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The effects of acute treatment with ramelteon, triazolam, and placebo on driving performance, cognitive function, and equilibrium function in healthy volunteers

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Abstract

Rationale

Hypnotics are widely used to treat insomnia but adverse effects of different hypnotics, especially benzodiazepine receptor agonists, are getting more attention lately. The effects of novel hypnotics have not been fully examined.

Objective

This study aims to assess the effects of two hypnotics, ramelteon and triazolam, on driving performance, cognitive function, and equilibrium function.

Methods

In this double-blinded, three-way crossover trial, 17 healthy males received acute doses of 8 mg ramelteon, 0.125 mg triazolam, and placebo. The subjects were administered three driving tasks—road-tracking, car-following, and harsh-braking—using a driving simulator and three cognitive tasks—Continuous Performance Test, N-back Test, and Trail-Making Test—at baseline and at 1 and 4 h post-dosing. The Stanford Sleepiness Scale scores and computerized posturography were also assessed.

Results

In the driving simulations, ramelteon and triazolam increased the number of subjects who slid off the road. Triazolam increased the standard deviation of lateral position compared to ramelteon and placebo at 1 h post-dosing. Ramelteon and triazolam significantly increased the time to complete of Trail-Making Test part A and the environmental area in posturography compared to placebo at 1 and 4 h post-dosing. Ramelteon and triazolam significantly increased subjective sleepiness compared to placebo at 1 h post-dosing.

Conclusions

Ramelteon may affect road-tracking performance, visual attention and/or psychomotor speed measured by Trail-Making Test part A, and body balance in acute dosing. Lower dose of triazolam also impaired performance worse than ramelteon. Physicians should consider risks and benefits when prescribing both drugs, especially in the initial period of administration.

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References

  • Bocca ML, Marie S, Lelong-Boulouard V, Bertran F, Couque C, Desfemmes T, Berthelon C, Amato JN, Moessinger M, Paillet-Loilier M, Coquerel A, Denise P (2011) Zolpidem and zopiclone impair similarly monotonous driving performance after a single nighttime intake in aged subjects. Psychopharmacology (Berl) 214:699–706

    Article  CAS  Google Scholar 

  • Botteman MF, Ozminkowski RJ, Wang S, Pashos CL, Schaefer K, Foley DJ (2007) Cost effectiveness of long-term treatment with eszopiclone for primary insomnia in adults: a decision analytical model. CNS Drugs 21:319–334

    Article  PubMed  Google Scholar 

  • Breslau N, Roth T, Rosenthal L, Andreski P (1996) Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry 39:411–418

    Article  CAS  PubMed  Google Scholar 

  • Calem M, Bisla J, Begum A, Dewey M, Bebbington PE, Brugha T, Cooper C, Jenkins R, Lindesay J, McManus S, Meltzer H, Spiers N, Weich S, Stewart R (2012) Increased prevalence of insomnia and changes in hypnotics use in England over 15 years: analysis of the 1993, 2000, and 2007 National Psychiatric Morbidity Surveys. Sleep 35:377–384

    PubMed Central  PubMed  Google Scholar 

  • Callicott JH, Bertolino A, Mattay VS, Langheim FJ, Duyn J, Coppola R, Goldberg TE, Weinberger DR (2000) Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb Cortex 10:1078–1092

    Article  CAS  PubMed  Google Scholar 

  • Callicott JH, Egan MF, Mattay VS, Bertolino A, Bone AD, Verchinksi B, Weinberger DR (2003) Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. Am J Psychiatry 160:709–719

    Article  PubMed  Google Scholar 

  • Carter CS, Maddock R, Chaderjian M, Post R (1998) Attentional effects of single dose triazolam. Prog Neuropsychopharmacol Biol Psychiatry 22:279–292

    Article  CAS  PubMed  Google Scholar 

  • Carter LP, Griffiths RR, Suess PE, Casada JH, Wallace CL, Roache JD (2007) Relative abuse liability of indiplon and triazolam in humans: a comparison of psychomotor, subjective, and cognitive effects. J Pharmacol Exp Ther 322:749–759

