Chantix and depression on stopping smoking.

Yesterday I saw a couple of newspaper reports on the potential link between Chantix and psychiatric side effects, including discussion of some of the stories reported by people on this blog.
http://www.nj.com/starledger/stories/index.ssf?/base/news-13/1203831450252170.xml&coll=1

I’ve written before about risks for depression on stopping smoking and we have also talked about psychiatric symptoms occurring while using Chantix. Right now we really don’t know whether these symptoms of depression are directly caused by Chantix, by stopping smoking or by other things but have captured the headlines because over 5 million people have used Chantix in a short space of time. One thing that is clear is that serious psychiatric side effects are rare while using Chantix – probably somewhere between 1% and one per thousand. So it is important to keep the risks in perspective and to bare in mind that right now we are not absolutely sure that Chantix has caused these serious adverse events. Its also important to bare in mind that continued smoking has 50% chance of killing you, and a virtual certainty that it will cause you to suffer non-fatal illnesses that affect your life.

But I’ve been contacted by a number of people who reported that their mood was fine before they started taking Chantix and they became uncharacteristically short tempered and depressed while on it. One particular question that I’ve been asked is how long do these feelings last for? We’ve discussed before how the mood disturbance on stopping smoking typically peaks in the first week and has largely resolved by the fourth week in smokers quitting without taking any medication, but of course that’s the average and there can be big differences between individuals.

So I’d really appreciate it if readers who quit smoking for a period of time could write in and comment on what kind of effect it had on their mood, and the time course of any mood disturbance (i.e. how long after stopping smoking was it at its worst, and how long before it was OK again). Please comment on whether or not you used any medicine (including NRT) at the time and whether you thought the medicine helped or made the mood disturbance worse. I think it may be helpful for those who have experienced mood swings while quitting smoking to hear the experiences of others.

Labels: Chantix, depression, jonathan foulds, smoking cessation, withdrawal

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Snus use in Sweden: another reply to Tomar.

I have previously discussed the role of snus in reducing smoking in Sweden, and criticized the IARC report’s coverage of this issue. Professor Scott Tomar (a member of the IARC committee) stated (as a comment to a posting criticising the new IARC monograph on smokeless tobacco):
“Using official Swedish data for smoking for 2004 (from the ULF survey conducted by Statistics Sweden), smoking quit rates (or what some call smoking quit ratios, defined as the proportion of ever smokers who are now former smokers), by age group and sex are:Age 16–24Men 13.2%Women 14.6%Age 25–44Men 37.8%Women 38.3%Age 45–64Men 54.5%Women 51.7% “

However, a colleague of mine based in Sweden (Lars Ramstrom), who is very familiar with Swedish surveys on tobacco use, has informed me that these figures on Swedish tobacco statistics are inaccurate in two ways:
1. They provide inaccurate numerical values for “the proportion of ever smokers who are now former smokers”
2. They inaccurately claim that the figures come from “the ULF survey conducted by Statistics Sweden”.

Statistics Sweden generally does not publish any figures on “the proportion of ever smokers who are now former smokers”. The main reason is that their ULF survey uses a questionnaire that does not include enough items to identify the subgroup “former occasional but never daily smokers who are now former smokers”. Since this subgroup must be part of both numerator and denominator of the calculation of such proportions, the ULF data are just unable to provide a basis for such calculations.

For this reason, we believe that the figures provided by Professor Tomar are likely to be inaccurate. However, the proportions in question can be calculated from other surveys that are performed by the Swedish research institute FSI, Research Group for Information and Societal Studies. These surveys are described in the literature (Ramström LM, Foulds J. Role of snus in initiation and cessation of tobacco smoking in Sweden. Tob. Control 2006;15;210-214). Using the same data base as the just mentioned article we get the following data:

Proportion of ever smokers (daily plus non-daily)
who are now former smokers
Age span Men Women
16-79 61% 54%
16-24 49% 42%
25-44 54% 53%
45-64 63% 55%
65-79 75% 68%

Professor Tomar made a point about the “similarity” between males and females quitting based on his original figures.
“Please explain why the quit rates in Sweden are so similar for men and women within each age stratum if snus had such a dramatic effect on cessation?”

