IF YOU鈥橰E hoping to find out about using pills to treat alcohol addiction, the website is the wrong place to look. Search there for 鈥渕edication鈥� and the closest you鈥檒l come is a warning about the dangers of turning to prescription drugs or narcotics as a substitute for alcohol.
The website of the in Palm Springs, California, reveals little more. It does at least discuss one possible medication to treat alcoholism, but the drug is curtly dismissed. 鈥淣altrexone is not a cure for alcoholism nor is it in any way a treatment,鈥� writes James West, the centre鈥檚 former medical director. 鈥淭he treatment of alcoholism involves a complete psychological, spiritual and emotional shift, whereby victims of the disease are released at the core of their being from the compulsion to drink.鈥�
Dig through the wealth of addiction support groups online and you鈥檒l come across two responses again and again 鈥� pharmacological treatments to alcohol addiction are either ignored, or they are actively rejected as a crutch that must be abandoned. 鈥淭he dogma has been that you can鈥檛 treat a chemical addiction with another chemical,鈥� says of the US National Institute on Alcohol Abuse and Alcoholism (NIAAA) in Bethesda, Maryland. 鈥淚t鈥檚 well-meaning but naive, and in the end very destructive.鈥�
Advertisement
That doctrine, however, is poised to crumble. Encouraged by advances in the neuroscience of addiction, positive results from clinical trials and stirrings of interest from big pharma, Heilig and his colleagues are pushing for medication to become a mainstream treatment. Today, the few drugs available to treat alcohol abuse are rarely used outside a small number of specialist centres, but NIAAA鈥檚 vision is for more and better drugs to be prescribed routinely by psychiatrists and even family doctors.
If they are successful, the result will be alcoholism鈥檚 鈥淧rozac moment鈥�, says , NIAAA鈥檚 head of treatment and recovery research, recalling the time when Prozac revolutionised the way depression was treated following its launch in 1986. By invoking Prozac, however, he will raise both hopes and fears. While it鈥檚 widely recognised that Prozac and other members of its class 鈥� selective serotonin reuptake inhibitors (SSRIs) 鈥� have helped to lift the stigma surrounding depression and greatly expanded treatment options, some analyses suggest that their benefits have been exaggerated.
What鈥檚 more, the pharmaceutical industry鈥檚 aggressive marketing of SSRIs to ever wider groups of patients, despite evidence that they may sometimes trigger suicidal feelings, has become a major controversy. In this light, could recent advances in developing anti-alcoholism drugs be the first tentative steps towards the medicalisation of social drinking?
A new line of attack
There is no doubt, at least, that a new line of attack is desperately needed in the war against alcoholism. NIAAA鈥檚 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) found that about were dependent on alcohol in 2001-2002. A further met the criteria for alcohol abuse 鈥� frequently drinking heavily despite clear negative consequences.
On the global scale, alcohol is responsible in some way 鈥� whether through drink-fuelled violence and accidents or direct medical effects 鈥� for 3.8 per cent of all deaths and 4.6 per cent of the burden of disease and disability (). Then there are the knock-on social consequences of excessive drinking, including broken families, unemployment and risky sexual behaviour.
Current treatment options 鈥� which often involve psychotherapy in a specialist rehab facility 鈥� have a limited reach, with less than a quarter of alcoholics in the US ever getting the help they need. 鈥淭here are many people who are desperately suffering in silence,鈥� says , who works on new pharmaceutical approaches at the Ernest Gallo Clinic and Research Center in Emeryville, California. If they could discreetly obtain a prescription from their doctor, rather than taking the big step of signing up for rehab, perhaps more would seek help.
Yet until recently, pharmaceutical companies seemed to have little interest in exploiting this market. They may have been reluctant to associate their names with the stigma of addiction. Probably more significantly, alcoholics were widely considered to be people on the poverty line whose lives had spiralled out of control, with their addiction often compounded by other psychiatric problems 鈥� not the sort of patient to make dollar signs flash in the eyes of drug company executives.
