"Will Chantix really help me quit smoking?"

by John R. Polito, Editor WhyQuit

August 25, 2006, last updated May 30, 2008

Click this link to watch a 4/1/08 FDA video clip discussing Chantix risk factors

WARNING: If you or your loved one is using or considering using Chantix or Champix be sure and watch the new safety warning video clip released by the U.S. Food and Drug Administration (FDA) on April 1, 2008 by clicking the image to the right, or read the warnings at the FDA website.

WARNING: Do not rely upon any information in this article to replace individual consultations with your doctor, pharmacist or other qualified health care provider.



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"Does Chantix really work?" "Tell me the truth, what are my chances?" Frankly, not good. Putting aside for the moment growing concern over FDA acknowledged links between Chantix and suicide, if Chantix (whose chemical name is varenicline) is used as a stand-alone quitting aid without ongoing counseling or support, your chances of quitting smoking for one year are probably less than 1 in 11. But when accompanied by 24 to 25 weekly counseling or support sessions of up to 10 minutes each your chances could rise to 1 in 5 or even 1 in 4.

Yet sadly, Pfizer is today marketing varenicline as having a 44% success rate at 12 weeks, when that figure is really rather meaningless. In clinical trials the treatment period was 12 weeks and heavily supported and counseled users were still under the chemical's rather amazing influence. If addicted to using an external chemical to steal brain dopamine, how significant is a boast about successfully substituting another chemical that allows continued stealing?

"What's it like using varenicline?"

On May 11, 2006 the U.S. Food and Drug Administration (FDA) announced approval of the prescription drug varenicline, to be sold under the trade name Chantix. Today it is marketed as Champix in 20 European nations (including England and Scotland), Australia, Korea, Brazil, Mexico and Japan, with 2007 worldwide sales of $883 million (see PDF page 37). Interestingly, in the U.S. the FDA refused to approve Pfizer's use of the name "Champix" asserting that from a promotional perspective, "it is overly fanciful and overstates the efficacy of the product" (PDF page 148).

Still, for some, varenicline does have potential to at least initially seem almost like a non-event quitting experience for those lucky enough to avoid, move past or endure one or more of the 165 potential side-effects listed on Pfizer's "Full Prescribing Information" sheet. Prior to January 18, 2008 Pfizer's Patient Information sheet only mentioned vomiting, nausea, abnormal dreams, sleep disturbance and constipation as "the most common side effects." It failed to alert smokers to less frequent yet vastly more serious risks mentioned on varenicline's Full Prescribing Information Sheet, including suicidal thoughts, hallucinations, psychotic events, kidney failure, joint pain, muscle pain and arthritis.

Varenicline is a partial agonist that activates release of 35 to 60% of the dopamine that nicotine would have caused to flow if sitting on the exact same acetylcholine receptors. But in that varenicline is in pill form, and if taken regularly, present and occupying these receptors 24 hours a day, within 4-5 days of taking it and achieving "therapeutic levels," smoked bursts of nicotine arriving in the brain (which would normally generate a dopamine "aaah" explosion within 8-10 seconds of a puff) should find most acetylcholine receptors already occupied.

One user described the expected but missing dopamine "aaah" sensations as though "smoking a carrot." It is why Pfizer asserting to the world that its varenicline studies were "blind," claiming that varenicline users could not tell whether or not they had been assigned to the group receiving the real pill, instead of a group whose pill did not contain varenicline (the placebo group), would be laughable if such representations didn't reflect such a serious breach and betrayal of basic scientific integrity. It is not a matter of "guessing" whether or not a foreign chemical is present and at work inside their brain. They knew it was there and most realized it before ever quitting smoking.

As with nicotine patch, gum or lozenge use, they will likely experience some degree of back-end withdrawal syndrome upon ending varenicline use. Users must adjust to living without chemically enhanced dopamine flow.

Pfizer, in its zeal to generate sales, is failing to adequately alert smokers to the fact that half of varenicline clinical trial users who successfully quit smoking for 12 weeks while using it had relapsed to smoking within a year. It fails to tell them that recent head to head competition with the nicotine patch suggests that without ongoing counseling and support possibly as few as 9 in 100 users will be smoke-free at 6 months. It also fails to disclose that its studies were not blind as claimed, making much heralded victories over placebo users rather meaningless.

While Pfizer does an outstanding job of explaining how varenicline occupies nicotine-type acetylcholine receptors, thereby blocking nicotine's ability to occupy the same receptor, it makes no attempt to explain what will happen should they inhale just one powerful puff of nicotine once Chantix/Champix is no longer present and blocking those receptors. Pfizer product marketing treats the topic of continued smoking while taking varenicline far too lightly (what it candy-coats as a "slip up"), thus setting the stage for relapse.

The message Pfizer should be pounding home is that after ending varenicline use, that within 8-10 seconds of taking a puff, that up to 50% of their brain's acetylcholine receptors will be occupied by nicotine. It will generate a powerful dopamine explosion that their mind's pay-attention pathways will make nearly impossible, in the short term, to forget. Their entire Chantix experience will have been for naught, as their brain will soon be begging for more nicotine.

What Pfizer also keeps hidden is the fact that we have no credible study data showing that Chantix is safe and effective for smokers having any significant medical condition, including alcohol abuse, as Pfizer intentionally excluded them from its five initial studies. Profits have again been elevated above the time and expense needed to produce quality risk assessment data. Excluded groups truly are human Guinea pigs, rolling risk dice and now being experimented upon, most without any warning whatsoever.

This fact was first brought on November 20, 2007, when U.S. Food and Drug Administration (FDA) announced that it "has received reports of suicidal thoughts and aggressive and erratic behavior in patients who have taken Chantix" and was conducting an investigation. What the FDA didn't disclose, but was documented by a November 29, 2007 news story, was that the FDA was aware that Chantix had been implicated in at least 55 suicides. By January 18, 2008, concerns over agitation, depression and suicide had grown so great that Pfizer announced that labeling had been changed to warn users.

As detailed below, Pfizer's varenicline studies reflect junk science at its worst. Designed to generate the highest quitting rates possible, sadly, real world quit smoking rates won't come close. It is my hope that after looking behind the study curtain, exploring reports of thousands of adverse reactions being attributed to varenicline, and reflecting on Public Citizen's call for smokers to avoid varenicline until safety issues are settled, that smokers will grow motivated to want to learn more about how nicotine keeps them enslaved. Why? Because knowledge is power, knowledge is a quitting method.

Chemically captive and residing between insula driven craves, urges and anxieties when we went too long between nicotine feedings, and dopamine pathway "aaah" reward sensations when we obeyed and replenished constantly falling nicotine levels (that declined by about half every two hours), how could we not come to falsely believe that smoking nicotine defined who we were, gave us our edge, helped us cope and that life without it would be horrible? After years of beatings and rewards, how easy would it be to remember the beauty of our pre-addiction mind, of going days, weeks and months without once wanting to smoke nicotine? Should using a quit smoking product that, when used alone, likely has a six-month failure rate near 90% be a life risking event? Is it rational to risk our life before educating our mind as to why we feel the need to risk it?

Think about it, what learning takes place by swallowing a pill? We will never be stronger than nicotine but then we don't need to be as it is only a chemical with an I.Q. of zero. It cannot plot, plan, think or conspire and is not some demon that dwells within. Our greatest nicotine dependency recovery weapon has always been our vastly superior intelligence but not if we continue to live in dependency ignorance and darkness. Education, understanding, coping skills and ongoing support truly are quitting methods, ones most smokers continue to overlook.

What impacted Pfizer's clinical trials more, counseling and support, or varenicline?

