Editor’s Note: What is the metric to be used to judge anti-smoking therapies? “Modified Risk” determinations are to apply to the entry of new tobacco products; should the metric being developed by the Institute of Medicine apply to anti-smoking therapies?
Siegel: Rest of the Story
The black box warning for Chantix notes the following:
“All patients being treated with CHANTIX should be observed for neuropsychiatric symptoms including changes in behavior, hostility, agitation, depressed mood, and suicide-related events, including ideation, behavior, and attempted suicide. These symptoms, as well as worsening of pre-existing psychiatric illness and completed suicide, have been reported in some patients attempting to quit smoking while taking CHANTIX in the postmarketing experience. … Advise patients and caregivers that the patient should stop taking CHANTIX and contact a healthcare provider immediately if agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior.”
The black box warning, then, advises physicians to observe patients being put on Chantix for “suicide-related events,” including “suicide.”
This simple question comes to mind: What use is it to observe patients for suicide? In what way does that protect the consumer? If a side effect of the medication is committing suicide within days of initiating therapy, how is monitoring the patient for suicide going to help?
The FDA itself has reported a typical case of Chantix-associated suicidal ideation as follows: “A 30 year-old female reported that she was taking varenicline 0.5 mg/day to help her quit smoking. She indicated that she had taken the pill for 5 days as directed. In her report, she stated, ‘I became very depressed for no apparent reason and started having suicidal thoughts. I worried that I was going to hurt myself or someone else. I was also in a state of panic and unable to eat. I thought that I might go crazy and felt completely out of sorts. I quit taking the pill. About 36 hours later, I felt like myself again.'”
Fortunately, this woman stopped taking the medication. However, the story could easily have been different. Instead of stopping the medication, she could have instead attempted or committed suicide in response to her suicidal ideation. Monitoring patients like this for suicide attempts makes no sense. The purpose of monitoring is to prevent these adverse consequences -especially death – from occurring.
There are three situations in which a black box warning can be effective in protecting consumers. I will describe each of these situations and show why Chantix does not meet any of these criteria:
1. Early Detection of Side Effects Can Prevent Serious Adverse Consequences
One situation in which a black box warning may be appropriate is when monitoring of early side effects can prevent serious consequences. For example, if a side effect of a medication is liver damage, then monitoring a patient’s liver enzymes for evidence of early liver injury can prevent serious disease by alerting the physician to this side effect so that the medication can be discontinued before it causes actual liver damage.
Chantix does not meet this criterion because its most worrisome side effect – sudden suicide – often occurs without warning, often in a matter of days following initiation of therapy. Relying on patients who become depressed to call their physician to report the symptoms is ineffective because one of the symptoms of depression is the inability to do just that. That the most worrisome side effect is not just depression but frank suicidality makes the black box warning ineffective in this regard.
2. Restricted Use of the Drug May Prevent Side Effects
A second situation in which a black box warning may be appropriate is when the severe side effects of the drug tend to occur only in certain patients. In this situation, warning physicians not to prescribe the drug to those patients can prevent the serious side effects. For example, if a drug causes blood clots only in people who are obese, then warning physicians not to prescribe the drug to patients who are obese will be effective in preventing this side effect.
This is not the situation with Chantix because its potentially lethal side effects have been observed to occur among all patients, not only those with existing psychiatric disease. In fact, FDA’s review of Chantix side effects revealed that of cases of Chantix-related suicidal behavior in which psychiatric history was known, 44% of victims had no prior history of psychiatric disease.
3. The Benefits of the Drug Far Outweigh the Costs and Despite the Severe Side Effects, Physicians Should Use the Drug if Benefits Outweigh Risks for a Specific Patient
The third situation in which a black box warning may be appropriate is if the benefits of the drug far outweigh the costs on a societal level and the warning will ensure that physicians weigh the costs and benefits of the drug for the specific patient. For example, a drug that is used to treat cancer might have a severe adverse side effect but its benefits might still outweigh this cost if there are no other treatments available and so this is the only choice that patients have. This criterion will generally not be met if there are lots of other drugs on the market that are equally effective.
In my view, this criterion is not met for Chantix because this drug is not uniquely effective. There are many other treatments on the market (including a variety of nicotine replacement medications) that are equally effective. Moreover, the overall success rate with Chantix is still exceedingly low, and in the overwhelming majority of cases, the use of Chantix will not succeed in getting the patient to quit.
Under these circumstances, I simply do not see how the benefits of keeping Chantix on the market outweigh the many deaths that it has caused. It is not like this is some sort of wonder drug that is very effective in helping people quit smoking, nor is it like this drug is so much more effective than other smoking cessation drugs on the market.
Since none of these three criteria is met, I do not believe that the black box warning is appropriate and I reiterate my call for the removal of Chantix from the market.