McGrane IR, Leung JG, St Louis EK, Boeve BF (2015) Melatonin therapy for REM sleep behavior disorder: a critical review of evidence. Sleep Med 16(1):19–26. https://doi.org/10.1016/j.sleep.2014.09.011

    Article  Google Scholar 

  64. Gilat M, Coeytaux Jackson A, Marshall NS, Hammond D, Mullins AE, Hall JM, Fang BAM, Yee BJ, Wong KKH, Grunstein RR, Lewis SJG (2020) Melatonin for rapid eye movement sleep behavior disorder in Parkinson’s disease: a randomised controlled trial. Mov Disord: Off J Mov Disord Soc 35(2):344–349. https://doi.org/10.1002/mds.27886

    Article  CAS  Google Scholar 

  65. Jun JS, Kim R, Byun JI, Kim TJ, Lim JA, Sunwoo JS, Lee ST, Jung KH, Park KI, Chu K, Kim M, Lee SK, Jung KY (2019) Prolonged-release melatonin in patients with idiopathic REM sleep behavior disorder. Ann Clin Transl Neurol 6(4):716–722. https://doi.org/10.1002/acn3.753

    Article  CAS  Google Scholar 

  66. Kunz D, Mahlberg R (2010) A two-part, double-blind, placebo-controlled trial of exogenous melatonin in REM sleep behaviour disorder. J Sleep Res 19(4):591–596. https://doi.org/10.1111/j.1365-2869.2010.00848.x

    Article  Google Scholar 

  67. St Louis EK, Boeve AR, Boeve BF (2017) REM sleep behavior disorder in Parkinson’s disease and other synucleinopathies. Mov Disord: Off J Mov Disord Soc 32(5):645–658. https://doi.org/10.1002/mds.27018

    Article  CAS  Google Scholar 

  68. Jung Y, St Louis EK (2016) Treatment of REM sleep behavior disorder. Curr Treat Options Neurol 18(11):50. https://doi.org/10.1007/s11940-016-0433-2

    Article  Google Scholar 

  69. During EH, Miglis MG (2019) Clinical trials in REM sleep behavior disorder: an urgent need for better evidence. Sleep Med 63:1–2. https://doi.org/10.1016/j.sleep.2019.06.001

    Article  Google Scholar 

  70. Videnovic A, Ju YS, Arnulf I, Cochen-De Cock V, Hogl B, Kunz D, Provini F, Ratti PL, Schiess MC, Schenck CH, Trenkwalder C, Treatment, Trials Working Group of the International RBDSG (2020) Clinical trials in REM sleep behavioural disorder: challenges and opportunities. J Neurol Neurosurg Psychiatry 91(7):740–749. https://doi.org/10.1136/jnnp-2020-322875

    Article  Google Scholar 

  71. Leung AKC, Leung AAM, Wong AHC, Hon KL (2020) Sleep Terrors: an updated review. Curr Pediatr Rev 16(3):176–182. https://doi.org/10.2174/1573396315666191014152136

    Article  Google Scholar 

  72. Chiaro G, Caletti MT, Provini F (2015) Treatment of sleep-related eating disorder. Curr Treat Options Neurol 17(8):361. https://doi.org/10.1007/s11940-015-0361-6

    Article  Google Scholar 

  73. Soca R, Keenan JC, Schenck CH (2016) Parasomnia overlap disorder with sexual behaviors during sleep in a patient with obstructive sleep apnea. J Clin Sleep Med: JCSM: Off Publ Am Acad Sleep Med 12(8):1189–1191. https://doi.org/10.5664/jcsm.6066

    Article  Google Scholar 

  74. Morgenthaler TI, Auerbach S, Casey KR, Kristo D, Maganti R, Ramar K, Zak R, Kartje R (2018) Position paper for the treatment of nightmare disorder in adults: an American Academy of Sleep Medicine position paper. J Clin Sleep Med: JCSM: Off Publ Am Acad Sleep Med 14(6):1041–1055. https://doi.org/10.5664/jcsm.7178