Yet NESARC painted a very different picture 鈥� more than of people dependent on alcohol don鈥檛 fit this stereotype (see 鈥淒iverse drinkers鈥�). They include young adults whose drink-sodden social lives are spinning out of control, and older, 鈥渇unctional鈥� alcoholics who mostly manage to hide an ongoing battle with the bottle. 鈥淭hey may be a little foggy in the morning, but they鈥檙e not missing work,鈥� says Willenbring. 鈥淭heir marriages aren鈥檛 going to heck. They鈥檙e coaching their kids鈥� soccer teams and going to church on Sunday.鈥�
Persuading people to seek help from their family doctors while they are still largely in control of their lives seems a much more realistic goal. And crucially in the US, the world鈥檚 biggest market for prescription drugs, these people will have health insurance. As big pharma views these favourable demographics alongside its expiring patents and drying pipelines in other disease areas, interest is stirring. 鈥淚t has changed dramatically in the past five years,鈥� Willenbring says.
The available drugs for alcoholism are unlikely to be the new Prozac, however. Naltrexone, for instance, which cuts the desire to drink by blocking opioid receptors in the brain鈥檚 reward system, has two major drawbacks. First, its benefits vary widely between patients, although genetic tests may help predict which people are likely to respond best to the treatment (see 鈥淒ifferent drinkers, different drugs鈥�).
Naltrexone鈥檚 biggest stumbling block, however, is that it fails to treat some of the more painful aspects of abstinence. Drinking dampens the brain鈥檚 response to stress 鈥� indeed, many heavy drinkers become hooked on alcohol for this reason alone. The result is that going cold turkey without also calming the brain鈥檚 stress pathways can be a distressing experience. 鈥淧eople feel just terrible,鈥� says , a specialist in the neurobiology of addiction at the Scripps Research Institute in La Jolla, California. 鈥淭hese individuals are miserable. They have panic attacks.鈥�
Targeting these drink-hijacked stress pathways 鈥� often without even touching the brain鈥檚 pleasure circuits 鈥� is now the hottest area in alcoholism research. In 2008 a team led by Heilig reported that an experimental drug called LY686017, made by Eli Lilly, suppressed cravings for alcohol in a small group of recently detoxified alcoholics (). The drug is known to block the brain鈥檚 neurokinin 1 receptor, which is involved in behavioural responses to stress.
Koob, meanwhile, is concentrating on the central player in the brain鈥檚 stress response: corticotropin-releasing hormone (). Some pharmaceutical companies are already attempting to target this hormone to treat anxiety and post-traumatic stress disorder, meaning suitable candidate drugs are already in the pipeline. The major hurdle, however, is finding one without undesirable side effects.
Besides the brain鈥檚 stress and pleasure pathways, there is another possible line of attack to treat alcohol addiction, which focuses on alcohol鈥檚 sedative properties. Alcohol reduces overall neural activity by boosting the inhibitory effects of the neurotransmitter GABA while damping down the excitation caused by the neurotransmitter glutamate. Prolonged heavy drinking causes long-lasting changes in the brain鈥檚 sensitivity to these neurotransmitters. As a result, the brains of alcoholics suffer from excessive neural excitation without booze, which may contribute to their agitation when they go cold turkey.
An existing drug called acamprosate had been considered the best hope to restore the balance between GABA and glutamate. But in a large clinical trial, it performed no better than a placebo ().
So the search is on for drugs with more powerful rebalancing effects. A contender is topiramate, a drug otherwise used to treat epilepsy. In a 14-week trial involving more than 370 heavy drinkers, topiramate decreased the number of days in which the men drank more than five standard drinks, or the women consumed more than four, by about 16 per cent compared with those taking a placebo ().
Drinking plummets
That may sound like a modest result, but for the patients who responded best, the effects were spectacular. 鈥淲e鈥檙e talking about moving from drinking a couple of bottles of wine a day to drinking about a glass,鈥� says at the University of Virginia in Charlottesville, who led the trial.
Importantly, these gains were achieved without first having to send the patients to a specialist detox clinic, which can cost thousands of dollars. A drug that can be prescribed to drinkers during their first visit to a doctor鈥檚 office, without needing to dry out first, could remove a big barrier to treatment.
With new discoveries about how to mitigate alcohol鈥檚 disruption of brain circuitry coming thick and fast, Willenbring鈥檚 optimism for alcoholism鈥檚 Prozac moment seems justified. 鈥淭here鈥檚 a change taking place and I think it鈥檚 largely being driven by accumulating knowledge in neuroscience,鈥� says Elliot Ehrlich, chief medical officer with , a company based in Cambridge, Massachusetts, that specialises in drugs for alcoholism.
