Transcript targeted
알코올 사용장애 환자의 치료 전략으로 Targeted medication은 가능한가? 건양대학병원 정신과 기 선 완 Medication Continuous Medication •Maintenance Treatment : antipsychotics Drug Holiday •ADHD : methylphenidate Long-term injectable formulation •Risperidone Depot Targeted Medication •PMDD : SSRI Open-label studies • Bohn et al, 1994 – Naltrexone and brief counseling to reduce heavy drinking, Am J Addict • Kranzler et al, 1997 – 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 placebocontrolled 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 Dopamine Opioid GABA Glutamate From: Koob GF, Alcohol Clin Exp Res, 2003, 27:232-243. 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 [http://203.200.24.140:8080/Neuroscience]. 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 2011 4. Nalmefene concept: – – – – Reduction of alcohol consumption No abstinence goal As needed use (when drinking is imminent) Developed without strong counseling programs Conclusion • Total abstinence를 Treatment goal로 철두철미하게 생각하는 치료 문화에 위배 : 정서적 거부감과 저항 • 특히 완전한 단주를 추구하나 간헐적인 slips or moderate drinking 하면서 제한적인 적응을 하고 있는 환자들에게 왜곡된 희망을 제공 할 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 Thank You for Attention