Monday, March 15, 2010

WARNING: Chantix Causes Suicide, Herpes, and Nocturnal Vaginal Itch Syndrome

Here is a brief tale of an American dream deferred...
"Tina Hurst is a suburban mother and a manager at a Fortune 500 company. Her life was great, but she had one dark secret...'I was a closet smoker,' Hurst said."  
Here is where the plot thickens...
"Her doctor prescribed a drug called Chantix to help her quit. Seven million Americans have taken it. Hurst says she took Chantix for two months and it worked great."
Then, tragedy struck...
"But when she stopped, 'I totally went off the deep end,' she said. Hurst says she started walking around the house in circles, crying and hallucinating. 'I thought somebody died. And I was freaked out,' Hurst said." 
But, it wasn't over just yet...
"An ambulance rushed Hurst to a hospital where records indicate she was very agitated and had to be restrained. She spent four days in a psych unit. Prior to this, Hurst said she never had a history of anxiety, depression or any mental problems. She thinks it was caused by Chantix. Her doctor's diagnosis? "Substance-induced psychotic disorder." (1
No, this isn't the plot of Gothika (2), this is an account of a woman who claims that she was adversely affected by Pfizer's anti-smoking drug Chantix (varenicline). Stories like this are common place now. Since the drug has come to market, it has racked up some 10,102 reports in the FDA's adverse events database (3).

Normally, I'm all for psychoactive drugs causing harm to people. However, I think a skeptical approach should be taken when it comes to this drug.

The most widely heard side-effect of Chantix is that it causes suicidality. For the sake of argument, let's forget that suicidality is a very complex and multifaceted human condition; we're going to pretend that this little pill can lead an otherwise normal and healthy person to want to kill himself (4).

First, let's examine the neurobiological reasons why this might happen...oh, wait a minute, there are no widely accepted (or proposed?) mechanisms of how this happens, just like there is no proposed mechanism for the supposed anti-depressant induced mania phenomenon (5) or the anti-depressant induced suicidality phenomenon.

What we do have is a temporal association (6). That is, event B happens around, near by, within some sort of proximity of event A. Once that happens, our minds automatically link events A and B together, and we have causation! No need for scientific investigation. Just turn on your computer, sign onto word press and start blogging about how "Chantix Causes Traffic Accident, Passengers Almost Die."

Here's why I am skeptical of the Chantix-suicidality link: smoking is associated with psychiatric illness (8, 9, 10). Specifically, individuals who smoke and have a comorbid psychiatric (i.e., Axis I or II) disorder make up 7% of the population, yet they consume 34% of all cigarettes smoked in the United States. Moreover, cigarette use is associated with most major psychiatric disorders. This means that 7% of 45 million smokers are mentally ill. That's a lot of people who are already at risk for suicide, regardless of whether they use Chantix or not.

Here is another interesting piece of research:
"This study examined the relation between smoking and suicide, controlling for various confounders...We found a positive, dose-related association between smoking and suicide among White men. Although inference about causality is not justified, our findings indicate that the smoking-suicide connection is not entirely due to the greater tendency among smokers to be unmarried, to be sedentary, to drink heavily, or to develop cancers." (11
I almost forgot about this study:
RESULTS: Current daily smoking, but not past smoking, predicted the subsequent occurrence of suicidal thoughts or attempt, independent of prior depression and substance use disorders (adjusted odds ratio, 1.82; 95% confidence interval, 1.22-2.69). Additionally, current daily smoking, but not past smoking, predicted the subsequent occurrence of suicidal thoughts or attempt, adjusting for suicidal predisposition, indicated by prior suicidality, and controlling for prior psychiatric disorders (adjusted odds ratio, 1.74; 95% confidence interval, 1.17-2.54).  (12)
Anybody ever abruptly stop their anti-depressant medication? Bad stuff happens, right? Here is a pretty picture from a study in the September 2003 issues of PENIS er, PNAS (13).

