Chuan-Yu Chen, PhD

Associate Investigator

National Health Research InstitutesInstitute of Population Health and Sciences

Division of Mental Health and Addiction Medicine

Predictors of the incidence and discontinuation of long-term use of benzodiazepines:

A population-based study

Team effortsTeam efforts

NHRI: 林克明教授，張憶壽教授

精神組:王聲昌醫師

衛政組:鄭竹珊博士

陳娟瑜、方芍又、葉雪涵

Collaborators 長庚 張家銘醫師

醫療財團法人徐元智先生醫療基金會遠東聯合診所 吳佳璇醫師

亞東醫院 吳其炘醫師

A series of research work

Cheng JS, Huang WF, Lin KM, Shih YT. Characteristics associated with benzodiazepine

usage in elderly outpatients in Taiwan. Int J Geriatr Psychiatry. 2008 23:618-24.

Chang CM, Wu ECH, Chang IS, Lin KM. Benzodiazepine and risk of hip fractures in older people: A nested case-control study in Taiwan. American Journal of Geriatric Psychiatry, 2008 16: 686-92.

Wu CS, Wang SC, Chang IS, Lin KM. The association between dementia and long-term use of Benzodiazepine in the elderly: nested case-control study using claims data. American Journal of Geriatric Psychiatry 2009 17: 614-20.

Fang SY, Chen CY, Chang IS, Wu CH, Chang CM, Lin KM. Predictors of the incidence and discontinuation of long-term use of Benzodiazepines: a population-based study. Drug and Alcohol Dependence, 2009.

Benzodiazepines (苯二氮平類)

Psychoactive medications

Indications: agitation (sedation), anxiety disorders (anxiolytics), insomnia (hypnotics), epileptic seizure, alcohol withdrawal..

Dose-dependent effects

CNS depressants

One of commonly prescribed medication categories

alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium) and lorazepam (Ativan)--listed among the top 100 most commonly prescribed medication

Benzodiazepines (苯二氮平類) Side effects

CNS depressants: psychomotor retardation, cognitive impairment..

Drug and drug/substance interactions

Abuse liability

Tolerance, abuse/dependence, withdrawal

Long-term use

Elderly and underage populations

Sources: prescription and street

Benzodiazepines (苯二氮平類)

Non-Benzodiazepines Z-drugs: Zolpidem （佐沛眠, StilnoxStilnox）、 Zopiclone （唑匹可隆Imovane ）與

Zaleplon （扎來普隆）

Class of schedule: Schedule III: Brotizolam, Triazolam（小白板）,Nimetazepam（一粒

眠）,Flunitrazepam (FM2、十字架)

Schedule IV: Diazepam, Alprazolam, Zolpidem, Zopiclone…

Source:http://www.nbcd.gov.tw/home/dep/list.aspx?did=200507071156777777777&pid=989

Benzodiazepines: 5~10%

Epidemiology of drug-using problems

Model of Disease

Environment

AgentHost

Micro-, exo-, and macro-system (e.g., family, neighborhood, school, peers, media, laws)

Age, sex, race/ethnicity, genetic predisposition, personality trait, life events

Drug type, route of administration, purity, polydrug use..

National Health Insurance Policy

Hospital characteristics Hospital level, region, hospital size,

specialty composition, years…

Physician characteristics Specialty, years of training,

gender, case loadings..

Psychotropics characteristics Dose, off-label, indication,

concurrent medication, source (e.g.,hospital or community

pharmacies)Individual characteristics

Age, gender, SES, comorbidity

OutcomeSymptom/injury, service utilization,

drug-related events, cost

Out-of-pocket payment, OTC, street drugs…

Psychotropic medication utilization in the context of single-payer health care system

Predictors of the incidence and discontinuation of long-term (LT) use of benzodiazepines (BZDs)

Shao-You Fang, Chuan-Yu Chen, I-Shou Chang, Erin Chia-Hsuan Wu,

Chia-Ming Chang, Keh-Ming Lin

Background: LT BZDs1. Prevalence of long-term use; few on incidence

2. Evidence primarily focused on the effects of individual characteristics; little information on organizational or system effects

Research aims:To understand individual, service-provider, and

pharmacological factors accounting for the incidence of long-term use and the discontinuity subsequent to extensive long-term use in the general population

Methodology Dataset:

1. 2000-2002 National Health Insurance Research Database

2. A random sample of 200,000 individuals drawn in 2000

3. A total of 187,413 individuals was recruited according to their health insurance and survival status.

4. Information on utilization of BZDs in the outpatient visits was retrieved from 2000 to 2002.

Methodology Outcome variables:

1. BZD: 24+ 2 Non BZDs

• Alprazolam, bromazepam, brotizolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, cloxazolam, diazepam, estazolam, fludiazepam, flunitrazepam, flurazepam, lorazepam, lormetazepam, medazepam, midazolam, nimetazepam, nitrazepam, nordazepam, oxazepam, oxazolam, prazepam, and triazolam.