    Article  CAS  PubMed  Google Scholar 

  • Chang CM, Wu EC, Chen CY, Wu KY, Liang HY, Chau YL, Wu CS, Lin KM, Tsai HJ (2013) Psychotropic drugs and risk of motor vehicle accidents: a population-based case–control study. Br J Clin Pharmacol 75:1125–1133

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Clay E, Falissard B, Moore N, Toumi M (2013) Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to the reduction of benzodiazepine and Z-drugs consumption in nine European countries. Eur J Clin Pharmacol 69:1–10

    Article  PubMed Central  PubMed  Google Scholar 

  • Cohen DA, Wang W, Klerman EB, Rajaratnam SM (2010) Ramelteon prior to a short evening nap impairs neurobehavioral performance for up to 12 hours after awakening. J Clin Sleep Med 6:565–571

    PubMed Central  PubMed  Google Scholar 

  • Cornblatt BA, Risch NJ, Faris G, Friedman D, Erlenmeyer-Kimling L (1988) The Continuous Performance Test, identical pairs version (CPT-IP): I. New findings about sustained attention in normal families. Psychiatry Res 26:223–238

    Article  CAS  PubMed  Google Scholar 

  • Demakis GJ (2004) Frontal lobe damage and tests of executive processing: a meta-analysis of the category test, stroop test, and trail-making test. J Clin Exp Neuropsychol 26:441–450

    Article  PubMed  Google Scholar 

  • Erman M, Seiden D, Zammit G, Sainati S, Zhang J (2006) An efficacy, safety, and dose–response study of ramelteon in patients with chronic primary insomnia. Sleep Med 7:17–24

    Article  PubMed  Google Scholar 

  • Farkas RH, Unger EF, Temple R (2013) Zolpidem and driving impairment—identifying persons at risk. N Engl J Med 369:689–691

    Article  CAS  PubMed  Google Scholar 

  • Fava M, McCall WV, Krystal A, Wessel T, Rubens R, Caron J, Amato D, Roth T (2006) Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder. Biol Psychiatry 59:1052–1060

    Article  CAS  PubMed  Google Scholar 

  • Fujimoto C, Murofushi T, Chihara Y, Ushio M, Sugasawa K, Yamaguchi T, Yamasoba T, Iwasaki S (2009) Assessment of diagnostic accuracy of foam posturography for peripheral vestibular disorders: analysis of parameters related to visual and somatosensory dependence. Clin Neurophysiol 120:1408–1414

    Article  PubMed  Google Scholar 

  • Gueorguieva R, Krystal JH (2004) Move over ANOVA: progress in analyzing repeated-measures data and its reflection in papers published in the Archives of General Psychiatry. Arch Gen Psychiatry 61:310–317

    Article  PubMed  Google Scholar 

  • Gustavsen I, Bramness JG, Skurtveit S, Engeland A, Neutel I, Morland J (2008) Road traffic accident risk related to prescriptions of the hypnotics zopiclone, zolpidem, flunitrazepam and nitrazepam. Sleep Med 9:818–822

    Article  PubMed  Google Scholar 

  • Hall MH, Muldoon MF, Jennings JR, Buysse DJ, Flory JD, Manuck SB (2008) Self-reported sleep duration is associated with the metabolic syndrome in midlife adults. Sleep 31:635–643

    PubMed Central  PubMed  Google Scholar 

  • Hallam KT, Olver JS, McGrath C, Norman TR (2003) Comparative cognitive and psychomotor effects of single doses of Valeriana officianalis and triazolam in healthy volunteers. Hum Psychopharmacol 18:619–625

    Article  CAS  PubMed  Google Scholar 

  • Hatta K, Kishi Y, Wada K, Takeuchi T, Odawara T, Usui C, Nakamura H, for the D-JG (2014) Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial. JAMA Psychiatry 71(4):397−403

  • Hoddes E, Zarcone V, Smythe H, Phillips R, Dement WC (1973) Quantification of sleepiness: a new approach. Psychophysiology 10:431–436

