Drug Treatment of Sleep Disorders pp 211-229

Part of the Milestones in Drug Therapy book series (MDT) | Cite as

Modafinil and Armodafinil

Chapter

Abstract

Wakefulness of adequately long duration and quality is in every respect essential for good quality of life. Inadequately low wakefulness named excessive daytime sleepiness (EDS) is defined as a reduced ability to maintain continuous wakefulness during the day. EDS may take the form of lapses into sleep or as periods of somnolence leading to sleep onset in favorable circumstances and longer total duration of sleep within 24 h. EDS lowers the quality of life and complicates or disallows many regular activities.

References

  1. Adler CH, Caviness JN, Hentz JG, Lind M, Tiede J (2003) Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinson’s disease. Mov Disord 18:287–293PubMedCrossRefGoogle Scholar
  2. Ali M, Auger RR, Slocumb NL, Morgenthaler TI (2009) Idiopathic hypersomnia: clinical features and response to treatment. J Clin Sleep Med 5:562–568PubMedCentralPubMedGoogle Scholar
  3. American Academy of Sleep Medicine (2014) International classification of sleep disorders, 3rd edn. American Academy of Sleep Medicine, DarienGoogle Scholar
  4. Anderson KN, Pilsworth S, Sharples LD, Smith IE, Shneerson JM (2007) Idiopathic hypersomnia: a study of 77 cases. Sleep 30:1274–1281PubMedCentralPubMedGoogle Scholar
  5. Bastuji H, Jouvet M (1988) Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil. Prog Neuropsychopharmacol Biol Psychiatry 12:695–700PubMedCrossRefGoogle Scholar
  6. Besset A, Tafti M, Villemin E, Billiard M (1993) The effects of modafinil (300 mg) on sleep, sleepiness and arousal in narcoleptic patients. Neurophysiol Clin 23:47–60PubMedCrossRefGoogle Scholar
  7. Besset A, Chetrit M, Carlander B, Billiard M (1996) Use of modafinil in the treatment of narcolepsy: a long term follow-up study. Neurophysiol Clin 26:60–66PubMedCrossRefGoogle Scholar
  8. Billiard M, Besset A, Montplaisir J, Laffont F, Goldenberg F, Weill JS, Lubin S (1994) Modafinil: a double-blind multicentric study. Sleep 17:S107–S112PubMedGoogle Scholar
  9. Billiard M, Bassetti C, Dauvilliers Y, Dolenc-Groselj L, Lammers GJ, Mayer G, Pollmacher T, Reading P, Sonka K (2006) EFNS guidelines on management of narcolepsy. Eur J Neurol 13:1035–1048PubMedCrossRefGoogle Scholar
  10. Billiard M, Nicolet A, Dauvilliers Y, Carlander B (2007) Modafinil: the European experience. In: Bassetti CL, Biliard M, Mignot E (eds) Narcolepsy and hypersomnia. Informa Healthcare, New YorkGoogle Scholar
  11. Black JE, Hirshkowitz M (2005) Modafinil for treatment of residual excessive sleepiness in nasal continuous positive airway pressure-treated obstructive sleep apnea/hypopnea syndrome. Sleep 28:464–471PubMedGoogle Scholar
  12. Black JE, Hull SG, Tiller J, Yang R, Harsh JR (2010) The long-term tolerability and efficacy of armodafinil in patients with excessive sleepiness associated with treated obstructive sleep apnea, shift work disorder, or narcolepsy: an open-label extension study. J Clin Sleep Med 6:458–466PubMedCentralPubMedGoogle Scholar
  13. Boele FW, Douw L, de Groot M, van Thuijl HF, Cleijne W, Heimans JJ, Taphoorn MJ, Reijneveld JC, Klein M (2013) The effect of modafinil on fatigue, cognitive functioning, and mood in primary brain tumor patients: a multicenter randomized controlled trial. Neuro Oncol 15:1420–1428PubMedCentralPubMedCrossRefGoogle Scholar
  14. Brioschi A, Gramigna S, Werth E, Staub F, Ruffieux C, Bassetti C, Schluep M, Annoni JM (2009) Effect of modafinil on subjective fatigue in multiple sclerosis and stroke patients. Eur Neurol 62:243–249PubMedCrossRefGoogle Scholar