• two Z-drugs (zolpidem and zopiclone)

2. Long-term use: 180 prescription days or above in any given calendar year

3. Denominator of incidence: those who hadn’t BZD prescriptions in the preceding year

Methodology Predicting variables:

1. Individual background

• Age, gender, enrollee category, physical disorders, mental disorders

2. Service providers

• Level of medical institution, specialty

3. Pharmacological agents

• Indication, half-life, number of BZD agents, use of opioids

Results 1:Selected attributes

2000(N=187,413) 2001BZD: 2,494(95.23)

Long: 2,121(85.04)

2002

BZD: 34,855(18.60)

Long: 3,650(10.47)

Not long: 31,205(89.53)

BZD: 3,417(93.62)

Longb: 2,619(76.65)

Not long: 798(23.35)

No-BZD: 233(6.38)

BZD: 14,950(47.91)

Long: 1,465(9.80)

No-BZD: 16,255(52.09)

No-BZD: 125(4.77)

BZD: 549(68.80)

No-BZD: 249(31.20)

BZD: 1,350(92.15)

No-BZD: 115(7.85)

No-BZD: 5,404(40.07)

Not long: 13,485(90.20)

Long: 163(29.69)

Not long: 386(70.31)

Long: 891(66.00)

Not long: 459(34.00)

Long: 779(9.64)

Not long: 7,302(90.36)

Not long: 373(14.96)

BZD: 8,081(59.93)

No-BZD: 152,558(81.40)

BZDa: 15,833(10.38)

No-BZD: 136,725(89.62)

Long: 372(2.35)

BZD: 321(86.29)

No-BZD: 51(13.71)

No-BZD: 9,856(63.75)

Not long: 15,461(97.65)

BZD: 5,605(36.25)

Long: 216(67.29)

Not long: 105(32.71)

Long: 474(8.46)

Not long: 5,131(91.54)

BZD: 10,894(7.97)

No-BZD: 125,831(92.03)

Long: 251(2.30)

Not Long: 10,643(97.70)

2000(N=187,413) 2001BZD: 2,494(95.23)

Long: 2,121(85.04)

2002

BZD: 34,855(18.60)

Long: 3,650(10.47)

Not long: 31,205(89.53)

BZD: 3,417(93.62)

Longb: 2,619(76.65)

Not long: 798(23.35)

No-BZD: 233(6.38)

BZD: 14,950(47.91)

Long: 1,465(9.80)

No-BZD: 16,255(52.09)

No-BZD: 125(4.77)

BZD: 549(68.80)

No-BZD: 249(31.20)

BZD: 1,350(92.15)

No-BZD: 115(7.85)

No-BZD: 5,404(40.07)

Not long: 13,485(90.20)

Long: 163(29.69)

Not long: 386(70.31)

Long: 891(66.00)

Not long: 459(34.00)

Long: 779(9.64)

Not long: 7,302(90.36)

Not long: 373(14.96)

BZD: 8,081(59.93)

No-BZD: 152,558(81.40)

BZDa: 15,833(10.38)

No-BZD: 136,725(89.62)

Long: 372(2.35)

BZD: 321(86.29)

No-BZD: 51(13.71)

No-BZD: 9,856(63.75)

Not long: 15,461(97.65)

BZD: 5,605(36.25)

Long: 216(67.29)

Not long: 105(32.71)

Long: 474(8.46)

Not long: 5,131(91.54)

BZD: 10,894(7.97)

No-BZD: 125,831(92.03)

Long: 251(2.30)

Not Long: 10,643(97.70)

Association estimates for incident LT BZDs use

Association estimates for discontinuation of LT BZDs use

Summary Roughly one in 42 ~43 incident users (2.35%) will take BZDs for

180 or more days within any given year; and the rate of complete discontinuation among extensive long-term users is an estimated 4.77%.

Factors in domains of individual sociodemographics, service providers, and pharmacological agents are shown to exert significant effects in the incidence of long-term BZD use.

Only factors pertaining to pharmacological agents appear salient in discontinuation

The prescription of BZDs should consider integrate a matrix that reflects different elements in patient and pharmacological characteristics;

Future programs or policies designed to reduce long-term BZD use and associated negative consequences should target certain subpopulations (e.g., the elderly) and address modifiable factors (e.g., prescribing behaviors). Service provider-based monitoring systems may be developed in order to minimize improper medication delivery, including the prescription of BZDs.

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