Quit-Smoking Medicines and Episodes of Violence

A new study published in Public Library of Science One (available here) reports that two drugs widely prescribed to help smokers quit -- varenicline (brand name Chantix) and bupropion (brand names Wellbutrin and Zyban) - are associated with thoughts or acts of violence towards others.

The study was conducted by Thomas Moore at the Institute for Safe Medication Practices, and colleagues from Harvard and Wake Forest Universities. Moore et. al. analyzed data from the FDA Adverse Event Reporting System, extracting all serious adverse event reports for drugs with 200 or more cases received from 2004 through September 2009. The researchers focused on homicide, homicidal ideation, physical assault, physical abuse and violence related symptoms. They reported the number of events, as well as proportional reporting ratios (PRRs), which allows for comparison of the proportion of violence events for each medicine with the proportion from all other evaluable drugs (those in wide clinical use with adequate post-marketing surveillance).

Moore found that “among 484 evaluable drugs, 31 drugs met the study criteria for
a disproportionate association with violence, and accounted for 1527/1937 (79%) of the violence cases…Varenicline has the largest number of reported violence cases (n = 408), [and] the highest proportion of violence cases (PRR= 18.0).”

The PRR for varenicline was so high that it was in a class all by itself. As Moore and colleagues noted, “We have previously examined varenicline’s association with serious psychiatric symptoms including aggression/violence [references omitted]. The aggression/violence case series for varenicline was consistent with these data but revealed other features that may or may not occur in cases attributed to other drugs. These features include early onset of psychiatric symptoms (usually within a few days), a senseless act of aggression/violence directed at anyone who happened to be near by, and resolution of the symptoms upon discontinuation.”

Moore also found that bupropion, an antidepressant prescribed to aid smoking cessation, was also associated with violence, although at a much lower rate (35 episodes, PRR = 3.9). As he and his associates note, “bupropion is indicated for both depression and as an aid to smoking cessation, so those results are not limited to the smoking cessation population.”

Moore also studied pharmaceutical nicotine, which was associated much less frequently with violent episodes (11 cases, PRR = 1.9).

Tobacco prohibitionists like the American Cancer Society often claim that tobacco harm reduction is unnecessary, since medicines represent the gold standard for smoking cessation. This study demonstrates that the gold standard is substantially tarnished. At a minimum, the Cancer Society should update its website discussion of smoking cessation (here). The current version promotes varenicline and bupropion, but fails to mention the drugs’ possible side effect of violent behavior.

POTUS Puffing?

On December 10, White House press secretary Robert Gibbs was asked pointed questions about whether President Obama had quit smoking. Gibbs responded by saying, “I've not seen or witnessed evidence of any smoking in probably nine months,” which prompted an optimistic headline in the Washington Post: “Obama Kicks His Smoking Habit.” But after watching the video of Gibbs’ actual comments (available here), one is left with the impression that the press secretary was practicing plausible deniability; he never actually said President Obama had quit smoking.

Two and a half years ago, in June 2008, I wrote to then-Senator and presidential candidate Obama, encouraging him to consider practicing tobacco harm reduction. I also submitted my letter to the Chicago Tribune, which published it on June 22. The text of that letter (also available here) is as relevant to millions of Americans, and very likely the President, as we move into 2011 as it was two years ago:

An Open Letter To Barack Obama

Dear Senator Obama:

I viewed with great interest your recent comments about your struggle to quit smoking. As a professor of medicine at the University of Louisville with a long-term research program focused on tobacco use and its consequences, I strongly believe that your discomfort is entirely unnecessary; your dependency on cigarettes can readily be resolved.

First, understand that you are not alone. Some 25 million adult Americans are inveterate smokers – that’s about 50% of all who smoke. They are unable or unwilling to stop using tobacco and nicotine. For them, conventional quit-smoking tactics, which require abstinence, simply don’t work.

A growing number of public health experts – including Britain’s Royal College of Physicians, one of the world’s oldest and most prestigious medical societies – believe that inveterate smokers could benefit from alternative tobacco products that are effective quit-smoking aids and vastly safer substitutes for cigarettes.

The Royal College has observed that “smokers smoke predominantly for nicotine” and “nicotine itself is not especially hazardous.” You probably appreciate that nicotine is among the most powerful of addictive substances. But nicotine doesn’t cause any smoking-related disease. In fact, nicotine itself is about as safe as caffeine, another addictive drug consumed safely by millions of Americans.

Research and consumer experience show that smokers can obtain satisfying doses of nicotine from smoke-free (and spit-free) tobacco products. Available as small packets or pellets of tobacco that are placed inside the upper lip, modern smokeless tobacco products can be used invisibly in all social settings, including stressful press conferences.

