<v ->Hello.</v> My name is Jill Williams, I'm a professor of psychiatry at Rutgers University, and I'll be speaking to you about the treatment of tobacco use disorder in primary care. I have no disclosures. And the goal of PCSS is to train healthcare professionals in evidence-based practices for substance use disorders. These are my objectives for today. To identify the available forms of clinical assessment, including the Time to First Cigarette measure; to demonstrate evidence-based pharmacotherapies for tobacco use disorder treatment, including nicotine replacement dosing; and also I will speak briefly on the role of counseling in increasing the success of quit attempts using the Ask, Advise and Refer model for primary care. I just want to review a bit about basics of understanding tobacco and tobacco use disorder. There's thousands of different chemical toxins associated with tobacco smoke exposure. And it's important to be aware that some of these are naturally occurring in the tobacco plant. Nicotine, for example, which causes the addiction, is naturally occurring in the plant. But so are nitrosamines. And nitrosamines are one of the most potent carcinogens found in tobacco. Since they're naturally occurring in the plant, this helps us understand why all forms of tobacco carry some risk for cancer. Some chemicals come from the manufacturing process. Flavors are added in cigarette manufacturing, things that change the way tobacco smells and burns, and it changes the pH of tobacco to make nicotine more addicting. But the source of many and most of the toxins associated with smoking comes from when you light tobacco on fire. This creates many and most of the most harmful toxins, including things like carbon monoxide. Tobacco is associated with many major health consequences, including risk for premature death, as well as heart disease, lung disease, and cancer. Tobacco smoking is also linked to other serious illnesses and raises the risk for serious complications from COVID illness. But in addition to the health consequences, there's many other ways that tobacco exposure negatively impacts people's lives. And you can think about it as a barrier to recovery. There are financial hardships that come from using tobacco related to the cost of cigarettes. It makes it harder to obtain and keep employment, as well as housing. Tobacco smoking is associated with worse mental health, including greater risk for suicidal ideation and suicide attempts. People who use tobacco tend to have more relapse back to drugs and alcohol if they're working on a goal of abstinence. There's the stigma of being a smoker, as well as that it contributes to worse appearance and is a risk for fatal fires in the home. So numerous ways that tobacco negatively impacts people's lives. And we can really think about this as a social justice issue. Cigarette smoking rates are on the decline in this country, but the people who remain smokers are often our most disadvantaged populations. Smoking rates are much higher in people with a mental illness, as well as in those with low socioeconomic status. It doesn't matter if you measure it by income, education, insurance status, smoking rates are always higher in those with lower socioeconomic status. And that's what this slide is showing. This is from the Surgeon General's Report of 2020, really confirming for the first time how smoking rates are higher in individuals with some type of mental illness, which includes individuals with a substance use disorder. Certainly, we know that tobacco industry has exploited this traditionally in terms of advertising and targeting vulnerable populations. We also know, unfortunately, that many adult smokers who see a healthcare professional do not receive advice to quit. In fact, many report trying to quit, but using non-evidence-based approaches. So we need to do more to help people link to evidence-based services. Nicotine, of course, is what causes the addiction to tobacco. And when nicotine is released into the body, it triggers the release of a variety of neuroactive hormones and neurotransmitters. It acts as a nicotinic acetylcholine receptor agonist in the brain and has a stimulant-like effect. It enhances concentration, attention, makes you feel slightly more awake, in addition to activating the reward pathway, which causes the experience of pleasure and contributes to its ability to cause addiction. Nicotine has a relatively short half-life in the body, just lasts for a few hours. And, again, we know that nicotine activates the reward pathways in the brain. These are also called the mesolimbic dopamine pathways. This is a series of deep brain structures that become activated in response to all addicting substances. So we know that cocaine, heroin, all drugs of abuse, essentially, act in the same way in order to activate this addiction pathway. And that nicotine meets all the criteria for being an addicting substance because it activates the reward pathway in much the same way. Tobacco use disorder is listed in the DSM-5, the Diagnostic and Statistical Manual used in the treatment of behavioral health conditions. Therefore, it is a behavioral health condition. Smoking is a highly addicting process because of the way that the drug is delivered to the body and to the brain. When you smoke a drug, a tremendous amount of drug can be rapidly absorbed through the lung, with rapid delivery subsequently to the brain, which really is the equivalent of shooting up a drug or putting it into your intravenous system. We don't often think about smoking in this way as having such a high addiction potential. Essentially, the equivalent of intravenous drug use. But because the delivery of the drug is so fast from smoking, we see that it really