    Article  Google Scholar 

  75. Cochen De Cock V (2016) Sleepwalking. Curr Treat Options Neurol 18(2):6. https://doi.org/10.1007/s11940-015-0388-8

    Article  Google Scholar 

  76. Beddis H, Pemberton M, Davies S (2018) Sleep bruxism: an overview for clinicians. Br Dent J 225(6):497–501. https://doi.org/10.1038/sj.bdj.2018.757

    Article  CAS  Google Scholar 

  77. Kato T, Thie NM, Huynh N, Miyawaki S, Lavigne GJ (2003) Topical review: sleep bruxism and the role of peripheral sensory influences. J Orofac Pain 17(3):191–213

    Google Scholar 

  78. Espana A, Clotman F (2012) Onecut factors control development of the Locus Coeruleus and of the mesencephalic trigeminal nucleus. Mol Cell Neurosci 50(1):93–102. https://doi.org/10.1016/j.mcn.2012.04.002

    Article  CAS  Google Scholar 

  79. Yoshida A, Moritani M, Nagase Y, Bae YC (2017) Projection and synaptic connectivity of trigeminal mesencephalic nucleus neurons controlling jaw reflexes. J Oral Sci 59(2):177–182. https://doi.org/10.2334/josnusd.16-0845

    Article  CAS  Google Scholar 

  80. Fuller PM, Sherman D, Pedersen NP, Saper CB, Lu J (2011) Reassessment of the structural basis of the ascending arousal system. J Comp Neurol 519(5):933–956. https://doi.org/10.1002/cne.22559

    Article  Google Scholar 

  81. Huynh N, Kato T, Rompre PH, Okura K, Saber M, Lanfranchi PA, Montplaisir JY, Lavigne GJ (2006) Sleep bruxism is associated to micro-arousals and an increase in cardiac sympathetic activity. J Sleep Res 15(3):339–346. https://doi.org/10.1111/j.1365-2869.2006.00536.x

    Article  CAS  Google Scholar 

  82. Khoury S, Rouleau GA, Rompre PH, Mayer P, Montplaisir JY, Lavigne GJ (2008) A significant increase in breathing amplitude precedes sleep bruxism. Chest 134(2):332–337. https://doi.org/10.1378/chest.08-0115

    Article  Google Scholar 

  83. Andrisani G, Andrisani G (2021) The neurophysiological basis of bruxism. Heliyon 7(7):e07477. https://doi.org/10.1016/j.heliyon.2021.e07477

    Article  CAS  Google Scholar 

  84. Manfredini D, Ahlberg J, Winocur E, Lobbezoo F (2015) Management of sleep bruxism in adults: a qualitative systematic literature review. J Oral Rehabil 42(11):862–874. https://doi.org/10.1111/joor.12322

    Article  Google Scholar 

  85. Sakai T, Kato T, Yoshizawa S, Suganuma T, Takaba M, Ono Y, Yoshizawa A, Yoshida Y, Kurihara T, Ishii M, Kawana F, Kiuchi Y, Baba K (2017) Effect of clonazepam and clonidine on primary sleep bruxism: a double-blind, crossover, placebo-controlled trial. J Sleep Res 26(1):73–83. https://doi.org/10.1111/jsr.12442

    Article  Google Scholar 

  86. Melo G, Duarte J, Pauletto P, Porporatti AL, Stuginski-Barbosa J, Winocur E, Flores-Mir C, De Luca CG (2019) Bruxism: an umbrella review of systematic reviews. J Oral Rehabil 46(7):666–690. https://doi.org/10.1111/joor.12801

    Article  Google Scholar 

  87. Manconi M, Garcia-Borreguero D, Schormair B, Videnovic A, Berger K, Ferri R, Dauvilliers Y (2021) Restless legs syndrome. Nat Rev Dis Primers 7(1):80. https://doi.org/10.1038/s41572-021-00311-z

    Article  Google Scholar 

  88. Trenkwalder C, Allen R, Hogl B, Clemens S, Patton S, Schormair B, Winkelmann J (2018) Comorbidities, treatment, and pathophysiology in restless legs syndrome. Lancet Neurol 17(11):994–1005. https://doi.org/10.1016/S1474-4422(18)30311-9