Pfizer's five initial clinical trials of varenicline were published in July and August 2006. Three are comparable in that they involved a 12-week treatment period using 1mg of Chantix twice daily. In the Chantix study headed by Gonzales, 21.9% of Chantix users were still not smoking at one year. In Oncken the rate was 22.4% and in Jorenby 23%.

That's an average one-year rate of 22% or, on the flip side, a relapse rate of 78%. But these rates were achieved under highly artificial clinic study conditions. History and common sense teach that use under real-world conditions will likely generate a significantly higher failure rate. The question is, how high?

What the prescription Chantix or varenicline box looks like when you buy or purchase it. If you are going to purchase Chantix search the Internet as the price may be cheaper than in your local pharmacyPfizer funded and co-authored the five initial studies and was involved in all study elements including design and monitoring. Pfizer appears to have spared no expense in creating what may be the most intense clinic quitting experiences ever. Frankly, it is surprising that the intensity of support and interaction did not produce even higher rates. Real-world quitters, alone with their pills, or even participating in Pfizer's GetQuit support plan, will be fighting under entirely different battlefield conditions. What was it like inside an early Chantix study?

Varenicline users received their varenicline for free in all clinical trials. They were reimbursed travel expenses associated with visiting their health provider to obtain it. They attended sixteen clinic visits involving brief one-on-one sessions with counselors trained in motivation and coping skills development. They received up to eight follow-up telephone support calls from their varenicline provider. In the earliest trials, they received two full physical exams, pondered the significance of a stream of questions in provider administered surveys, had their urine and blood checked seven times, sensed the seriousness associated with undergoing six EKGs, and watched their weight, vital signs and expired carbon monoxide breath tests recorded sixteen times?

How much of Chantix's 22% one-year quitting rate is due to Chantix and how much attributable to the 26 times in the Jorenby study that participants spent one-on-one time with their Chantix provider? How many real-world quitters will have the support benefit of 26 sessions with their prescribing physician? Any? If so, at what financial cost? If not, at what cost in terms of performance?

April 16, 2008 - With free ongoing individual or group counseling and support, UK Stop Smoking Services may offer cessation services of higher caliber than present in Pfizer's clinical trials. Table 6, PDF page 12 of a new study shows that at 4 weeks after starting varenicline treatment that 63% of Champix users were still not smoking as compared to 51% who, of their own accord, quit without it.

At four weeks varenicline users were still under its influence, had not yet adjusted to living without chemically enhanced dopamine levels, yet its advantage over those quitting without it was then modest. It shows what would have happened if Pfizer had pitted varenicline against those wanting to quit cold turkey instead of quitters wanting medication but instead getting assigned to the placebo group and thrown into full blown nicotine withdrawal.

While 51% of non-medication UK quitters were still smoke-free at 4 weeks, in Pfizer's clinical trials only about 18% of placebo group quitters in the Jorenby study, 21% in the Oncken study and about 23% in the Gonzales study were smoke-free at 4 weeks. We know that varenicline's 12 week rate will decline by roughly half between weeks 12-52. We also know that cold turkey quitters able to quit for a full month will from then on show significantly lower relapse rates than pharmacology quitters who have yet to end pharmacology use. It's why conducting intellectually honest clinical trials is so important. It's why, with billions in profits at stake, we should not expect to see it happen.

On some unknown date during 2007 Pfizer started offering Chantix users live telephone support. Why? We don't know. What we do know is that since Chantix's approval in May 2006 that Pfizer's GetQuit Chantix support website has allowed it to collect a massive body of nearly "real-world" use data (at least for customers having Internet access), data that so far has been treated as if "top secret." Users going to Pfizer's GetQuit site are now offered a "Choice of regular check-in e-mails or phone support for up to a full year." I reviewed a number of Pfizer's early support emails and was generally in agreement with most user comments I'd received indicating that Pfizer's email support was pretty lame. The only comments I've so far received regarding telephone support have been positive.

Those who don't know cessation study history are destined to repeat it

Chantix entered the quitting product market as a prescription aid at a time when nicotine replacement therapy or NRT was the clear front-runner. Nicotine gum was first approved by the FDA for prescription use in 1984 and was followed by the nicotine patch in 1991. Both the gum and patch were approved for over-the-counter (OTC) sales in 1996, the same year prescription nicotine nasal spray was approved. The nicotine inhaler and bupropion (Zyban) joined as prescription products in 1997. In 2002 the lozenge become the first nicotine delivery device to enter the market directly as an OTC product.

There was a feast to starvation difference between the intensity of support in randomized clinical trials and the OTC NRT studies. The OTC studies were needed to validate the FDA allowing the nicotine gum and patch to go from prescription to OTC in '96. OTC study participants sometimes received little more than the instructions that came inside the box.

A 2002 study by pharmaceutical industry consultants combined and averaged the seven over-the-counter nicotine patch and gum studies found that just 7% were still not smoking at six-months - a 93% relapse rate. Although another well-kept industry secret, the one-year OTC NRT rate is likely a bit less than 5%. Yes, a 95% failure rate and near 100% failure for second time users.

But NRT's extremely dismal quitting rate did not become visible until forced to stand on its own and be evaluated for OTC use. Until then, NRT was allowed to hide behind an intensity-rich clinic experience which nourished quitting motivations far longer than normal. Let's look back to a few of the more heralded early nicotine gum studies which often had heavy education, counseling and/or support elements too. How did their results compare to Chantix's initial 22% one-year rate?

Is Chantix/Champix a step forward or back?

A 1976 nicotine gum study headed by Russell found that 23% of nicotine gum users were still not smoking at 1 year. The 1980 nicotine gum study by Raw produced a whopping 38% rate, in 1982 Jarvis found a 31% rate, in 1983 Schneider 30%, in 1984 Hialmarson 29%, in 1986 Daughton 31%, in 1987 Kornitzer 32%, and in 1989 Tonnesen boasted a 44% one year quit smoking rate.

The history of nicotine gum studies provided Pfizer confidence that intensively supportive Chantix (varenicline) studies should generate rather hefty and newsworthy one-year quitting rates. But it also knew that naked and alone, outside clinic doors, that nicotine gum proved at least three times less effective (using the low of 23% above to OTC NRT's 7% six-month rate).

Clearly, taking a Chantix pill twice daily is vastly easier than chewing piece after piece of nicotine gum, often after the onset of a crave episode. True, but aside from the discouraging cost of a 12-week supply ranging from $321 to $516 (U.S.), Chantix users face the possibility of a long list of discouraging side effects that, without counseling, explanation or ongoing support may cause users to abandon its use. More about side-effects in a moment.

When used as a stand alone product, will Chantix's OTC quitting rate compare to NRT's OTC rate and be at least three times lower than the 22% average generated in Pfizer's three comparable studies? We don't yet know. Let's hope that the above nicotine gum rates are not comparable as it could mean that Chantix's real-world rate might actually be worse than nicotine gum's.

When OTC NRT's dismal six-month 7% quitting rate is contrasted to the boasts within pharmaceutical industry NRT marketing commercials, clearly both smokers contemplating quitting and children contemplating smoking are being seriously deceived about the ease of quitting with replacement nicotine.

Pfizer could have turned a new page in placing honesty and openness above corporate profits. But instead it has rewritten Aesop's tortoise and hare fable to suggest that a "hare" who wanted varenicline too but whose expectations were shattered by assignment to the placebo group, can be fairly compared to a cold turkey who expected to endure and successfully navigate full-blown withdrawal. Pfizer knows that it cannot fairly pit its tortoise against real turkeys -- who want to quit cold turkey -- in open label/open method clinical trials without losing race after race, being exposed and forfeiting billions in profits.