approximates that. And, therefore, this helps us understand why smoking is such an addicting process. The delivery of a drug to the body through smoking is much faster than through alternative delivery forms such as snorting or ingesting a drug. In terms of tobacco assessment, there is a measure that is quite good in understanding someone's level of addiction to tobacco. This is called the Time to First Cigarette, or the TTFC measure. It's part of the Heaviness of Smoking Index which is a brief way to do tobacco assessment. We ask people how many minutes in the morning until they smoke their first cigarette. And this is a highly sensitive measure for understanding how addicted people are to tobacco. If they report smoking in the first 30 minutes of waking up in the morning, this is an indicator of at least moderate levels of nicotine dependence. And this is a good crude estimate that the person will likely need the benefit of treatment, including pharmacotherapy, to be successful in trying to stop. Without treatment, they are likely to experience a lot of tobacco withdrawal symptoms. People may actually tell you they smoke in the first five minutes of waking up, which is an indicator of higher or more severe levels of nicotine dependence. This measure is important because it has implications for treatment outcome. The more addicted you are, the more difficult it is to quit. Again, it's also helping us understand who needs treatment, including medication, and maybe even a more intensive treatment approach. This was a publication which showed the strong relationship between the number of cigarettes per day smoked and the individual's likelihood of meeting criteria for tobacco use disorder according to the DSM-5. We can see here that even people who smoke relatively low numbers of cigarettes per day, such as one to four cigarettes per day, many of them are still meeting criteria for tobacco use disorder. More than 60%. And by the time people are smoking 10 cigarettes a day or more, we can see that 80% of those populations essentially are meeting criteria for having tobacco use disorder. So many people who use this drug, in fact, meet criteria for having an addiction or meet the DSM-5 criteria for tobacco use disorder. Another aspect of being able to do assessment is to take carbon monoxide readings from people. Carbon monoxide, as we mentioned, is one of the things that's produced when tobacco smoke burns. Cigarette smokers are ingesting carbon monoxide chronically. It comes from anything that burns. And you can measure the amount of carbon monoxide in the body in this small handheld meter, which is easy to use. Carbon monoxide then is a product of combustion. It comes from anything that burns, including cigarettes. Anybody who smokes cigarettes daily tends to have a carbon monoxide reading greater than or equal to four parts per million. What carbon monoxide does in the body is that it attaches to red blood cells with high affinity. It is able to displace the oxygen off the red blood cells, which puts considerable strain on the heart, especially when someone has been smoking for many years, and raises the risk for cardiovascular disease, including heart attack. This meter can be useful to document smoke exposure and provide people with feedback that gives them information about the impact that their smoking is having on their body. This can serve as a motivator, giving people this kind of feedback and motivating them to want to change this behavior. One of the nicest things about being able to do a carbon monoxide reading is that this is a reversible effect from smoking. So that your body is always making new red blood cells. Three to four days after you quit smoking, your carbon monoxide level would essentially be zero. It would go back to normal. So, again, this impact on your cardiovascular system that comes from smoking is entirely reversible. And, again, can be motivating to help people to understand it's never too late to try to quit. These are the symptoms of tobacco withdrawal. This is a real drug withdrawal syndrome. It can emerge within hours of someone's last cigarette due to the short half-life of nicotine. It can include symptoms of sad or depressed mood, irritability, frustration, or anger, anxiety, trouble concentrating, restlessness, and feeling hungry, increased appetite. Over several days, it can also contribute to difficulty sleeping or insomnia. And this syndrome can last within weeks after someone's last cigarette, although it's generally most intense in the first few days. As you can imagine, this undermines a lot of people's ability to quit, especially if they're not receiving the benefit of treatment, including medication. So why is it so hard to quit smoking? Well, we've seen some of the reasons already today. Smoking a drug is a highly addictive way to deliver drug to your body and to your brain. There's easy access to this drug as a legal substance. And it's normalized, frankly, in many behavioral health treatment settings. We could argue that treatment options are limited. There's no levels of care for tobacco use the way there are for other types of behavioral health problems and addictions. Most people receive brief or no counseling support. And utilization of treatment tends to be poor. Again, people may not want to use the counseling or they may use the medications in too low a dose or for not long enough time period. So although we know that many people want to try to stop and may actually make attempts to stop, we know that without the benefit of treatment, the success rates can be quite low. And with the use of treatment, success rates are greatly increased. In terms of brief interventions, there is evidence that even brief advice can be helpful in