New study of Chantix in comparison with NRT

Recently there has been some concern over side-effects experienced by a minority of people using Chantix (varenicline). Although Chantix had a remarkably good safety and efficacy record in the clinical trials conducted prior to its launch, those trials excluded patients with complex medical or psychiatric problems (normal practice in pre-approval clinical trials). So when a number of patients (albeit a tiny proportion of the millions who have used Chantix) have reported unpleasant and serious mood disturbances or even suicidal thoughts and acts while taking Chantix since it was launched, this has led to a concern that perhaps Chantix may have more serious side-effects in regular patients with complex medical and psychiatric problems.

A new study by John Stapleton and colleagues was published this week in the journal, Addiction, that addressed this issue. The study reports on the clinical outcomes of 412 patients being treated at a tobacco dependence clinic in London, UK. 204 patients were treated with nicotine replacement therapy (NRT) between May and November, 2006 (prior to Chantix being launched in the UK), and 208 patients were treated with Chantix from January to April 2007. Although the two groups were not randomly allocated to treatments, they were very similar on a number of baseline measures - for example 47% of those treated with NRT were men and 50% of those treated with varenicline were men. The daily cigarette consumption of the two groups was 21 and 22 cigarettes per day respectively. The only signs of baseline differences between the groups were that 69% of those treated with NRT were white, compared with 79% of those treated with Chantix. Those treated with Chantix also rated themselves as being slightly more “determined to quit” at baseline. All of the patients were treated in weekly stop-smoking groups for 7 weeks, with the target quit date coming at the third group meeting. Some of the patients using NRT used “combination” NRT (typically the patch plus either nicotine gum, lozenge, nasal spray or inhaler). At the end of group treatment (i.e. four weeks after the target quit date), 66% of those using a single NRT, 75% of those using combination NRT and 80% of those using Chantix were no longer smoking (not a puff in the previous two weeks). So Chantix produced higher quit rates than a single NRT product, but similar to combination NRT.

111 of these patients were receiving treatment for a mental illness, and the pattern of results for those patients was similar to that of the group as whole, with higher quit rates for those using Chantix. In the whole sample, those using Chantix reported significantly lower craving scores, with no differences on ratings of withdrawal symptoms (e.g. irritability, poor concentration, etc).

An analysis of adverse drug reactions found only one that was more commonly reported with NRT than with Chantix (skin irritation related to patch use). However, 12 symptoms were reported more frequently among those using Chantix. Those symptoms were, nausea (38%), disturbed sleep (30%), vivid dreams (13%), drowsiness (12%), constipation (11%), headache (10%), dyspepsia (8%), dry mouth (7%), bad taste (7%), depression/low mood (5%), diarrhoea (5%), and disorientation/confusion (5%). 7 patients reported moderate/severe anxiety/panic while on Chantix, compared with only one on NRT. Two patient had adverse reactions while using Chantix that were of sufficient severity to be reported to the Medicine’s Regulatory Authority in the UK. One of these was for a “severe psychological reaction likened to a bad LSD trip, including anxiety, paranoia, and confusion.”

It should be noted that around 80% of the patients in this study had previous experience trying to quit smoking using NRT. It is possible that those taking the new drug (Chantix) would have a stronger tendency to note side effects than those using an NRT that they were familiar with.

Overall, these results are broadly consistent with the evidence from clinical trials and post-launch clinical experience with Chantix. They are consistent with the ideas that (a) Chantix may result in slightly higher chances of success in quitting smoking than another single medicine/NRT (b) Quitting success rates on Chantix are broadly similar to those with combination NRT, (c) Chantix results in more side effects than NRT, of which some are common (e.g. nausea, disturbed sleep and vivid dreams) and some less common (<5%) – including depressed mood, disorientation and anxiety. The single patient experiencing a severe psychological reaction while using Chantix may be an indication that such reactions can occur but are rare (<1%).

It should be noted that all of the patients in this study were being treated in a specialist tobacco treatment clinic, within the context of support groups facilitated by experienced clinicians. In that context adverse effects of medications can be monitored, and if necessary patients promptly switched to different medications. Many of the psychological side effects were 3-5 times more common among patients using Chantix than among patients using NRT.

The research continues to show that Chantix is an effective drug for smoking cessation, that offers renewed hope for those who have tried and failed with other treatments. However, I think patients who are not planning on maintaining regular contact with an experienced clinician during their quit attempt (i.e. a clinician who can monitor side effects and provide supportive advice on a regular basis) should give serious consideration to using combination NRT (patch plus one other NRT) as a first choice. This treatment has the advantage that the patient is not taking a “new drug” – just the same one (nicotine) they have been taking, but without the 4000 other toxic chemicals.