In these figures we can see similarity in one age group only, 25-44. In this very age group a large proportion of women are planning or going through pregnancy and are thereby met the very forceful encouragement and treatment for quitting smoking that is very well established in the Swedish maternal health care system. This is a gender-specific condition that explains why this age group shows a different men/women comparison than the others.

The relevant question is rather opposite to the one asked by Professor Tomar:

Why are overall quit rates generally higher in men than in women in Sweden?

The answer is given by the following data picked up from the above mentioned article:
(These data refer to quit rate for daily smoking, while the data above refer to quit rate for all smoking. Therefore the numerical values differ a little)

Proportion of ever daily smokers
who are now former smokers
Men Women
Overall 59% 49%
With a history of daily snus use 72% 71%
Without history of daily snus use 51% 48%

These data illustrate that gender comparisons have to be made between truly comparable subgroups in order to yield meaningful conclusions.

In each one of the two lower lines there are comparisons between men and women who are comparable with respect to snus use. In each case there is no difference.

In each one of the gender columns the two lower lines give gender-specific comparisons indicating the influence of snus use. Both for men and women there are large differences in quit rate according to presence or absence of a history of snus use.

The above observations demonstrates that the overall difference between men and women does not stem from factors related to gender itself but to the fact that snus use, as a cessation promoting factor, is more prevalent among men than among women.

In summary, contrary to Professor Tomar’s thesis, the Swedish statistics on smoking cessation suggest that snus use is having a substantial effect in promoting cessation of smoking among men. Of course this is self evident from the simple fact that 24-30% of male Swedish ex-smokers used snus to quit smoking. My thanks to Lars Ramstrom for providing clarification on the pattern of tobacco use in Sweden.

Incidentally, the issue of snus for smoking cessation was recently debated in the British Medical Journal, at:
http://www.bmj.com/cgi/content/full/336/7640/358

For the record (again), I don’t believe that health professionals should recommend snus to their patients. I believe that we have medicines and counseling that can be effective treatments for addiction to cigarettes (or at least as efficacious as snus) and that these are what we should be recommending to patients. However, I do believe that the public should have accurate information about the relative risks of snus and cigarettes. Currently the public underestimates the risks from cigarettes, relative to snus or nicotine replacement therapy.

Labels: jonathan foulds, nicotine, nicotine nasal spray smoking cessation, smokeless, snus, tobacco

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What is in cigarette smoke?

More than 4000 different chemicals have been identified in cigarette smoke. Most of us have a very basic idea that these chemicals can be harmful to health and that the mechanisms whereby this complex mixture of toxins contained in tobacco smoke leads to specific diseases are complex. However, I thought it might be helpful to some readers to provide a very basic description of the ways in which some of these components of cigarette smoke cause ill-health.

The simplest categorization of the components if cigarette smoking identifies 3 major components: tar, nicotine, and cabon-monoxide (CO).

Tar is the black sticky mass that coats the lungs and the airways. There are many hundreds of different chemicals within the tar, some of which have been shown to be carcinogenic in animals and/or humans. The deposition of particles of tar in the lungs and upper airways leads to the blocking of airways and to serious breathing problems, including Chronic Obstructive Pulmonary Disease (COPD). The toxic chemicals also cause inflammation and reduce the elasticity of the lungs and hence the ability to inhale and exhale normally.

The carbon-monoxide in smoke replaces oxygen in the hemoglobin (a component of blood), adversely affecting oxygen transport and energy supply, and requiring the heart to do more work to supply the same amount of oxygen to the body. A large number of smoke constituents, and particularly components of the gaseous phase of the tobacco smoke, cause immunologic responses and inflammation in the cells. This causes increased stickiness of the blood which increases the risk of clots. These processes increase the likelihood of a heart attack, stroke or other problems with the cardiovascular system.