So what's the bottom line? What are your chances with Chantix or Champix? Clearly we do not yet know varenicline's odds when used as a stand-alone aid. If gum's performance is any indication we should not be surprised to see one year rates in the neighborhood of 1 in 20. But if a quitter is able to fully duplicate the richness and intensity of support offered in Pfizer's formal clinical trials shouldn't they expect to experience 1 in 5 odds of success or 22% at one year? Although we wish it were true, maybe not.

Newer Studies - New varenicline efficacy studies, comparing it to controls or other quitting methods have become available since this article was originally written in August, 2006. Studies providing insight into varenicline's true value as a real-world stand alone quitting aid (its effectiveness), without intensely artificial and highly unrealistic levels of provider contact and interaction, will be shared under this subsection.

February 13, 2008 Aubin Varenicline/Nicotine Patch Study (link to free full text PDF copy) - This 52 week Pfizer funded study compared 12 weeks of varenicline (1mg twice daily) by 376 users to 10 weeks of stepped-down nicotine patch use (21mg to 7mg patches) by 370 patch users.

The 2008 Aubin study excluded 21% of applicants including but not limited to all with any "serious or unstable disease," depression or other psychological disorder, or drug or alcohol dependence, abnormal lab tests or using any medication that might interfere with the study.

As with Pfizer's five initial studies, the 2008 Aubin study did not seek to demonstrate how varenicline would compare to nicotine patch use under real-world battlefield conditions, but instead was designed to generate the most highest one-year rates possible. Like the initial studies it created intensely artificial study conditions that few if any real-world users will ever experience.

According to the study, "Counselling also occurred during every subsequent telephone and clinic visit." The study identified 1 baseline visit, 12 treatment phase visits for varenicline users (10 for patch users), with clinic visits on weeks 13, 16, 24, 32, 40, 48 and 52, interspersed with telephone counseling on day 3, and weeks 14, 20, 28, 36 and 44. That's at least 25 provider counseling sessions, each up to 10 minutes in length.

This intense counseling and support format resulted in proof that, at one year, 20.3% of nicotine patch users and 26.1% of varenicline users had most probably not smoked a cigarette within 4-5 hours of blowing into a carbon monoxide detector (carbon monoxide's chemical half-life).

As with all varenicline studies to date, this study provides zero evidence that any participant actually arrested their chemical dependency upon nicotine - none. Instead, it focuses exclusively upon a single form of nicotine delivery, the most destructive, smoking, as evidenced by two factors: (1) "use of NRT during the 9 months of follow-up did not disqualify a subject," and (2) self-reported abstinence was checked by sampling exhaled carbon monoxide levels that were permitted to be twice as high as recommended by some studies, 10ppm versus 5 ppm (parts per million).

More telling were actual participant answers when asked whether or not they had smoked a cigarette within the prior 7 days, what researchers term "7-day point prevalence of abstinence." Amazingly, the study's authors conclude that there ...

"were no significant differences" between Chantix and nicotine patch users at either 6 months (varenicline 38.6% vs. patch 34.1%) or one year (varenicline 34.8% vs. patch 31.4%).

If Chantix performance without 25 counseling sessions declines proportionally to accepted nicotine patch rates generated under real-world conditions, just 7% at six months (see Hughes' 2003), the 2008 Aubin study will someday be looked back upon as having foretold Chantix and Champix's true worth as a stand-alone quit smoking pill, when used without counseling or support.

But which 2008 Aubin figures should we believe, the one-year expired carbon monoxide readings which would proportionally put Chantix's six-month stand-alone rate at 9% (7/20=9/26), or one-year participant answers when asked whether or not they had smoked within the past 7 days, which produces a slightly lower six-month rate of 8% (7/31.4%=8/38.6%)?

Both 8% and 9% are lower than controls in U.S. Guideline evidence tables suggesting a natural six-month "on-your-own" quitting rate of 10-11%. If true the question becomes, in conducting varenicline risk-benefit analysis, after factoring in escalating concerns over loss of life, should the FDA immediately order Chantix to be pulled from the market (see "FDA Chantix Handling Betrayed Public Health" for additional insights).

28% applying for initial studies were denied participation

A second factor that could significantly diminish Chantix's real-world performance rate is associated with a substantial percentage of smokers who applied to participate in each study but were denied.

In Gonzales 1,843 smokers were screened and 458 were excluded (25%), in Oncken 980 were screened and 333 excluded (34%), and in Jorenby 1,413 were screened and 386 excluded (27%). But why?

A partial list of those excluded includes those suffering from cardiovascular disease, alcohol abuse, major depression, panic disorder, systolic blood pressure greater than 150 or diastolic pressure greater than 95, a history of cancer, a body mass index (calculated as weight in kilograms divided by height in meters squared) of less than 15 or higher than 38; weight less than 45kg, those with a "clinically significant medical disease," those over age 75 or younger than age 18, those smoking fewer than 10 cigarettes per day, and those known to have recently relapsed during NRT or Zyban quitting attempts. But why?

Most within these groups reflect populations that have historically been the most challenging to assist in quitting, including youth who often smoke fewer than ten per day. You would think that prior to any government approving any new medication, it would demand that early studies include all known human conditions, or that smokers reflected by any groups intentionally excluded be warned in all product marketing that it has not yet been tested for safety or efficacy in regard to them.

Clearly, Pfizer knew in advance that including difficult to treat populations, such as alcohol abusers, would have resulted in greater relapse rates, making final cessation figures less impressive. Looking at the seriousness, types and quantity of adverse events now being reported (see safety discussion below), one has to wonder if some of the excluded groups, if included, would have revealed serious safety concerns sooner. If so, prior to excluding them, was Pfizer aware that excluding them would, to some degree, hide safety concerns? In other words, did Pfizer believe in advance that excluding the above groups would both elevate quitting rates and diminish safety concerns?

Pfizer's Chantix marketing has aggressively assaulted all smokers, including most that it intentionally excluded from its studies. A visit to Chantix.com on December 3, 2007, at first glance, appears inviting to nearly all smokers. The page asks "if Chantix is right for me" but provides few answers. Instead, Pfizer is crafty in shifting the information burden to U.S. physicians, by telling smokers to ask their doctor if Chantix is right for them.

But if you are within any of the excluded groups, your group probably has yet to be the focus of any serious study, and thus, at best, your doctor can only guess as to how Chantix or Champix will interact with your condition or medication. Most excluded groups will find that, as of today, we have little or no idea of your odds of success with Chantix or Champix, or your potential to experience adverse events, some of which may not yet appear on Pfizer's "Full Prescribing Information" sheet.

Go to PubMed and search "varenicline" + key words associated with your condition or concern, to find out if it has yet been the focus of any study. Escalating concerns regarding varenicline side-effects are just now beginning to generate risk assessment papers for some excluded groups. But the number of quitters being evaluated and/or the haste with which these studies are being thrown together provides little confidence in relying upon their implications or conclusions.

For example, Pfizer's studies excluded those with mental health issues. We now have an August 2007 case study of one smoker diagnosed with bipolar disorder, whose condition was stable for five years while taking valproic acid. This man started experiencing manic symptoms within a week of taking 1mg of varenicline twice daily, and had to be admitted to an inpatient psychiatric unit. Although noteworthy, bipolar patient mixing valproic acid and varenicline does not a "study" make.

