On January 25, Pfizer was able to share some good news: Japan—where 40.2 percent of all men still smoke—had green-lighted the manufacturing and marketing of its smoking-cessation drug. But a few days later, the Chantix news was less cheering. On February 1, the Food and Drug Administration warned that Chantix, which had fourth-quarter sales of $280 million (up from $68 million a year ago), could cause serious psychiatric problems, including suicidal thinking. Several weeks earlier, Pfizer had independently changed the small-print booklet that accompanies all drugs to say “All patients … should be observed for neuropsychiatric symptoms including changes in behavior, agitation, depressed mood, suicidal ideation and suicidal behavior.” (Previously the fine type had listed suicidal ideation as a rare adverse reaction.)
Now, after investigating an escalating number of complaints from doctors, patients, and health-care providers, the FDA was citing 34 suicides and 420 instances of suicidal behavior in the U.S. Couldn’t those cases have had to do with depression brought on by nicotine withdrawal, compensatory dopamine notwithstanding? Perhaps, said the agency, but some occurred among people who were still smoking while taking the pill.
Varenicline, Chantix’s chemical name, was approved by the FDA in 2006. In development for over a decade, it is the first smoking-cessation medicine designed to work specifically on nicotine receptors, and at first glance, it would appear that it performed quite well in testing. “At week 12, we looked at how many of the smokers didn’t touch a cigarette for the last four weeks of treatment,” says Dr. Anjan Chatterjee, a medical director at Pfizer. “Forty-four percent.” But the tortoise in the ad doesn’t say how patients fared later on. “About 23 percent still hadn’t taken a puff from week 9 to week 52,” Chatterjee admits. “So the relapse rate was about 77 percent.” Still, that’s not bad given that only 7 percent of smokers using the nicotine patch or gum are still off cigarettes after six months.
A total of 3,659 people were handpicked for the Chantix tests before it came on the market, an almost equal number of men and women, with an average age of 43. Nearly all were white, and the tests excluded anyone with a history of depression, panic disorder, heart disease, kidney or liver problems, alcohol or drug abuse, and diabetes. These exclusions aren’t mentioned in the original “Who Should Not Take Chantix” part of the patient-information sheet, which merely states that the drug wasn’t tested on people under 18. (Pfizer does tell patients they should let their doctors know if they have kidney problems or take insulin.)
For me, self-destructive fantasies began cropping up as cartoonish flights of fantasy—nagging chatter that became a little more concrete with every passing day.
Around 5 million prescriptions have been filled in the U.S. thus far. So why would so many groups have been excluded from the testing, particularly for a drug with such potential mass appeal? “In order to satisfy the FDA’s criteria, we have to isolate all the different variables that could affect the outcome,” says Chatterjee. “We can’t use very sick people or people who would not tolerate the drug.” An FDA spokesperson acknowledges this: “It’s not unusual to exclude people with major medical or psychiatric illnesses from some clinical trials,” says Susan Cruzan.
“When they tested the drug, the sample they chose simply isn’t representative of the people they’re targeting,” says Dr. Daniel Seidman, the director of Smoking Cessation Services at Columbia University Medical Center. “By excluding drinkers, you’re artificially inflating your results, potentially. I run a clinic, and two out of three [smokers] I see have a psychiatric or mood problem. None of these people would have been part of the original trials.”
Public Citizen, a consumer-advocacy group, recommends that people not use Chantix—or most new drugs, for that matter—for seven years. “The first seven years are when problems will occur,” says Dr. Sidney Wolfe, editor of Worstpills.org.
“I remember hearing that argument,” Chatterjee said, a few weeks before the FDA’s new warning was issued. “And it’s just so illogical. If no one uses the drug for seven years, there’s no one to report experiences at the end of seven years—so you’re exactly where you were at the beginning.”
While I was on Chantix, I didn’t scan Websites for news about it. As my dream life continued plunging into strange and increasingly grotesque territory, I did think of Carter Albrecht a couple of times, but his story still seemed strictly outlier, a freakish occurrence. As Chatterjee would explain, “What we know of the story has only come from the press. But the level of alcohol in his body was over three times the legal drinking limit in Texas. In the controlled clinical trial, these kinds of changes in behavior were extremely rare, occurring almost as often as the placebo. Based on the tests, we have no evidence of any kind of consistent relationship between Chantix and aggressive behavior.” Nor was the rate of depression any different between those taking Chantix and those on a placebo.