Irritants such as nitric oxide cause hypersecretion of mucus and substances such as acrolein, acetone and acetaldehyde cause damage to the small hair-like strands that line the airways (cilia). This damage to the cilia impairs the ability of the cilia to clear mucus, causing breathi9ng difficulties. Years of smoking and daily coating of the lungs and airways in tar leads to irreversible lung damage and ultimately death from COPD .

Acute nicotine (critical for the development of addiction), increases heart rate, blood pressure and causes peripheral vasoconstriction (i.e. impairs peripheral circulation and thus exacerbates Reynauds’ Disease and erectile dysfunction). However, studies of smokeless tobacco users (who have high nicotine exposure like smokers, but without the smoke) compared with smokers, suggest that most of the cardiovascular problems are not caused by nicotine. It therefore appears that it is the thrombogenic effects of tobacco smoke exposure (primarily oxidant gases), combined with reduced oxygen supply (carbon monoxide) and increased myocardial oxygen demand (nicotine) that cause the cardiovascular harms from smoking.

Some of the chemicals found in cigarette smoke are listed below.

Carbonyls
Formaldehyde, Acetaldehyde, Acetone, Acrolein, Propionaldehyde, Crotonaldehyde, Methyl-Ethyl-Ketone, Butyraldehyde
Phenolics
Hydroquinone, Resorcinol, Catechol, Phenol, Cresol (m+p and o)
Aromatic Amines
3- and 4-aminobiphenyl, 1- and 2- aminonapthlene, o-toluidine, o-anisidine
Oxides of Nitrogen NO,
Hydrogen Cyanide
Ammonia
Volatiles
Benzene, Toluene, 1,3-butadiene, Isoprene, Acrylonitrile
Semi-Volatiles
Pyridine, Quinoline, Styrene
Trace Metals
Nickel (Ni), Cadmium (Cd) Lead (Pb) Chromium (Cr) Arsenic (As) Selenium (Se), Mercury (Hg)
Tobacco Specific Nitrosamines
N-Nitrosonornicotine (NNN)N-Nitrosoanabasine (NAB) Nitrosoanatabine (NAT)4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK)
Volatile Nitrosamines
N,N-Nitrosodimethylamine (NDMA)N-Nitrosopyrrolidine (NPYR), N,N-Nitrosodiethylamine (NDEA)N,N-Nitrosoethylmethylamine (NEMA), N,N-Nitrosodipropylamine (NDPA)N,N-Nitrosodibuthylamine (NDBA), N-Nitrosopiperidine (NPIP)
Polycyclic Aromatic Hydrocarbons
Naphthalene, 1-Methylnaphthalene, 2-methylnaphthalene, AcenaphthyleneAcenaphthene, Fluorene, Phenanthrene, Anthracene, FluoranthenePyrene, Benzo(a)anthracene, Chrysene, Benzo(b)fluorantheneBenzo(k)fluoranthene, Benzo(j)fluoranthene, Benzo(g,h,l)peryleneBenzo(e)pyrene, Benzo(a)pyrene, PeryleneIndeno(1,2,3,-cd)pyrene, Dibenzo(a,h)anthraceneDibenz(a,j)acridine, Dibenz(a,h)acridine, Dibenz(a,e)pyreneDibenz(a,h)pyrene, Dibenz(a,i)pyrene, Dibenz(a,l)pyrene7H-Dibenzo(c,g)carbazole,
Heterocyclic Aromatic Amines
2-Amino-3-methylimidaszo(4,5-f)quinoline (IQ)2-Amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ)2-Amino-3-methyl-9H-pyrido(2,3-b)indole (MeAaC)2-Amino-9H-pyrido(2,3-b)indole (AaC)1-Methyl-9H-pyridol(3,4-b)indole (Harman)9H-Pyrido(3,4-b)indole (Norharman)

Labels: cancer, chemicals, cigarette, jonathan foulds, nicotine, smoke, tar, toxins

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New study compares Chantix to the nicotine patch

We have already talked about the studies showing that Chantix (varenicline or Champix outside the US) is more effective than both placebo pills and Zyban (bupropion) for smoking cessation. There has also been one study comparing smoking cessation outcomes before and after Chantix was available (by John Stapleton and colleagues in the UK).

