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1、慢性失眠及安眠藥物的使用,個案描述一,28歲的王先生，唸專科時期開始就有經常睡不好，經常得要躺超過一個小時才能入睡，遇到有考試壓力或者和朋友之間有些爭執時就更不好睡，就算睡著了，一有聲響很容易就醒過來，又得躺好一陣子才能再入睡。學校畢業後因為家庭經濟因素開始工作，睡眠狀況還是不理想。王先生曾經在一般開業醫師診所處方過安眠藥，效果還不錯。但是他很擔心常用會成癮，總是盡量不用安眠藥，有時一整個星期都沒有一天睡得好。他聽別人說什麼方法可以治失眠，都會去試，但是效果都不好。到後來每天一天黑就覺得要找一點上床準備睡覺，但是又覺得害怕、怕那一天又會睡不好或睡不著。長期下來，白天不但會常頭暈，而且越來越沒耐
2、性，常常提不起勁來，感覺自己快要垮了，近半年來已經把休假請光，還請了不少病假，最近才由朋友介紹到精神科看門診。,個案描述二,36歲的陳女士離婚後因為背負卡債及家庭經濟重擔，有入睡困難和睡眠中斷的睡眠障礙已有4、5年。剛開始看精神科時，吃1、2顆安眠鎮靜藥物就可以睡上幾個小時，但是總覺得睡不夠，半夜一醒過來就再吃2顆，有時已經塞了7、8顆安眠藥還是睡不好。後來藥不夠時她就到另一家醫院的精神科開藥。雖然有醫師建議她應該要嘗試其他改善睡眠的方法，並且控制使用安眠藥，但是她就是擔心不吃睡不著，雖然她也知道其實吃了也不一定睡得好，有時候就乾脆把安眠藥配著啤酒吃，最近喝酒的量也漸漸多起來。,問題討論,問題
3、一：慢性失眠應用藥物治療治療前應有的評估及處置？問題二：安眠藥到底是持續用好還是盡量不要用？問題三：安眠藥的療效究竟如何？,Insomnia Has Several Definitions,NHLBI.Am Fam Physician.1999;59(abstract).,Difficulty falling asleep,Next-day consequences,Difficulty staying asleep,Non-refreshing sleep,Early morning awakenings,+,Given adequate opportunity to sleep,Chron
4、ic Insomnia:Definition,Chronic insomnia vs.Acute insomniaAcute insomnia may occur in anyone at one time or anotherVaried definitions for chronic insomniaDurations ranging from 30 days 6 monthsChronic insomnia is often associated with a wide range of adverse conditions including:Mood disturbancesDiff
5、iculties with concentration and memorySome cardiovascular,pulmonary,and gastrointestinal disorders,NIH Statement.Sleep.2005;28:1049-1057.,Insomnia is the most common sleep complaint across all stages of adulthood,and for millions,the problem is chronicInsomnia can be a symptom of other disorders,lik
6、e depression,or it can be a primary disorder in itself,The Majority of Insomniacs is Chronically Ill,Mild insomnia,Severe insomnia,Insomnia(DSM-III-R),Elderly,difficulty falling asleep,Elderly,disturbed sleep continuity,%,%,%,%,%,Mean 68%,%Isomniacs with Persistence of Complaints in Two-Years Follow
7、-Up in Primary Care Surveys,Ganguli et al.1996;Hohagen et al.1993;Katz and McHorney 1998,Chronic Insomnia:Epidemiology,Prevalence,30%of general population complains of sleep disruption 10%has daytime functional impairment,Natural History,Few studies describe the course and duration of insomnia,Incid
8、ence,Very little is known about chronic insomnias incidence Only a few studies have examined incidence,Risk Factors,Higher prevalence of insomnia in:Women(especially postmenopausal)Divorced,separated,widowed adults Psychiatric and physical illnesses,Other risk factors include cigarette smoking,alcoh
9、ol,coffee consumption,and numerous prescription drugs,NIH Statement.Sleep.2005;28:1049-1057.,Chronic Insomnia:Consequences,Some evidence suggests a relationship between chronic insomnia and impaired memory,cognitive functioning,and depressed mood,Consequences,Associated with high health care utiliza
10、tion Direct and Indirect Costs:estimated in the tens of billions of dollars annually,Quality of Life,Reduces quality of lifeHinders social functioningRelated to impaired work performance,NIH Statement.Sleep.2005;28:1049-1057.,Comorbidities,Seldom appears without one or more other disorders Common co
11、morbidities:depression,generalized anxiety,substance abuse,attention deficit,and a variety of physical problems,Public Health Burden,Difficult to evaluate because literature is not developed Focus is on populations rather than people,Comorbid Psychiatric Disorders With Insomnia,*P.001 compared with
12、those with no sleep complaint.P.05 compared with those with no sleep complaint.Ford DE et al.JAMA.1989;262:1479-1484.,Percentage,*,*,*,*,Medical Conditions Associated With Insomnia,*P.001;P.05.P.01.CHF=congestive heart failure;COPD=chronic obstructive pulmonary disease.Katz DA et al.Arch Intern Med.