Most importantly, smokeless tobacco products are 98% safer than smoking. While no tobacco product is completely safe, the majority of cigarette smokers are routinely misinformed – by government agencies and by anti-tobacco extremists – about the relative safety of smokeless products. Unlike cigarettes, smokeless does not cause lung cancer, heart disease or emphysema. Smokers rightfully worry about mouth cancer, but they should take comfort in the fact that the risk for mouth cancer with smokeless is far lower than it is with cigarettes. Statistically, smokeless users have about the same risk of dying from mouth cancer as automobile users have of dying in a car wreck.

In fact, switching from cigarettes to smokeless provides almost all of the health benefits of complete tobacco abstinence.

Substituting satisfying and vastly safer sources of nicotine for cigarettes is called “tobacco harm reduction”. Tobacco harm reduction has worked in Sweden, where men have smoked less and used more smokeless tobacco over the past century than in any other Western country. The result: Swedish men have the lowest rates of lung cancer – indeed, of all tobacco-related deaths – in the developed world.

A colleague and I recently published research, based on an analysis of the federal government’s National Health Interview Survey, documenting that tobacco harm reduction has also worked for American smokers.

The Royal College characterized harm reduction as “a fundamental component of many aspects of medicine and, indeed, everyday life, yet for some reason effective harm reduction principles have not been applied to tobacco smoking.” It concluded, “If nicotine could be provided in a form that is acceptable and effective as a cigarette substitute, millions of lives could be saved.”

Senator, your genuine desire to quit tobacco altogether is commendable. But if you find this goal unachievable, like millions of inveterate smokers, I urge you to switch to smokeless tobacco for your physical and emotional wellbeing. In doing so, you can provide inspiration for American smokers, and you can effect a profound positive change in the nation’s public health. Yes, you can.

Sincerely,

Brad Rodu
Professor of Medicine
Endowed Chair, Tobacco Harm Reduction Research
University of Louisville

Snus Not Linked to Colorectal Cancer

Researchers from the Swedish Karolinska Institute have published a study in the International Journal of Cancer showing that snus use is not a risk factor for cancers of the colon, rectum and anus among Swedish men (abstract here).

Caroline Nordenvall, from the Department of Medical Epidemiology and Biostatistics, and colleagues studied over 300,000 male Swedish construction workers who enrolled in a health program from 1971 to 1992. The workers were followed for up to 37 years, and Nordenvall calculated the relative risks (RRs) for cancer of the colon, rectum and anus among smokers and snus users.

Compared with non-users of tobacco, smokers had RRs of 1.08 (95% Confidence Interval = 0.99 – 1.19) for colon cancer and 1.16 (CI = 1.04 – 1.30) for rectal cancer. These are very small increases, and only the latter is statistically significant. The RR for anal cancer among smokers was 2.41 (CI = 1.06 – 5.48). Although smoking has been implicated for many years as a risk factor for anal cancer, the sexually transmitted human papillomaviruses are known causes of this malignancy. Information on sexual behavior or venereal infections, not found in this study, might affect Nordenvall’s risk estimate for smoking.

Snus users did not have significantly elevated risks for any of these cancers. The RRs were 1.08 (CI = 0.91 – 1.29) for colon cancer, 1.05 (CI = 0.85 – 1.31) for rectal cancer and 0.61 (CI = 0.07 – 5.07) for anal cancer.

Nordenvall concluded her study with the following: “Our results from a large and homogenous cohort of Swedish male construction workers with up to 37 years of
follow-up do not convincingly support an important role of tobacco use in the etiology of colorectal cancer. As expected, an increased risk of anal cancer was associated with smoking.”

Distorting Tobacco Facts to Sway Major League Baseball

Tobacco prohibitionists have for many years pressed Major League Baseball (MLB) to ban player use of smokeless tobacco. Despite decades of misinformation from advocates like Joe Garagiola (example here), many ballplayers still use smokeless products. The U.S. Congress entered the fray in April, when House Health Subcommittee Chairman Henry Waxman convened a hearing to browbeat baseball executives for failing to implement a ban. Witnesses pitched a barrage of misinformation. I responded in this blog (here and here).

More misinformation flowed on November 19, when the presidents of ten organizations dedicated to tobacco prohibition called on the commissioner and the director of the MLB players’ association to ban smokeless tobacco use. Their rationale for a ban was wholly unscientific; earlier this week I wrote the commissioner and the MLB association to set the record straight. The text of my letter follows:

December 6, 2010

Mr. Allen H. (Bud) Selig
Commissioner
Major League Baseball
245 Park Avenue, 31st Floor
New York, NY 10167

Mr. Michael Weiner
Executive Director
Major League Baseball Players Association
12 East 49th Street, 24th Floor
New York, NY 10017

Dear Commissioner Selig and Mr. Weiner:

On November 19, 2010, the presidents of ten organizations dedicated to tobacco prohibition wrote you “…to urge Major League Baseball and the Major League Baseball Players Association to prohibit the use of all tobacco products, including smokeless tobacco, by players, coaches, managers, and other team personnel, at all Major League Baseball venues.” The letter (available here, hereafter referred to as Myers et al.) contains distorted and inaccurate statements about the health risks of smokeless tobacco.

