By John P. Sader MD, ASAM certified, ABAM Diplomate Campbellton, NB October 2017

Transcription

1 By John P. Sader MD, ASAM certified, ABAM Diplomate Campbellton, NB October 2017

2 NRT = Nicotine Replacement Therapy: Patches 21 mg/14 mg/7 mg Gum 2 mg/4 mg Lozenges 1 mg/2 mg (Thrive) and 2 mg/4 mg (Nicorette) Vaporizer Inhaler Bupropion (Zyban/Wellbutrin) Varenicline (Champix) 2

3 E-Cig Beedies (cigarettes from India with tobacconicotine in addition to Betel nuts, spices and herbs) Hypnosis Acupuncture Laser-acupuncture 3

4 Known effects: Dopaminergic: Pleasure + Attention/concentration/memory + Anti-depressant effect Monoamine oxidase inhibitor: Anxiolytic effect (serotonin, noradrenaline, histamine) Anti-depressant effect (serotonin, noradrenaline, dopamine) Cholinergic: Reduction of neuroleptic side effects Endorphinic: Pain relieving and anti-loneliness effect Antipsychotic: Through the effects on information sorting Induction of P450 cytochromes Increased metabolism of certain prescriptions (all xanthines including caffeine/theophyllines, Zyprexa, Clozapine, Coumadin) 4

5 The individual loses: The effects on: Pleasure Attention/concentration/memory Anxiety Depression Pain Loneliness Psychosis In addition to seeing the metabolism of their prescriptions/caffeine change, sometimes dramatically In addition to losing the peripheral inflammatory effects due to the effects of smoke exposure, which result in lower insulin resistance. 5

6 The Cocktail effect: In a crowd/party, we end up focusing on the conversation that matters to us and ignoring the others that do not interest us. The Chips effect: Sweet Salty Spicy Everyone likes chips but sometimes for different reasons! If we want to transfer the chips onto something else, we have to know what the consumer likes in them. 6

7 Today, we can separate smokers into two groups: Group A: Those who have been smoking a long time and who have tried to quit several times Group B: Those who have been smoking only a few years Recent studies suggest that in Group A, the hidden psychiatric comorbidity is approximately 80%. And in Group B, the hidden psychiatric comorbidity is approximately 40%. So, be on the lookout for psychiatric decompensations and the appearance of new symptoms. Do not hesitate to treat them accordingly. 7

8 We will make more progress with current smokers if the approach is customized. It is important for smokers to identify the effects of smoking that they enjoy. When quitting smoking, it will be important for them to offset the removal of the effects they enjoy with other healthy behaviours that will accomplish the same thing: Sports, reading, music, socialization, volunteering Sometimes, in addition to assisted withdrawal, an adjustment of the prescription will be useful as a transition or replacement of smoking. 8

9 Quitting smoking should be experienced as letting go of an unhealthy relationship and replacing it with a healthier one. So, the emphasis must not be placed so much on Stopping as on Starting something else Focus on the positive! 9

10 First, the process to follow; If the smoker has a preference for one tool over another, we can allow ourselves to go in the smoker s direction initially. If ineffective or not tolerated, we can look at the other tools together. The smoker will often choose a tool that worked for a friend there is no need to have a problem with that: Affinity increases over time 10

11 The simple fact of strongly suggesting to the smoker to quit increases his chances of abstaining to 4% (from 2%) Use of placebo = 10% Hypnosis, acupuncture 10% effective NRT 20% effective, so two times more than the placebo Bupropion also 20% effective Bupropion with NRT 20% effective (not better) Varenicline around 28% effective Combined NRT around 30% effective 11

12 The NRT replaces how the nicotine is delivered Benefits: Patients wean off the habit of bringing a cigarette to their mouth (except for the inhaler, vaporizer) They can control their exposure to nicotine to some extent (all NRTs) Disadvantages: They can smoke a real cigarette anyway and have its additional nicotine buzz and the reinforcing effects Side effects such as hiccups, skin irritation 12

13 Varenicline: a nicotine receptor partial agonist at the dopaminergic level Benefits: It weans the habit of bringing a cigarette to the mouth The medication STIMULATES the DA receptor while BLOCKING any pleasurable effect of the exogenous nicotine thus forcing the smoker to disconnect the learned psychological link between an unpleasant emotion and the use of tobacco to soothe it. This effect is called EXTINCTION. This is highly likely the effect that is responsible for the increased effectiveness in comparison with the other pharmacological tools. 13

