Quitting can be different this time

In May of 2009, 34-year-old Sean Wain of Economy, Pennsylvania, murdered his wife of fourteen years with a shotgun blast before turning the gun on himself, leaving their four small children orphaned. Neighbors and the family pastor said they had seen no sign of any marital discord prior to the shootings. In July of 2010, 33-year-old delivery driver Andrew Case of Fordingbridge, England, stabbed his wife Vicki to death, then smothered their two little girls and covered all three victims with a blanket before hanging himself. In December of that same year, 49-year-old Darwin Stout of Eugene, Oregon stabbed his only son to death, then used the knife to end his own life. Two days earlier, Mr. Stout had entered a mental hospital for evaluation but was discharged after a nurse practitioner and a social worker interviewed him and concluded he was not a danger to himself or others.

Part 1: A fantastic individual Part 2: Quitting can be different this time Part 3: Is suicide an expected event? Part 4: Unnecessary public alarm Part 5: Rages that make no sense at all Each one of these tragedies took place shortly after the killer began taking Pfizer’s blockbuster stop-smoking drug Chantix. The generic name for Chantix is varenicline. Outside the United States, the drug is marketed as Champix. Chantix was approved by the FDA on the basis of five studies, all funded by Pfizer and published in July and August of 2006. The designers of these studies seem to have pulled out all the stops in their efforts to stack the deck in Pfizer’s favor. As many as one-third of prospective study participants were turned away for any of a dizzying variety of conditions including but not limited to a history of cancer, cardiovascular disease, chronic obstructive pulmonary disease, a history of alcohol or drug abuse, major depression, panic disorder, bipolar disorder, systolic blood pressure greater than 150 or diastolic pressure greater than 95, a body mass index of less than 15 or higher than 38, weight less than 45kg, those with "clinically significant abnormalities in the screening laboratory values…” The list goes on and on. Obviously, to whatever extent these conditions compounded the difficulty of quitting smoking, the exclusion of subjects suffering from them would cause the studies to overestimate the overall efficacy of Chantix.

---

The studies also excluded those who were known to have relapsed after attempting to quit smoking with the aid of nicotine replacement therapy (NRT) or another competing product. Common sense would tend to indicate that people who had already failed to quit with the aid of one product would be more likely than average to fail with Chantix. Again, to whatever extent that is true, their exclusion would cause these studies to overestimate the overall effectiveness of Chantix.   There’s more. The designers of these studies created a clinical experience par excellence for would-be quitters. Study participants received all their Chantix for free. They also were treated to weekly one-on-one counseling sessions to assist in problem solving and training for relapse prevention. After Chantix was discontinued, the stop-smoking support continued in the form of extra counseling sessions as well as follow-up telephone calls for a total of 52 weeks. In addition, they underwent repeated complete physical exams, including taking the patient’s smoking history as well as an electrocardiogram, hematology, blood chemistry analysis, and urinalysis. Their weight, vital signs, and expired carbon monoxide were measured at each clinic visit – all opportunities to contemplate their health and mortality, to impress upon them the gravity of the matter at hand. In short, they had available to them stop-smoking assistance probably beyond the wildest dreams of your rank-and-file smoker. And what did the researchers find? Three of the studies – those by Gonzales et al., Jorenby et al., and Onken et al. – assessed the effect of 1 mg Chantix administered twice a day for twelve weeks, in addition to intensive stop-smoking support that continued for a total of 52 weeks. Average results were very close for all three clinical trials: approximately 46% of study participants were smoke-free at the end of the first twelve weeks, and 22% were still smoke-free at the end of the 52 weeks. Flipping that around, that’s a 78% failure rate. The study by Tonstad et al. found that 70.5% of those receiving Chantix for twelve weeks along with intensive stop-smoking support for a total of 52 weeks were smoke-free at the end of 52 weeks. That sounds pretty good, but it turns out that the study subjects were recruited from those who had already managed to emerge smoke-free from a previous twelve-week trial. Let’s assume that the success rate for this trial at twelve weeks was the same as the average of that of the three above-mentioned trials, or 46%. Now, 70.5% of 46% is 32%. Again flipping it around, we can deduce that after 24 weeks of Chantix as well as intensive stop-smoking support continuing for one year, the failure rate was something like 68%. The last study, by Nides et al., found that for subjects receiving Chantix for six weeks plus intensive stop-smoking support for a total of one year, the success rate at the end of that year was a dismal 14.4%. That’s a failure rate of 85.6%. How will smokers in the real world, who cannot hope to call upon the kind of stop-smoking support these folks had, fare? We don’t know, but we can take a guess, in the light of previous experience with NRT. Clinical trials of NRT, along with intensive stop-smoking support similar to what the Chantix trial participants received, reported spectacular success rates – in one case as high as 44%. But the twelve-month success rate for over-the-counter NRT is a dismal seven percent. For those attempting quitting for the second time, the rate is virtually zero. John Polito is a former trial lawyer, a smoking-cessation counselor, and the founder and director of whyquit.com. In a telephone interview he stated “The Chantix studies don’t replicate how the product is actually used. All of the original founding studies had over 20 counseling and support sessions in them. Smokers buying that product don’t receive that kind of counseling and support, so it’s a bait-and-switch product. Pfizer got Chantix approved by letting a chemical ride the back of something we knew worked, counseling.” Nides and his co-authors had a sunnier view of things, concluding “Varenicline tartrate demonstrated both short-term and long-term efficacy vs. placebo. Varenicline was well tolerated…” Advertisements for Chantix chirped “Quitting can be different this time.” In its first full year on the market, Chantix racked up an impressive $883 million in sales. Not everyone was so sanguine about all this. In stark contrast to Pfizer’s diligence in stacking the deck in favor of Chantix in clinical trials is its downright lackadaisical behavior when it came to reporting untoward side effects. Like suicide. Next: Part 3: Is suicide an expected event? List of Sources

1. John Polito, telephone interview, 23 November 2015.
2. Miller, M. 2011. Lawsuit claims Economy murder-suicide caused by stop-smoking drug. Times May 10 2011.
3. Daily Mail Reporter 2011. Father who murdered his family had been on anti-smoking medication that caused depression. Daily Mail April 6 2011.
4. Associated Press 2013. Chantix, smoking cessation drug, blamed in murder-suicide.
5. Associated Press 2006. Nicotine-free anti-smoking pill is approved.
6. Gonzales, D. et al. 2006. Varenicline, an αβ2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 2006;296(1):47-55.
7. Jorenby, D.E. et al. 2006. Efficacy of varenicline, an αβ2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-released bupropion for smoking cessation: a randomized controlled trial. JAMA 2006;296(1):56-63.
8. Oncken, C. et al. 2006. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Archives of Internal Medicine 2006; 166(15):1571-1577.
9. Tonstad, S. et al. 2006. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA 2006; 296(1):64-71.
10. Nides, M. et al. 2006. Smoking cessation with varenicline: a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Archives of Internal Medicine 2006; 166(15):1561-1568.
11. Tonnesen, P. et al. 1988. Effect of nicotine chewing gum in combination with group counseling on the cessation of smoking. NEJM 1988; 318(1):15-18.
12. Hughes, J.R. et al. 2003. A meta-analysis of the efficacy of over-the-counter nicotine replacement. Tobacco Control 2003; 12:21-27.
13. Tonnesen, P. et al. 1993. Recycling with nicotine patches in smoking cessation. Addiction 1993; 88(4):533-539.