    Article  CAS  PubMed  Google Scholar 

  • Horak FB (2006) Postural orientation and equilibrium: what do we need to know about neural control of balance to prevent falls? Age Ageing 35(2):ii7–ii11

    PubMed  Google Scholar 

  • Huang Y, Mai W, Cai X, Hu Y, Song Y, Qiu R, Wu Y, Kuang J (2012) The effect of zolpidem on sleep quality, stress status, and nondipping hypertension. Sleep Med 13:263–268

    Article  PubMed  Google Scholar 

  • Ishizaki K, Mori N, Takeshima T, Fukuhara Y, Ijiri T, Kusumi M, Yasui K, Kowa H, Nakashima K (2002) Static stabilometry in patients with migraine and tension-type headache during a headache-free period. Psychiatry Clin Neurosci 56:85–90

    Article  PubMed  Google Scholar 

  • Iwamoto K, Takahashi M, Nakamura Y, Kawamura Y, Ishihara R, Uchiyama Y, Ebe K, Noda A, Noda Y, Yoshida K, Iidaka T, Ozaki N (2008) The effects of acute treatment with paroxetine, amitriptyline, and placebo on driving performance and cognitive function in healthy Japanese subjects: a double-blind crossover trial. Hum Psychopharmacol 23:399–407

    Article  CAS  PubMed  Google Scholar 

  • Iwamoto K, Kawano N, Sasada K, Kohmura K, Yamamoto M, Ebe K, Noda Y, Ozaki N (2013) Effects of low-dose mirtazapine on driving performance in healthy volunteers. Hum Psychopharmacol 28:523–528

    Article  CAS  PubMed  Google Scholar 

  • Johnson DN, Weingartner HJ, Andreason P, George DT (1995) An effect of triazolam on visual attention and information processing. Psychopharmacology (Berl) 121:145–149

    Article  CAS  Google Scholar 

  • Johnson MW, Suess PE, Griffiths RR (2006) Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects. Arch Gen Psychiatry 63:1149–1157

    Article  CAS  PubMed  Google Scholar 

  • Karim A, Tolbert D, Cao C (2006) Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia. J Clin Pharmacol 46:140–148

    Article  CAS  PubMed  Google Scholar 

  • Kato K, Hirai K, Nishiyama K, Uchikawa O, Fukatsu K, Ohkawa S, Kawamata Y, Hinuma S, Miyamoto M (2005) Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist. Neuropharmacology 48:301–310

    Article  CAS  PubMed  Google Scholar 

  • Kuehn BM (2013) FDA warning: driving may be impaired the morning following sleeping pill use. JAMA 309:645–646

    Article  CAS  PubMed  Google Scholar 

  • Kyriacou CP, Hastings MH (2010) Circadian clocks: genes, sleep, and cognition. Trends Cogn Sci 14:259–267

    Article  PubMed  Google Scholar 

  • Laugsand LE, Vatten LJ, Platou C, Janszky I (2011) Insomnia and the risk of acute myocardial infarction: a population study. Circulation 124:2073–2081

    Article  PubMed  Google Scholar 

  • Laurell H, Tornros J (1986) The carry-over effects of triazolam compared with nitrazepam and placebo in acute emergency driving situations and in monotonous simulated driving. Acta Pharmacol Toxicol (Copenh) 58:182–186

    Article  CAS  Google Scholar 

  • Leufkens TR, Vermeeren A (2009) Highway driving in the elderly the morning after bedtime use of hypnotics: a comparison between temazepam 20 mg, zopiclone 7.5 mg, and placebo. J Clin Psychopharmacol 29:432–438

    Article  PubMed  Google Scholar 

  • Leufkens TR, Lund JS, Vermeeren A (2009) Highway driving performance and cognitive functioning the morning after bedtime and middle-of-the-night use of gaboxadol, zopiclone and zolpidem. J Sleep Res 18:387–396

