Chantix was approved by the FDA on 11 May 2006. A study published by Thomas Moore and his colleagues at the non-profit Institute for Safe Medication Practices found that by the fourth quarter of 2007, Chantix surpassed all other drugs for serious events reported to the FDA, including but not limited to hostility, aggression, paranoia, hallucinations, psychosis, heart arrhythmias, heart attacks, visual disturbances, seizures, falls, traffic accidents, homicidal ideation, suicidal ideation, and suicide attempts, along with 28 actual suicides.
The Institute notified the FDA, which on 1 July 2009 issued an alert and required Pfizer to include a black box warning -- the strongest sanction possible short of banning a drug -- on all packages of Chantix, cautioning users and health professionals to be on the lookout forchanges in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide.
What's more, fourteen of these case reports provided dechallenge information; in thirteen of these, symptoms resolved a few days after Chantix was discontinued, while in the fourteenth, symptoms had improved but not fully resolved at the time of the report. In three of these cases, rechallenge information was provided as well; in all three cases symptoms reappeared when the drug was re-started.
David Healy is a medical doctor, the author of Pharmageddon, and an outspoken critic of the pharmaceutical industry. In a telephone interview, he stressed the importance of challenge-dechallenge-rechallenge case histories such as those describes by Moore and his colleagues in establishing causality, and blasted those who would liken such reports to the kind of anecdotes often cited by anti-vaxxers in support of their position. "You might get a kid vaccinated and later this kid gets autism, but that doesn't prove anything. It doesn't prove the vaccine caused autism, and you're being led to believe the Chantix anecdote in the same way doesn't prove that Chantix causes people to become suicidal. Now, that's wrong. What we get in Chantix, we certainly get challenge and dechallenge and rechallenge. And the difference with the vaccine story is, you give the vaccine, that is the challenge, but you cannot dechallenge and you cannot rechallenge."
The same month the challenge-dechallenge-rechallenge case histories were published, the FDA sent a letter of warning to Pfizer, accusing them of a whole slew of irregularities in the company's reporting of adverse drug experiences with respect to a wide variety of drugs. These include failure to submit adverse drug experience reports to the FDA as required, misclassifying and/or downgrading reports to non-serious without reasonable justification, and inadequate written procedures for the surveillance, receipt, and reporting of adverse events. The letter goes on and on for six pages, detailing a pattern of alleged violations, many of which, the letter claims, had already been brought to Pfizer's attention before.
In December of that year, yet another report by the ISMP provided further evidence of a link between Chantix and violence. Moore and his colleagues analyzed adverse drug event reports submitted to the FDA for the period beginning in 2004 and ending with the third quarter of 2009. Only drugs for which at least 200 adverse events were reported were included in their analysis -- a total of 484 drugs in all. For each of these drugs, Moore et al. tabulated the incidence of violence case reports, which they defined as violence-related symptoms, physical abuse, physical assault, homicidal ideation, and homicide.
For the majority of these 484 drugs, there were no violence case reports. For most of the rest, there were only one or two such reports. Chantix stood out from the pack with a whopping 408 violence case reports, or 21% of the total. The proportion of violence case reports for Chantix was eighteen times the average for all other drugs.
The following May, still another report by the ISMP noted a spike in the number of violence case reports for the third quarter of 2010 due to a large number of adverse events which occurred in previous quarters but had not been previously tabulated by the FDA due to irregularities in Pfizer's reporting system.
How did this happen? The FDA's expedited review system requires drug companies to report within fifteen days adverse events that are both serious and unexpected. Less-serious and expected events are submitted quarterly, in so-called "periodic reports." Pfizer was including suicides in the periodic reports. Moreover, Pfizer was lumping individual reports along with case summaries into a single text file, and these individual reports were not tabulated by the FDA.
These adverse events included 150 suicides, more than doubling the total number of suicides linked to Chantix.
All this raises a question: Is suicide of Chantix users an "expected event?"
Meanwhile, more bad news lay ahead for Pfizer.
Next: Part 4: "Unnecessary public alarm"List of Sources
David Healy, telephone interview 26 November 2015.
Moore, T.J. et al. 2010. Thoughts and acts of aggression/violence toward other reported in association with varenicline. Annals of Pharmacotherapy 2010;44:1389-1394.
Healy, D. 2012. Pharmageddon. University of California Press.
