Aktuelle Therapie der Narkolepsie

Zusammenfassung

Die Behandlung der Narkolepsie hat durch die Verfügbarkeit neuer Medikamente in den letzten Jahren einen Wandel erfahren. Basierend auf der „International Classification of Sleep Disorders” (ICSD-2) der amerikanischen Academy of Sleep Medicine von 2005 werden die klinischen Symptome, Genetik, Pathophysiologie und das aktuelle diagnostische Vorgehen zusammengefasst und die aktuellen Therapiemöglichkeiten basierend auf den europäischen und deutschen Leitlinien dargestellt. Seitdem Natriumoxybat und Modafinil in der Behandlung der Narkolepsie zugelassen sind, haben sich die Empfehlungen für die Therapie verändert und ehemalige Medikamente der 1. Wahl sind nun erst zweitrangig in Betracht zu ziehen. Zur Therapie der Tagesschläfrigkeit als ein Hauptsymptom der Narkolepsie mit und ohne Kataplexien wird nun Modafinil, Methylphenidat und Natriumoxybat empfohlen, Amphetamine und Selegilin sind Medikamente der 2. Wahl. Die Europäische Leitlinie zur Therapie der Narkolepsie empfiehlt nun zur Therapie der Kataplexie Natriumoxybat und erst in zweiter Linie Antidepressiva, einschließlich Clomipramin und Selegilin. Auch zur Therapie des gestörten Nachtschlafes wird Natriumoxybat empfohlen und bietet so die beste Alternative zur Therapie aller Narkolepsiesymptome.

Abstract

Treatment for narcolepsy with and without cataplexy has changed in the last few years due to the availability of new drugs. This article recounts the clinical symptoms, pathophysiology, genetics and current diagnostic criteria as stated in the International Classification of Sleep Disorders (ICSD-2) by the American Academy of Sleep Medicine in 2005 and presents current therapeutic options based on the European and German guidelines. Since sodium oxybate and modafinil are available now, recommendations regarding the symptomatic treatment have changed and the former first-line drugs are now second choice. Recommended treatment for excessive daytime sleepiness as a major symptom of narcolepsy with or without cataplexy consists of modafinil, methylphenidate and sodium oxybate; the formerly recommended amphetamines and selegiline are now second choice. European treatment recommendations for cataplexy now list sodium oxybate as first choice and antidepressants, particularly clomipramine, and selegiline as second choice drugs. Disturbed night time sleep can also be treated with sodium oxybate, thus adding this new drug to the list of hypnotics that used to be the best option for all narcolepsy symptoms.

