Immediate and delayed quitting

Last week I attended the 4th annual meeting of the Society for Research on Nicotine and Tobacco (Europe) in Madrid. This is a conference where the top researchers present their latest research findings. As you can imagine a lot of fascinating stuff was presented. One that I particularly liked was presented by David Gonzales of the Health and Sciences University in Portland. He presented data on immediate quitting (i.e. those who succeeded in quitting on their target quit date with no lapses) and delayed quitting (i.e. those who had some lapses after the initial target quit date but then managed to get quit and stay quit) among patients treated with either varenicline (Chantix), bupropion (Zyban), or placebo.

For me the interesting thing was that Chantix and Zyban each improved the proportion who initially quit (over placebo), but Chantix also increased the proportion who managed to achieve abstinence after their initial target quit date. Dr Gonzalez presented a nice diagram showing that the number of patients achieving abstinence continued to increase across the first 12 weeks among those on Chantix or Zyban (although it increased faster among those on Chantix).

Colleagues have remarked that patients taking Chantix are less focused on the target quit day (typically day 8 of taking Chantix) than we are used to. We think that’s because almost all of the patients we treated before Chantix were also using nicotine replacement therapy (sometimes combined with Zyban/bupropion). The NRT (patch, gum etc) is typically started on the target quit day and so patients are very aware of the importance of that day. We don’t typically combine Chantix with NRT (as the Chantix is supposed to block the nicotine receptors in the brain) and so on Chantix its easier to see the target quit date as less distinct from any other day and just continue reducing cigarette consumption rather than quitting completely.

The take-home message for patients is that it still makes sense to select a target quit-date (day 8) and to try to quit smoking completely on that day. However, if you don’t immediately get quit, don’t give up on yourself or on the medicines. The evidence suggests that if you keep trying you will likely achieve abstinence, and that Chantix improves your chances, so long as you keep trying and keep taking the medicine. On the other hand, its important to be clear that the aim of the game is to quit completely, and its better in the long run to throw away the cigarettes and get on with it.

Labels: bupropion, Chantix, cigarette smoking, quit, varenicline, Zyban

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Does it help to add nicotine gum to bupropion?

Bupropion (marketed as Zyban for smoking cessation and Wellbutrin for depression) is approved by the US Food and Drug Administration as safe and effective for smoking cessation. It is taken in tablet form. There are also a number of nicotine replacement therapies (nicotine gum, patch, lozenge, inhaler and nasal spray) that are also approved treatments. Some previous studies have suggested that combining medications may improve smoking cessation success rates, and this has become normal practice at the tobacco treatment clinic here at UMDNJ.

Our experience in clinical practice has been that highly addicted smokers have better outcomes if they combine bupropion with NRTs. However, the only way to properly evaluate this is via a randomized placebo-controlled clinical trial. Such as study was just published in the journal, Nicotine & Tobacco Research, by Piper and colleagues at University of Wisconsin. They randomized 608 smokers to receive either (a) bupropion SR tablets plus 4mg nicotine gum, (b) buropion SR tablets plus placebo gum, or (c) placebo tablets and placebo gum, for 8 weeks, along with 6 brief counseling sessions. No more treatment was provided after the 8th week, but the participants were followed up at 6 and 12 months after the initial target quit date.

One week after the quit date, significantly more people had quit smoking while using active bupropion plus 4mg gum (47%), as compared with active bupropion plus placebo gum (38%) or placebo tablets and placebo gum (22%). At the end of treatment (8 weeks), the double medication group still had more successes (38%), as compared with active bupropion (31%) or double placebo (17%). However, at longer term follow-up (i.e. after the participants had stopped taking the medicines) the differences were relatively small. For example, at one year the quit rate was 21% for the double active group, 19% for active bupropion and 14% for double placebo.

So what does all of this mean? Firstly, it suggests that the advantage of adding nicotine gum to bupropion is real and statistically significant, but is quite small, even early in treatment. Secondly, it looks as though much of the advantage of early combination pharmacotherapy disappears at long term follow-up (off all medications). The other thing to note in this study is that the participants only used 4 pieces of gum per day. This is perhaps part of the reason for the smallish effects – the participants were only using smallish amounts of gum. Some may interpret these results as failing to demonstrate that adding nicotine gum to bupropion improves quit rates. Personally, I see a 38% quit rate at end of treatment as being meaningfully better than 31%. The drop-off after the medications are withdrawn is no surprise, and simply challenges us to consider why we continue to treat this chronic condition (tobacco dependence) with acute medications treatments. If a relative of mine was an addicted smoker seeking advice on which medicines to use, I’d probably still encourage something like bupropion plus the 21mg nicotine patch plus 4mg nicotine gum. I’d also encourage them to keep taking the full dose of all these medicines until they had experienced 14 consecutive days with no cravings, withdrawal symptoms or near lapses, and would be surprised if that day came within the first 6 months. Although each individual piece of this treatment may only add a few percent to their chances, this could be a life-saving treatment and every extra chance is worth the effort.