  15. Broughton RJ, Fleming JA, George CF, Hill JD, Kryger MH, Moldofsky H, Montplaisir JY, Morehouse RL, Moscovitch A, Murphy WF (1997) Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Neurology 49:444–451PubMedCrossRefGoogle Scholar
  16. Bruce J, Hancock L, Roberg B, Brown A, Henkelman E, Lynch S (2012) Impact of armodafinil on cognition in multiple sclerosis: a randomized, double-blind crossover pilot study. Cogn Behav Neurol 25:107–114PubMedCrossRefGoogle Scholar
  17. Chapman JL, Kempler L, Chang CL, Williams SC, Sivam S, Wong KK, Yee BJ, Grunstein RR, Marshall NS (2014) Modafinil improves daytime sleepiness in patients with mild to moderate obstructive sleep apnoea not using standard treatments: a randomised placebo-controlled crossover trial. Thorax 69:274–279PubMedCrossRefGoogle Scholar
  18. Czeisler CA, Walsh JK, Roth T, Hughes RJ, Wright KP, Kingsbury L, Arora S, Schwartz JR, Niebler GE, Dinges DF (2005) Modafinil for excessive sleepiness associated with shift-work sleep disorder. N Engl J Med 353:476–486PubMedCrossRefGoogle Scholar
  19. Czeisler CA, Walsh JK, Wesnes KA, Arora S, Roth T (2009) Armodafinil for treatment of excessive sleepiness associated with shift work disorder: a randomized controlled study. Mayo Clin Proc 84:958–972PubMedCentralPubMedCrossRefGoogle Scholar
  20. Duteil J, Rambert FA, Pessonnier J, Gombert R, Assous E (1979) A possibe alpha-adrenergic mechanism for drug (CRL 40028)-induced hyperactivity. Eur J Pharmacol 59:121–123PubMedCrossRefGoogle Scholar
  21. Duteil J, Rambert FA, Pessonnier J, Hermant JF, Gombert R, Assous E (1990) Central alpha 1-adrenergic stimulation in relation to the behaviour stimulating effect of modafinil; studies with experimental animals. Eur J Pharmacol 180:49–58PubMedCrossRefGoogle Scholar
  22. Erman MK, Rosenberg R, Modafinil Shift Work Sleep Disorder Study Group (2007) Modafinil for excessive sleepiness associated with chronic shift work sleep disorder: effects on patient functioning and health-related quality of life. Prim Care Companion J Clin Psychiatry 9:188–194PubMedCentralPubMedCrossRefGoogle Scholar
  23. FDA (2007) NDA 20–717 PROVIGIL® (modafinil) tablets FDA approved labeling. http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020717s020s013s018lbl.pdf. Accessed 21 Apr 2014
  24. Goldenberg F, Weil JS, Vonfrenckeel V (1987) Effects of modafinil on diurnal variation of objective sleepiness in normal subjects. Sleep Res 16:91Google Scholar
  25. Goss AJ, Kaser M, Costafreda SG, Sahakian BJ, Fu CH (2013) Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry 74:1101–1107PubMedCrossRefGoogle Scholar
  26. Harsh JR, Hayduk R, Rosenberg R, Wesnes KA, Walsh JK, Arora S, Niebler GE, Roth T (2006) The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Curr Med Res Opin 22:761–774PubMedCrossRefGoogle Scholar
  27. Hermant JF, Rambert FA, Duteil J (1991) Awakening properties of modafinil: effect on nocturnal activity in monkeys (Macaca mulatta) after acute and repeated administration. Psychopharmacology (Berl) 103:28–32CrossRefGoogle Scholar
  28. Hirshkowitz M, Black JE, Wesnes K, Niebler G, Arora S, Roth T (2007) Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome. Respir Med 101:616–627PubMedCrossRefGoogle Scholar
  29. Hogl B, Saletu M, Brandauer E, Glatzl S, Frauscher B, Seppi K, Ulmer H, Wenning G, Poewe W (2002) Modafinil for the treatment of daytime sleepiness in Parkinson’s disease: a double-blind, randomized, crossover, placebo-controlled polygraphic trial. Sleep 25:905–909PubMedGoogle Scholar
  30. Jha A, Weintraub A, Allshouse A, Morey C, Cusick C, Kittelson J, Harrison-Felix C, Whiteneck G, Gerber D (2008) A randomized trial of modafinil for the treatment of fatigue and excessive daytime sleepiness in individuals with chronic traumatic brain injury. J Head Trauma Rehabil 23:52–63PubMedCrossRefGoogle Scholar