motivating some people to try to quit. This is one model for doing that, which is referred to as 2As and an R, where it stands for Ask, Advise and Refer. So this evidence-based approach suggests that for every tobacco user, we ask, "Do you use tobacco?" And conduct some type of brief assessment. How much, what kinds? It also recommends we give people some brief feedback or advice, or ask them, in fact, how they feel about quitting or changing this behavior. And then working to link them or refer them to an evidence-based treatment. Treatment for tobacco use disorder works. And these are some strategies that we can all employ in our practices. Everyone should receive at least a brief assessment of their tobacco use disorder. We should think about interventions that reach people at all different motivational levels, not only those who are immediately ready to quit. We want to encourage people to use evidence-based treatment, which includes a combination of counseling and medications. And even in the language that we use, we can be more engaging and not use terms like smoking cessation, which can be quite limiting and attractive only to people who are in preparation. Using more umbrella terms, like treatment, can be more engaging and allow us to discuss options with people at all different levels of motivation. In terms of what's new, this is just a brief overview of some of the many new strategies that are being investigated and explored. Again, messaging I think has changed in terms of thinking about this addiction more broadly and offering people greater access to treatment with greater emphasis on engagement, not framing everything merely as quit attempts. Similar to that are what are called opt out approaches, again, which try to deliver treatment universally, allowing people to refuse, but in a more proactive way. There's more evidence for the use of pharmacotherapy perhaps in ways that are more aggressive than in the past, as well as there's been developments in healthcare delivery that have allowed for greater access to these treatments. I'll speak briefly about thinking about first-line treatments, including combination nicotine replacement, or varenicline, as first line in terms of an algorithm, as well as more alternative uses for the medication, such as during periods of temporary abstinence. We can think about a greater role for harm reduction alternatives. Again, engaging people to try treatment. Even if they're not able to make a commitment to quit, ultimately, they might want to reduce to quit using pharmacotherapy. They may be willing to try brief quit attempts or practice quit attempts as well as some role that's emerging for switching to non-combustible products, which can be thought about on a continuum of harm. There are some advances in counseling approaches, including use of the ACT model, as well as some evidence that you can deliver effective counseling through apps. And there's been an extension in terms of a new role for tobacco treatment specialists with a certification for this as a clinical subspecialty. So these are the predictors of abstinence or the factors which lead to greater success in a quit attempt. They include things like lower level of dependence, higher socioeconomic status, older age. There are some gender effects with some evidence that it's a little bit easier for men versus women. Not having a lot of friends who smoke makes it easier for you to quit. Not having a behavioral health condition or a comorbidity, again, is a factor associated with greater success. But perhaps the most important one here is the use of treatment. We know that with treatment, success rates will be greatly enhanced, and we should encourage all tobacco users to quit with the benefit of treatment. In terms of gender issues, again, there is emerging evidence that women on a given quit attempt have somewhat reduced success compared to men. It's not known why this is. Some of the theories are looking at the role of mood, negative affect, depression, as well as the possible role of socioeconomic issues. Perhaps women are less likely to use medication. So lots of different potential factors there that may contribute to that reduced success. Although there also seems to be some differential medication effects. And in at least one analysis, varenicline was more effective than a nicotine patch for women. That same effect was not seen for men where quit rates were essentially equivalent using those two different approaches. And, again, this has been shown both in clinical trials and epidemiologic studies. So when I say that people should have the benefit of treatment, what we're really referring to is some combination of counseling and medication. Both of these are effective when delivered alone. So medication alone is effective, counseling alone is effective. However, we see the greatest success rates when people get a combination of both. I'm going to discuss now some key aspects of pharmacological treatment, which is shown to be a cost-effective strategy. The main way that these medications work is to reduce or eliminate the uncomfortable symptoms of tobacco withdrawal, which limit someone's ability to successfully quit. The medications also have additional benefits of reducing the weight gain associated with quitting smoking and they block some of the pleasure associated with smoking, which are other ways that they may contribute to overall success. We know that the use of these medications generally raises the chances that someone can successfully quit smoking by two to three times. That comes from studies comparing these medications to placebos. This is a table summarizing the overall results from many of the medication studies that have been conducted on these different