GHB and Alcoholism: I'll (Not) Drink To That

The following was originally posted to the HCPlive Network blog Thought Broadcast.

Alcoholism is a societal scourge, with alcohol dependence affecting nearly a quarter of the US population at some point in their lives, and many more with a history of abuse. Treatment of this disorder is an enormous challenge, and motivating alcoholics to achieve controlled drinking or abstinence is difficult; even the most effective of several diverse approaches only show a moderate degree of success.

Because of the conventional paradigm that addiction is rooted in biology, it is not surprising that researchers worldwide are investigating biological treatments for alcoholism. Antabuse, naltrexone (ReVia), and acamprosate (Campral) are three drugs that have been approved by the FDA for treatment of alcoholism, and while their efficacy is modest at best, scientists and drug companies have persisted in their search for a better pill.

An article in the January 2011 issue of the journal Alcohol and Alcoholismadds another potential name to this list: GHB. Gamma hydroxybutyrate, or GHB, also known as sodium oxybate and sold as “Xyrem”, may be effective in treating alcohol withdrawal and in preventing relapse, according to a recent literature review.

GHB is structurally similar to GABA, the main inhibitory transmitter in the brain; GHB was widely available in the 1980s as a nutritional supplement (to induce sleep or to increase muscle mass), but after it was linked to several reports of date rape (or, in the literature, “drug-facilitated sexual assault”) it was placed on Schedule I of the US Controlled Substances Act, severely limiting its use and availability. Since 2000, GHB has occupied a “split” position on the controlled substances hierarchy: the illicit drug GHB remains on Schedule I, while the compound “when used for medical purposes” is Schedule III.

In 2002, Jazz Pharmaceuticals obtained FDA approval for the use of GHB in complications of narcolepsy (interestingly, it was originally developed as an “orphan” drug because of the rarity of narcolepsy, so Jazz received government assistance to bring it to market). GHB is marketed under the name Xyrem. Xyrem has a fairly strong sedative effect, due to its binding to GABA receptors in the brain; low concentrations may also release dopamine, and it can also induce growth hormone release (hence its illicit use in the bodybuilding community).

GHB’s benefit in treating alcohol withdrawal may also stem from its ability to mimic GABA, since it is widely assumed that the symptoms of alcohol withdrawal (irritability, anxiety, insomnia, tremor) arise from a loss of GABA activity in the brain. The mechanism by which it might decrease alcohol craving is not quite as clear, but the literature review shows that GHB improved “controlled drinking” and reduced the number of drinks consumed, compared to placebo. It also beat naltrexone and Antabuse in maintenance of abstinence.

GHB has not yet been approved for use in alcoholics, and I don’t know whether Jazz intends to seek approval. But should they do so, certain concerns arise. First, should we be concerned about prescribing a drug that is known to be abused for the treatment of an addictive behavior? The authors of the review point out that benzodiazepines (which can also be abused) have been used for years in the treatment of alcohol withdrawal, and that the tight controls that are placed upon prescribers of Xyrem by its manufacturer seems to have largely prevented its illicit use.

I’ve always been skeptical of the idea of treating one substance addiction with another substance, despite the efficacy of agents like methadone and Suboxone. I also question the use of an abusable substance in patients who, by definition, abuse at least one substance (and likely others as well), and many of whom have a history of ignoring consequences of their actions.

Moreover, clinical trials require an enormous amount of money, energy, and time, and even if Xyrem is approved for alcoholism, the tight controls put on its use will also create a costly administrative burden for prescribers and users of the drug. (Moreover, the drug is currently extremely expensive, about $20,000 a year without insurance coverage.) I wonder whether the expense and time to bring Xyrem to market might be better spent in developing residential or psychosocial treatment programs for alcoholics, managing medical complications of alcohol abuse, creating educational programs on the dangers of alcoholism, or working to limit or control alcohol advertising to vulnerable groups. Far be it from me to dictate how Jazz Pharmaceuticals spends its R&D dollars (and yes, I know their primary motivation for bringing Xyrem to market would not be their great compassion for alcoholics, but because that target market is overwhelmingly larger than the market for a narcolepsy drug), but I believe alcoholism—perhaps even more than other mental illnesses—deserves individualized treatment.

More effort should be devoted to understanding how patients’ drinking problems arise from their own unique histories, and treatment programs should be developed to address these. True, another pill might help, but let’s make sure we (i.e., providers, patients, and those who pay for treatment) don’t become too enamored of the idea that an easy fix is around the corner, because it’s probably not.