  31. Kaiser PR, Valko PO, Werth E, Thomann J, Meier J, Stocker R, Bassetti CL, Baumann CR (2010) Modafinil ameliorates excessive daytime sleepiness after traumatic brain injury. Neurology 75:1780–1785PubMedCrossRefGoogle Scholar
  32. Kingshott RN, Vennelle M, Coleman EL, Engleman HM, Mackay TW, Douglas NJ (2001) Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of residual excessive daytime sleepiness in the sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 163:918–923PubMedCrossRefGoogle Scholar
  33. Lagarde D, Milhaud C (1990) Electroencephalographic effects of modafinil, an alpha-1-adrenergic psychostimulant, on the sleep of rhesus monkeys. Sleep 13:441–448PubMedGoogle Scholar
  34. Lange R, Volkmer M, Heesen C, Liepert J (2009) Modafinil effects in multiple sclerosis patients with fatigue. J Neurol 256:645–650PubMedCrossRefGoogle Scholar
  35. Lavault S, Dauvilliers Y, Drouot X, Leu-Semenescu S, Golmard JL, Lecendreux M, Franco P, Arnulf I (2011) Benefit and risk of modafinil in idiopathic hypersomnia vs. narcolepsy with cataplexy. Sleep Med 12:550–556PubMedCrossRefGoogle Scholar
  36. Lecendreux M, Bruni O, Franco P, Gringras P, Konofal E, Nevsimalova S, Paiva T, Partinen M, Peeters E, Peraita-Adrados R, Plazzi G, Poli F (2012) Clinical experience suggests that modafinil is an effective and safe treatment for paediatric narcolepsy. J Sleep Res 21:481–483PubMedCrossRefGoogle Scholar
  37. Ledinek AH, Sajko MC, Rot U (2013) Evaluating the effects of amantadin, modafinil and acetyl-L-carnitine on fatigue in multiple sclerosis–result of a pilot randomized, blind study. Clin Neurol Neurosurg 115(Suppl 1):S86–S89PubMedCrossRefGoogle Scholar
  38. Lin JS, Roussel B, Akaoka H, Fort P, Debilly G, Jouvet M (1992) Role of catecholamines in the modafinil and amphetamine induced wakefulness, a comparative pharmacological study in the cat. Brain Res 591:319–326PubMedCrossRefGoogle Scholar
  39. Littleton ET, Hobart JC, Palace J (2010) Modafinil for multiple sclerosis fatigue: does it work? Clin Neurol Neurosurg 112:29–31PubMedCrossRefGoogle Scholar
  40. Lokk J (2010) Daytime sleepiness in elderly Parkinson’s disease patients and treatment with the psychostimulant modafinil: a preliminary study. Neuropsychiatr Dis Treat 6:93–97PubMedCentralPubMedCrossRefGoogle Scholar
  41. Lou JS, Dimitrova DM, Park BS, Johnson SC, Eaton R, Arnold G, Nutt JG (2009) Using modafinil to treat fatigue in Parkinson disease: a double-blind, placebo-controlled pilot study. Clin Neuropharmacol 32:305–310PubMedCrossRefGoogle Scholar
  42. Mayer G, Benes H, Bitterlich M, Young P, Rodenbeck A (2013) Modafinil for the treatment of idiopathic hypersomnia. Results of a randomized, double blind, placebo controlled study. Sleep 36(Suppl):A255Google Scholar
  43. Mignot EJ (2012) A practical guide to the therapy of narcolepsy and hypersomnia syndromes. Neurotherapeutics 9:739–752PubMedCentralPubMedCrossRefGoogle Scholar
  44. Moldofsky H, Broughton RJ, HILL JD (2000) A randomized trial of the long-term, continued efficacy and safety of modafinil in narcolepsy. Sleep Med 1:109–116PubMedCrossRefGoogle Scholar
  45. Moller F, Poettgen J, Broemel F, Neuhaus A, Daumer M, Heesen C (2011) HAGIL (Hamburg Vigil Study): a randomized placebo-controlled double-blind study with modafinil for treatment of fatigue in patients with multiple sclerosis. Mult Scler 17:1002–1009PubMedCrossRefGoogle Scholar
  46. Monderer R, Thorpy MJ (2011) Modafinil/armodafinil in the treatment of excessive daytime sleepiness. In: Thorpy MJ, Billiard M (eds) Sleepiness: causes, consequences, and treatment. Cambridge University Press, CambridgeGoogle Scholar