Today a new study has been published comparing the effects of a standard course of Chantix (12 weeks) with a normal course of the nicotine patch (10 weeks) for stopping smoking. This was a randomized “open-label” study, meaning that neither the participants nor the researchers were able to choose which participants got which treatment, (they were allocated to treatment on the basis of random numbers), but that everyone new which treatment they got (i.e. there were no placebo or dummy patches or pills).

The study by Aubin and colleagues was carried out across 5 countries (Europe and USA), with 376 smokers being assigned to Chantix and 370 to the patch. All the participants smoked at least 15 cigarettes per day (average = 23 per day). The participants were required to be relatively healthy with no unstable illnesses within the previous 6 months (including psychological problems or substance dependence). None had used nicotine replacement therapy in the previous 6 months. About half (48%) had previously tried the nicotine patch, and almost 90% had previously tried to quit. The average age of participants was 43, and they had smoked for around 26 years. 93% of the participants were white.

Participants attended weekly appointments for the first 12 weeks, then had 7 further appointments up to the one year follow-up, as well as 5 telephone contacts.

3 months after the target quit date, 56% of those treated with Chantix had not used any tobacco during the prior month, as had 42% of those treated with the nicotine patch. This advantage for Chantix treatment was statistically significant. At the one year follow-up (i.e. after about 9 months without treatment medications) 26% of those allocated Chantix treatment remained remained quit, as did 20% of those treated with the patch (also a statistically significant difference). During the first 7 weeks of treatment, those treated with Chantix reported significantly lower craving, negative affect (bad mood) and restlessness.

About twice as many patients treated with Chantix (8%) as the patch (4.3%) had to discontinue the medicine due to an adverse event. The most frequent adverse events were nausea (37% on Chantix versus 10% on the patch), insomnia (around 20% in both groups) and headache (19% Chantix, 10% patch).

There has been some recent concern (discussed on this forum) about Chantix potentially causing depression and suicidal thoughts. In this trial, one person became depressed and it was believed to be caused by Chantix, and another person had suicidal thoughts (causing hospitalization) 11 days after completing Chantix treatment. These low rates of serious depression (<1%) in association with Chantix treatment are consistent with prior reports. It is interesting that ratings of “negative affect” were significantly lower among those taking Chantix than the patch during the first 7 weeks (meaning that Chantix users experienced, on average less bad moods/depressive thoughts than those wearing the patch). So the etiology of depression while taking Chantix remains a mystery. One possibility is that Chantix, because it is slightly more effective than prior medications, enables some people to successfully quit who would not otherwise have succeeded, and some of those people may be more prone to depression in association with quitting smoking.

Overall, the results from this study are consistent with previous studies in showing that Chantix is probably the most effective single medicine for smoking cessation, that it frequently causes mild side effects (e.g. transient nausea) and that serious adverse events are uncommon.

Ref:
Aubin HJ et al. Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomized, open-label trial. Thorax published online Feb 8, 2008.

Labels: cessation, Chantix, cigarette smoking, jonathan foulds, Nicotine Replacement, patch, varenicline

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What does a tobacco treatment clinic do?

Most people who try to quit smoking do so on their own with little or no outside assistance. This doesn’t mean it’s the best way to do it. Nowadays most people also have access to a telephone quitline and over-the-counter nicotine replacement therapy. These treatment components have been proven to increase your chances of success. Some people are fortunate enough to live near a specialist face-to-face tobacco treatment service (e.g. there are such services in Minnesota, Massachusetts, New Jersey, Ohio and Mississippi), but many do not and may wonder about what kind of services are provided by a tobacco treatment clinic. So to give an idea of the kind of work carried out by such services, I’ve summarized below the work carried out at the service I work at.

