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Pharmacogenetic Approaches to Addiction Management Can Improve Outcomes
San Diego, CA—Choosing the best pharmacotherapies for patients with addiction problems based on their own genetic makeup can improve patient outcomes and help promote recovery, according to Thomas Kosten, MD, Jay H. Waggoner chair and professor of psychiatry, neuroscience, pharmacology, immunology, and pathology at Baylor College of Medicine.
“Overall, these matchings between patient genetics and specific medications can markedly improve the treatment response of patients and prevent using medications in patients who will either have no benefit from them or will develop significant side effects,” Dr Kosten said. New tools have emerged to treat addictions through pharmacotherapy, whether its pharmacogenetic strategies such as nalmefene for alcohol addiction or vaccines used to treat those with a dependence on methamphetamines. One such strategy, using the OPRM1 Asn40Asp polymorphism to match severe alcoholic patients with naltrexone treatment, is nearing clinical application. Naltrexone, an orally active opiate antagonist, has been shown to substantially decrease drinking, and the drug has been found to be effective for patients with OPRM1 Asn40Asp polymorphism.
According to Dr Kosten, those patients who are more complex and severely dependent with a strong family history of alcoholism may be better for naltrexone. The drug works by raising the ß-endorphin through feedback inhibition from the presynaptic opioid receptors. It also reduces alcohol stimulation and craving by maximizingβß-endorphin stimulation.
Nalmefene, another orally active opiate antagonist, is still pending FDA approval. The drug has shown promising results with fewer liver toxicities than naltrexone. Research has shown that it significantly reduces the number of heavy drinking days as well as total alcohol consumption.
Pharmacotherapies can also be a valuable tool in treating patients with cocaine addictions. Doxazosin is a promising medication that blocks the ADRA1A brain receptor, a receptor stimulated by norepinephrine. The more stimulated the ADRA1A receptor is by the release of norepinephrine the greater the high is that is produced by the drug. Thus, by blocking this receptor, the drug is able to reduce the cocaine high. One study found that doxazosin 4 mg significantly attenuated the effects of 20 mg of cocaine.
Clinical trials have also shown that the use of doxazosin produced significantly more patients who were able to abstain from cocaine use for ≥2 weeks compared with a placebo.
The drug may be particularly effective for patients with the ADRA1A CC “normal” variant gene. Research has found that the percentage of cocaine-free urines in patients with the this gene variant was 30% after taking doxazosin, compared with 10% in patients with the CT/TT gene variant.
According to Dr Kosten, vaccines are also very safe treatments for blocking the effects of certain abused drugs including nicotine, opiates, and stimulants like methamphetamine and cocaine.
“They can be very useful as agents to prevent relapse in patients who have stopped using the abused drug,” he said.
In animal studies, a methamphetamine vaccine has been found to generate anti-bodies that are able to bind to modest amounts of injected methamphetamines and reduce the drug’s entry into the brain. Human studies of the vaccine will not begin until 2016.—Jill Sederstrom