    Article  CAS  Google Scholar 

  89. Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB, International Restless Legs Syndrome Study G (2014) Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria–history, rationale, description, and significance. Sleep Med 15(8):860–873. https://doi.org/10.1016/j.sleep.2014.03.025

    Article  Google Scholar 

  90. American Academy of Sleep Medicine (2014) International classification of sleep disorders, 3rd ed. American Academy of Sleep Medicine., Darien, IL

  91. Earley CJ, Connor J, Garcia-Borreguero D, Jenner P, Winkelman J, Zee PC, Allen R (2014) Altered brain iron homeostasis and dopaminergic function in restless legs syndrome (Willis-Ekbom Disease). Sleep Med 15(11):1288–1301. https://doi.org/10.1016/j.sleep.2014.05.009

    Article  Google Scholar 

  92. Mogavero MP, Mezzapesa DM, Savarese M, DelRosso LM, Lanza G, Ferri R (2021) Morphological analysis of the brain subcortical gray structures in restless legs syndrome. Sleep Med 88:74–80. https://doi.org/10.1016/j.sleep.2021.10.025

    Article  Google Scholar 

  93. Lanza G, Ferri R (2019) The neurophysiology of hyperarousal in restless legs syndrome: Hints for a role of glutamate/GABA. Adv Pharmacol 84:101–119. https://doi.org/10.1016/bs.apha.2018.12.002

    Article  CAS  Google Scholar 

  94. Manconi M, Ferri R, Zucconi M, Oldani A, Fantini ML, Castronovo V, Ferini-Strambi L (2007) First night efficacy of pramipexole in restless legs syndrome and periodic leg movements. Sleep Med 8(5):491–497. https://doi.org/10.1016/j.sleep.2006.10.008

    Article  Google Scholar 

  95. Manconi M, Ferri R, Zucconi M, Clemens S, Giarolli L, Bottasini V, Ferini-Strambi L (2011) Preferential D2 or preferential D3 dopamine agonists in restless legs syndrome. Neurology 77(2):110–117. https://doi.org/10.1212/WNL.0b013e3182242d91

    Article  CAS  Google Scholar 

  96. Collado-Seidel V, Kazenwadel J, Wetter TC, Kohnen R, Winkelmann J, Selzer R, Oertel WH, Trenkwalder C (1999) A controlled study of additional sr-L-dopa in L-dopa-responsive restless legs syndrome with late-night symptoms. Neurology 52(2):285–290. https://doi.org/10.1212/wnl.52.2.285

    Article  CAS  Google Scholar 

  97. Wetter TC, Stiasny K, Winkelmann J, Buhlinger A, Brandenburg U, Penzel T, Medori R, Rubin M, Oertel WH, Trenkwalder C (1999) A randomized controlled study of pergolide in patients with restless legs syndrome. Neurology 52(5):944–950. https://doi.org/10.1212/wnl.52.5.944

    Article  CAS  Google Scholar 

  98. Satija P, Ondo WG (2008) Restless legs syndrome: pathophysiology, diagnosis and treatment. CNS Drugs 22(6):497–518. https://doi.org/10.2165/00023210-200822060-00004

    Article  CAS  Google Scholar 

  99. Allen R (2004) Dopamine and iron in the pathophysiology of restless legs syndrome (RLS). Sleep Med 5(4):385–391

    Article  Google Scholar 

  100. Allen RP, Earley CJ (2007) The role of iron in restless legs syndrome. Mov Disord 22 Suppl 18:S440–8.:S440-S448

  101. Earley CJ, Connor JR, Beard JL, Malecki EA, Epstein DK, Allen RP (2000) Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology 54(8):1698–1700

    Article  CAS  Google Scholar 

  102. Allen RP, Barker PB, Wehrl F, Song HK, Earley CJ (2001) MRI measurement of brain iron in patients with restless legs syndrome. Neurology 56(2):263–265

    Article  CAS  Google Scholar 

  103. Earley CJ, Heckler D, Allen RP (2004) The treatment of restless legs syndrome with intravenous iron dextran. Sleep Med 5(3):231–235. https://doi.org/10.1016/j.sleep.2004.03.002

