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安眠藥物使用的爭議─ 以 Zolpidem 為例. 財團法人彰化基督教醫院 鹿東分院籌備處 精神科 睡眠醫學中心 邱南英醫師. 個案描述. 42 歲王女士,自 20 歲開始有失眠的問題,使用 benzodiazepine 治療約一年情況改善,不過當她逐漸減少 benzodiazepine 的劑量至停止後數日失眠又復發,在那時她並未濫用或依賴藥物。 - PowerPoint PPT Presentation
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Zolpidem
4220benzodiazepinebenzodiazepine316diazepamflunitrazepambenzodiazepine
36bromazepam1benzodiazepinebenzodiazepine
2zolpidem10zolpidemzolpidemzolpidemzolpidem
3030 2007
-DSM-IV
The majority of insomniacs is chronically ill Mild insomniaSevere insomniaInsomnia (DSM-III-R)Elderly, difficulty falling asleepElderly, disturbed sleep continuity%%%%%Mean 68%% Isomniacs with Persistence of Complaints in Two-Years Follow-Up in Primary Care SurveysGanguli et al. 1996; Hohagen et al. 1993; Katz and McHorney 1998
What causes insomniaSleep disordersPrimary insomniaConditioned arousal at bedtime?Sleep-disruptive habits?Inability to sleep at night or nap during the dayPossible harbinger of a psychiatric disorder, especially depressionRestless legs syndrome Periodic limb movement disorderParasomnias (nightmares, sleep terror, sleepwalking, confusional arousals, dissociative disorders, nocturnal eating disorders)Circadian rhythm disorders (shift work, jet lag, delayed sleep)Poor sleep hygiene
What causes insomniaPsychiatric illnessesPsychiatric and other medicationsSubstance use/abuse/dependenceMedical disordersPainful disordersBed partner with a sleep disorder (e.g., bed partner with snoring, irregular breathing, or movements during sleep)Have patient whose bed partner has a sleep disorder estimate partner sleep quality and length and any changes in mood and performance, especially daytime sleepiness (patients complain more about fatigue and cognition than sleepiness and partners of sleepy patient complain about their partners sleepiness)Have bed partner referred for evaluation and treatment of his sleep disorder
Medications Associated with Insomnia
Insomnia and psychiatric illnessesInsomnia as a psychiatric vital signNo remission unless sleep normalized Increased risk of relapse unless sleep normalizedPanic disorders and nocturnal panic : insomnia through conditioned arousal / conditioned insomniaPTSD : nightmares , decreased stage 3/4 sleep , increased arousal and conditioned arousal , conditioned insomniaDepression : increased and disrupted REM sleep , decreased stage 3/4 sleepSchizophrenia , mania : severe insomnia may precede relapseSchizophrenia : Stage 3/4 sleep decreases as negative symptoms increase
Insomnia and medical illnessesThe more diagnosed medical illnesses you have, the more insomnia you havePerimenopause : nocturnal awakenings correlate with hot flushes , hypothalamic dysregulation , and relapse / onset of major depressionDementia : disrupted sleep correlates with cognitive decline , especially disturbed circadian rhythm and sundowning, nocturnal wandering , daytime sleepinessParkinsons disease : nighttime pain and rigidity as meds wear off , nightmares , hallucinations , REM behavior disorder , sleep talking , and narcolepsy-like daytime symptoms Activation of HPA in OSA , obesity and diabetes is a risk factor for insomnia with decreased sleep associated with increased weight and appetite
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2007
circadian rhythm??Epworth??2007
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2007
2007
Sleep hygiene approachesIncrease daily exercise ( not in the evening)Reduce daytime nappingReduce caffeine or alcohol intake, especially before bedtimeUse the bed only for sleepingUse anxiety management or relaxation techniquesDevelop a regular routine of rising and retiring at the same time each day
-2007
rebound insomnia
Pharmacokinetic Comparison of Medications Used as Sedative-Hypnotics
Pharmacokinetic Comparison of Medications Used as Sedative-Hypnoticswww.theannals.com The Annals of Pharmacotherapy 2001 November. Volume 35
Dosing Recommendations for Hypnotic Medicationswww.theannals.com The Annals of Pharmacotherapy 2001 November. Volume 35
Effects of BZD hypnotics, zopiclone, zolpidem, zaleplon in controlling insomnia
ZolpidemClassNon-benzodiazepine hypnotic; alpha 1 isoform selective agent of GABA-A/benzodiazepine receptorsIndication Short-term treatment of insomniaMechanismBinds selectively to a subtype of the benzodiazepine receptor, the alpha 1 isoformMay enhance GABA inhibitory actions that provide sedative hypnotic effects more selectively than other actions of GABA Boosts chloride conductance through GABA-regulated channelsInhibitory actions in sleep centers may provide sedative hypnotic effectsOnsetGenerally takes effect in less than an hourEffectivenessImproves quality of sleepEffects on total wake-time and number of nighttime awakenings may be decreased over time
Alpha 1 Selective and Distinctive Binding of Zaleplon and Zolpidem
Stilnox 10mg tablets 021531[]Tablet) Zolpidem hemitartate.10[][] 656510STILNOX4-2-5-2-3STILNOX4
zolpidem
Usual therapeutic dose of zolpidemDosage range of adult:5-10mg/day (The Maudsley Prescribing Guidelines, 9th Edition,2007)Dose range: 10mg/day Dose in the elderly: 5mg/day (sleep medicine, 2006)Dosage: 5-10mg/day (sleep disorders, 2002)Usual dose: 10mg/day (sleep disorders, 2008)Usual dosage range: 10mg/day (Essential Psychopharmacology-The Prescribers Guide, 2005)
SIDE EFFECTS OF ZOLPIDEMHow Drug Causes Side EffectsActions at benzodiazepine receptors that carry over to the next day can cause daytime sedation, amnesia, and ataxiaLong-term adaptations of zolpidem not well studied, but chronic studies of other alpha 1 selective non- benzodiazepine hypnotics suggest lack of notable tolerance or dependence developing over timeNotable Side EffectsSedationDizziness, ataxia Dose-dependent amnesiaHyper-excitability, nervousnessRare hallucinationsDiarrhea, nauseaHeadacheLife Threatening or Dangerous Side EffectsRespiratory depression, especially when taken with other CNS depressants in overdose
Zolpidem
zolpidemzolpidem( reinforcing effects) benzodiazepines zolpidem (hallucination )confusionagitationsensory distortionamnesia
Relative Abuse LiabilityPentobarbitalMethaqualoneDiazepamFlunitazepamLorazepamGamma-hydroxybutyrateTemazepamZaleplonEszopicloneTriazolamZopicloneFlurazepamZolpidemEstazolamOxazepamDiphenhydramineQuazepamTrazodoneRamelteon
ScoreGriffiths Sr, Johnson MW. J Clin Psychiatry. 2005.
zolpidem?2007zolpidem320032.17zolpidem200655200713520081380
Zolpidem94195129616
Zolpidem94195129616
Zolpidem94966Zolpidem6462100(941-966 )
Zolpidem
90933.37~5.59%41.36~48.79% 90180
Zolpidem10mg204180ICSD-11insominaZolpidem
80trazodonemirtazapinequetiapineprimarysecondary
sleep apnea
PSGBMI
barbiturateantihistaminechlorcl hydrate1960BZDs BZD
BZDpolypharmacyBZDnon-BZDzolpidemzopicloneBZD
insommia1chronic insomnia 180
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ZolpidemZolpidem
Wish all of you have a good sleep