Targeted medication 은 가능한가 ? 알코올 사용장애 환자의 치료 전략으로 건양대학병원 정신과 기 선 완

Maintenance Treatment : antipsychotics Continuous Medication ADHD : methylphenidate Drug Holiday Risperidone Depot Long-term injectable formulation PMDD : SSRI Targeted Medication Medication

Open-label studies Bohn et al, 1994 –Naltrexone and brief counseling to reduce heavy drinking, Am J Addict Kranzler et al, 1997 early problem drinkers –21 subjects (52% male, early problem drinkers) received brief coping skills training weekly tor 4 weeks, along with naltrexone (50 mg), which they were instructed to use 2 to 5 times per week in anticipation of high-risk drinking situations. –intensity of drinking↓, correlated with medication use –3 months after treatment, effective

Kranzler et al, 2003 Journal Of Clinical Psychopharmacology 8-week, double-blind, placebo-controlled trial Early problem drinkers(N=153, male 58%) naltrexone (50 mg) or placebo on a daily or targeted basis There was a reduced likelihood of heavy drinking, both for patients who received naltrexone and for patients who were in the targeted groups (either naltrexone or placebo) Naltrexone reduced the risk of heavy drinking by 19% –Daily group, throughout the treatment period –Targeted group, only during the first half of the study Zero inflated Poisson regression model –Naltrexone, targeted superior to placebo, daily

Kranzler et al, 2009 Journal Of Clinical Psychopharmacology 12-week trial, 163 individuals (58.3% male), problem drinkers naltrexone 50 mg or placebo daily or targeted to situations identified by them as being high risk for heavy drinking primary outcome measure, mean drinks per day –men in the targeted naltrexone group drank significantly less than patients in the other groups did. secondary outcome measure, drinks per drinking day, during week 12 –the targeted naltrexone group drank significantly less than the other groups did, with no moderating effect of sex. These results support the use of a targeted approach to reduce drinking among heavy drinkers, particularly men

Targeted nalmefene with simple medical management in the treatment of heavy drinkers: a randomized double-blind placebo-controlled multicenter study. ACER 2007 Nalmefene=opioid antagonist(μ-receptor) –half-life 29hours –Two randomized studies Mason(1999) reduced relapse rate to heavy drinking + CBT Anton(2004) (-) heavy drinking + MET Finland, 28-week, 15 sites multicenter study 20mg nalmefene –1 dose per study day –2 tablets after 2 weeks in treatment BRENDA, simple medical management

Biological Makers

Tolerability and Safety

Addiction, presented in 2005 APA meeting, Koob Acute stage Positive affective state Pleasure seeking Impulse control Positive reinforcement HPA axis change Chronic stage Negative affective state Anxiety relief Compulsive behavior Negative reinforcement CNS change

From: Koob GF, Alcohol Clin Exp Res, 2003, 27: Dopamine Opioid GABA Glutamate

Neurochemical Changes Associated with the Transition from Drug Use to Dependence From:Roberts AJ and Koob GF, Alcohol: ethanol antagonists/amethystic agents. in Adelman G and Smith BH (Eds.), Encyclopedia of Neuroscience, 3rd edn, Elsevier, New York, 2003 [

European-wide study 1.Target indication of Nalmefene: For “the reduction of alcohol consumption in alcohol dependent patients” 2.Nalmefene mode of action: A specific opioid receptor antagonist 3.Development status: global phase IIIa clinical trial is on-going, Asian study is planned in Nalmefene concept: –Reduction of alcohol consumption –No abstinence goal –As needed use (when drinking is imminent) –Developed without strong counseling programs

Conclusion Total abstinence 를 Treatment goal 로 철두철미하게 생각하는 치료 문 화에 위배 : 정서적 거부감과 저항 특히 완전한 단주를 추구하나 간헐적인 slips or moderate drinking 하 면서 제한적인 적응을 하고 있는 환자들에게 왜곡된 희망을 제공할 가능성 예방적 치료에 보험 수가 적용 ? More well-designed clinical trial data needed Target population : Only not advanced, early problem drinkers Targeted medication + medical management + motivated patients Biology + Psychoeducation + Public awareness

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