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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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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Wish all of you have a good sleep