products. It's sort of comparing them using statistics. And we can see that the odds ratio for patch, gum, nicotine inhaler, nasal spray, and bupropion are all essentially two, which mean that they all double the chances that you can successfully quit smoking if you use one of these treatments compared to if you received a placebo. We can see that the odds ratio for varenicline is three, suggesting that it does have a higher efficacy when used as a monotherapy in helping people to quit smoking. These medications have been studied extensively and there is a lot of evidence that they do not increase the risk for serious cardiovascular disease. That includes not only nicotine replacement products, but also bupropion and varenicline that there's currently no evidence that these products are linked to increased heart or circulatory problems. In summary, according to cardiologists, these products carry a low risk for harm and we should be using them more because the benefits outweigh the relatively low risk of serious adverse cardiovascular events. We know that tobacco is quite lethal and dangerous to the cardiovascular system. And so, again, the the risk-benefit ratio supports greater use. So I'll go through each of the products individually and make some general comments. Nicotine replacement medication, you may be familiar with, it's referred to as NRT. And it includes five or six products that I'll discuss. The patch, the gum, the lozenge, and the soon to be released oral spray are all available as over-the-counter products. But we do generally recommend that we provide patients with prescriptions whenever possible for these products because then there's a greater chance that they can get that product for free through their commercial health insurance or through their state Medicaid program. There's also two prescription nicotine replacement products, the nicotine inhaler and nasal spray. These are some of the themes or rules for using nicotine replacement more successfully. We want to be able to use them in a high enough dose. We know that generally, most people achieve higher nicotine levels in their body from smoking than they do from nicotine replacement products. It's actually a challenge. So we want to encourage people to use enough products that they can be successful with them. Similarly, we want to encourage people to use them for a long enough time period. There's really no reason for people to stop them or to taper off them after just a few weeks. If they feel they might benefit from longer duration, that's generally okay. So no strict tapers have to be followed in terms of reducing dose of nicotine replacement. Nicotine can be safely combined with other treatments like bupropion and we can give people two nicotine medications together in combination, which is actually a highly effective strategy. There's almost no one who would be a true contraindication, who would not be able to take nicotine replacement, because, again, it's the same nicotine that people are receiving from their tobacco products, but in a safer delivery form with the toxin and carcinogens removed. Nicotine has no drug-drug interactions. And for all of these reasons, it's safe enough to be an over-the-counter medication. We know that people's outcome using nicotine replacement will be better if they understand how to use them effectively. So medication education is an important component of providing good care. The FDA, several years ago, issued labeling updates, again, to reassure the community and the medical community that there are no significant safety concerns with using two nicotine products at the same time. Similarly, if people are smoking some amount of cigarettes and using nicotine concurrently, that there are no significant safety concerns associated with that, and that use longer than 12 weeks is safe. The nicotine patch is fairly straightforward. It has a slow onset of action where nicotine is slowly absorbed through the skin into the bloodstream continuously, generally for a period of 24 hours. The usual dose that most people will start with is 21 milligrams per day. The patch is fairly easy to use and has good compliance associated with it. And, again, there's no need for strict tapering or timeline in terms of reducing the patch dose. One of the main nicotine side effects is that of irritation. So people can feel some slight skin irritation or a sense of the skin tingling or burning as a result of the nicotine, but for most people, this is generally safe and is not a reason to discontinue the patch. Nicotine in the evening, if you wear the patch while you sleep, it's possible that it could cause insomnia. But we generally recommend that people try to wear it through the night so that they get the benefit of the 24-hour delivery and so that they do not wake up in the morning with high levels of craving and withdrawal. There's many formulations of nicotine that go in through the lining of the mouth. Nicotine cannot be swallowed as a pill. Delivery, that's a poor way to provide nicotine replacement to the body because of the liver, because of first pass metabolism. So the way these oral formulations work, they all have something in common where the nicotine is delivered to the mouth and there's a slow delivery of nicotine through the lining of the cheek into the bloodstream. That's how nicotine is absorbed with these products. So people have to know something about that and use them correctly for them to be effective. That's most important, really, with the nicotine gum that it really requires you to chew it fairly slowly and to hold the gum in your cheek over a period of maybe 10 to 20 minutes to allow the nicotine time to be absorbed through the lining of the cheek. But the nicotine lozenge and