14 ACTIVITY 1: Partial agonist activity Varenicline binds to the receptor, which partially stimulates the release of dopamine. ACTIVITY 2: Antagonist activity By binding to the receptor, varenicline prevents the binding of nicotine to the receptor. Through its partial agonist activity on the 42 nicotinic acetylcholine 1, 2 receptors, varenicline: would relieve the craving and the withdrawal symptoms provoked by abstinence (agonist activity); would reduce the reward and reinforcement effects of nicotine associated with the return to smoking by blocking the attachment capacity of nicotine (antagonistic activity). 1. Summary of Champix features Pfizer Ltd, Sandwich, UK Coe JW, et al. J Med Chem 2005;48: CHAMPIX Monograph, Pfizer Canada inc., May

15 Varenicline: Disadvantages: Side effects of nausea/dizziness, especially in association with doses that are too high in smokers using: Less than 15 cig/day Cigarettes with a relatively low nicotine content 15

16 Tolerated but illegal in Canada A vaporizer that heats the e-liquid, which contains a mix of propylene glycol, glycerine, nicotine (generally) and flavours. An incorrect vaping technique is common. Probably less harmful to the health than the cigarette (but caution: glycerine, carbonyls, nanoparticles, etc.) A significant increase in pulmonary infections among animals exposed to the e-cig was recently demonstrated in an animal model. This would be secondary to impairment of the immune system. (PLOS ONE February 4, 2015) 16 16

17 Not more effective than the patch for quitting. Former ex-smokers use the e-cig to have it both ways. Note that the tobacco companies acquired the e-cig companies several years ago now. Concerns: The contents of the e-liquid are in no way safe for children. Since nicotine is a cholinergic poison, we have good reason to be concerned for children and animals. In 2010 in the USA, one case per month In 2014 in the USA, 215 cases per month and growing, and 59% were children five and under In 2015 in the USA, 300 cases per month of which 70% were among children five and under December 13, 2014; first mortality = one-year-old baby Child Nicotine Poisoning Prevention Act passed in the USA in January 2016 and requires childproof packaging of e-liquid Teens are increasingly adopting the e-cig The vaporizers can be used for cannabis (and with no odour!) 17 17

18 I can't sleep anymore! Patient who was smoking one pack a day for 15 years Has made several attempts to quit with the patch This time, he decides to go with the patch once again. After only three days on the 21 mg patch, he starts having problems with insomnia. He blames the patch, after all, he still thinks that by quitting smoking he should feel better! 18

19 In addition, he feels nervous, nauseous and has slight trembling in his hands. What's happening? The patch should not make him nervous or have insomnia (especially since he does not wear it at night). 19

20 Questions to ask yourself: Does he have an anxiety disorder that is surfacing? This would be surprising since he only quit smoking a few days ago. Is it depression that is surfacing? In only a few days, this would also be surprising. And caffeine? He was drinking seven coffees a day before he quit smoking and has been drinking 12 a day since he quit smoking! The answer: Caffeinism! 20

21 What we could have done before reaching this point: Asked him about his coffee consumption Suggest that he reduce this consumption at least 10 days BEFORE quitting smoking Now, we must reassure him and ask him to cut back by 50% explaining to him that the sleep problems and nervousness will resolve themselves in a few days. 21

22 Young woman, 30 years old, athletic, lawyer, a bit of a superwoman, single Smoked 1/2 a pack a day Her physician prescribed her bupropion two weeks ago based on the normal dosing. She is complaining of insomnia, nervousness and significant restlessness. 22

23 We want to know? Caffeine?...None History of anxiety?...none History of depression?...none Indicator: her greatest fear about stopping smoking was gaining weight. Is bupropion considered a contraindication for some people? 23

24 Nervousness and irritability are increasing from day to day. She feels like she is at the breaking point. What's happening? She admits to having an eating disorder in the past. 24

25 For unknown reasons, bupropion can lead to seizures in patients who have had eating disorders, even a long time ago. The warning sign is often irritability with significant nervousness. Bupropion must be stopped immediately. All the other NRT options and varenicline are acceptable. In my experience, it is especially pleasure-resistant anorexics who react adversely in this way. 25

26 Female, 40 years old, single, accountant Smoked two packs a day Has had three episodes of major depression since age 20 and has been without medication for five years. She started the gum with patches two weeks ago: 21 mg patch and 20 pieces of gum a day 26

27 DEPRESSION Depressive mood Anxiety Irritability Fatigue Insomnia Difficulty concentrating Anhedonia Guilt Tachycardia Change in appetite WITHDRAWAL Yes Yes Yes Yes Yes Yes Yes No No, bradycardia Yes So, the two resemble one another