    Article  PubMed  Google Scholar 

  • Lim J, Oh IK, Han C, Huh YJ, Jung IK, Patkar AA, Steffens DC, Jang BH (2013) Sensitivity of cognitive tests in four cognitive domains in discriminating MDD patients from healthy controls: a meta-analysis. Int Psychogeriatr 25:1543–1557

    Article  PubMed  Google Scholar 

  • Lustman PJ, Griffith LS, Clouse RE, Freedland KE, Eisen SA, Rubin EH, Carney RM, McGill JB (1995) Effects of alprazolam on glucose regulation in diabetes. Results of double-blind, placebo-controlled trial. Diabetes Care 18:1133–1139

    Article  CAS  PubMed  Google Scholar 

  • Mayer G, Wang-Weigand S, Roth-Schechter B, Lehmann R, Staner C, Partinen M (2009) Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia. Sleep 32:351–360

    PubMed Central  PubMed  Google Scholar 

  • McKean A, Vella-Brincat J (2011) Ten-year dispensing trends of hypnotics in New Zealand. N Z Med J 124:108–110

    PubMed  Google Scholar 

  • Mets MA, Volkerts ER, Olivier B, Verster JC (2010) Effect of hypnotic drugs on body balance and standing steadiness. Sleep Med Rev 14:259–267

    Article  PubMed  Google Scholar 

  • Mets MA, de Vries JM, de Senerpont Domis LM, Volkerts ER, Olivier B, Verster JC (2011) Next-day effects of ramelteon (8 mg), zopiclone (7.5 mg), and placebo on highway driving performance, memory functioning, psychomotor performance, and mood in healthy adult subjects. Sleep 34:1327–1334

    PubMed Central  PubMed  Google Scholar 

  • Mintzer MZ, Griffiths RR (1999) Triazolam and zolpidem: effects on human memory and attentional processes. Psychopharmacology (Berl) 144:8–19

    Article  CAS  Google Scholar 

  • Mintzer MZ, Kuwabara H, Alexander M, Brasic JR, Ye W, Ernst M, Griffiths RR, Wong DF (2006) Dose effects of triazolam on brain activity during episodic memory encoding: a PET study. Psychopharmacology (Berl) 188:445–461

    Article  CAS  Google Scholar 

  • Miyata S, Noda A, Ozaki N, Hara Y, Minoshima M, Iwamoto K, Takahashi M, Iidaka T, Koike Y (2010) Insufficient sleep impairs driving performance and cognitive function. Neurosci Lett 469:229–233

    Article  CAS  PubMed  Google Scholar 

  • Morin CM, Belanger L, LeBlanc M, Ivers H, Savard J, Espie CA, Merette C, Baillargeon L, Gregoire JP (2009) The natural history of insomnia: a population-based 3-year longitudinal study. Arch Intern Med 169:447–453

    Article  PubMed  Google Scholar 

  • Nakamura M, Ishii M, Niwa Y, Yamazaki M, Ito H (2005) Temporal changes in postural sway caused by ultrashort-acting hypnotics: triazolam and zolpidem. ORL J Otorhinolaryngol Relat Spec 67:106–112

    Article  CAS  PubMed  Google Scholar 

  • Nakano T, Araki K, Michimori A, Inbe H, Hagiwara H, Koyama E (2001) Nineteen-hour variation of postural sway, alertness and rectal temperature during sleep deprivation. Psychiatry Clin Neurosci 55:277–278

    Article  CAS  PubMed  Google Scholar 

  • National Highway Traffic Safety Administration, U.S. Department of Transportation (2013) Traffic safety facts 2011, Washington DC

  • National Police Agency Transportation Authority (2013) Generation status of traffic accidents during the 24-years of the Heisei Era, Tokyo

  • Nikaido AM, Ellinwood EH Jr (1987) Comparison of the effects of quazepam and triazolam on cognitive-neuromotor performance. Psychopharmacology (Berl) 92:459–464

    Article  CAS  Google Scholar 

  • O’Hanlon JF (1984) Driving performance under the influence of drugs: rationale for, and application of, a new test. Br J Clin Pharmacol 18(1):121S–129S