But now it's as if Pfizer is scrambling to plug leaks in a damn. Imagine trying to pass off old NRT and varenicline use data - data that included a brief medical history, with at least one question about mental health conditions - as a November 2007 safety study of varenicline use in patients with mental illness. Imagine declaring varenicline use safe in patients with mental illness when: (1) only 53 patients asserting mental illness thereafter used varenicline; (2) none of the 53 underwent any objective mental health evaluation (see DSM-IV and ICD-10 standards) at any time during the study (nor did the control group); and (3) the study makes no reference whatsoever to any mental health medication taken by any of the 53 patients. What this junk "mental illness" study did find was greater depression in varenicline users. Also one user experienced a "severe psychological reaction likened to a bad LSD trip, including anxiety, paranoia, confusion and impaired motor control."

Serious controversy brewing: are Chantix and Champix safe?

This article was originally written in August 2006. Since then there has been mounting concern regarding varenicline's safety. Due to a number of recent developments, this article's safety discussion is presented in chronological order. Each underlined date is a link to the development's online source.

May 10, 2006 - The FDA approves Chantix's Patient Information Sheet. The "Sheet" warns users of five "common side effects": nausea, changes in dreaming, constipation, gas, and vomiting. What it fails to alert patients to is the fact that varenicline's "Full Prescribing Information" sheet lists 160 additional potential adverse events. But as pointed out in a TV news interview with Dr. Ponni Subbiah, a Pfizer employee, all 165 "aren't necessarily associated with the drug, a causal association. It's just they were reported in the trials."

Additional Full Prescribing Information sheet adverse events listed include: (1) nightmares (2) headaches (3) dysgeusia a/k/a reduced sense of taste (4) somnolence a/k/a drowsiness (5) lethargy (6) fatigue/malaise/asthenia (7) rhinorrhea a/k/a runny nose (8) dyspnoea a/k/a difficulty breathing (9) upper respiratory tract disorder (10) rash (11) pruritis a/k/a itching (12) increased appetite (13) decreased appetite/anorexia (14) anemia (15) lymphadenopathy (16) luckocytosis (17) thrombocytopenia (18) splenomegaly a/k/a enlarged spleen (19) angina pectoris a/k/a chest pain (20) arrhythmia a/k/a irregular heart rate (21) bradycardia a/k/a heart rate less than 60 beats per minute (22) ventricular extrasystoles (23) myocardial infarction (24) palpitations (25) tachycardia (26) atrial fibrillation (27) cardiac flutter (28) coronary artery disease (29) cor pulmonale (30) acute coronary syndrome (31) tinnitus a/k/a ear ringing (32) vertigo (33) deafness (34) Meniere's disease (35) thyroid gland disorders (36) conjunctivitis (37) dry eye (38) eye irritation (39) vision blurred (40) visual disturbance (41) eye pain (42) acquired night blindness (43) blindness transient (44) cataract subcapsular (45 sleep disorder (46) ocular vascular disorder (47) photophobia (48) vitreous floaters (49) diarrhea (50) gingivitis (51) dysphagia (52) enterocolitis (53) eructation (54) gastritis (55) gastrointestinal hemorrhage (56) mouth ulceration (57) esophagitis (58) gastric ulcer (59) intestinal obstruction (60) acute pancreatitis (61) chest pain (62) influenza like illness (63) edema a/k/a swelling (64) thirst (65) chest discomfort (66) chills (67) pyrexia a/k/a fever (68) gall bladder disorder (69) hypersensitivity (70) drug hypersensitivity (71) liver function test abnormal (72) weight increased (73) electrocardiogram abnormal (74) muscle enzyme increased (75) urine analysis abnormal (76) diabetes mellitus (77) hyperlipidemia (78) hypokalemia (79) hyperkalemia (80) hypoglycemia (81) arthralgia a/k/a joint pain (82) back pain (83) muscle cramp (84) musculoskeletal pain (85) myalgia a/k/a muscle pain (86) arthritis (87) osteoporosis (88) myositis a/k/a muscle inflammation (89) disturbance in attention (90) dizziness (91) sensory disturbance (92) amnesia (93) migraine (94) parosmia (95) psychomotor hyperactivity (96) restless legs syndrome (97) syncope a/k/a fainting (98) tremor (99) balance disorder (100) cerebrovascular accident a/k/a stroke (101) convulsion (102) dysarthria a/k/a motor speech disorder (103) facial palsy a/k/a facial drooping (104) mental impairment (105) multiple sclerosis (106) nystagmus a/k/a involuntary eye movement (107) psychomotor skills impaired (108) transient ischemic attack a/k/a mini stroke (109) visual field defect (110) anxiety (111) depression (112) emotional disorder (113) irritability (114) restlessness (115) aggression (116) agitation (117) disorientation (118) dissociation (119) decreased libido a/k/a reduced sexual desire (120) mood swings (121) abnormal thinking (122) bradyphrenia a/k/a slowed thought processes (123) euphoric mood (124) hallucination (125) psychotic disorder (126) suicidal ideation a/k/a suicidal thoughts (127) polyuria a/k/a excessive volume of urination (128) nephrolithiasis a/k/a forming kidney stones (129) nocturia a/k/a waking during the night to urinate (130) urine abnormality (131) urethral syndrome (132) acute renal failure a/k/a kidney failure or injury (133) urinary retention (134) menstral disorder (135) erectile dysfunction (136) sexual dysfunction (137) epistaxis a/k/a nose bleeding (138) respiratory disorders (139) asthma (140) pleurisy (141) pulmonary embolism (142) hyperhidrosis (143) acne (144) dermatitis (145) dry skin (146) eczema (147) erythema (148) psoriasis (149) urticaria (150) photosensitivity reaction (151) hot flush (152) hypertension (153) hypotension (154) peripheral ischemia (155) thrombosis (156) abdominal pain (157) dyspepsia a/k/a indigestion (158) gastroesophageal reflux disease (159) dry mouth and (160) insomnia.

Both Pfizer, on the Patient Information Sheet, and the FDA, at its website, could have easily advised smokers of the identity of groups included in and excluded from clinical studies, yet both chose to keep smokers in darkness. Instead of only revealing the five most common side effects, the Patient Information Sheet could have told readers of the existence of 160 additional known risk concerns and directed them to either examine the Full Prescribing Information sheet or online FDA documents to see a complete list.

There, potential users would have learned the actual odds of experiencing the most common side effects, but, again, only for the types of smokers included within the studies. They would have read that nausea was seen in 30% of users, insomnia in 18%, abnormal dreams in 13%, sleep disorder in 5%, nightmares in 1%, constipation in 8%, gas in 6% and vomiting in 5%.

They would also have noticed that Pfizer had classified all 165 potential side effects as either: (1) common; (2) frequent; (3) infrequent; or (4) rare. Although Pfizer's Chantix website directs smokers to ask their doctor, "Is CHANTIX™ (varenicline) right for me," the Full Prescribing Information sheet fails to provide physicians with the information needed to answer this critical question. The sheet both fails to advise physicians of the identity of all groups Pfizer intentionally excluded from its five clinical trials, or define critical terms such as "frequent," "infrequent" and "rare."

Although the Prescribing sheet advised doctors that the five most common side effects (nausea, sleep disturbance, constipation, flatulence and vomiting) were experienced by greater than 5% of varenicline users, and that 19 other side effects listed as "common" occurred in greater than 1% of 1mg Chantix users, the terms "frequent," "infrequent" and "rare" are not defined. All physicians are told is that these events reflect "a list of treatment-emergent adverse events reported by patients treated with CHANTIX during all clinical trials," which, the sheet indicates was "over 4,500 individuals."

It's as if Pfizer is toying with physicians, leaving clues here and there. For example, if your doctor had read the bottom of a September 18, 2007 Dallas Morning News story, Pfizer would have revealed to her or him that adverse events reported as "infrequent" occurred at a rate somewhere between 1 in 100 and 1 in 1,000 patients.