Schlüsselwörter

Narkolepsie - Therapie - Kataplexie

Key words

narcolepsy - treatment - cataplexy

Literatur

• 1 Silber M H, Krahn L E, Pankratz V S. The epidemiology of narcolepsy in Olmstead County, Minnesota: a population based study.  Sleep. 2002;  25 197-202
• 2 Hublin C, Kaprio J, Partinen M. et al . The prevalence of narcolepsy: an epidemiological study of the Finnish twin cohort.  Ann Neurol. 1994;  35 709-716
• 3 Mignot E, Ling L, Laurel F. et al . Correlates of sleep-onset REM periods during the Multiple Sleep Latency Test in community adults.  Brain. 2006;  129 1609-1623
• 4 American Academy of Sleep Medicine .International Classification of Sleep Disorders, 2nd ed.: Diagnostic and coding manual. Westchester, Illinois; American Academy of Sleep Medicine 2005
• 5 Mayer G, Kesper K, Ploch T. et al . The implications of gender and age at onset of first symptoms in narcoleptic patients in Germany - results from retrospective evaluation of hospital records.  Somnologie. 2002;  6 13-18
• 6 Dauvilleirs Y, Montplaisir J, Molinari N. et al . Age at onset of narcolepsy in two large populations of patients in France and Quebec.  Neurology. 2001;  57 2029-2033
• 7 Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy.  Lancet. 2007;  369 499-511
• 8 Gerloff C, Bassetti C, Mayer G, Pollmächer T. Narkolepsie. In: Kommission „Leitlinien der Deutschen Gesellschaft für Neurologie” (Hrsg) Leitlinien für Diagnostik und Therapie in der Neurologie. Thieme 2005: 31-34 http://www.uni-duesseldorf.de/WWW/AWMF/ll/ll_neuro.htm
• 9 Billiard M, Bassetti C, Dauvilliers Y. et al . EFNS guidelines on management of narcolepsy.  Eur J Neurol. 2006;  13 1035-1048
• 10 Nishino S. Clinical and neurobiological aspects of narcolepsy.  Sleep Med. 2007;  8 373-399
• 11 Roth B. Narcolepsy and hypersomnia. Basel; Karger 1980
• 12 Honda Y. Clinical features of narcolepsy. In: Honda Y, Juji T (eds) HLA in Narcolepsy. Berlin; Springer-Verlag 1988: 24-57
• 13 Sturzenegger C, Bassetti C. The clinical spectrum of narcolepsy with cataplexy: a reappraisal.  J Sleep Res. 2004;  13 1-13
• 14 Billiard M, Pasquie-Magnetto V, Heckman M. et al . Family studies in narcolepsy.  Sleep. 1994;  17 54-59
• 15 Mignot E. Genetic and familial aspects of narcolepsy.  Neurology. 1998;  50 (Suppl 1) 16-22
• 16 Hublin C, Partinen M, Kaprio J. et al . Epidemiology of narcolepsy.  Sleep. 1994;  17 7-12
• 17 Dement W, Rechtschaffen A, Gulevich G. The nature of the narcoleptic sleep attack.  Neurology. 1966;  16 18-33
• 18 Broughton R, Valley V, Aguirre M. et al . Excessive daytime sleepiness and pathophysiology of narcolepsy-cataplexy: a laboratory perspective.  Sleep. 1996;  9 205-215
• 19 Mignot E, Lammers G J, Ripley B. et al . The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias.  Arch Neurol. 2002;  59 1553-1562
• 20 Lin L, Faraco J, Li R. et al . The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor gene.  Cell. 1999;  98 365-376
• 21 Mayer G. Narkolepsie, Taschenatlas spezial. Stuttgart, New York; Georg Thieme Verlag 2006
• 22 Nishino S, Kanbayashi T. Symptomatic narcolepsy, cataplexy and hypersomnia, their implications in the hypothalamic hypocretin/orexin system.  Sleep Med Rev. 2005;  9 269-310
• 23 Beusterien K M, Rogers A E, Walsleben J A. et al . Health-related quality of life effects of modafinil for treatment of narcolepsy.  Sleep. 1999;  22 757-765
• 24 Billiard M, Besset A, Montplaisir J. et al . Modafinil: A double-blind multicentric study.  Sleep. 1994;  17 54-59
• 25 Broughten R, Fleming J, George C. et al . Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy.  Neurology. 1997;  49 444-451
• 26 US Modafinil in Narcolepsy Multicenter Study Group . Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy.  Ann Neurol. 1998;  43 88-97
• 27 US Modafinil in Narcolepsy Multicenter Study Group . Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy.  Neurology. 2000;  54 1166-1175
• 28 Thorpy M. Therapeutic advances in narcolepsy.  Sleep Med. 2007;  8 427-440
• 29 Xyrem® International Study Group . A double blind placebo controlled study demonstrates sodium oxybate is effective for the treatment of excessive sleepiness in narcolepsy.  J Clin Sleep Med. 2005;  1 391-397
• 30 Mitler M M, Shafor R, Hajdukovich R. et al . Treatment of narcolepsy: objective studies on methylphenidate, pemoline and protriptyline.  Sleep. 1986;  9 260-264
• 31 Teter C J, Guthrie S K. A comprehensive review of MDMA and GHB: two common club drugs.  Pharmacotherapy. 2001;  21 1486-1531
• 32 Broughton R, Mamelak M. Effects of nocturnal gammahydroxybutyrate on sleep/waking patterns in narcolepsy-cataplexy.  Can J Neurol Sci. 1980;  7 23-31
• 33 US Xyrem® Multicenter Study Group . A randomized, double blind, placebo-controlled multicenter trial comparing the effects of three doses of orally administered sodium oxybate with placebo for the treatment of narcolepsy.  Sleep. 2002;  25 42-49
• 34 US Xyrem® Multicenter Study Group . A 12-month, open-label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy.  Sleep. 2003;  26 31-35
• 35 Black J, Houghton W C. Sodium oxybate improves daytime sleepiness in narcolepsy.  Sleep. 2006;  29 939-946
• 36 Scharf M B, Lai A A, Branigan B. et al . Pharmacokinetics of gamma-hydroxybutyrate (GHB) in narcoleptic patients.  Sleep. 1998;  21 507-514
• 37 Borgen L, Lane E, Lai A. Xyrem® (sodium oxybate). A study of dose proportionality in healthy subjects.  J Clin Pharmacol. 2000;  40 1053
• 38 Borgen L, Okerholm R A, Scharf M B. The pharmacokinetics of sodium oxybate following acute and chronic administration to narcoleptic patients.  J Clin Pharmacol. 2004;  44 253-257
• 39 Xyrem® International Study Group . Further evidence supporting the use of sodium oxybate for the treatment of cataplexy: a double blind, placebo controlled study in 228 patients.  Sleep Med. 2005;  6 415-421
• 40 Mayer G, Meier-Ewert K. Selegiline hydrochloride treatment in narcolepsy. A double-blind, placebo controlled study.  Clin Neuropharmacol. 1995;  18 306-319
• 41 Hublin C, Partinen M, Heinonen E H. et al . Selegiline in the treatment of narcolepsy.  Neurology. 1994;  44 2095-2101
• 42 Daniels E, King M, Smith I. et al . Health-related quality of life in narcolepsy.  J Sleep Res. 2001;  10 75-81
• 43 Dodel R, Peter H, Spottke A. et al . Health-related quality of life in patients with narcolepsy.  Sleep Med. 2007;  8 733-741
• 44 U. S. Xyrem® Multicenter Study Group . Sodium oxybate demonstrates long-term efficacy for the treatment of cataplexy in patients with narcolepsy.  Sleep Med. 2004;  5 119-123
• 45 Guilleminault C, Wilson R A, Dement W C. A study on cataplexy.  Arch Neurology. 1974;  31 255-261
• 46 Martinez-Rodriguez J, Iranzo A, Santamaria J. et al . Status cataplecticus induced by abrupt withdrawal of clomipramine.  Neurologia. 2002;  17 113-116
• 47 Poryazova R, Siccoli M, Werth E. et al . Unusually prolonged rebound cataplexy after withdrawal of fluoxetine.  Neurology. 2005;  65 967-968
• 48 Langdon N, Shindler J, Parkes J D. et al . Fluoxetin in the treatment of cataplexy.  Sleep. 1986;  9 371-373
• 49 Frey J, Darbonne C. Fluoxetin suppresses human cataplexy: a pilot study.  Neurology. 1994;  44 707-709
• 50 Thorpy M J, Snyder M, Aloe F S. et al . Short-term triazolam use improves nocturnal sleep of narcoleptics.  Sleep. 1992;  15 212-216