    Article  PubMed Central  PubMed  Google Scholar 

  • O’Hanlon JF, Haak TW, Blaauw GJ, Riemersma JB (1982) Diazepam impairs lateral position control in highway driving. Science 217:79–81

    Article  PubMed  Google Scholar 

  • Ohayon MM, Lader MH (2002) Use of psychotropic medication in the general population of France, Germany, Italy, and the United Kingdom. J Clin Psychiatry 63:817–825

    Article  PubMed  Google Scholar 

  • Otmani S, Metzger D, Guichard N, Danjou P, Nir T, Zisapel N, Katz A (2012) Effects of prolonged-release melatonin and zolpidem on postural stability in older adults. Hum Psychopharmacol 27:270–276

    Article  CAS  PubMed  Google Scholar 

  • Pandi-Perumal SR, Srinivasan V, Poeggeler B, Hardeland R, Cardinali DP (2007) Drug insight: the use of melatonergic agonists for the treatment of insomnia-focus on ramelteon. Nat Clin Pract Neurol 3:221–228

    Article  CAS  PubMed  Google Scholar 

  • Roache JD, Cherek DR, Bennett RH, Schenkler JC, Cowan KA (1993) Differential effects of triazolam and ethanol on awareness, memory, and psychomotor performance. J Clin Psychopharmacol 13:3–15

    Article  CAS  PubMed  Google Scholar 

  • Robin DW, Hasan SS, Lichtenstein MJ, Shiavi RG, Wood AJ (1991) Dose-related effect of triazolam on postural sway. Clin Pharmacol Ther 49:581–588

    Article  CAS  PubMed  Google Scholar 

  • Roehrs T, Rosenthal L, Koshorek G, Mangano RM, Roth T (2001) Effects of zaleplon or triazolam with or without ethanol on human performance. Sleep Med 2:323–332

    Article  PubMed  Google Scholar 

  • Roth T, Stubbs C, Walsh JK (2005) Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment. Sleep 28:303–307

    PubMed  Google Scholar 

  • Roth T, Coulouvrat C, Hajak G, Lakoma MD, Sampson NA, Shahly V, Shillington AC, Stephenson JJ, Walsh JK, Kessler RC (2011) Prevalence and perceived health associated with insomnia based on DSM-IV-TR; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision; and Research Diagnostic Criteria/International Classification of Sleep Disorders, Second Edition criteria: results from the America Insomnia Survey. Biol Psychiatry 69:592–600

    Article  PubMed  Google Scholar 

  • Rush CR, Griffiths RR (1996) Zolpidem, triazolam, and temazepam: behavioral and subject-rated effects in normal volunteers. J Clin Psychopharmacol 16:146–157

    Article  CAS  PubMed  Google Scholar 

  • Rush CR, Higgins ST, Hughes JR, Bickel WK (1993) A comparison of the acute behavioral effects of triazolam and temazepam in normal volunteers. Psychopharmacology (Berl) 112:407–414

    Article  CAS  Google Scholar 

  • Rush CR, Madakasira S, Hayes CA, Johnson CA, Goldman NH, Pazzaglia PJ (1997) Trazodone and triazolam: acute subject-rated and performance-impairing effects in healthy volunteers. Psychopharmacology (Berl) 131:9–18

    Article  CAS  Google Scholar 

  • Rush CR, Baker RW, Wright K (1999) Acute behavioral effects and abuse potential of trazodone, zolpidem and triazolam in humans. Psychopharmacology (Berl) 144:220–233

    Article  CAS  Google Scholar 

  • Sack RL (2010) Clinical practice. Jet lag. N Engl J Med 362:440–447

    Article  CAS  PubMed  Google Scholar 

  • Sasada K, Iwamoto K, Kawano N, Kohmura K, Yamamoto M, Aleksic B, Ebe K, Noda Y, Ozaki N (2013) Effects of repeated dosing with mirtazapine, trazodone, or placebo on driving performance and cognitive function in healthy volunteers. Hum Psychopharmacol 28:281–286

