Psychiatric pharmacogenetics for drug and alcohol treatment

Psychiatric pharmacogenetics refers to the use of genetic testing to predict the effectiveness of pharmacotherapy for individuals with psychiatric illnesses, including alcohol, drug and addiction problems. Some individuals, for instance, may have a genetic variation that interferes with or enhances the metabolism of a particular drug. Researchers from Baylor College of Medicine recently published an article that reviews psychiatric pharmacogenetics for drug and alcohol treatment (Haile, Kosten & Kosten, 2008).

Most FDA-approved pharmacotherapies for addiction treatment are for either alcohol or opiates, and the current study focused on these two addictive substances. The researchers used Medline to conduct a literature review, searching terms related to alcohol and opiates and their pharmacotherapies crossed with related genetic studies.

The study found that alcohol’s physiological and subjective effects are associated with enhanced beta-endorphin release. (Beta-endorphin is an endogenous opioid peptide neurotransmitter. It acts as a natural analgesic, binding to and activating opioid receptors to reduce pain and numb the body.)

The action of naltrexone (Revia, Depade, Vivitrol), an opioid receptor antagonist, is enhanced by a putative functional single nucleotide polymorphism (SNP) in the opioid mu receptor gene (Al18G) which alters receptor function. Patients with this particular SNP, a variation in a single nucleotide of the DNA sequences for the receptor, have significantly lower alcohol relapse rates when treated with naltrexone. This finding suggests that patients with the SNP would have a better response to naltrexone. A genetic test for the SNP would inform decisions for the practitioner as well as the patient.

As for opiates, the researchers found that Caucasians with various forms of the CYP2D6 enzyme generally have a “poorer metabolizer” phenotype and are thus protected from developing opioid dependence (because their bodies cannot properly metabolize opiates). On the other hand, other individuals with “ultra-rapid metabolizer” phenotypes are more likely to have frequent withdrawal symptoms and have a hard time with methadone maintenance. Individuals with the “ultra-rapid metabolizer” phenotype do better with buprenorphine maintenance, as buprenorphine is not significantly metabolized by the CYP2D6 enzyme.

Psychiatric pharmacogenetics has great potential for improving drug and alcohol treatment outcome in the future. A simple genetic test will allow practitioners to identify genetic variants which influence how particular illicit substances and medications will affect an individual. Such tests will allow doctors to choose medications that are more likely to succeed in drug and alcohol treatment and identify drugs that are more likely to be habit-forming for the patient. Currently, pharmocogenetics is not widely utilized because genetic testing is still expensive. In the future, however, the cost of gene sequencing will drop, and genetic testing might become more commonplace in doctor’s officers and drug rehab centers.

However, the history of addiction treatment has been filled with many promising possibilities that, after careful study, are worthless or of little value. Even if we can use genetic testing to identify which individual drinkers or opiate users will recover better on which medications, it will still be necessary for the drinker or user to take the medication (and many will refuse). Ultimately addiction treatment is based on motivation to change. When that motivation is high, many different approaches to treatment are likely to be helpful, if treatment is needed at all.

Haile CN, Kosten TA, Kosten TR. Pharmacogenetic treatments for drug addiction: alcohol and opiates. American Journal of Drug and Alcohol Abuse. 2008; 34(4): 355-381.