The National Insitute on Drug Abuse (NIDA) continues its active funding of research into new and more effective treatments for various kinds drug and alcohol dependence. Alcohol dependence afflicts about 4 percent of the adult U.S. population, and is the third leading cause of preventable death in this country – but only about 10 to 15 percent actually seek treatment for the disease. A great deal of positive press has been generated over the past year or so regarding the drug topiramate in the treatment of heavy drinkers, especially in the area of relapse prevention.
It is believed that topiramate dampens the desire to drink, perhaps by reducing dopamine release by neurons in the brain’s reward circuitry. Dopamine is the surge experienced by alcoholics when they consume a drink.
Results of International Research
As recently as February 2009, the Director’s Report of NIDA published findings of an international research study in Brazil, “Comparing Topiramate with Naltrexone in the Treatment of Alcohol Dependence.” The double-blind, 12-week, placebo-controlled Brazil study included 155 patients between the ages of 18 and 60 who had been diagnosed with alcohol dependence. After a 1-week detoxification period, patients were randomly assigned to receive either topiramate (induction to 300mg/day), naltrexone (50 mg/day) or a placebo.
Measurement consisted of time to relapse – designated as consumption of more than 60 grams of ethyl alcohol, duration of cumulative abstinence, and weeks of heavy drinking. The analyses of intention-to-treat showed topiramate to be superior to the placebo in a number of important measures. These included time to first relapse (7.8 versus 5.0 weeks), duration of cumulative abstinence (8.2 versus 5.6 weeks), weeks of heavy drinking (3.4 versus 5.9 weeks), and percentage of study subjects abstinent at 4 weeks (67.3 versus 42.6 percent), and 8 weeks (61.5 versus 31.5 percent), but not 12 weeks (46.2 versus 27.8 percent). Authors of the study report that results remained significant after controlling for attendance in Alcoholics Anonymous, which was also higher in topiramate than in other groups.
While there were reportedly no significant differences between the naltrexone versus placebo or naltrexone versus topiramate groups, naltrexone did show trends toward inferior outcomes compared to those of topiramate. The study authors conclude that the results support the efficacy of topiramate in relapse prevention of alcoholism. They point to the need for future research with larger sample sizes to verify the suggestive evidence obtained for topiramate’ superiority versus naltrexone in the treatment of alcoholism.
Previous U.S. Study
Published in the June 2008 issue of Archives of Internal Medicine, a 14-week trial by the University of Virginia Health System team found that topiramate decreased heavy drinking and reduced the physical and psychosocial damage caused by dependence on alcohol. Among heavy alcohol drinkers, physical organs are at risk, particularly the heart and liver. The overall quality of life of alcoholics also suffers to a great degree.
Topiramate has the following benefits, according to the study authors:
• Reduces hypertension – Topiramate significantly reduces drinking and also significantly decreases blood pressure. Many alcoholics are prescribed anti-hypertensive medication for their hypertension, which can complicate alcohol-dependence treatment. Topiramate alone can be used instead of several medications.
• Lowers blood pressure and cholesterol levels – By lowering plasma cholesterol levels a significant amount, and reducing systolic and diastolic blood pressure levels, topiramate may reduce the heart disease risk in alcohol-dependent patients.
• May reduce risk of fatty liver disease – As a result of lowering cholesterol and liver enzyme levels, topiramate may help reduce the risk of fatty liver disease – which often leads to cirrhosis of the liver. Cirrhosis is a consequence of end-stage liver disease which often ends in death of alcoholics.
• Reduces alcohol cravings – Researchers found that topiramate contgributed to a significant decease in drug cravings, the obsessive compulsions and thoughts about using alcohol.
• Improved quality of life – Overall quality of life improved among subjects taking topiramate, as copared to a placebo, in areas such as general and leisure activities, performing household chores and tasks, and in limiting sleep disturbances.
Following release of the trial findings, Mark Willenbring, director of treatment and recovery research at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) commented that topiramate’s “level of effectiveness seemed to be at least as good as naltrexone and maybe better.”
Ortho-McNeil Neurologics, Inc., the manufacturer of topiramate, funded the UVA study.
Status of Topiramate for Alcohol Treatment
Following three promising trials, much still needs to be done to clear the way for topiramate to be approved for the treatment of alcoholism. Currently, the U.S. Federal Drug Administration (FDA) has only approved topiramate, marketed as Topamax, for the treatment of epileptic seizures and migraine headaches.
Before the drug can be considered for approval for alcohol treatment, further and more in-depth studies with larger sample sizes need to be conducted.
Current FDA-Approved Drugs for Treatment of Alcoholism
Currently, only three drugs have been approved by the FDA for the treatment of alcoholism.
• The first one approved was Disulfiram, marketed as Antabuse. Antabuse blocks alcohol metabolism, and gives the drinker a toxic reaction when they drink. According to numerous sources, disulfiram has fallen out of favor with many doctors. An alcoholic can easily stop taking the drug before deciding to go on a binge, so it is not truly effective in all cases.
• The second drug approved was naltrexone, marketed as ReVia, Depade, and Vivitrol, which the FDA approved in 1995. Nalrexone works by blocking opoid receptors and, through monthly injections, curtails euphoria of alcohol.
• The third, and most recently approved drug was acamprosate, marketed as Campral, approved in 2004. Campral is a non-addicting drug and appears to reduce the desire to drink, but it may not be effective in those who still drink.