New Medication Appears Effective In Helping Smokers Kick The Habit

Smoking is the leading cause of preventable death in the United States and worldwide. Currently available pharmacotherapies for smoking cessation include nicotine replacement therapy (NRT)--such as gum, skin patches, tablets, nasal spray and inhalers--and the antidepressant drugs bupropion hydrochloride and nortriptyline hydrochloride. These have shown limited success rates, with success at one year averaging approximately seven percent to 30 percent, according to background information in the articles.

The new drug varenicline tartrate mimics the effects of nicotine to help offset cravings, and in the presence of nicotine it helps suppress some of the reinforcing effects of smoking.

Mitchell Nides, Ph.D., of Los Angeles Clinical Trials, and colleagues with the Varenicline Study Group conducted a randomized, double-blind, placebo-controlled study to evaluate the efficacy, tolerability and safety of varenicline for smoking cessation. Healthy smokers aged 18 to 65 years were randomly assigned to receive varenicline in a dosage of .3 milligrams once daily, 1 milligram once daily, or 1 milligram twice daily for six weeks, plus placebo for one week; to 150 milligrams of sustained-release bupropion hydrochloride twice daily for seven weeks; or to placebo for seven weeks.

The authors report that varenicline, in combination with brief behavioral counseling, was more effective for short- and long-term smoking cessation than placebo.

"Efficacy improved as the dose increased, with varenicline tartrate, 1 milligram twice daily, providing the highest rates of continuous abstinence across all treatment groups, including bupropion," they write. Four-week continuous quit rates were 48 percent for varenicline, 1 milligram twice daily; 37.3 percent for varenicline, 1 milligram daily; 33.3 percent for bupropion hydrochloride; and 17.1 percent for placebo. Long-term quit rates from four weeks to one year were 14.4 percent for the group that received varenicline, 1 milligram twice daily, vs. 4.9 percent for placebo.

"In this study, varenicline tartrate, 1 milligram twice daily, effectively helped subjects quit smoking, with response rates three times higher than those for placebo while demonstrating a good tolerability profile in this population of smokers who on average had smoked approximately 20 cigarettes per day for approximately 24 years," the authors write. "Efficacy was maintained in the non--drug treatment phase through week 52. The significant reductions in craving and in some of the rewarding effects of smoking seen with varenicline tartrate, 1 milligram twice daily, may assist in promoting abstinence and preventing relapse," they conclude. (Arch Intern Med. 2006;166:1561-1568. Available pre-embargo to the media at http://www.jamamedia.org.)

Pfizer Inc. provided funding for this study and was involved in all elements of the study, including, but not limited to, the study design and monitoring.

In an accompanying article, the same research team reports that varenicline taken over 12 weeks was effective in helping smokers quit, and was generally well tolerated.

Cheryl Oncken, M.D., of the University of Connecticut Health Center, Farmington, and colleagues studied 647 patients to evaluate the efficacy, safety and tolerability of four varenicline dose regimens--two with titrated, or progressive, dosing over the first week, and two with a non-titrated, or fixed, dosing schedule, for promoting smoking cessation. Healthy smokers aged 18 to 65 years randomly received varenicline, .5 milligrams twice daily non-titrated, .5 milligrams twice daily titrated, 1 milligram twice daily non-titrated, 1 milligram twice daily titrated or placebo for 12 weeks, then with a 40-week follow-up period to assess long-term efficacy.

"In this study, treatment with varenicline tartrate at doses of .5 milligrams and 1 milligram twice daily, was associated with significantly higher smoking cessation rates compared with placebo," the authors report. At weeks nine to 52, the abstinence rates were 22.4 percent in the 1-milligram group, 18.5 percent in the .5-milligram group and 3.9 percent in the placebo group.

Among those who were treated with varenicline, 16 percent to 42 percent experienced nausea. Reports of nausea were lower among those who received progressive dosing.

"In summary, varenicline tartrate (.5-milligram and 1-milligram doses taken twice daily for 12 weeks) significantly improved short- and long-term abstinence rates compared with placebo," the authors conclude. "Future studies are warranted to compare the efficacy of varenicline to other smoking cessation pharmacotherapies and to determine whether a longer duration of medication treatment improves smoking cessation rates." (Arch Intern Med. 2006;166:1571-1577. Available pre-embargo to the media at http://www.jamamedia.org.)

Pfizer Inc. provided funding for this study and was involved in all elements of the study, including, but not limited to, the study design and monitoring.

Editorial: "No More Excuses to Delay Treatment"

The results of the studies by the Varenicline Study Group demonstrate that varenicline is a novel medication to aid in smoking cessation, writes Bankole A. Johnson, D.Sc., M.D., Ph.D., of the University of Virginia, Charlottesville, in an accompanying editorial.

Dr. Johnson also summarizes other approaches to treating nicotine addiction now in development, including medications and a vaccine.

"In sum, pharmacological and immunological studies are opening up new vistas for safe, efficacious and potent treatments for nicotine dependence," he writes. "Molecular genetic studies also are investigating how to identify those individuals vulnerable to becoming nicotine dependent and, once they are dependent, the treatments that might work best for them. All these advances will deliver real aid to curbing smoking. Now, a smoker who wants help to quit no longer has a legitimate excuse to delay seeking treatment." (Arch Intern Med. 2006;166:1547-1550. Available pre-embargo to the media at http://www.jamamedia.org.)

Dr. Johnson has consulting agreements with Ortho-McNeil Pharmaceutical Inc., Alkermes Inc., Sanofi-Aventis, and TransOral Pharmaceuticals Inc. This study was supported by grants from the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism.

Largely Unnoticed Agent May Be Effective Smoking Deterrent

A plant-derived medication that has been used to treat tobacco dependence in Eastern Europe for 40 years may be effective for smoking cessation, but it remains largely unnoticed in English-language literature, according to a review article in the same issue.

Cytisine is an alkaloid found in a plant known as the golden rain tree, or Cytisus laburnum. It has been used for decades as a smoking cessation drug in Eastern European countries, according to background information in the article.

Jean-Francois Etter, Ph.D., M.P.H., of the University of Geneva, Switzerland, reviewed the literature on the effect of cytisine on smoking cessation. Ten studies were found, and all were conducted in Bulgaria, Germany, Poland and Russia between 1967 and 2005.

"Research conducted during the past 40 years suggests that cytisine is effective for smoking cessation," Dr. Etter reports. "Thus, an apparently effective smoking cessation drug that has been used for decades in Germany and Eastern European countries remained unnoticed in other countries."

Most of the articles reviewed by Dr. Etter were never cited in English-language literature. Recent reviews of the efficacy of smoking cessation drugs omitted cytisine, and little research on the drug has been conducted in recent years.

Dr. Etter suggests the omission may be explained because studies on the efficacy of cytisine were not published in English and because the available research is based on studies that do not conform to current standards in conducting and reporting drug trials.

"An apparently effective treatment for the first avoidable cause of death in developed countries remained largely unnoticed, despite research published during the past 40 years," he concludes. "How many other effective drugs are there for which efficacy remained unnoticed because existing trials were not published in English in Western countries?" (Arch Intern Med. 2006;166:1553-1559. Available pre-embargo to the media at http://www.jamamedia.org.)