the inhaler and the oral spray all have in common that they're delivering nicotine through the lining of the mouth. Again, that does not deliver a high dose of nicotine. And if somebody is a heavier smoker or smokes within the first 30 minutes of waking up in the morning, it's generally recommended that they use the higher strength or the four-milligram dose of the gum or lozenge. For these to be effective, they have to be dosed frequently throughout the day. People can use them as much as every one or two hours during the day. They should be advised not to use them at the same time that they have coffee or soda or other beverages in their mouth. These beverages are generally acidic, which will reduce the absorption of nicotine through the lining of the mouth. If people tell you that they use them and they've developed indigestion or hiccups, that generally means that they've swallowed too much of the nicotine, and then they can have those side effects. The newest nicotine replacement is the oral nicotine spray. The spray is delivered through the mouth into a small droplet formulation. It went through preliminary approval through the FDA, but did not receive final approval, so it's not yet available. Although it is an over-the-counter product that's been available in Canada and Europe for several years. This product has perhaps a faster absorption of nicotine because the droplet size is fairly small. Although it's generally equivalent to other forms of oral nicotine replacement, it may provide a greater craving relief, again, because it has the potential to be absorbed slightly faster than the other forms of oral nicotine replacement. One issue with this product may be that it contains a very small amount of alcohol. Less than a teaspoon. However, for some people who avoid use of mouthwash and other commercial products because of the use of alcohol, because they're in alcohol recovery, that may be a consideration. There's also two forms of prescription nicotine, although these tend to get used less often. Cost can also be a barrier, as well as insurance coverage. The nicotine nasal spray, which delivers nicotine to the lining of the nasal mucosa, and the inhaler, which we said is an oral delivery product. Smoking, when people are using nicotine replacement at the same time, is generally felt to be a safe practice. There is some risk for nicotine toxicity, but that's generally self limited to feeling dizzy or feeling nauseated and is generally not more serious than that. People will enjoy their cigarettes less if they're using medication including nicotine replacement. And that may be a way to help people to smoke less over time and work towards reducing their smoking and eventually quitting. In fact, some analyses have showed that use of nicotine replacement, even in populations of unmotivated smokers, did result in about 7% successfully quitting. So we can think about the medications having a greater role in terms of reducing some of the enjoyment of smoking, reducing the associated withdrawal symptoms that may be associated with reduction and increasing the likelihood of subsequent quitting. Bupropion is another one of the FDA-approved treatments. It's effective not only as an antidepressant but as a smoking cessation treatment. It's generally used at the same doses, which is 150 to 300 milligrams daily. It is effective. It can be a great choice for someone with depression who also smokes. However, its effect is independent of depression, which means it works in people even with no history of depression or current symptoms of depression. We generally start it about two weeks before the time that somebody is going to try to quit. It's contraindicated in those with a history of seizures or eating disorders. And its overall efficacy is similar to nicotine replacement. Out of all of the treatments, it may have the lowest risk for weight gain, especially when given at a 300-milligram dose. And you can also use in addition to the SR formulation, which was the one that was FDA approved, the XL or the newer formulation. As I mentioned, there's a lot of evidence now for combination nicotine replacement therapies. This is generally done as giving somebody a long acting nicotine patch and having them supplement throughout the day with a short acting form of nicotine replacement, such as the gum, or lozenge, or inhaler. These strategies deliver a higher dose of nicotine replacement to the individual, which likely reduces their withdrawal and provides greater craving relief. There's also evidence that these strategies enhance outcomes significantly. We think about other potential combinations, such as patch and bupropion. But that really is only marginally better than either of those treatments when delivered as a monotherapy. So there's less evidence that that's an effective strategy. And there's currently a lot of mixed evidence about the usefulness of varenicline and nicotine as a combination. And this is generally not recommended. Varenicline works in a different way as a partial agonist at the alpha-4 beta-2 nicotinic receptor. It partially stimulates the receptor and perhaps maintains tone in the reward pathways. It also works to reduce withdrawal and craving in the context of someone quitting smoking because it's affinity for the receptor is higher, so it blocks nicotine's ability to activate the reward pathway. In controlled trials, it's been shown to be superior to bupropion or nicotine patch when those were used as a monotherapy. This was shown in the EAGLES study, which included both psychiatric and non-psychiatric groups of smokers. The safety of varenicline has also been studied extensively and there's no significant differences in the rates of moderate and severe neuropsychiatric