  47. Morgenthaler TI, Kapen S, Lee-Chiong T, Alessi C, Boehlecke B, Brown T, Coleman J, Friedman L, Kapur V, Owens J, Pancer J, Swick T (2006) Practice parameters for the medical therapy of obstructive sleep apnea. Sleep 29:1031–1035PubMedGoogle Scholar
  48. Morgenthaler TI, Kapur VK, Brown T, Swick TJ, Alessi C, Aurora RN, Boehlecke B, Chesson AL Jr, Friedman L, Maganti R, Owens J, Pancer J, Zak R (2007) Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep 30:1705–1711PubMedCentralPubMedGoogle Scholar
  49. Niepel G, Bibani RH, Vilisaar J, Langley RW, Bradshaw CM, Szabadi E, Constantinescu CS (2013) Association of a deficit of arousal with fatigue in multiple sclerosis: effect of modafinil. Neuropharmacology 64:380–388PubMedCrossRefGoogle Scholar
  50. Nieves AV, Lang AE (2002) Treatment of excessive daytime sleepiness in patients with Parkinson’s disease with modafinil. Clin Neuropharmacol 25:111–114PubMedCrossRefGoogle Scholar
  51. Nishino S, Mignot E (2011) Wake-promoting medications: basic mechanisms and pharmacology. In: Kryger MH, Roth T, Dement WC (eds) Principles and practice of sleep medicine. Elsevier, St. LouisGoogle Scholar
  52. Ondo WG, Fayle R, Atassi F, Jankovic J (2005) Modafinil for daytime somnolence in Parkinson’s disease: double blind, placebo controlled parallel trial. J Neurol Neurosurg Psychiatry 76:1636–1639PubMedCentralPubMedCrossRefGoogle Scholar
  53. Orlikowski D, Chevret S, Quera-Salva MA, Laforet P, Lofaso F, Verschueren A, Pouget J, Eymard B, Annane D (2009) Modafinil for the treatment of hypersomnia associated with myotonic muscular dystrophy in adults: a multicenter, prospective, randomized, double-blind, placebo-controlled, 4-week trial. Clin Ther 31:1765–1773PubMedCrossRefGoogle Scholar
  54. Ozaki A, Inoue Y, Hayashida K, Nakajima T, Honda M, Usui A, Komada Y, Kobayashi M, Takahashi K (2012) Quality of life in patients with narcolepsy with cataplexy, narcolepsy without cataplexy, and idiopathic hypersomnia without long sleep time: comparison between patients on psychostimulants, drug-naive patients and the general Japanese population. Sleep Med 13:200–206PubMedCrossRefGoogle Scholar
  55. Pack AI, Black JE, Schwartz JR, Matheson JK (2001) Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea. Am J Respir Crit Care Med 164:1675–1681PubMedCrossRefGoogle Scholar
  56. Philip P, Chaufton C, Taillard J, Capelli A, Coste O, Leger D, Moore N, Sagaspe P (2014) Modafinil improves real driving performance in patients with hypersomnia: a randomized double-blind placebo-controlled crossover clinical trial. Sleep 37:483–487PubMedCentralPubMedGoogle Scholar
  57. Rammohan KW, Rosenberg JH, Lynn DJ, Blumenfeld AM, Pollak CP, Nagaraja HN (2002) Efficacy and safety of modafinil (Provigil) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study. J Neurol Neurosurg Psychiatry 72:179–183PubMedCentralPubMedCrossRefGoogle Scholar
  58. Roth T, White D, Schmidt-Nowara W, Wesnes KA, Niebler G, Arora S, Black J (2006) Effects of armodafinil in the treatment of residual excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome: a 12-week, multicenter, double-blind, randomized, placebo-controlled study in nCPAP-adherent adults. Clin Ther 28:689–706PubMedCrossRefGoogle Scholar
  59. Roth T, Rippon GA, Arora S (2008) Armodafinil improves wakefulness and long-term episodic memory in nCPAP-adherent patients with excessive sleepiness associated with obstructive sleep apnea. Sleep Breath 12:53–62PubMedCentralPubMedCrossRefGoogle Scholar
