Monday, July 21, 2008
Drugs for Alcoholism
Different meds for different drinkers
Although there are still only three drugs officially approved by the FDA for the treatment of alcoholism, the research picture is beginning to change. In an article by Greg Miller published in the 11 April 2008 edition of Science, alcoholism researcher Stephanie O'Malley of Yale University said: "We have effective treatments, but they don't help everyone. There's lots of room for improvement."
The medications legally available by prescription for alcoholism are: disulfiram (Antabuse), naltrexone (Revia and Vivitrol), and acamprosate (Campral), the latest FDA-approved entry. A fourth entry, topiramate (Topamax), is currently only approved by the Food and Drug Administration (FDA) for use against seizures and migraine. The controversial practice of “off-label” prescribing—using a drug for indications that are not formally approved by the FDA—has become so common that Johnson & Johnson said it had no plans to seek formal approval for the use of Topamax as a medicine for addiction. (See my post,"Topamax for Alcoholism: A Closer Look").
Addiction experts are beginning to focus on which treatment drugs work best for different types of alcoholics. Two recent discoveries might help clarify the picture. Psychopharmacologist Charles O'Brien at the University of Pennsylvania reported that alcoholics with a specific variation, or allele, of a prominent opioid receptor gene were more likely to respond positively to treatment with naltrexone. Other work reported in the February 2008 Archives of General Psychiatry came to the same conclusion.
The second research insight builds on a lifetime of work by Robert Cloninger at Washington University in St. Louis. Cloninger discovered that alcoholics come in two basic flavors--Type 1 and Type 2. Type 1, the more common form, develops gradually, later in life, and does not necessarily require structured intervention. Type 1 alcoholics do not always experience the dramatic declines in health and personal circumstances so characteristic of acute alcoholism. These are the people often found straddling the line between alcoholic and problem drinker. In contrast, so-called Type 2 alcoholics are in serious trouble starting with their first taste of liquor during adolescence. Their condition worsens with horrifying speed. They frequently have a family history of violent and antisocial behavior, and they often end up in prison. They are rarely able to hold down normal jobs or sustain workable marriages for long. Type 2s, also known as “familial” or “violent” alcoholics, are likely to have had an alcoholic parent.
Type 1 drinkers, who only get in trouble gradually, are also known as "anxious" drinkers, and research suggests that they may respond better to medicines that alleviate alcohol-related anxiety, such as Lilly's new suppressor of stress hormones, known as LY686017. (See my post, "Drug That Blocks Stress Receptor May Curb Alcohol Craving "). Researchers at the National Institute of Alcohol Abuse and Alcoholism (NIAAA), working with colleagues at Lilly Research Laboratories and University College in London, announced the discovery of a drug that diminished anxiety-related drug cravings by blocking the so-called NK1 receptor (NK1R). The drug “suppressed spontaneous alcohol cravings, improved overall well-being, blunted cravings induced by a challenge procedure, and attenuated concomitant cortisol responses.”
The NIAAA researchers are making effective use of recent findings about the role played by corticotrophin-releasing hormone (CRH) in the addictive process. CRH is crucial to the neural signaling pathway in areas of the brain involved in both drug reward and stress. As it happens, NK1R sites are densely concentrated in limbic structures of the mid-brain, such as the amygdala, or so-called “fear center.”
Researchers are understandably excited about these developing insights. Psychopharmacologist Rainer Spanagel of Germany's Central Institute of Mental Health in Mannheim called such research "a milestone in pharmacogenetics." In Greg Miller's Science article, Willenbring of NIAAA predicted that the field is poised for a "Prozac moment," marked by the discovery of "a medication that's perceived as effective, that's well-marketed by a pharmaceutical company, and that people receive in a primary-care setting or general-psychiatry setting."
In "Days of Wine and Roses, " the 1960s film about alcoholism, Jack Lemmon played a character who embodied Type 2 characteristics--early trouble with alcohol, extreme behavioral dysregulation, poor long-term planning, and a hollow leg. His wife, played by Lee Remick, demonstrates the slower, more measured descent from problem drinking into clinical alcoholism that characterizes Type 1 alcoholics. Research now suggests that Lee Remick might do better on LY686017, while Jack Lemmon's character would be a promising candidate for treatment with naltrexone.
Photo credit: About Alcohol Information