This would seem to suggest that "frequent" would be more often than in 1 in 100 patients and "rare" less than 1 in 1,000 patients. But if "frequent" is defined as events occurring more often that 1 in 100, where do "common" events fit into the puzzle? Nearly all physicians attempting to analyze and properly advise patients regarding varenicline's risk puzzle are clearly left guessing as to how often adverse events should be expected, which among the 165 listed are actually caused by Chantix or Champix, and how their patient's chronic medical condition, and medications prescribed to treat it, will mesh with varenicline use.

October 4, 2006 - On this date a Chantix user named Suzy posted to a message board at WrongDiagnosis.com complaining of significant joint and muscle pain which started three days after she started taking Chantix and continued long after its use ended. Suzy closed by asking, "has anyone else experienced this?" Suzy had received 1,010 responses as of April 23, 2008, many documenting Chantix muscle and joint pain nightmares significantly worse than hers.

June 1, 2007 - On this date a physician named Antonio Howell, MD began replying to Chantix user comments to his blog, a blog in which he listed the psychiatric disorders mentioned on Chantix's Full Prescribing Information sheet: "Frequent: Anxiety, Depression, Emotional disorder, Irritability, Restlessness. Infrequent: Aggression, Agitation, Disorientation, Dissociation, Libido decreased, Mood swings, Thinking abnormal. Rare: Bradyphrenia, Euphoric mood, Hallucination, Psychotic disorder, Suicidal ideation."

On June 1, 2007, Deanna told Dr. Howell how her husband had never had any mental health problems but tried to take his own life after being on Chantix for 13 days. On August 27, 2007 Zezrie wrote Dr. Howell telling him how her brother-in-law shot and killed himself while on Chantix. Since then Dr. Howell has been overwhelmed by additional mental health horror stories. He recently started a poll asking visitors if Chantix should be taken off the market until additional safety studies are done. As of December 2, 2007, 70% responding said "yes" (38 of 56).

September 18, 2007 - A Dallas Morning News story reports on the Labor Day death of Carter Albrecht, a local musician who mixed heavy alcohol use (3 times the Texas legal driving limit, a fact first reported on October 22, 2007) with Chantix use, became delusional, aggressive, assaulted his girlfriend, and minutes later was "shot and killed breaking into a neighbor's house."

A statement by Pfizer attached to the bottom of the Carter Albrecht story seems to blame his death on the act of quitting, not varenicline. Pfizer asserts, "It is important to note that a vast body of medical literature has shown that smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms and has also been associated with the exacerbation of underlying psychiatric illnesses."

Before accepting Pfizer's contention (which the FDA now appears to be buying into hook, line and sinker) we'd be wise to ask ourselves, with more than 46.5 million Americans having already successfully quit smoking, and CDC data indicating that almost 90% quit cold turkey, how many news stories have any of us ever read in which quitting cold turkey (without using any pharmacology product) was blamed for someone committing suicide, hallucinating, developing a psychotic disorder, horrible muscle or joint pain, or during which the quitter vomited for twelve straight weeks? Any?

September 24, 2007 - CBS 11 News in Dallas/Fort Worth broadcasts a story entitled "Miracle Drug or Dangerous Problem" (click link to watch the video clip). It reports on Carter Albrecht's death. It also pictures Karen from Maryland and Deborah in Oregon who both felt suicidal while using Chantix, and Candace in Arizona who experienced aggression. It interviews Scott Mullins who experienced bad dreams and horrible thoughts. "As much as I hate to admit it," says Scott, "there have been times that I thought about ending my life."

September 2007 - Public Citizen, a nonprofit, nonpartisan group which champions U.S. consumer interest, placed varenicline on its worst pills list, recommending that consumers not use it until 2014. Public Citizen cites varenicline's common side-effects being reported by more than one-third of clinical trial users and contends that safety information is currently inadequate.

October 25, 2007 - CBS 11 News in Dallas broadcasts a second story entitled "Drugs Tested on Few Before Released to Masses." It questions how Chantix could be approved for use after testing upon only 4,500 smokers. In it, CBS 11 News claims to have accessed the U.S. Food and Drug Administration (FDA) side effects data base and found "thousands of similar and very serious reactions to Chantix."

It notes that Pfizer tested varenicline on roughly 5,000 users prior to FDA approval and although its physician "Full Prescribing Information" sheet warns doctors of a potential risk of "suicidal ideation," "aggression" and "nervous system disorders" that the only risks mentioned on Pfizer's Patient Information sheet are the five most common side effects.

The CBS 11 story asserts that new signals have caused the European Commission on Human Medicines to put Champix on its list of "New Drugs Under Intensive Surveillance" and that it is now keeping a close eye on potential "suicidal thoughts and behaviour" in European patients prescribed Champix.

October 25, 2007 - Omer Jama, a popular 39 year-old UK television editor is found dead with his wrists slashed at his Bolton, England home, four weeks after starting Champix. According to his brother, "He's got no history of depression and was never the sort of person you would see feeling sorry for himself."

November 20, 2007 - The FDA announces that it "has received reports of suicidal thoughts and aggressive and erratic behavior in patients who have taken Chantix." It reports that "preliminary assessment reveals that many of the cases reflect new-onset of depressed mood, suicidal ideation, and changes in emotion and behavior within days to weeks of initiating Chantix treatment" and that as soon as its "analysis is completed, FDA will communicate its conclusions and recommendations to the public."

My question regarding the FDA's 11/20/07 announcement is who actually wrote it, the FDA or Pfizer, and whose interests are being protected, Pfizer's or the consumers? Why does the announcement fail to share the gravity of the situation by at minimum revealing the total number of suicides among U.S. Chantix users that have thus far been reported to the FDA? Is this fact a national secret?

Compare the actual language from a statement Pfizer had the Dallas Morning News attach to its Chantix suicide story on September 18, 2007, to the actual language contained in the FDA's investigation announcement that was written 2 months and 2 days later. Then ask yourself, who authored the FDA announcement?

According to a November 26, 2007 Chantix article, the Prescription Drug User Fee Act is a 1992 law that allows the FDA to bill pharmaceutical companies for the cost of approving their products, with the FDA estimating 2007 collections under the Act exceeding $259 million.

The article shares the insights of Dr. Sidney Wolfe, director of health research for Public Citizen. Dr. Wolfe indicates that the Act has resulted in a cultural shift at the FDA with quicker turnaround times and a more accommodating attitude toward drugmakers. "The (pharmaceutical) industry is viewed by some people in the FDA as 'our client. ‘They're paying our salaries.' Twenty years ago, if a drug went through clinical trials and there were more serious questions, the attitude was, ‘Let's do more studies.'" According to Dr. Wolfe, "'Not anymore.'"

November 28, 2007 - A Texas television station announces it used the Freedom of Information Act to obtain "a computer disc ... with 5,157 complaints, which were all filed in just one week after the News 8 report aired." This report asserts that, "suicide was reported 55 times," suicidal thoughts were mentioned in 199 cases, 417 people complained of depression and there were hundreds of mentions of anger, aggression, amnesia, hallucination and homicidal thoughts.

December 10, 2007 - Australia's Therapeutic Goods Administration (TGA) announces that it has reviewed reports submitted to the US FDA and ordered Pfizer to issue "Dear Doctor" letters and amend the Champix product information sheet. The warning states, "there have been reports of depressed mood, agitation, changes in behaviour, suicidal ideation and suicide in patients attempting to quit smoking while taking Champix." Sale of Champix is scheduled to commence in Australia on January 1, 2008.