events when compared to bupropion or patch. There was a voluntary recall of varenicline in September 2021. This was due to a potential contamination in the manufacturing process. In response to the shortage, the FDA has temporarily exercised regulatory flexibility and discretion in allowing Apotex's distribution of Health Canada-approved generic Apo-Varenicline in the United States. This is still happening, but it's worth checking at your local pharmacy to see that it's available. Varenicline is generally dosed twice a day with food to reduce risk for the main side effect, which is nausea. Varenicline is also associated with higher risk for insomnia and abnormal dreams. It's generally given in a titration that increases to the full strength of one milligram BID. Varenicline has no drug-drug interactions in the liver. It's excreted almost entirely by the kidney through the urine. These were the main findings from the EAGLES study that I previously mentioned, showing that varenicline when used as a monotherapy was superior to treatment with either bupropion or nicotine patch. This included more than 8,000 smokers. So this is really the largest smoking cessation study which has ever been done. It was done in a triple dummy design. As I mentioned as well, it included more than 4,000 patients with psychiatric illness, which is shown in the center part of the graph. And the same trends are true where varenicline is the most effective treatment even in the individuals with comorbid psychiatric illness. But you can see that the overall success of the patients who had a comorbid psychiatric illness is somewhat lower than those without psychiatric illness, which is shown on the far left. There's many studies and analyses which have now demonstrated the safety of varenicline in terms of neuropsychiatric side effects. The first of these was a meta-analysis of more than 39 randomized controlled trials, placebo-controlled studies, which included more than 10,000 participants, which showed no increased risk for suicide, suicidal ideation, depression, irritability, or aggression associated with the use of varenicline. There's been smaller randomized controlled trials in subpopulations, including smokers with major depressions, schizophrenia, and bipolar disorder, which also showed an absence of side effects as well as no evidence of worsening of mental illness in the context of trying to quit smoking. The EAGLES study, which I mentioned, also showed no increased risk of moderate or severe adverse events in the groups receiving varenicline. This was a really comprehensive study which had really analyzed numerous measures of symptoms as listed on this slide. There's also been some interesting new analyses that come from insurance claim and other large database studies which show that varenicline use in the population is associated with less likelihood of being hospitalized for a cardiovascular problem as well as reduced risk for being hospitalized with psychiatric illness. So considerable evidence of medication safety. So we now have a lot of evidence that either varenicline used as a monotherapy or combination of two nicotine replacement products, referred to as combination NRT, are really very effective strategies and we should be considering them as first-line treatment because we have evidence that these are better than other treatments. Of course, we would hope that in using medication, people are also receiving behavioral support, which would give them the greatest chance for success. In terms of using, thinking about the combination of varenicline and nicotine replacement, as I mentioned, it's generally not recommended. There have been some published studies. Although the results are mixed, there's not a clear mechanism of how nicotine replacement would improve the outcomes associated with varenicline since varenicline is already bound to the nicotinic receptor and working as a partial agonist. Perhaps it'll be useful in the future. It could be demonstrated to be more useful in those with severe dependence. But I would hold off on it at this point because study results are mixed and there's evidence that people also experience more side effects with this combination. This is just the most recent study that was published by Baker et al in JAMA, which, again, did not demonstrate that varenicline and patch was better than varenicline alone. Should we use medications more for people who are not immediately ready to quit? The answer is yes. As I said already, if people are able to use these medications, it will reduce some of the enjoyment associated with smoking and it may allow them to reduce the number of cigarettes per day that they smoke. You can think about that as a form of harm reduction. And over time, if they're able to reduce their cigarettes significantly, they'll be lessening their dependence and increasing their likelihood of subsequent quitting. Individuals who are able to reduce their cigarettes by 50% or more do have significantly greater odds of subsequent quitting. We also can use these medications more during what we call periods of temporary abstinence when people are unable to smoke for periods of several hours or more because it will also minimize the withdrawal associated with that. And there's now been a Cochrane review published which shows that if people are reducing their number of cigarettes per day using medication, that's going to be a more effective strategy than reducing to quit without medication. Presumably, using medication aids by reducing the amount of withdrawal that people experience and increases their likelihood of success. This was a published study looking at reduction in individuals not willing to immediately quit smoking. They were randomized to either