Here is a comparison of a smoker and nonsmoker and the amount of monoamine oxidase throughout their bodies. Smoking lowers the amount of this enzyme, which breaks down the catecholamines (5HT, DA, NE). Without this enzyme, the levels of these neurotransmitters rises. This is how the class of anti-depressants known as monoamine oxidase inhibitors are supposed to work.

Here are the instructions for how a patient is supposed to use Chantix:

 That is, they quit smoking one week after starting Chantix. Since Chantix is a partial-nicotinic agonist and not an MAOI, this could have the same effect as abruptly stopping your anti-depressant medication.

What if the instructions read like this instead. "Patients should be instructed to set a date to quit smoking and to stop their antidepressant medication and to initiate CHANTIX treatment one week before the quit date." Would you still take it?

Earlier, I mentioned the FDA's adverse events database. This is a system, where if an adverse reaction to a drug is suspected, it can be reported.

Here is a link (14) to the FDA's adverse events database on those who quit smoking cold turkey.

You'll notice that there is no real link because there is no actual database for this. The data that is collected by the FDA's actual database is biased, there are too many confounds that are not accounted for.

What about actual research? If you search PubMed for the terms "varenicline" and "suicide" you get 19 hits. Only three are actual prospective studies that looked at the matter (15, 16). The first study only had 1 suicide, but the patent's psychiatric background is unknown since the study is not complete. In the second study,
"There was no evidence that varenicline was associated with an increased risk of depression or suicidal thoughts."
The third study uses an adverse events reporting paradigm (17):
"All patients with suicidal events either had a past medical history of psychiatric illness prior to starting varenicline and/or a precipitating factor for the event. Clinicians should closely monitor patients with pre-existing psychiatric illness who are taking varenicline."
I'm not defending Chantix or Pfizer; over 10,000 reported adverse events for a drug that has been on the market for less that 4 years is a lot. Also, I have no explanation for how seemingly normal people such as Ms. Hurst have such horrible reactions. But, let's not always play the "drug companies are evil" card either. Chantix is the most effective smoking cessation drug on the market. It actually has helped 2 or 3 people.

Just remember, things are not always as they seem; do your own research; and don't trust the shit you read on blogs!


Dr John said...

Wow, this may have been my favorite post of yours of all time. Never have I heard smoking lowered levers of monoamineoxidase. I do not like to prescribe this drug and prefer to have people slowly taper their smokes over 6-8 weeks to address behavioral issues surrounding smoking. I feel even more strongly about that now regardless of what Chantix does or does not do. Thanks for this post!

David said...

Very glad to see that you're back and posting. It's great work like this that led us at Health and Life to list you as a top Pharma blogger and resource.

Thanks! =)

Neuroskeptic said...

Two things confuse me about drug-induced "suicidality":

1. So many drugs seem to cause it. Antidepressants, as everyone knows, but also, pretty much all anticonvulsants, varenicline, CB1 antagonists, and others.

2. Most of these drugs are either new drugs, or use has greatly expanded in the past 20 years or so, but suicide rates have fallen in all (Western) countries over that period.

This doesn't mean that none of these drugs really cause suicidality (I'm pretty sure CB1 antagonists do, for one thing) but there's clearly something we're missing here.

NeuroPsych said...

I think part of that confusion is due to the FDA's system. If one drug within a class, SSRI antidepressants for example, is shown to be associated with increased suicidality, then the FDA adds a black box warning to all drugs within that class (e.g., antidepressants) regardless of the mechanism of action. Last year that was the case with anticonvulsants. The study was a meta-analysis of all different types and the conclusion was (paraphrasing) taking as a whole there was an increased risk, even though only a minority of actual drugs was shown to have that association.

ella said...

The only risk with herpes and having children is during delivery during an outbreak. If there is a current outbreak is in the vaginal canal during natural childbirth, then the baby can potentially contract herpes in the eye. That is not a good thing.

allison said...

Very glad to see that you're back and posting. It's great work like this that led us at Health and Life to list you as a top Pharma blogger and resource.