Topiramate Has Physical and Psychosocial Benefits in Heavy Drinkers

Pauline Anderson

June 11, 2008

June 11, 2008 — A drug already used to treat seizures and migraine headaches has once again been proven effective in curbing heavy drinking.

The current study, published in the June 9 issue of the Archives of Internal Medicine, not only found that topiramate (Topamax, Ortho-McNeil-Janssen Pharmaceuticals) reduced the amount of drinking among alcohol-dependent adults but also showed for the first time that the drug has a beneficial effect on the physical and psychosocial consequences of alcoholism dependence.

"Alcoholism is a devastating disease, and the major sequelae result in damage to internal organs such as the heart and liver," said lead author Bankole A. Johnson, MD, PhD, from the department of psychiatry and neurobehavioral sciences at the University of Virginia, in Charlottesville. "It's encouraging that topiramate not only reduces drinking but may reduce the risk of hypertension, heart disease, and liver cirrhosis in alcohol-dependent individuals."

Dr. Johnson and colleagues enrolled 371 alcohol-dependent men and women aged 18 to 65 years at 17 sites across the United States between January 27, 2004 and August 4, 2006. The male subjects had been consuming 35 or more — and female subjects 28 or more — standard drinks per week. A standard drink is about equal to 295.7 mL of beer, 118.3 mL of wine, or 29.6 mL of 100-proof liquor.

Reducing Alcohol's Reinforcing Effects

The subjects were randomly assigned to receive placebo (188 subjects) or topiramate (183 subjects), a sulfamate-fructopyranose derivative that has been shown to decrease excessive drinking. It does so by reducing the reinforcing effects of alcohol, probably through glutamate and dopamine neurotransmitters, among others, said Dr. Johnson.

Throughout the 14-week study, subjects received weekly Brief Behavioral Compliance Enhancement Treatment (BBCET), a 15-minute therapy session that emphasizes the importance of medication adherence to changing drinking behavior.

And during the study, subjects were regularly monitored. On the physical side, researchers assessed vital signs (blood pressure, pulse, and temperature) and body-mass index (BMI). They also measured plasma cholesterol and liver-enzyme levels, including gamma-glutamyltransferase, a widely accepted biomarker of alcohol consumption.

The researchers also rated psychosocial function, including obsessional thoughts and compulsions about alcohol using the Obsessive Compulsive Drinking Scale (OCDS), the harmful consequences of drinking (Drinker Inventory of Consequences Scale), general mood (Profile of Mood States), sleep quality, quality of life, and adverse events.

Reduced Heart Disease Risk Factor

The study found a significant reduction in plasma cholesterol levels for patients taking topiramate compared with placebo (mean difference, 13.30 mg/dL [95% CI, 5.09 – 21.44 mg/dL]; P = .002). Since long-term heavy drinkers tend to have elevated lipid levels and signs of fatty-liver disease, this ability to significantly reduce cholesterol "adds considerably to its general medical utility in treating alcohol-dependent people," the authors write.

The researchers also found that topiramate was more effective than placebo in decreasing all liver-function test values. "Taken together with the lowered lipid levels and the consequent reduced risk of fatty-liver degeneration, the propensity toward progressive liver disease and eventual cirrhosis could, perhaps, be diminished if alcohol-dependent individuals were treated with topiramate," they note.

As another health benefit, topiramate was better than placebo at reducing BMI, possibly because it reduced craving for food. As well, the drug did better at reducing both systolic and diastolic blood pressure. At the end of the study, those subjects on topiramate achieved blood pressure levelsat about the threshold for prehypertension (mean, 123.0 mm Hg systolic and 75.5 mm Hg diastolic) while those on placebo exceeded this cutoff.

Mean Difference in BMI, Blood Pressure With Topiramate vs Placebo

End Point Mean Difference 95% CI P
BMI 1.08 0.81 – 1.34 < .001
Systolic BP (mm Hg) 9.70 6.81 – 12.60 < .001
Diastolic BP (mm Hg) 6.74 4.57 – 8.90 < .001

In terms of psychosocial measures, topiramate again proved superior to placebo in decreasing obsessional thoughts and compulsions about using alcohol, increased their psychosocial well-being, and improved some aspects of quality of life, they note, "thereby diminishing the risk of relapse and longer-term negative outcomes." In 1 model, the odds ratios for topiramate vs placebo in general activities, leisure-time activities, and household duties on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) were 1.45 (= .23), 2.27 (P = .03), and 2.05 (P = .04), respectively. And compared with placebo, topiramate had a greater tendency to reduce sleep disturbance (mean difference, 5.31 [95% CI, 1.33 - 9.28]; P = .01)


These positive responses were fairly uniform across sex and age groups, said Dr. Johnson, adding that in most cases, the response to the drug is relatively fast — within 3 to 4 weeks.

Lightening the Load

The drug appears to change subjective experiences relating to alcohol, so drinkers don't feel as much need for their next drink, Dr. Johnson told Medscape Psychiatry. “Patients say that it's almost like the alcohol isn't there.”

A major advantage of topiramate is that it can be given to patients while they’re still drinking heavily, "so you can start treatment during a crisis," said Dr. Johnson. "This is a paradigm shift from other medicines, which require abstinence to be initiated. Thus, topiramate can be useful in general practice, thereby increasing the public-health impact of intervention for heavy drinking."

With such office-based tools, family physicians should be able to better treat alcohol-dependent patients, lightening the load of addiction specialists across the country, added Dr. Johnson.

As with most agents, topiramate did have some adverse effects. Effects reported in at least 10% of subjects included paresthesia, headache, taste perversion, fatigue, anorexia, nausea, insomnia, and difficulty with concentration. However, said Dr. Johnson, these effects are moderated if the drug is titrated slowly. And, he added, many people respond to the drug at doses lower than the 300 mg/day "ceiling."


Ortho-McNeil-Janssen Scientific Affairs provided the medication and funding for this study. The sponsor was involved in all stages from study design through interpretation of the results, including critical review of the manuscript. Dr. Johnson has been a consultant for Ortho-McNeil-Janssen Scientific Affairs and is a consultant for Organon and TransOral Pharmaceuticals. Disclosures for coauthors appear in the paper.


Arch Intern Med. 2008;168:1188-1199. Abstract


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