Labels: bupropion, Grand Rounds Nicotine Replacement, smoking cessation

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Can quitting smoking trigger depression?

Adolescent smokers are more likely than non-smokers to subsequently develop depression, and adult smokers are more likely to have either current depression or a history of depression than adult non-smokers. So although some have suggested that tobacco may have some component that “medicates” depression, the evidence for this is not at all clear. But for the smoker who has previously suffered a major depressive episode it is reasonable to wonder whether stopping smoking might increase the risk of suffering another episode of depression.

Depression is one of the most common and most unpleasant of all illnesses. It is characterized by feeling consistently sad, hopeless and pessimistic for more than 2 weeks (usually much longer), and often involves sleep disturbance, fatigue and changes in appetite. Perhaps most importantly, major depression is a risk factor for both attempted and completed suicide. So anyone who has ever suffered from major depression may understandably be very reluctant to do anything that may increase the risk of feeling that bad again. Remembering that low/depressed mood (which is not the same as full blown depression) is one of the symptoms of nicotine withdrawal, one can understand why someone with a history of depression would become concerned when they experience the onset of depressive symptoms after quitting smoking. Some studies find that people with a history of depression have a lower quit rate when they try to quit smoking, compared to those without such a history. One reason for this may be that onset of depressive symptoms raises the concern that a major depressive episode may return and triggers a return to smoking. However, a critical question is whether such fears are justified. Can quitting smoking increase the risks of onset of major depression?

Professor John Hughes, of the University of Vermont recently reviewed all the published studies providing evidence relevant to this question. The rate of major depression in the year after successfully quitting varied considerably across studies, from as low as 1% to as high as 31%. There was fairly consistent evidence that people with a history of major depression were more likely to have another episode after quitting, but this is not surprising as people with a prior history of depression are more likely to have another episode regardless of whether they quit smoking or not. Two studies by Professor Stan Glassman at Columbia University found that depression occurred more frequently in people with a history of depression who succeeded in quitting smoking compared with those who continued to smoke. In his review, Professor Hughes commented that none of the studies provided conclusive evidence and that there was a high risk of “publication bias”. This refers to the tendency for studies that don’t find a difference/effect to be less likely to be published. So what can we conclude from all this?

It looks likely that having a history of major depression is associated with slightly greater difficulty quitting smoking, and an increased risk of recurrence of depression in the months/years after quitting smoking. It remains uncertain whether quitting smoking can actually trigger an occurrence of depression, although it is clear that the majority (69-99%) of people who quit (even those with a history of depression) do NOT experience major depression within a year of quitting.
But how might this affect the choice of treatment, particularly for those with a history of depression? If I had a close relative who wanted to quit smoking but had a history of major depression, my advice would be as follows:
1. To ensure that you get the best advice and support, attend a treatment center with staff who have been trained to provide tobacco treatment, including access to medical staff with experience providing the range of tobacco treatment medications.
2. To increase the chances of successfully quitting AND preventing unpleasant withdrawal symptoms make sure you use an adequate dose of medication approved for smoking cessation. For the heavy smoker that should involve discussing with the doctor the potential advantages of combination therapy, such as Zyban (bupropion), plus the nicotine patch, plus one of the acute dosing nicotine replacement therapies (nicotine gum, lozenge, inhaler or nasal spray).
3. Make use of all the counseling support services available – ideally combining attendance at regular group or individual appointments, plus registering with a smoking cessation website (e.g. www.quitnet.com ), plus use of a telephone quitline.
4. Don’t start reducing the prescribed medication until you are feeling very confident about maintaining abstinence from tobacco and have discussed it with your prescriber. As a rule of thumb, don’t consider reducing your prescribed smoking cessation medications until you have had fourteen consecutive days with no cravings, withdrawal symptoms or near lapses.
5. Stay engaged in counseling for at least a few months (and ideally longer) after you have come off your smoking cessation medications. This could be as simple as scheduled monthly appointments or telephone calls, but even this relatively infrequent contact during months 4-12 after quitting smoking will help maintain focus on abstinence and will enable the counselors to monitor symptoms and treat as required.

Now all of this may sound like a great deal more work than people typically plan on when they try to quit smoking. It is. But I would remind my relative that this is a difficult but life-saving behavior change they are about to embark on. One likely to add ten healthy years to their life. Its well worth the effort both to successfully quit and to look after ones mental health in the process.

Labels: bupropion, cessation, depression, nicotine addiction cigarette smoking tobacco

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