Larger drug firms remain cautious, but some of the NIAAA鈥檚 recent research should help persuade them that bringing alcoholism drugs to market is a challenge worth pursuing. Howard Moss, NIAAA鈥檚 associate director for clinical research, took the results from a population survey on risky drinking behaviour and related them to a proprietary marketing database called PRIZM to identify who in the US could be targeted to seek help for their alcohol abuse ().
The highest proportion of binge drinkers fell into a group labelled in the PRIZM database as 鈥淐yber-Millennials鈥� 鈥� described as 鈥渢ech-savvy singles and couples living in fashionable neighborhoods on the urban fringe鈥�. That鈥檚 a key finding, because advertisers already know that these people are easily reachable: they read Wired, and watch the Travel Channel, MTV and pro basketball.
Moss framed his research in terms of health promotion efforts. But in the US, where prescription drugs can be advertised directly to patients, the same information could be used to market pharmaceutical products. 鈥淚 suspect the next alcoholism drug will be marketed direct-to-consumer,鈥� says Moss.
Mission creep
It鈥檚 an idea that is ringing warning bells for critics of the pharmaceutical industry, who fear a potential for 鈥渕ission creep鈥� in how the drugs are used. 鈥淭his year you鈥檒l have to drink so much to be an alcoholic; next year it will be less,鈥� predicts of Cardiff University in the UK, who has questioned the increasingly widespread use of SSRIs and other drugs in psychiatry. 鈥淎nd then it will be: 鈥楬ey, you drink a bit too much, so maybe you鈥檙e at risk of being an alcoholic. Why don鈥檛 we treat you before the problem develops?'鈥�
Even among people clearly diagnosed as alcoholics under current criteria, it鈥檚 not obvious who is a suitable candidate for drug treatment. For instance, most young people with drink problems sober up with age as the responsibilities of work and family take hold. 鈥淪o one would have to ask whether it鈥檚 appropriate to target this group,鈥� says of the University of California, San Francisco, who studies the social and health consequences of alcohol use.
Proponents of pharmaceutical treatments for alcoholism will also face a backlash from therapists who favour a behavioural approach. Still, NIAAA officials stress that they only propose medication alongside behavioural therapy. 鈥淭his is never going to be a disease where we simply prescribe a pill,鈥� says Moss.
How the story unfolds will depend on the precise risks and benefits of the drugs in question. Potential side effects, in particular, may give doctors pause for thought before they reach for their prescription pad: topiramate, for example, can cause vision problems, suicidal thoughts and a potentially dangerous acidification of the blood.
鈥淧otential side effects, in particular, may give doctors pause for thought before they reach for their prescription pads鈥�
For his part, Willenbring is convinced it鈥檚 only a matter of time before a suitable candidate emerges that trumps these doubts and warrants a Prozac-style marketing campaign. 鈥淚t could be next year. It could be 10 years away. But I know it鈥檚 going to happen.鈥�
Different drinkers, different drugs
Nearly a quarter-century after the launch of Prozac, there are now a number of other drugs in its class that can also be prescribed for depression. But finding the right selective serotonin reuptake inhibitor for each patient is usually a matter of trial and error, as it鈥檚 currently impossible to predict which will work best.
Drugs for alcoholism will face a similar hurdle, but researchers hope they can overcome the challenge using genetic tests to work out which patients will respond best to the treatments. So far, the most promising results have come from studies of naltrexone: alcoholics with a particular variant of the gene for the opioid receptor targeted by the drug appear to benefit most.
Two teams, one led by of the University of Pennsylvania in Philadelphia, the other by of the Medical University of South Carolina in Charleston, are now running trials to obtain the data needed to convince the US Food and Drug Administration that the drug鈥檚 prescribing information should recommend a genetic test. 鈥淚f these studies are positive there will be a labelling change based on genetics,鈥� says O鈥橞rien. 鈥淚t will be the first one in psychiatry.鈥�
In the long run, O鈥橞rien hopes it will be possible to identify a series of genetic variants to classify alcoholics into groups likely to respond well to a particular class of drug, and to highlight people likely to suffer adverse reactions. 鈥淒octors will be genotyping patients and prescribing medications based on that,鈥� he says.