13、1998;158:1099-1107.,*,*,Adjusted Odds Ratio,Impact of Sleep Difficulties on Daily Functioning,Rating Ability as Poor(%),Doghramji PP.J Clin Psychiatry.2001;62(suppl 10):18-26.,Greater Impaired Function,Impact of Insomnia on Physical and Emotional Health and Social Functioning,*Scale ranges from 0 to
14、 100,with higher scores reflecting greater quality of life.Adapted from Zammit GK et al.Sleep 1999;22(suppl 2):S379-S385.,SF-36 Subscales*,*P0.0001,Greater Interference,Impact of Insomnia in the Workplace,Daytime functioning and loss of productivityTwo to three times as many days of poor productivit
15、y and concentration in individuals with insomnia as in good sleepersAbsenteeismSevere insomniacs were absent from work twice as often as good sleepersWork accidentsSeven times higher rate of work accidents in insomniacs than in good sleepers,Metlaine A,et al.Industrial Health.2005;43:1119.,Therapeut
16、ic Goals in Treating Insomnia,Sleep Onset,Sleep Maintenance,Number of awakeningsDuration of awakenings,Time to fall asleep,Sleep Duration,Total sleep time,AlertnessFunctioningVitality,Next-Day Functioning,Initial ScreeningNature of complaintDaytime consequencesFrequencyDuration,Precipitating eventsE
17、xacerbating factorsSleep-wake scheduleOther nocturnal symptoms,Associated behaviorsCognitionsPrevious treatmentsPsychiatric disorders,Substance abuseConcomitant medicationsMedical/neurological illnessOther sleep disorders,Assessment of Insomnia,Adapted from Winkleman,Additional History for Persisten
18、t Insomnia,Chronic Insomnia:Treatment Considerations,TREATMENT,Cognitive Behavioral Therapy(CBT),Benzodiazepine Receptor Agonist BenzodiazepinesNon-Benzodiazepines,Antidepressants*,Atypical Antipsychotics*,OTC,Alternative Meds:Melatonin and Herbal Remedies,*Not FDA approved for treatment of insomnia
19、NIH Statement.Sleep.2005;28:1049-1057.,Treat Insomnia with Drugs,Before treating insomnia with drugs,consider:Is the underlying cause being treated(depression,mania,breathing difficulties,urinary frequency,pain,etc.)?Are other drugs being given at appropriate times(i.e.stimulating drugs in the morni
20、ng,sedating drugs at night)?Are the patients expectations of sleep realistic(sleep requirements decrease with age)?Have all sleep hygiene approaches(see table below)been tried?,Guidelines for Prescribing Hypnotics,Use the lowest effective doseUse intermittent dosing(alternate nights or less)where po
21、ssiblePrescribe for short-term use(no more than 4 weeks)in the majority of casesDiscontinue slowlyBe alert for rebound insomnia/withdrawal symptomsAdvise patients of the interaction with alcohol and other sedating drugsAvoid the use of hypnotics in patients with respiratory disease or severe hepatic
22、 impairment and in addiction-prone individuals,Prescribing Guidelines,The Maudsley,2007,The efficacy and safety of drug treatments for chronic insomnia in adults:a meta-analysis of RCTs,J Gen Intern Med.2007 Sep;22(9):1335-50.Epub 2007 Jul 10 BACKGROUND:Hypnotics have a role in the management of acu
23、te insomnia;however,the efficacy and safety of pharmacological interventions in the management of chronic insomnia is unclear.OBJECTIVE:The objective of this paper is to conduct a systematic review of the efficacy and safety of drug treatments for chronic insomnia in adults.DATA SOURCES:Twenty-one e
24、lectronic databases were searched,up to July 2006.STUDY SELECTION:Randomized double-blind,placebo-controlled trials were eligible.Quality was assessed using the Jadad scale.Data were pooled using the random effects model.DATA SYNTHESIS:One hundred and five studies were included in the review.Sleep o
25、nset latency,as measured by polysomnography,was significantly decreased for benzodiazepines(BDZ),(weighted mean difference:-10.0 minutes;95%CI:-16.6,-3.4),non-benzodiazepines(non-BDZ)(-12.8 minutes;95%CI:-16.9,-8.8)and antidepressants(ADP)(-7.0 minutes;95%CI:-10.7,-3.3).Sleep onset latency assessed