receive varenicline or placebo, and the reduction and subsequent quit rates were significantly higher in those individuals who received varenicline. This study was so effective that, in fact, this is included in the package insert for varenicline. So this is considered an on-label use of varenicline that you can consider a gradual approach to quitting for patients who are not able to or not willing to quit abruptly by using varenicline. So just to briefly review these treatments, nicotine has no drug-drug interactions. Varenicline, essentially, has none as well. Bupropion has the potential for some. And remember that tobacco smoke itself has the most interactions. It induces the 1A2 cytochrome P450 enzyme, which is important in the metabolism of several psychiatric medications, including antipsychotics and antidepressants, as well as caffeine. So we have to be mindful of changing drug levels in the context of people stopping and starting smoking. In terms of counseling, I'll review just some of the basic evidence-based approaches. We learned briefly about the role of brief counseling. Every tobacco user should at least receive an intervention of Ask, Advise and Refer. We can always be giving people even brief medication education to increase their likelihood of using those medications successfully. But, certainly, there's a role as well for what we would refer to as intensive counseling. It can be delivered in either a group or in an individual setting. And this can include a variety of strategies, including the telephone quit line, as well as more traditional approaches for relapse prevention, social support, and there's evidence for the success of the ACT strategy as well. Telephone counseling, you may be familiar with, it's available in all states and is generally free because it's state funded. It includes assessment as well as a series of brief follow-up calls with a tobacco treatment specialist. It can be great for overcoming barriers, like transportation, or cost, or insurance status. It's generally delivered in variety of languages and is associated with increasing the chances of likelihood of success. Sometimes these programs also offer or include free nicotine replacement products. There's not really time to go through all of these treatments, but just to remind people that there is evidence of the benefit of behavioral support or psychosocial treatment in helping people to quit, including the Quit Line. There's some emerging evidence for the use of mobile phone apps, as well as e-cigarettes, or providing incentives through contingency management. And there's at least one study of the usefulness of deep transcranial magnetic stimulation, although it's not clear how often that's being used in clinical practice. There's still no evidence of a benefit of alternative therapies, including use of internet-only strategies, exercise, acupuncture, or hypnotherapy. In terms of working with pregnant populations, this is, of course, a priority and high-risk group because of the tremendous risk to the fetus. In terms of these interventions, this is a recent report that was published, looking at the evidence for these treatments in pregnant women. There is evidence that counseling works. There's less evidence supporting the use of nicotine replacement. That may be for a variety of factors, including that women tend to have low adherence to the medications even in studies. They also have higher rates of metabolism related to pregnancy, which may limit the usefulness of the medications. However, in studies looking at treatments including nicotine replacement, you can generally show that although they don't increase the overall success rates of the women conclusively, they are associated with better outcomes in the baby, such as higher birth weight. And there's no evidence of adverse effects currently on the baby in terms of from exposure to nicotine replacement. Factors like depression and low social support make it more difficult for these women to quit. So at this point, I would say there's conflicting evidence to say whether or not nicotine replacement works to absolutely increase the abstinence rates in pregnant smokers, but we can use nicotine replacement with close supervision. And after consideration of the risks and benefits, clearly, if the woman's not able to stop smoking on her own, there may be a role for the use of medication including nicotine replacement. Finally, I'll just briefly talk about the role of e-cigarettes. There's tremendous concern about youth uptake of electronic cigarettes and vaping for many reasons. It seems to undermine the success we've had in this country in lowering smoking rates over decades. Use of e-cigarettes in teens is associated not only with nicotine addiction but with higher risk for subsequent cigarette initiation, as well as higher use of THC and cannabis in youth. It's very controversial about whether we should be using these to help older smokers, particularly if they've been not successful in quitting with other means. And I'll make some comments about that. Generally, we can think about these products as safer than smoking because they are noncombustible. The tobacco, the nicotine, it's not burning when delivered through these products. It's being heated with a heating element, creating a mist or vape. But, technically, there's no burning, there's no smoke, there's no carbon monoxide. So the overall exposure to toxin, carcinogen, although there may be some, is generally much lower than one would receive from a combustible cigarette. Estimates are that vape contains about 1% of the toxin and carcinogen that's contained in cigarette smoke. So you can think about them in terms of a continuum of risk where nicotine replacement would be the