  60. Saletu B, Frey R, Krupka M, Anderer P, Grunberger J, Barbanoj MJ (1989) Differential effects of a new central adrenergic agonist–modafinil–and D-amphetamine on sleep and early morning behaviour in young healthy volunteers. Int J Clin Pharmacol Res 9:183–195PubMedGoogle Scholar
  61. Schwartz JR, Feldman NT, Bogan RK, Nelson MT, Hughes RJ (2003a) Dosing regimen effects of modafinil for improving daytime wakefulness in patients with narcolepsy. Clin Neuropharmacol 26:252–257PubMedCrossRefGoogle Scholar
  62. Schwartz JR, Feldman NT, Fry JM, Harsh J (2003b) Efficacy and safety of modafinil for improving daytime wakefulness in patients treated previously with psychostimulants. Sleep Med 4:43–49PubMedCrossRefGoogle Scholar
  63. Schwartz JR, Hirshkowitz M, Erman MK, Schmidt-Nowara W (2003c) Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea: a 12-week, open-label study. Chest 124:2192–2199PubMedCrossRefGoogle Scholar
  64. Schwartz JR, Nelson MT, Schwartz ER, Hughes RJ (2004) Effects of modafinil on wakefulness and executive function in patients with narcolepsy experiencing late-day sleepiness. Clin Neuropharmacol 27:74–79PubMedCrossRefGoogle Scholar
  65. Schwartz JR, Feldman NT, Bogan RK (2005) Dose effects of modafinil in sustaining wakefulness in narcolepsy patients with residual evening sleepiness. J Neuropsychiatry Clin Neurosci 17:405–412PubMedCrossRefGoogle Scholar
  66. Schwartz JR, Khan A, McCall WV, Weintraub J, Tiller J (2010) Tolerability and efficacy of armodafinil in naive patients with excessive sleepiness associated with obstructive sleep apnea, shift work disorder, or narcolepsy: a 12-month, open-label, flexible-dose study with an extension period. J Clin Sleep Med 6:450–457PubMedCentralPubMedGoogle Scholar
  67. Sforza E, Krieger J (1992) Daytime sleepiness after long-term continuous positive airway pressure (CPAP) treatment in obstructive sleep apnea syndrome. J Neurol Sci 110:21–26PubMedCrossRefGoogle Scholar
  68. Sheng P, Hou L, Wang X, Huang C, Yu M, Han X, Dong Y (2013) Efficacy of modafinil on fatigue and excessive daytime sleepiness associated with neurological disorders: a systematic review and meta-analysis. PLoS ONE 8:e81802PubMedCentralPubMedCrossRefGoogle Scholar
  69. Spathis A, Fife K, Blackhall F, Dutton S, Bahadori R, Wharton R, O'Brien M, Stone P, Benepal T, Bates N, Wee B (2014) Modafinil for the treatment of fatigue in lung cancer: results of a placebo-controlled, double-blind, randomized trial. J Clin Oncol 32:1882–1888PubMedCrossRefGoogle Scholar
  70. Stankoff B, Waubant E, Confavreux C, Edan G, Debouverie M, Rumbach L, Moreau T, Pelletier J, Lubetzki C, Clanet M (2005) Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study. Neurology 64:1139–1143PubMedCrossRefGoogle Scholar
  71. Thorpy M (2007) Modafinil: the U.S. experience. In: Bassetti CL, Billiard M, Mignot E (eds) Narcolepsy and hypersomnia. Informa Healthcare, New YorkGoogle Scholar
  72. U.S. Modafinil in Narcolepsy Multicenter Study Group (1998) Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. US Modafinil in Narcolepsy Multicenter Study Group. Ann Neurol 43:88–97CrossRefGoogle Scholar
  73. U.S. Modafinil in Narcolepsy Multicenter Study Group (2000) Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy: US Modafinil in Narcolepsy Multicenter Study Group. Neurology 54:1166–1175CrossRefGoogle Scholar
  74. Walsh JK, Randazzo AC, Stone KL, Schweitzer PK (2004) Modafinil improves alertness, vigilance, and executive function during simulated night shifts. Sleep 27:434–439PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of NeurologyCharles UniversityPragueCzech Republic
  2. 2.Prague Psychiatric CenterPragueCzech Republic
  3. 3.Department of Public HealthSt. Elisabeth UniversityBratislavaSlovakia

Personalised recommendations