Pharmacogenetic treatments for drug addiction: alcohol and opiates.
OBJECTIVE
Psychiatric pharmacogenetics involves the use of genetic tests that can predict the effectiveness of treatments for individual patients with mental illness such as drug dependence. This review aims to cover these developments in the pharmacotherapy of alcohol and opiates, two addictive drugs for which we have the majority of our FDA approved pharmacotherapies.


METHODS
We conducted a literature review using Medline searching terms related to these two drugs and their pharmacotherapies crossed with related genetic studies.


RESULTS
Alcohol's physiological and subjective effects are associated with enhanced beta-endorphin release. Naltrexone increases baseline beta-endorphin release blocking further release by alcohol. Naltrexone's action as an alcohol pharmacotherapy is facilitated by a putative functional single nucleotide polymorphism (SNP) in the opioid mu receptor gene (Al18G) which alters receptor function. Patients with this SNP have significantly lower relapse rates to alcoholism when treated with naltrexone. Caucasians with various forms of the CYP2D6 enzyme results in a 'poor metabolizer' phenotype and appear to be protected from developing opioid dependence. Others with a "ultra-rapid metabolizer" phenotype do poorly on methadone maintenance and have frequent withdrawal symptoms. These patients can do well using buprenorphine because it is not significantly metabolized by CYP2D6.


CONCLUSIONS
Pharmacogenetics has great potential for improving treatment outcome as we identify gene variants that affect pharmacodynamic and pharmacokinetic factors. These mutations guide pharmacotherapeutic agent choice for optimum treatment of alcohol and opiate abuse and subsequent relapse.
Haile
Colin N
CN
Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas 77030, USA.
Kosten
Therese A
TA
Kosten
Thomas R
TR
D000437:Alcoholism / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D002047:Buprenorphine / Q000494:pharmacology* / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009271:Naltrexone / Q000494:pharmacology* / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects / Q000235:genetics; D011237:Predictive Value of Tests; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000235:genetics; D001615:beta-Endorphin / Q000097:blood / Q000187:drug effects
D009292:Narcotic Antagonists; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D002047:Buprenorphine; D009271:Naltrexone; D001615:beta-Endorphin; D019389:Cytochrome P-450 CYP2D6