    Article  CAS  PubMed  Google Scholar 

  • Schmidt C, Collette F, Leclercq Y, Sterpenich V, Vandewalle G, Berthomier P, Berthomier C, Phillips C, Tinguely G, Darsaud A, Gais S, Schabus M, Desseilles M, Dang-Vu TT, Salmon E, Balteau E, Degueldre C, Luxen A, Maquet P, Cajochen C, Peigneux P (2009) Homeostatic sleep pressure and responses to sustained attention in the suprachiasmatic area. Science 324:516–519

    Article  CAS  PubMed  Google Scholar 

  • Shahly V, Berglund PA, Coulouvrat C, Fitzgerald T, Hajak G, Roth T, Shillington AC, Stephenson JJ, Walsh JK, Kessler RC (2012) The associations of insomnia with costly workplace accidents and errors: results from the America Insomnia Survey. Arch Gen Psychiatry 69:1054–1063

    Article  PubMed  Google Scholar 

  • Spreen OSE (1998) A compendium of neuropsychological tests and norms, 2nd edn. Oxford University Press, New York

    Google Scholar 

  • Staner L, Ertle S, Boeijinga P, Rinaudo G, Arnal MA, Muzet A, Luthringer R (2005) Next-day residual effects of hypnotics in DSM-IV primary insomnia: a driving simulator study with simultaneous electroencephalogram monitoring. Psychopharmacology (Berl) 181:790–798

    Article  CAS  Google Scholar 

  • Stewart SA (2005) The effects of benzodiazepines on cognition. J Clin Psychiatry 66(2):9–13

    CAS  PubMed  Google Scholar 

  • Tada K, Sato Y, Sakai T, Ueda N, Kasamo K, Kojima T (1994) Effects of zopiclone, triazolam, and nitrazepam on standing steadiness. Neuropsychobiology 29:17–22

    Article  CAS  PubMed  Google Scholar 

  • Takahashi M, Iwamoto K, Kawamura Y, Nakamura Y, Ishihara R, Uchiyama Y, Ebe K, Noda A, Noda Y, Yoshida K, Iidaka T, Ozaki N (2010) The effects of acute treatment with tandospirone, diazepam, and placebo on driving performance and cognitive function in healthy volunteers. Hum Psychopharmacol 25:260–267

    Article  CAS  PubMed  Google Scholar 

  • Troy SM, Lucki I, Unruh MA, Cevallos WH, Leister CA, Martin PT, Furlan PM, Mangano R (2000) Comparison of the effects of zaleplon, zolpidem, and triazolam on memory, learning, and psychomotor performance. J Clin Psychopharmacol 20:328–337

    Article  CAS  PubMed  Google Scholar 

  • Uchiyama Y, Ebe K, Kozato A, Okada T, Sadato N (2003) The neural substrates of driving at a safe distance: a functional MRI study. Neurosci Lett 352:199–202

    Article  CAS  PubMed  Google Scholar 

  • Vermeeren A (2004) Residual effects of hypnotics: epidemiology and clinical implications. CNS Drugs 18:297–328

    Article  CAS  PubMed  Google Scholar 

  • Vermeeren A, Riedel WJ, van Boxtel MP, Darwish M, Paty I, Patat A (2002) Differential residual effects of zaleplon and zopiclone on actual driving: a comparison with a low dose of alcohol. Sleep 25:224–231

    PubMed  Google Scholar 

  • Verster JC, Veldhuijzen DS, Volkerts ER (2004) Residual effects of sleep medication on driving ability. Sleep Med Rev 8:309–325

    Article  PubMed  Google Scholar 

  • Verster JC, Bervoets AC, de Klerk S, Roth T (2013) Lapses of attention as outcome measure of the on-the-road driving test. Psychopharmacology (Berl) 231(1):283−292

  • Vgontzas AN, Liao D, Bixler EO, Chrousos GP, Vela-Bueno A (2009a) Insomnia with objective short sleep duration is associated with a high risk for hypertension. Sleep 32:491–497