The Tobacco Dependence Clinic, part of the Tobacco Dependence Program (TDP) at the University of Medicine and Dentistry of New Jersey (UMDNJ)-School of Public Health, opened in January 2001 to provide specialist assessment and treatment for people who want help with tobacco dependence. A multidisciplinary team of specialists in tobacco dependence treatment, including psychologists, clinical social workers, and physicians, work closely with other staff and faculty to provide tobacco dependence treatment based on the evidence-based assessment and treatment procedures outlined in the US Public Health Service Clinical Practice Guideline on Treating Tobacco Use and Dependence (1) and the New Jersey Guidelines for Tobacco Dependence Treatment (2). The clinical staff is also involved in training and consulting to the network of tobacco dependence treatment clinics throughout New Jersey, known as New Jersey Quitcenters, and to other providers of tobacco treatment. Furthermore, the Clinic is involved with several ongoing projects that target special populations, including Latinos, young smokers, medically-ill smokers, and smokers with co-occurring mental health and/or addiction problems.

All patients receive a comprehensive individual assessment, with core information from that assessment being coded into a database. Around 95% of patients assessed select a Target Quit Date (TQD), and these patients are then followed up either in person or by telephone 4 weeks and 6 months after their initial TQD. At the end of the assessment a treatment plan is developed that includes a recommendation on medications and whether or not the patient will attend group or individual appointments or both.

More than half of the patients who attend beyond the assessment are treated in group. The most common group model used is a closed 6 (weekly) session group format, with the group’s quit day on the second session. Patients attending group have significantly better outcomes than those only attending individual treatment, even after controlling for baseline characterisitics3. The clinic provides on-site tobacco treatment groups at local employers (including Pfizer Corp, Firmenich, Clinphone, and Rutgers University) which have proven very successful (http://www.tobaccoclinic.org/ ). An open (daytime) group for people with disabilities (primarily serious mental illness), and an open weekly relapse prevention group (in the evening) are also provided. In addition to counseling, over 90% of our patients use tobacco treatment medication and of these most use more than one form of pharmacotherapy. Initial quit rates appear to relate to how many medications patients use4. Overall, around 45% of patients report abstinence (no tobacco use in previous week) at one month follow-up and 31% are abstinent at 6 month follow-up (3). These data count all patients lost to follow-up (30-40%) as continuing smokers.

The treatment philosophy at the Tobacco Dependence Clinic is that tobacco dependence is a life threatening chronic illness that warrants as intensive a treatment for as long a period as is required to enable the patient to quit and stay quit. Patients are advised to continue on the full prescribed medication dose until they have experienced 14 consecutive days without any cravings, withdrawal symptoms or near lapses. Over a quarter of patients followed up at 6 months are still using medication (4). Interestingly, around 20% of new patients are now smokers who have attended the Clinic in a previous year. These repeat patients tend to be more dependent and more have a history of mental health treatment, but they have reasonable six-month quit rates on repeat treatment (23%, 22% and 20% at first, 2nd and 3rd treatment episode) (5). When including repeat treatment episodes, the proportion of patients who achieve abstinence at 6 months follow-up is 33%. (5) Other notable findings are (a) African American (AA) and Latino smokers of regular cigarettes have the same quit rates as whites, but AAs and Latinos who smoke menthols have about half the quit rate, even after controlling for other predictors of outcome (3,6) and (b) 50% of patients awaken to smoke at night and this is predictive of poor treatment outcome (7).

In January, 2007 the TDP opened a new clinic in Newark, New Jersey, and by December 2007 over 3500 patients have been treated at the Clinics, which aim to treat over 500 new patients per year. Both clinics are fully integrated into the local healthcare systems, receiving referrals from community providers and hospitals via a Fax-to-Quit system, as well as linkages with the University and Hospitals’ electronic medical records system. The New Brunswick clinic serves Middlesex and adjacent New Jersey counties, and more than twice as many Middlesex county residents attend the clinic for tobacco treatment than engage in counseling on New Jersey’s excellent free Quitline (8). Also, with support from a grant from the Robert Wood Johnson Foundation, the proportion of Latino patients has increased from 3% in 2001 to 15% in 2006.