26、by sleep diaries was also improved(BDZ:-19.6 minutes;95%CI:-23.9,-15.3;non-BDZ:-17.0 minutes;95%CI:-20.0,-14.0;ADP:-12.2 minutes;95%CI:-22.3,-2.2).Indirect comparisons between drug categories suggest BDZ and non-BDZ have a similar effect.All drug groups had a statistically significant higher risk of
27、 harm compared to placebo(BDZ:risk difference RD:0.15;non-BDZ RD:0.07;and ADP RD:0.09),although the most commonly reported adverse events were minor.Indirect comparisons suggest that non-BDZ are safer than BDZ.CONCLUSIONS:Benzodiazepines and non-benzodiazepines are effective treatments in the manage
28、ment of chronic insomnia,although they pose a risk of harm.There is also some evidence that antidepressants are effective and that they pose a risk of harm.,Insomnia:Challenges for PhysiciansInitiating Treatment,Insomnia is challenging for clinicians because of the lack of guidelines for assessment
29、and treatmentGeneral populations poor understanding of the importance of insomnia and available treatmentsForty percent of insomniacs self-medicate either with over-the-counter medications or with alcoholOnly 0.9%of patients in a large managed care group reported visiting a physician specifically fo
30、r sleep problemsYet,34.2%of these patients reported symptoms of insomniaOne in 3 patients seeking health care is likely to have insomnia with daytime dysfunction,but is unlikely to seek care for that specific problem,Benca RM.Psychiatr Serv.2005;56:332343.Ancoli-Israel S,Roth T.Sleep.199922(suppl 2)
31、:S347-S353.Doghramji PP.J Clin Psychiatry.2004;65(suppl 16):23-26.,Insomnia:Challenges for Physicians,In an international study of consequences of insomnia over a 12-month periodMany respondents took no action to alleviate their insomnia symptoms,and this may be due to fear of the implications of tr
32、eatment,including the possible risks of dependence on medicationsFocus groups of patients describing their insomnia experience reported that they felt that the impact of insomnia on their lives was pervasive and misunderstood by others who were significant to them or treating their sleep complaintsM
33、ore research is necessary to determine the long-term effects of insomnia treatmentsCurrent treatment options do not address the needs of difficult-to-treat patients with chronic insomnia,such as the elderly,and those with comorbid medical and psychiatric conditions.,Benca RM.Psychiatr Serv.2005;56:3
34、32343.Lger D,Poursain B.Curr Med Res Opin.2005;21:1785-1792.Carey TJ et al.Behav Sleep Med.2005;3:73-86.,台灣鎮靜安眠類藥品使用盛行率以及相關後遺症之研究,行政院衛生署管制藥品管理局九十六年度委託科技研究計畫報告,民國97年,吳佳璇、張家銘、張憶壽、林克明、賴虹均、王金龍、蔡芳榆。分析健保歸人檔資料獲得鎮靜安眠類藥品使用年盛行率，使用量，使用方式，以及使用者相關之人口學背景與醫療使用率。預定連續分析數年(20012004)健保資料，探討變化趨勢。,The prevalence,using a
35、mount and characters of BZD users from 2001 to 2004,台灣鎮靜安眠類藥品使用盛行率以及相關後遺症之研究,行政院衛生署管制藥品管理局九十六年度委託科技研究計畫報告,民國97年,The prescribing pattern among different specialities from 2001-2004,台灣鎮靜安眠類藥品使用盛行率以及相關後遺症之研究,行政院衛生署管制藥品管理局九十六年度委託科技研究計畫報告,民國97年,The prescribing frequency among different BZDs from 2001-200
36、4,台灣鎮靜安眠類藥品使用盛行率以及相關後遺症之研究,行政院衛生署管制藥品管理局九十六年度委託科技研究計畫報告,民國97年,The prescribing amount among different BZDs from 2001-2004,台灣鎮靜安眠類藥品使用盛行率以及相關後遺症之研究,行政院衛生署管制藥品管理局九十六年度委託科技研究計畫報告,民國97年,ZOLPIDEM 使用率與使用量增加趨勢值得關注,ZOLPIDEM 單品項使用率在2001至2004年間增加幅度明顯，與同屬於BZD receptor agonists的ZOLPICLONE相對平穩的使用率相較，ZOLPIDEM被廣泛使用
37、，其原因除可能的藥理優越性外，值得進一步探討。BZD receptor agonists是否依賴性與成癮性均優於傳統的BZD，雖有報告*，仍有待更多資料檢驗。但將近六成醫師認同上列陳述，讓醫師傾向以BZD receptor agonists取代長效的BZD，成為處理睡眠障礙的藥物首選。因應BZD receptor agonists（特別是ZOLPIDEM）近年大量使用之趨勢，宜有全面性、系統性的評估，以證實其療效並瞭解可能的不良反應，必要時制定相關使用準則，以確保治療效果及用藥安全。*Jerome H.Jaffe,Roger Bloor,Ilana Crome,Malcolm Carr,Farrukh Alam,Arnol Simmons&Roger E.Meyer(2004).A postmarketing study of relative abuse liability of hypnotic sedative drugs.Addiction,99,165173.,Thanks for Your Attentions!,