December 14, 2007 - The European Medicines Agency (EMEA) announced that "updated warnings to doctors and patients are needed to increase awareness of cases of suicidal ideation and suicide attempts reported in patients using Champix (varenicline)."

January 18, 2008 - Pfizer announced that it had "updated the Chantix label in the U.S. to include a warning that patients who are attempting to quit smoking with Chantix should be observed for serious neuropsychiatric symptoms, including changes in behavior, agitation, depressed mood, suicidal ideation and suicidal behavior."

January 18, 2008 - Pfizer updated the safety information section of its Chantix website to warn visitors that, "You should be aware that some patients have reported depressed mood, agitation, changes in behavior, suicidal thinking or behavior when attempting to quit smoking while taking CHANTIX. If you experience any of these symptoms, or if your family or caregiver observes these symptoms, please tell your doctor immediately." "If you have ever had depression or other mental health problems, tell your doctor before taking CHANTIX. Quitting smoking, with or without CHANTIX, can result in nicotine withdrawal symptoms (such as depressed mood, agitation) or a worsening of underlying psychiatric illness, such as depression."

January 18, 2008 - Pfizer revised the Patient Information sheet to include an extremely weak and watered-down warning that suggests that all quitters, including Chantix quitters, may experience suicidal thoughts. It reads, "Tell your doctor if you experience agitation, depressed mood or suicidal thoughts. These symptoms have been reported in patients trying to stop smoking with or without Chantix. It is not known if these symptoms are related to Chantix."

Shockingly, the Patient Information sheet keeps hidden what Pfizer reveals to those having Internet access, to those visiting its Chantix website, that we are not just talking about suicidal "thoughts" but suicidal "behavior." Also, Pfizer continues to suggest that a normal and expected risk factor of quitting smoking cold turkey -- for those attempting to extend or save their lives -- is that they actually do the opposite and think about killing themselves. We have 48 million comfortable ex-smokers in America. Where are the news stories sharing details about how quitting brings with it a risk of suicidal thoughts or behavior? We have more than 200 nicotine replacement therapy (NRT) studies that followed tens of thousands of quitters, that detail the side effects and risks experienced by each group within each study? Where are the NRT studies mentioning suicidal thoughts, suicide, aggressive behavior or psychotic events?

January 18, 2008 - Pfizer updated its Full Prescribing Information sheet to warn physicians abut "Neuropsychiatric Symptoms." The warning reads, "Serious neuropsychiatric symptoms have occurred in patients being treated with CHANTIX. Some cases may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking; however, some of these symptoms have occurred in patients who continued to smoke. All patients being treated with CHANTIX should be observed for neuropsychiatric symptoms including changes in behavior, agitation, depressed mood, suicidal ideation and suicidal behavior. These symptoms, as well as worsening of pre-existing psychiatric illness, have been reported in patients attempting to quit smoking while taking CHANTIX in the post-marketing experience. Patients with serious psychiatric illness such as schizophrenia, bipolar disorder, and major depressive disorder did not participate in the pre-marketing studies of CHANTIX and the safety and efficacy of CHANTIX in such patients has not been established. Patients attempting to quit smoking with CHANTIX and their families and caregivers should be alerted about the need to monitor for these symptoms and to report such symptoms immediately to the patient's healthcare provider."

While Pfizer at last reveals to healthcare providers that varenicline use was never studied in psychiatric patients, it continues to keep them in darkness as to all other classes of patients who were excluded from clinical trials, for which varenicline risks were not studied and are still unknown, including all with clinically significant medical conditions and all abusing alcohol.

February 1, 2008 - The FDA announces "important revisions to the WARNINGS and PRECAUTIONS sections of the prescribing information for Chantix regarding serious neuropsychiatric symptoms experienced in patients taking Chantix. These symptoms include changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicide."

The FDA's February 1, 2008 "Public Health Advisory" goes to the extreme of enlisting families of varenicline users to remain "alert to and monitor for changes in mood and behavior in patients treated with Chantix. Symptoms may include anxiety, nervousness, tension, depressed mood, unusual behaviors and thinking about or attempting suicide. In most cases, neuropsychiatric symptoms developed during Chantix treatment, but in others, symptoms developed following withdrawal of varenicline therapy."

February 10, 2008 - New York Magazine publishes "This is My Brain on Chantix," a firsthand Chantix use account by Derek de Koff, a features writer, who after taking Chantix experienced vivid dreams, blackouts, hallucinations and contemplated suicide.

April 1, 2008 - The FDA release a new two and a half minute Chantix safety warning video clip that for the first time admits "links" to serious neuropsychiatric problems in users, including suicide.

April 2, 2008 - WhyQuit article expresses concerns over FDA video clip not advising users of the actual number of suicides and not sharing honest efficacy and effectiveness info needed to make informed use decisions.

April 3, 2008 - FDA pulls video clip. WhyQuit makes video pulled clip available for viewing. Public Citizen calls upon the FDA to issue a "black box" Chantix warning, a warning reserved for drugs linked to serious or life-threatening adverse events, the strongest warning the FDA can mandate.

May 7, 2008 - USHHS released updated tobacco treatment Guideline giving Chantix equal recommendation weight with NRT and Zyban. Interestingly, the Guideline recommends use of Chantix on PDF pages 5, 7, 25, 60 and 62 but waits until page 63 to first mention its association with suicide. The 25 member private-sector panel authoring the Guideline had significant pharmaceutical industry financial ties.

May 16, 2008 - The FDA announced a name change and updating of the "Patient Information" sheet, which is now referred to as a "Medication Guide," and updating of the "Prescribing (labeling) Information" sheet, with an updated "Information for Healthcare Professionals" page. The Medication Guide moves patient notice regarding risks of changes in behavior, agitation, depressed mood, and suicidal thoughts or actions from the tail end of the 01/18/08 version to the front of the revised guide. But in the paragraph following the warning the FDA permits Pfizer to use the normal, temporary sense of emotional loss accompanying all cessation attempts, to water down the above warning by asserting, "When you try to quit smoking, with or without CHANTIX, you may have symptoms ... including ... depressed mood ... irritability ... anger ..." The revised Prescribing sheet tells providers to advise patients to not only report behavioral symptoms but immediately stop taking Chantix.

May 21, 2008 - A media firestorm hits Chantix as an ISMP study is released examining 6,363 U.S. Food and Drug Administration adverse drug reaction reports implicating Pfizer's quit smoking pill Chantix, and 3,063 are found to involve serious injuries, including 78 deaths, only 28 of which were from suicide. FDA is criticized for only focusing almost exclusively on behavioral death risks when numerous reports suggest cardiac causes, both thromboembolic and arrhythmic. It states that by the end of 2007 "varenicline accounted for more reports of serious drug adverse events in the United States than any other drug." The study recommends in part that smokers "consider the use of alternative approaches to smoking cessation."

May 21, 2008 - The Federal Aviation Administration banned pilots and air traffic controllers from using Chantix based upon the above ISMP study implicating Chantix in contributing to 173 serious accidental injuries.

May 22, 2008 - Impacting truckers and bus drivers, the Federal Motor Carrier Safety Administration announced that, "medical examiners should not certify a driver taking Chantix because the medication may adversely affect the driver's ability to safely operate a commercial motor vehicle."

May 29, 2008 - Pfizer goes into damage control mode and purchases full-page Chantix ads in America's 5 largest newspapers, including this ad from the New York Times.

Cessation pharmacology history has never before seen the frequency and severity of the adverse events now being attributed to Chantix and Champix, with many lingering long after its use ends, and some permanent or fatal. If varenicline's "real-world" benefits (if any) do not significantly exceed the degree of risk it poses, times the probability of those risks occurring, it should not have been allowed on the market.