Labels: Chantix, cigarette smoking, foulds, nicotine, NRT

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Which nicotine replacement therapy?

Nicotine replacement therapy (NRT) is the name given to FDA-approved medicines containing nicotine that are used to reduce nicotine withdrawal symptoms and cravings and to help smokers quit. Currently there are 5 main types: patch, gum, lozenge, nasal spray and inhaler. These latter two (nasal spray and inhaler) are only available via prescription in the United States, although they are available over-the-counter in many other countries (e.g. UK).

Each type of NRT has its own advantages and disadvantages. The patch is by far the most commonly used NRT, largely because it is the easiest to use, requiring only a single patch application per day. Another advantage of the patch is that its side effects are usually mild – primarily mild skin irritation and itching. The main disadvantage is that there is nothing one can do with the patch to increase the dose when you feel the need for more nicotine.

The gum and the lozenge are broadly similar in terms of dose (each available in 2mg and 4mg formats) and route of administration. The main challenge facing the gum chewer is to adopt a “chew and park” style, such that you chew the gum a few times to release a peppery taste (nicotine) and then park it in the side of your mouth for a few minutes before chewing again. The labeling on the gum suggests that people who smoke less than 25 cigarettes per day should use 2mg (rather than 4mg) and the labeling on the lozenge states that those who don’t smoke within 30 minutes of waking in the morning should use the 2mg lozenge. In practice many clinicians have learned that this labeling (especially the gum) is a recipe for under-dosing and advise all but the lightest smokers to use the 4mg formulation of each product. To get a real benefit from these products you need to use enough. Most users only take 3 or 4 per day in response to cravings. You can get a far greater benefit by taking one per hour (to prevent cravings and withdrawal symptoms) plus another whenever you have a breakthrough craving.

I described the nicotine nasal spray in some detail a few days ago. It appears to be particularly helpful for heavy addicted smokers who are willing to persevere despite the initial nasal irritation. Make sure you have some Kleenex handy when you first try the spray. The initial doses sting and will make you sneeze. But, just as with smoking, you will get used to it within a few days, and within a week will probably like it!

The inhaler‘s main advantage is that it enables the smoker to continue with a similar hand/mouth habit, but it helps to gradually wean them off nicotine. The main thing to note is that one puff on a cigarette delivers a similar amount of nicotine to ten puffs on the inhaler. This means that in order to obtain a therapeutic dose, the ex-smoker has to be puffing on the nicotine inhaler almost all the time. We recommend puffing on the inhaler for 20 minutes out of ever waking hour. Again, people who get into that regular use habit early on tend to do very well with the inhaler.

Some years ago Professor Peter Hajek and colleagues at the University of London conducted a randomized trial comparing the nicotine patch, gum, nasal spray and inhaler. In practice they all had similar quit rates (around 20-25% complete abstinence 3 months later), although women did better on the inhaler than the gum and men were the opposite. Prior to their quit attempt, participants were shown videos describing each NRT and were then allowed to rate their preferences. They were each then randomly allocated to one product. This meant that some people were allocated the product that was their first preference, whereas most were not. However, at the end of the study the smoking cessation outcomes were similar for those receiving their preferred NRT versus those being randomly allocated to a less preferred NRT. Also, people came to prefer the product they were given after they had used it for a week.

One final thing to consider is that the products differ in the risk of inducing dependence. It is extremely rare for someone to have any difficulty coming off the patch (which typically have a built-in reduction plan, involving using smaller sized patches over 4 weeks). However, some people (about 5-10%) find themselves using the gum, inhaler or lozenge long term (i.e. over 3 months and possibly continuing for years). The nicotine nasal spray has the highest dependence potential, with around 10-15% of those who use it continuing use after 3 months. The risk of becoming dependent is related to the speed of nicotine delivery from the product (spray fastest, but still slower and lower dose than a cigarette, whereas the patch delivers nicotine very slowly). It also seems to be related to how addicted the person was to their cigarettes. Thus people who smoked over a pack a day and smoke within 30 minutes of waking in the morning (or wake at night to smoke) are more likely to become a long term user of their NRT product. However, in the placebo-controlled trials these were precisely the people who were much less likely to succeed in quitting if they received the placebo. The thing to remember here is that it is much better to be a long term user of an NRT product delivering only nicotine, than a continuing user of a product that delivers a higher dose of nicotine plus 4000 other toxic chemicals (i.e. a cigarette).

Recently a group of experts in the treatment of tobacco addiction got together to produce a consensus statement guiding consumers on the most effective ways to use NRT to help them quit smoking. You can find a copy of the paper and the summary (in both English and Spanish) at: http://proyectovidanofume.org/publication.htm

Labels: addiction, cigarette, nicotine, NRT, replacement, Smoking, therapy, tobacco

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