28 Despite the full replacement of nicotine, she has the same symptoms as when she is depressed and she is afraid. She cries, has a loss of appetite, problems sleeping, dark thoughts and even suicidal thoughts Her physician is not available for a month. What to do? 28

29 She says she avoided Champix because she thought it might make her depressed, but it has happened anyway! Any medication or alternative method that separates smokers from their cigarettes results in a loss of the MAOI effect for the smoker! So if she has been unwittingly self-medicating a substantive level of depression, still present but hidden, for a long time, this can come back full force when the MAOI effect is removed due to the cessation of smoking! 29

30 The quickest solution is to discontinue the smoking cessation process! She must stop quitting! Studies show that everything returns to normal in hours!!! In future, an antidepressant medication would need to be prescribed in therapeutic doses for at least three months before another attempt to quit smoking. During the next attempt to quit, I suggest an open prescription that allows the patient to increase the doses of her antidepressant as needed throughout the quitting process. 30

31 Effects of varenicline on smoking cessation in adults with stably-treated current or past major depression: a randomized trial. Ann Intern Med Sep 17;159(6): doi: / Anthenelli RM, Morris C, Ramey TS, Dubrava SJ, Tsilkos K, Russ C, Yunis C. Purpose: Assess abstinence from smoking and the change in mood and anxiety in smokers with depression or history of depression treated with varenicline versus placebo Findings: There were no clinically significant differences between the groups regarding suicidal ideation or behaviour and no aggravation of depression or anxiety in the two groups. The most common side effect was nausea (varenicline, 27.0%; placebo, 10.4%). Two participants in the varenicline group died in the non-treatment phase. Conclusion: Varenicline increased abstinence among smokers with a history of depression in active treatment and those who had a previous history of depression without exacerbating the depression or the anxiety. N.B. Not registered according to the official monograph 31 31

32 Lancet, April 22, 2016 Ordered by the FDA in the USA Comparison of the safety and efficacy of varenicline, bupropion and the patches among patients with and without psychiatric disorders Double-blind and randomized with placebo control (4,000 patients/4 groups) Four major conclusions: 1. No significant difference in adverse psychiatric events among patients who used varenicline, bupropion and patches 2. Varenicline was more effective (RR 3.61) than the placebo, the patch (RR 1.68) and bupropion (RR 1.75) 3. Bupropion was superior to the placebo (RR 2.07) 4. The patch was superior to the placebo (RR 2.15) Anthenelli et al., The Lancet, April 22,

33 Male, 35 years old, smoker since age 15, first cigarette upon waking (-30 minutes) Varenicline is prescribed to him as follows: 0.5 mg once a day for three days 0.5 mg twice a day for four days 1 mg twice a day for 11 weeks After six days, he notices that he has become nauseous and dizzy and that this is getting worse each day. 33

34 On the questionnaire: He takes no other medication. He is taking his tablets twice a day every hours. As permitted, he is smoking about 12 cigarettes a day as usual and is enjoying them less and less. He had reduced his coffee intake by 50% as suggested. What's happening? 34

35 He is INTOXICATED by the nicotinic stimulation! Note that the dose of 1 mg twice a day is the average dose for a smoker who smokes one pack a day. He smokes his first cigarette very early in the morning but only smokes 12 a day. He merely needs to decrease the dose to feel significantly better. Note that some brands are quite low in nicotine and that even if smokers smoke a pack a day, they can feel intoxicated! 35

36 1. One patch two patches Patch and gum or lozenge or inhaler 2. Avoid withdrawal stages that correspond with the premenstrual week, especially if it is difficult. 36

37 3 Patients must develop other activities and pleasures to replace the effects they are seeking from smoking. To guide them, simply ask: So: What does that do for you? 4. Keep in mind that in the current population of smokers ANY METHOD used to help the smoker quit smoking can result in the emergence of a potentially significant psychiatric comorbidity. 37

38 5. Idem for the Coumadin watch the NRTs as in induction of anticoagulation. 6. Do not be afraid to treat with NRT or Champix for more than weeks. 7. Soon, for certain patients, we should consider maintenance on NRT. John Sader MD, ASAM certified ABAM Diplomate,

39 Textbook: Helping the Hard-core Smoker: A Clinician s Guide By Daniel F. Seidman, Lirio S. Covey Psychology Press, pages C&printsec=frontcover&hl=fr&source=gbs_ge_su mmary_r&cad=0#v=onepage&q&f=false EAGLES, Anthenelli et al., The Lancet, April 2016 Reduce to Quit built based on Ebbert et al., JAMA 2015 Gonzales et al., Retreatment with varenicline, Clin. Pharm. and Therapeutics, June 2014 John Sader MD, ASAM certified ABAM Diplomate,