Today, no government can tell us if varenicline's benefits exceed its risks as honest and quality studies that could have answered this question were not conducted prior to approving varenicline's sale. Our current drug approval process is upside down, with governments catering to industry profit concerns instead of consumer safety and effectiveness.

When Zyban (bupropion) came on the market, smokers were provided extremely detailed information regarding its potential to trigger a seizure. It allowed us to make informed decisions. If Pfizer knows the actual odds of experiencing any "rare" yet significant side effect, does it have an obligation to share the actual odds with users? In regard to "frequent" and "infrequent" side effects, if Pfizer does not know the actual odds of experiencing those it has listed, should it? Are Chantix and Champix users, and their physicians, entitled to the relative-risk information needed in order to make informed and intelligent cessation decisions?

Users Encouraged to Report All Adverse Events

All Chantix or Champix users experiencing significant adverse events are strongly encouraged to report them to your government's adverse event reporting agency. Varenicline is a new drug and without user feedback, medication safety officials may remain in relative darkness regarding some risks for years or even decades. The following are links to online reporting forms: Australia | Canada | New Zealand | United Kingdom | United States

Pfizer Giving Refunds

I am receiving reports of Pfizer giving purchase price refunds to users experiencing reactions and unable to continue taking varenicline. Rachael from Tennessee had used Chantix for 5 days before developing a rash on her face. She contacted Pfizer and they sent her a refund request form which she completed and returned.

On February 14, 2008 I telephoned Pfizer to verify the refund process and was told that, Rachael is correct. Patients experiencing adverse reactions could receive refunds either by calling and requesting a refund form or by sending Pfizer a copy of their pharmacy purchase receipt, accompanied by a short letter requesting a refund and explaining why. I requested the proper mailing address but they would not release it and I was told that the actual user, not a cessation educator, would need to call 1-800-533-4535 to obtain it. This link is to Pfizer's Customer Service page.

Dependency and withdrawal concerns

Can Chantix users get hooked on it, or more accurately, permanently transfer their nicotine dependency to it? Chantix users visiting Topix.net are sharing stories of withdrawal syndrome type symptoms when attempting to end varenicline use. But how common is this?

Varenicline is a partial agonist that produces up to 60% of the dopamine release generated by nicotine, while actually blocking nicotine molecules from occupying nicotinic acetylcholine receptors (the alpha 4, beta 2 subtype), thereby preventing nicotine from releasing dopamine. Is 60% of the dopamine production generated with nicotine sufficient to foster or maintain chemical dependency?

When nicotine gum was first introduced in '84 there was no mention of the possibility of getting hooked on the cure. Today GlaxoSmithKline consultants estimate that nearly 40% of nicotine gum "users" are dependent upon it, or as the consultants put it, "are persistent users."

The varenicline studies make no mention of possible dependency transfer concerns. A November 2003 study found that as many as 6.7% of nicotine gum "quitters" were still chronic users at six months, three months beyond FDA use guidelines. Although two completely different studies but conducted in the same year and involving the same authors, if only 7% of OTC gum users are able to quit smoking for six months but 6.7% are then hooked on it, then what percentage actually breaks free from nicotine by chewing it? It has been a major defect of pharmacology studies.

Rarely have any clinical trials (including Chantix & Champix) examined and reported body fluid nicotine, bupropion and varenicline levels (from saliva, urine or blood) at long-term follow-up, to see if participants had actually arrested their chemical dependency or simply transferred it. It's as if researchers don't care.

Is there a similar dependency transfer concern with varenicline but possibly to some lesser degree? If so, why wouldn't Pfizer want to fully disclose those concerns up front so that smokers can make fully informed decisions. If none, in light of nicotine gum, patch, lozenge and inhaler dependency issues, why wouldn't Pfizer want to reassure smokers?

A related question, arising from what may be the sloppiest portion of the Chantix studies, is how widespread was NRT use within the five studies and how much of Chantix's 22% one-year rate is attributable to elevated dopamine output generated by NRT, once Chantix's elevated dopamine output ceased at the end of the 12-week treatment period?

We know that records were kept of "use of nicotine containing products." We also know, from the Oncken study, that once Chantix treatment ended after twelve weeks that "use of nicotine replacement therapy did not disqualify subjects from being considered abstinent." The obvious questions becomes, how many actively feeding nicotine addicts did Pfizer count among the cured and why was the NRT use data not published or released?

Chantix and Champix studies were not blind as Pfizer continues to assert

It's hard to imagine any smoker who has not heard the NRT marketing assertion that it "doubles" their chances of quitting. If Pfizer and Chantix follow the path taken in marketing NRT, regardless of how low Chantix's quitting rate eventually becomes, smokers will only be told its victory margin over the study's placebo group, not the actual percentage of users succeeding.

In fact, it's already happening. Pfizer's May 11, 2006 Chantix press release fails to disclose that nearly 4 out of 5 Chantix clinical study participants relapsed to smoking. Instead it boasts, "In two identically designed studies, patients receiving a 12-week course of Chantix therapy (1 mg twice daily) nearly quadrupled the likelihood of quitting than those taking placebo."

Let's examine these massive Chantix placebo victories. In Pfizer's Chantix (varenicline) clinical trials those screened and not excluded were randomly assigned into at least one of two study arms: the active group which would receive Chantix and the control group which would receive an identical looking placebo pill.

Each of the five Chantix studies represents that it was double blind. If true, neither participants nor researchers should have been able to determine participant assignment to receive either a placebo pill or the active chemical varenicline. Surprisingly, the studies do not mention whether or not researchers actually conducted blinding assessments to test and validate the study's blind.

Blinding is extremely important to the study's core validity. If randomized participants can determine their group assignment then the study's final odds ratio victory (if any) may reflect frustrated and/or fulfilled expectations rather then the actual merits of the chemical tested. Blinding failures actually occurred in NRT studies and it is almost impossible to believe that they didn't happen in Chantix studies too.

Nicotine is a psychoactive chemical that generates a potent dopamine/adrenaline high. The pharmaceutical industry has known since at least a 1994 study that smokers can quickly be trained to reliably distinguish various doses of nicotine from placebo. Smokers with any quitting history have experienced their own withdrawal syndrome and should be expected to recognize both its onset and intensity.

The Chantix studies found that varenicline significantly diminished a smoker's withdrawal syndrome. Cravings were consistently reduced when varenicline, 1.0 mg twice daily, was compared with placebo. All three comparable studies found that varenicline significantly reduced the urge to smoke compared to placebo.

Approximately 90% of participants in the Chantix studies had previously attempted quitting, failed and had some degree of memory of what it felt like to sense the onset of the anxieties and craves associated with their withdrawal syndrome.

A June 2004 study by Mooney reviewed 73 allegedly double-blind NRT studies and declared that the limited number of studies assessing blindness were not generally blind as claimed in that "subjects accurately judged treatment assignment at a rate significantly above chance."

Mooney warned researchers that, "To determine the prevalence of failure, clinical trials of NRT should uniformly test the integrity of study blinds. Moreover, if blindness failure is observed, subsequent efforts should be made to determine if blindness failure is related to study outcome and, if so, to provide an estimate of treatment outcome adjusted for blindness bias. Without these methods and analyses, the validity of NRT clinical trial results could be questioned."