I am a professor of medicine, and I hold an endowed chair in tobacco harm reduction research at the University of Louisville. I have conducted research for two decades on the health effects of smokeless tobacco use, and I believe you are entitled to know what tobacco research and policy experts consider an indisputable scientific fact: the health risks from smokeless tobacco use are so low that they are difficult or impossible to measure with modern epidemiologic methods.

Myers et al. make unsupported allegations that smokeless tobacco causes a litany of cancers. They cite no scientific evidence for their claims, because the risks are either barely measurable or completely nonexistent. In 2009, a comprehensive analysis (Reference 1) of all available epidemiologic studies documented that smokeless tobacco users do not have significantly elevated risks for ANY of the cancers listed by Myers et al.

Myers et al. also claim that “Tobacco use is the number one preventable cause of death in the United States.” This is grossly misleading, as it combines smoking’s dramatic fatality figures with the far more benign use of smokeless tobacco (2). For example, the U.S. Centers for Disease Control and Prevention estimate that over 400,000 Americans die every year from smoking-attributable diseases (3), but the comparable number attributed to smokeless tobacco use is so low that the CDC has never attempted to provide an estimate. American Cancer Society Vice President Emeritus Michael J. Thun participated in a 2004 study concluding that “…smokeless tobacco products pose a substantially lower risk to the user than do conventional cigarettes. This finding raises ethical questions concerning whether it is inappropriate and misleading for government officials or public health experts to characterize smokeless tobacco products as comparably dangerous with cigarette smoking.” (4)

The use of smokeless tobacco may be a legitimate topic of discussion between Major League Baseball and the Major League Baseball Players Association. However, the facts about smokeless tobacco vs. cigarettes should not be twisted to satisfy an anti-tobacco agenda or to influence public health policy.

Please do not hesitate to contact me if you would like more factual information on this important subject.

Sincerely,

Brad Rodu
Professor of Medicine
Endowed Chair, Tobacco Harm Reduction Research

References

1. Lee PN, Hamling JS. Systematic review of the relation between smokeless tobacco and cancer in Europe and North America. BMC Medicine 7: 36, 2009. Available here.

2. Rodu B, Godshall WT, 2006. Tobacco harm reduction: an alternative cessation strategy for inveterate smokers. Harm Reduction Journal 3:37. Available here.

3. Centers for Disease Control and Prevention. Smoking-attributable mortality, morbidity, and economic costs (SAMMEC). Available here.

4. Levy DT, Mumford EA, Cummings KM, Gilpin EA, Giovino G, Hyland A, Sweanor D, Warner KE. The relative risks of a low-nitrosamine smokeless tobacco product compared with smoking cigarettes: estimates of a panel of experts. Cancer Epidemiology Biomarkers and Prevention 13: 2035-2042, 2004.

A Medical Association in Denial on Smokeless Tobacco

A few weeks ago I highlighted misinformation about smokeless tobacco from the Mayo Clinic (here). The foolishness continues, this time from the American Academy of Otolaryngology - Head and Neck Surgery (here). Commonly called Ear, Nose and Throat specialists, or ENTs, these physicians are often involved in the treatment of oral and throat cancers. Regrettably, the Academy and spokesman Dr. Daniel Deschler are perpetuating myths about smokeless tobacco and harm reduction.

“Using smokeless tobacco products, like chew, is not a safe way to quit or a healthier alternative to smoking,” says Dr. Deschler in an Academy press release. He asserts that smokeless tobacco users run the same risks of gum disease, heart disease, high blood pressure, and addiction as cigarette users, but an even greater risk of oral cancer. Only one of these claims is true: Smokeless users are just as addicted to nicotine as smokers, and that is exactly why smokeless is an excellent alternative to cigarettes.

The reality is that smokeless users have almost no risks for gum disease, heart disease or high blood pressure. They certainly don’t have “an even greater risk for oral cancer” than smokers. This gross misstatement should not be made by a physician-spokesman for a professional medical society. As I have documented many times, the oral cancer risk for smokeless use is barely measurable in most epidemiologic studies, and negligible when compared with smoking.

Is the American Academy of Otolaryngology - Head and Neck Surgery deliberately misleading the public? In an effort to correct websites that had false and misleading information about smokeless tobacco, tobacco harm reduction colleagues at the University of Alberta sent a detailed letter to the Academy describing misinformation on its site and explaining why it was potentially harmful to inveterate smokers (read about it here). The organization never responded.

Patients believe their doctors make decisions based on sound science, not on moral judgments. Physicians and organizations that mischaracterize medical facts violate the sacred trust upon which our health care system is based. The American Academy of Otolaryngology - Head and Neck Surgery should correct its message.