    Article  Google Scholar 

  104. Kemlink D, Sonka K, Pretl M, Benakova H (2007) Suggestive evidence of erythropoietin level abnormality in patients with sporadic and familial cases of the restless legs syndrome. NeuroEndocrinolLett 28(5):643–646

    CAS  Google Scholar 

  105. Allen RP (2002) Race, iron status and restless legs syndrome. Sleep Med 3(6):467–468

    Article  Google Scholar 

  106. Winkelmann J, Allen RP, Hogl B, Inoue Y, Oertel W, Salminen AV, Winkelman JW, Trenkwalder C, Sampaio C (2018) Treatment of restless legs syndrome: evidence-based review and implications for clinical practice (Revised 2017)( section sign). Mov Disord: Off J Mov Disord Soc 33(7):1077–1091. https://doi.org/10.1002/mds.27260

    Article  Google Scholar 

  107. DelRosso LM, Mogavero MP, Baroni A, Bruni O, Ferri R (2021) Restless legs syndrome in children and adolescents. Child Adolesc Psychiatr Clin N Am 30(1):143–157. https://doi.org/10.1016/j.chc.2020.08.010

    Article  Google Scholar 

  108. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL (2017) Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med: JCSM : Off Publ Am Acad Sleep Med 13(2):307–349. https://doi.org/10.5664/jcsm.6470

    Article  Google Scholar 

  109. Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, Espie CA, Garcia-Borreguero D, Gjerstad M, Goncalves M, Hertenstein E, Jansson-Frojmark M, Jennum PJ, Leger D, Nissen C, Parrino L, Paunio T, Pevernagie D, Verbraecken J, Weess HG, Wichniak A, Zavalko I, Arnardottir ES, Deleanu OC, Strazisar B, Zoetmulder M, Spiegelhalder K (2017) European guideline for the diagnosis and treatment of insomnia. J Sleep Res 26(6):675–700. https://doi.org/10.1111/jsr.12594

    Article  Google Scholar 

  110. Contreras-Gonzalez N, Tellez-Alanis B, Haro R, Jimenez-Correa U, Poblano A (2015) Executive dysfunction in patients with chronic primary insomnia treated with clonazepam. Neurol Res 37(12):1047–1053. https://doi.org/10.1080/01616412.2015.1114740

    Article  CAS  Google Scholar 

  111. Uguz F (2021) A New Safety Scoring System for the Use of Psychotropic drugs during lactation. Am J Ther 28(1):e118–e126. https://doi.org/10.1097/MJT.0000000000000909

    Article  Google Scholar 

  112. Picchietti DL, Hensley JG, Bainbridge JL, Lee KA, Manconi M, McGregor JA, Silver RM, Trenkwalder C, Walters AS (2015) Consensus clinical practice guidelines for the diagnosis and treatment of restless legs syndrome/Willis-Ekbom disease during pregnancy and lactation. Sleep Med Rev 22:64–77. https://doi.org/10.1016/j.smrv.2014.10.009

    Article  Google Scholar 

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Funding

Funding for this study was provided by the Italian Ministry of Health Grant RC n. 2773803; the Italian Ministry of Health had no further role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication.

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Authors and Affiliations

  1. Unit of Neurology, G.B. Morgagni – L. Pierantoni Civic Hospital, 34 Via Carlo Forlanini, 47121, Forlì, Italy

    Alberto Raggi

  2. Institute of Molecular Bioimaging and Physiology, National Research Council, Milan, Italy

    Maria Paola Mogavero

  3. Sleep Disorders Center, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy

    Maria Paola Mogavero

  4. Seattle Children’s Hospital and University of Washington, Seattle, WA, USA

    Lourdes M. DelRosso

  5. Sleep Research Centre, Oasi Research Institute – IRCCS, Troina, Italy

    Raffaele Ferri

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  1. Alberto Raggi
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  2. Maria Paola Mogavero
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  3. Lourdes M. DelRosso
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  4. Raffaele Ferri
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Correspondence to Alberto Raggi.

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Raggi, A., Mogavero, M.P., DelRosso, L.M. et al. Clonazepam for the management of sleep disorders. Neurol Sci 44, 115–128 (2023). https://doi.org/10.1007/s10072-022-06397-x

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