    PubMed Central  PubMed  Google Scholar 

  • Vgontzas AN, Liao D, Pejovic S, Calhoun S, Karataraki M, Bixler EO (2009b) Insomnia with objective short sleep duration is associated with type 2 diabetes: a population-based study. Diabetes Care 32:1980–1985

    Article  PubMed Central  PubMed  Google Scholar 

  • Vgontzas AN, Liao D, Pejovic S, Calhoun S, Karataraki M, Basta M, Fernandez-Mendoza J, Bixler EO (2010) Insomnia with short sleep duration and mortality: the Penn State cohort. Sleep 33:1159–1164

    PubMed Central  PubMed  Google Scholar 

  • Zammit G, Erman M, Wang-Weigand S, Sainati S, Zhang J, Roth T (2007) Evaluation of the efficacy and safety of ramelteon in subjects with chronic insomnia. J Clin Sleep Med 3:495–504

    PubMed Central  PubMed  Google Scholar 

  • Zammit G, Schwartz H, Roth T, Wang-Weigand S, Sainati S, Zhang J (2009a) The effects of ramelteon in a first-night model of transient insomnia. Sleep Med 10:55–59

    Article  PubMed  Google Scholar 

  • Zammit G, Wang-Weigand S, Rosenthal M, Peng X (2009b) Effect of ramelteon on middle-of-the-night balance in older adults with chronic insomnia. J Clin Sleep Med 5:34–40

    PubMed Central  PubMed  Google Scholar 

  • Zee PC, Wang-Weigand S, Wright KP Jr, Peng X, Roth T (2010) Effects of ramelteon on insomnia symptoms induced by rapid, eastward travel. Sleep Med 11:525–533

    Article  PubMed  Google Scholar 

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Acknowledgments

We sincerely thank the healthy volunteers for participating in our study. This work was supported in part by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Ministry of Health, Labor and Welfare of Japan;  the Center of Innovation Program from Japan Science and Technology Agency, JST; NEXCO Group Companies’ Support Fund to Disaster Prevention Measures on Expressways; the General Insurance Association of Japan; the Daiwa Syoken Health Foundation; the Mitsui-Sumitomo Wellness Foundation; and the Japan Foundation for Neuroscience and Mental Health.

Conflict of interest

Dr. K. Iwamoto has received speakers’ honoraria from Dainippon Sumitomo, Eisai, Eli Lilly, GlaxoSmithKline, Meiji Seika Pharma, Mochida, Otsuka, and Tanabe Mitsubishi. Dr. S. Iritani has received speakers’ honoraria from Eisai and Pfizer. Dr. N. Ozaki has received research support or speakers’ honoraria from, or has served as a consultant to Abbvie, Asahi Kasei Pharma, Astellas, Dainippon Sumitomo, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Meiji Seika Pharma, Mochida, MSD, Novartis Pharma, Ono, Otsuka, Pfizer, Shionogi, Takeda, Tanabe Mitsubishi, Sanofi, and Yoshitomi.

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Authors and Affiliations

  1. Department of Psychiatry, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan

    Akemi Miyata, Kunihiro Iwamoto, Naoko Kawano, Kunihiro Kohmura, Maeri Yamamoto, Branko Aleksic, Shuji Iritani & Norio Ozaki

  2. Toyota Central R&D Labs., Inc., Nagakute, Aichi, Japan

    Kazutoshi Ebe

  3. Department of Biomedical Sciences, Chubu University, Kasugai, Aichi, Japan

    Akiko Noda

  4. Division of Clinical Science and Neuropsychopharmacology, Meijo University, Graduate School of Pharmacy, Nagoya, Aichi, Japan

    Yukihiro Noda

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  1. Akemi Miyata
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Correspondence to Kunihiro Iwamoto.

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Miyata, A., Iwamoto, K., Kawano, N. et al. The effects of acute treatment with ramelteon, triazolam, and placebo on driving performance, cognitive function, and equilibrium function in healthy volunteers. Psychopharmacology 232, 2127–2137 (2015). https://doi.org/10.1007/s00213-014-3843-4

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