The major challenge faced by the clinics is in the area of billing and reimbursement from health insurance. 53% of the patients have private health insurance, 13% Medicaid, 12% Medicare and 22% have no health insurance. Even for those with private health insurance most plans do not cover the counseling provided by the clinic and in many cases medications (e.g. NRT, Zyban, or Chantix) are not covered either. Lack of systematic and comprehensive insurance coverage for high quality tobacco dependence treatment is a major barrier to helping smokers quit.

The success of the Tobacco Dependence Clinic at UMDNJ-School of Public Health shows that there is a demand for high quality tobacco dependence treatment among smokers, even in a state that already provides free high-quality telephone and internet support for smoking cessation. The smoking cessation outcomes show that quit-rates comparable to or greater than those achieved in research studies can be achieved by a clinical service implementing the Guideline on Treating Tobacco Use and Dependence (1). Full details of all patient characteristics and outcomes are provided in Clinic Annual Reports (9) . Further details of this work and publications can be found at www.tobaccoprogram.org .


Acknowledgements:
The clinic is part of the Tobacco Dependence Program at UMDNJ-School of Public Health which is funded by New Jersey Department of Health and Senior Services, as part of New Jersey’s Comprehensive Tobacco Control Program (NJ CTCP). The Tobacco Dependence Program also receives funding from NJ CTCP for youth cessation in schools, training health professionals, and community education and outreach. The TDP is also supported by grants from Robert Wood Johnson Foundation, Rutgers Community Health Foundation, and the Cancer Institute of New Jersey.

References.
pdfs of many of these are available at: http://www.tobaccoprogram.org/staffarticles.htm

1. Fiore MC, Bailey WC, Cohen SJ, et al. Treating Tobacco Use and Dependence: Clinical Practice Guideline. Rockville, MD US Department of Health and Human Services. Public Health Service 2000.
2. Slade J, Zeidonis D, Foulds J, Lindberg D and Order-Conners B. New Jersey Guidelines for Tobacco Dependence Treatment. New Jersey Department of Health and Senior Services, 2001. http://www.tobaccoprogram.org/pdf/njguidelines.pdf
3. Foulds J, Gandhi KK, Steinberg MB, Richardson D, Williams J, Burke M, Rhoads GG. Factors associated with quitting smoking at a tobacco dependence treatment clinic. American Journal of Health Behavior 2006; 30:400-412
4. Steinberg MB, Foulds J, Richardson DL, Burke MV, Shah P. Pharmacotherapy and smoking cessation at a tobacco dependence clinic. Preventive Medicine 2006; 42:114-119.
5. Han ES, Foulds J, Steinberg MB, Gandhi KK, West B, Richardson D, Zelenetz S, Dasika J. Characteristics and smoking cessation outcomes of patients returning for repeat tobacco dependence treatment. International Journal of Clinical Practice 2006 September; 60(9): 1068-1074.
6. Gandhi KK, Foulds J, Steinberg MB, Lou SE, Williams J. Lower quit rates among menthol cigarette smokers at a tobacco treatment clinic. (Internal report submitted for publication).
7. Bover MT, Foulds J, Steinberg MB, Richardson D, Marcella SW. Waking at night to smoke as a marker for tobacco dependence: patient characteristics and relationship to treatment outcome. International Journal of Clinical Practice Feb 2008; 62(2): 182-190..
8. Foulds J, Steinberg MB, Williams JM, Ziedonis DM. Pharmacotherapy for tobacco dependence: past , present and future. Drug and Alcohol Review Jan 2006; 25:57-69
9. Tobacco Dependence Clinic Annual Reports available at: http://www.tobaccoprogram.org/clinic.htm

Labels: clinic, jonathan foulds, nicotine addiction cigarette smoking tobacco, treatment

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