The blinding analysis in a 2005 study by Dar found that 3.3 times as many placebo group members correctly guessed that they had received placebo (54.5%) as guess nicotine (16.4%). Although the Dar study focused on smoking reduction, Tonnesen's 1993 nicotine inhaler quitting study produced strikingly similar placebo group findings in that 3.8 times as many in the placebo group correctly guessed placebo (58%) as guessed nicotine (15%). Among inhaler users, Tonnesen found that 3.5 times more correctly guessed inhaler (46%) as guessed placebo (13%), while 42% on active and 27% on placebo did not know which treatment they had received.

Participants were recruited to the Chantix studies by being told that the study involved evaluation of a medication. Most seeking participation knew their withdrawal syndrome and clearly hoped the medication would diminish the rising tide of anxieties and craves they now associated with withdrawal.

Pfizer knew that NRT studies were plagued by blinding failures and that frustrated and rewarded expectations likely played a substantial role in both relapse and cessation. Pfizer also knew that Chantix placebo group members would not receive anything different than received by NRT placebo group members - an inert placebo. For them, the exact same set of elements was in play - the expectation of relief, the onset of withdrawal and frustrated expectations. It knew that the active group would sense a "significant" reduction in their withdrawal syndrome and thus likely be more inclined to remain and take advantage of the study's heavy and lengthy support structure.

Mooney warned researchers more than two years ago that a study's core validity could be questioned if full blinding assessments were not conducted. If the Chantix studies failed to stop and assess blinding, why? Did Pfizer know in advance that its varenicline studies would not be blind and that blinding bias would impact performance?

Quoting from the Dar 2005 study, "The present secondary analysis of the data elucidates these placebo effects by showing that reduction of smoking was strongly related to participants beliefs about their drug assignment. Smoking reduction was larger in those who believed that they had received nicotine compared with those who believed they had received placebo, regardless of actual drug assignment. Moreover, after adjustment to perceived drug assignment, the association between actual drug assignment and smoking reduction was no longer statistically significant."

Approximately 80% of the placebo group members in the varenicline studies relapsed to smoking within two weeks. A brief blinding assessment within two weeks could have quickly and easily revealed each participant's assignment belief. Where is it? As far as we know, no blinding assessment was conducted. Why?

It makes one wonder who at the FDA is actually reading studies like Mooney and demanding quality cessation study design prior to drug approval. In fact, the FDA's May 11, 2006 press release suggests that the studies were in fact blind. Also noteworthy is the FDA's failure to mention that 4 out of 5 Chantix users relapsed.

The above paragraphs on study blinding were written on August 25, 2006, prior to trading correspondence with scores of varenicline users and learning how smoking between days 4 through 7 of varenicline use (as directed by Pfizer) was strange in that the normal and expected dopamine "aaah" sensation that had occurred within seconds 10 seconds of every cigarette they'd ever smoked no longer occurred. Thus, it would seem that many or possibly most assigned to the active varenicline group in Pfizer's clinical trials had "actual" knowledge of their assignment prior to ever quitting.

Did confidence in actual assignment combine with varenicline elevated dopamine levels to allow a greater percentage of the varenicline group to relax, take advantage of, and benefit from, what may have been the most intense counseling and support format offered in any quitting study to date? This factor worked to create distance between frustrated placebo group quitters whose assignment actually punished them by throwing them into full blown drug withdrawal.

Employing the double-blind study format in drug addiction studies, the only area of pharmacology research where assignment to the placebo group actually punishes participation by throwing quitters into full blown chemical withdrawal, is a licence to steal. Think about medication studies for headaches, high blood pressure or cholesterol. Would it be fair to make those assigned to the placebo group suffer far more than when you found them, to add full-blown nicotine withdrawal to whatever condition with which they arrived?

Pfizer's assault upon cold turkey and the smoker's natural instincts

The U.S. Federal Trade Commission (FTC), charged with enforcing truth in advertising, has allowed the NRT industry to make outlandish marketing claims and distort NRT's true effectiveness (if any). One of the worst offenses was the assertion that NRT competed against and defeated cold turkey quitters within NRT randomized clinical trails. The representation is false and deceptive, as it simply did not happen.

The only subjects applying for these studies are a population that is self-seeking medication, medication they hope will somehow diminish their withdrawal symptoms and syndrome, the exact opposite of a quitter who fully expects to meet, greet and overcome full blown withdrawal. There were no cold turkey quitters in NRT clinical studies. There were no cold turkey quitters in any clinical Chantix study, just a frustrated placebo group whose expectations that medication would diminish their withdrawal syndrome went totally unfulfilled.

A key industry marketing tactic has been a two-decade campaign that bashes and trashes confidence in abrupt nicotine cessation quitting by suggesting that it's almost impossible, that "few" cold turkey quitters succeed. What motivation is there for Pfizer to be honest with smokers when teaching them the truth about their own natural cessation instincts? It is extremely rare when any journalist exposes the pharmaceutical industry for the ongoing falsehood that roughly 40 million U.S. cold turkey success stories is "few."

Table 3 from American Cancer Society's Cancer Facts and Figures 2003 report indicating that 91.4% of smokers quit smoking entirely on their own.Pfizer needs to remember two important facts. First, as suggested by the these two tables, during 2006 80-90% of all successful long-term quitters are again expected to be cold turkey quitters (see American Cancer Society Cancer Facts & Figures 2003, Table 3; and Doran, May 2006).

Second, long-term NRT quitters have never once prevailed over those quitting without it in any real-world quitting method survey published to date (see the California JAMA survey, Quebec Quit & Win, Minnesota Insurance Survey, London, Western Maryland, Ferguson's UK NHS Smoking Cessation Services survey, Australia Family Practice Survey, U.S. National Cancer Institute).

Maybe real-world Chantix evaluation will someday prove superior to those quitting without it. Let's hope so. But if cessation pharmacology study history is any indication, we shouldn't hold our breath. Until then, what is certain is that the pharmaceutical cessation industry will continue to work study design to its economic advantage, spinning results to foster unrealistic expectations, hiding each study's actual relapse rates, ignoring obvious blinding failures, boasting about odds ratio victories flowing from them, and proclaiming victory over foes who were not present.

Quitting methods chart prepared by WhyQuit.com using data from a May 2006 study in Addictive Behaviors, Volume 31, at page 764

If Pfizer wanted to design and recruit for a study that fairly compares a cold turkey quitting program such as WhyQuit's to its varenicline quitting program it would have to: (1) limit creating pharmacology use expectations by advertising only that it was recruiting for a "quitting program" without any mention of "medicine" or "quitting products," (2) randomise participants to either the varenicline or cold turkey arm of the study without blinding (and only then conduct face-to-face informed consent); and (3) fairly acknowledge the differences in the two cessation methods by allowing the cold turkey program to devote the bulk of its education, skills development and support time to the first two weeks of cessation, while allowing varenicline users needed guidance and support in both learning to adapt to using it and adjusting to ending use at treatment's end. But don't expect to ever see this happen as billions in profits are at stake and it's far more profitable for the pharmaceutical industry to "pretend" that the expectations of frustrated placebo participants were identical to those of real cold turkey quitters.

The next time you hear a pharmaceutical industry commercial suggest that quitting cold turkey is nearly impossible, take your own survey of all long-term ex-smokers who have been off of all sources of nicotine and all cessation dopamine enhancing chemicals for at least one year. Once you complete your own survey we invite you to explore WhyQuit and the wonderful world of educated and supported abrupt nicotine cessation. Quitting need not be a life threatening event. There is still only one rule that if followed offers a 100% guarantee of success to all ... no nicotine, just one day at a time ... Never Take Another Puff, Dip or Chew!

XXX

No Copyright - This Article is Public Domain

John R. Polito is solely responsible for the content of this article.
Any factual error will be immediately corrected upon receipt of credible authority
in support of the writer's contention. E-mail comments to john@whyquit.com



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