safest option for someone, cigarette smoking is the worst option, and e-cigarettes fall somewhere in between. One of the issues in this country is that they're not regulated or tested to any extent. There's no limits currently on advertising and there's wide variability in products. So you really don't know or have any sense of what you're putting into your body. And there's risk associated with that as well. People who use them become addicted to nicotine. It has not yet been studied how we will help people to quit e-cigarettes once they develop that addiction. But you can use your clinical judgment that the same treatments would generally work since this is also nicotine addiction. One of the other challenges in this area is the co-use of THC and cannabis and sort of the development of vaping culture where there's sort of a continuum where people may use a variety of products and not nicotine alone. Just to contrast, what's happening in the United States is to present the view in the UK based on the current evidence. Electronic cigarettes are very popular in terms of people using them as an aid to quit smoking. And even assuming that they have the same efficacy as other products, they have the potential to reach more people because they also don't require insurance and are no cost to the healthcare system. So you may not agree with that point of view, but just to present an interesting point of view that's coming out of the UK. And there have now been a few really well done studies using placebos or other alternative treatment groups, randomization, to look at the use of e-cigarettes in helping some smokers to quit. This is one of the studies which has been published where people were randomized to either receive a refillable starter pack of an electronic cigarette, or they received combination NRT. This was a group that were motivated and they also received counseling to help them to quit. And the success rates using the e-cigarette were actually comparable or slightly better than using combination NRT. Although one possible concern may be that 80% were still using their e-cigarette at the end of the year compared with very low rates that continue to use nicotine replacement. Suggesting, again, people remain addicted to nicotine as a result of using these products, but that overall their health benefits would be worthwhile because they're no longer being exposed to cigarette smoke. There was also a study recently published that came out of New Zealand which looked at patches versus e-cigarettes for smoking cessation, using very low levels of counseling, behavioral support. And, again, showing that the combination of patch and e-cigarette together had the greatest chances of success, significantly better than patch alone. Finally, this was a population-based study looking at 1,600 smokers who were not intending to quit in a large epidemiologic study. Many of them were highly addicted, half of them smoked more than 20 cigarettes per day. They have about a natural history of a 6% quitting over the subsequent five years. However, that raises to 28% if they had in that time period switched to using e-cigarettes daily, which was an eight times greater chance of quitting. 46% quit daily smoking, even if they did not quit entirely if they also switched to e-cigarettes. Not using your e-cigarette every day or using it occasionally, essentially, had no impact on quitting. So the take home message here is that people were really successful in quitting if they switched entirely to e-cigarettes. And we do know that people can actually continue to have health consequences even if they're smoking small amounts of cigarettes per day. So when people switch entirely from combustible to non-combustible products, again, they seem to have the greatest benefit in terms of health outcome and also success in quitting. We have to, of course, temper this with EVALI, e-cigarette or vaping associated lung injury, which we know was a very significant problem in the country and resulted in 60 deaths. It was linked to contamination of the product vitamin E acetate, which was quite toxic to lung tissue. This was generally found in mostly THC containing products. Most of the individuals who developed EVALI reported vaping THC products. However, some reported vaping nicotine alone. And this is a risk certainly as well. So just to conclude, some of the things that we spoke of today, treatment, not cessation is really a better approach in our language. It's more engaging, it's more consistent with motivational interviewing, and it suggests there's a role for everyone in what we have to offer. We can think about brief strategies, like Ask, Advise and Refer, to employ in all of our healthcare systems. We want to think about medications and treatment support for anyone who smokes within the first 30 minutes of waking up in the morning, in particular, although we certainly want to think about it for all tobacco users. Combination NRT and varenicline can be thought of as first-line treatments in our algorithm or in the way we present treatments to people. We want to think about an increased role for helping people reduce to quit with the benefit of pharmacotherapy. And, certainly, we want to include other treatments, such as behavioral support through the variety of modalities that I mentioned. Thank you so much for your attention today. These are just some references from the talk. PCSS has a active mentor program, helping people to deliver evidence-based treatments which is provided at no cost. If you have a question, please contact us. And thank you for attending.

tobacco use disorder

primary care

clinical assessment

counseling

smoking rates

pharmacological treatments

e-cigarettes

harm reduction

health benefits