Pharmacological Treatments for Smoking Cessation

1. Pharmacological Treatments for Smoking Cessation Allen Y. Masry, MD Assistant Professor �Addiction Psychiatrist Department of Psychiatry UMass Memorial Medical Center/ UMass Medical School 1

2. Quick FactsMental Illnesses & Tobacco � 7.1% of the U.S. population has a psychiatric illness; however, this population consumes over 34.2% of all cigarettes. (Grant et al., 2004) � In the U.S., persons with mental illnesses represent an estimated 44.3% of the tobacco market and are dependent at rates 2-3 x�s the general population. (Grant et al., 2004) � Smoking quit rates for individuals with psychiatric illness are NOT significantly lower than the general population. (el-Guebaly et al., 2002) 2

3. Session goals: Some info on smoking and psychotropics Review of available medications for Smoking Cessation, both nicotine and non- nicotine. Role of medications in smoking cessation and maintenance of smoking. Review Smoking and SMI 3

4. 4

5. Ranking of nicotine in relation to other drugs in terms of addiction 5

6. Tobacco Effects on Psychiatric Medication Blood Levels Smoking induces the P450�s 1A2 isoenzyme secondary to the polynuclear aromatic hydrocarbons Smoking increases the metabolism of some medications Haldol, Prolixin, Olanzapine, Clozapine, Mellaril, Thorazine, etc Caffeine is metabolized through 1A2 CHECK for medication SE or relapse to mental illness with changes in smoking status Nicotine does not change medication blood levels (2D6) NRT doesn�t affect medication blood levels Nicotine may modulate cognition, psychiatric symptoms, and medication side effects 6

7. Nicotine Replacement Therapy (NRT) -Patch (OTC) -Gum (OTC) -Lozenge (OTC) -Oral Inhaler (Rx) -Nasal Spray (Rx) Non-Nicotine Medications -Varenicline (Chantix, Rx) -Bupropion Hydrochloride (Rx) First-Line Medications 7 Medications used in tobacco dependence treatment are classified as first-line and second-line medications depending on how safe and effective they are. Except for sustained release Bupropion all medications classified as first-line replace the mode of nicotine delivery, so they are called nicotine replacement therapy.Medications used in tobacco dependence treatment are classified as first-line and second-line medications depending on how safe and effective they are. Except for sustained release Bupropion all medications classified as first-line replace the mode of nicotine delivery, so they are called nicotine replacement therapy.

8. 8

9. Reasons for Using NRT It works: roughly doubling success rates. It helps the person feel more comfortable (treats nicotine withdrawal syndrome). It is very safe: the person is getting �clean� nicotine instead of �dirty� nicotine with 4000 plus chemicals. 9

10. Nicotine withdrawal Withdrawal syndrome is a collection of signs and symptoms caused by abstinence Nicotine or cigarette withdrawal? Nicotine replacement reduces severity of withdrawal symptoms 10

11. Sign of Nicotine Toxicity Extremely RARE IN SMOKERS & thus even more rare in NRT use. Nausea and/or vomiting Sweating Vertigo and/or Light-headedness Tremors Confusion Weakness Racing heart 11 ..

12. Nicotine Patch Dosing: < 10 cigs/day: 14 mg patch = 10 cigs/day: 21 mg patch Length of Treatment: Up to 12 weeks (PDR) Use: Apply to clean skin area (upper trunk/ arms) 24 or 16 hour dosing, try 24 to dec. morning craving Watch for nightmares Given with or without taper 12

13. Nicotine Gum Dosing: 2mg < 25 cigarettes/day 4mg > 25 cigarettes/day Length of Treatment: 8-10 weeks (PDR) 13

14. 14

15. Nicotine Lozenge Use: Allow to dissolve (Don�t Chew but Suck like a hard candy.) Pros: Flexible dosing (Up to 20 lozenges/ day) More discreet than gum; Keep mouth busy; OTC; Cons: Need to use correctly (don�t chew, suck) May cause insomnia, some nausea, hiccups, heartburn, coughing 15

16. Nicotine Nasal Spray Dosing: 1-2 doses per hour 1 does = 2 spays (1 spray/nostril) Use enough to control withdrawal symptoms Length of Treatment: 3-6 months weeks (PDR) 16

17. Nicotine Nasal Spray Use: Spray (don�t sniff, swallow, or inhale) PRN or fixed-schedule (1-2 doses/hour) Pros: Rapid delivery though nasal mucosa Flexible dosing (up to 40 doses) Cons: Nasal irritation, rhinitis, coughing, & watering eyes. Some dependence liability Rx needed 17

18. Nicotine Medications Use high enough dose Scheduled better than PRN Use long enough time period Can be combined with Bupropion Don�t combine with Varenicline Can be combined with eachother Have very few contraindications Have no drug-drug interactions 18

19. Efficacy of NRT medications 19

20. 20

21. Some strategies Recommended doses of nicotine replacement therapy are inadequate for many smokers In heavy smokers, under dosing may limit the effectiveness of patch Patch plus Gum Improves abstinence rates (Kornitzer 1995, Puska 1995) Decreased withdrawal (Fagerstrom 1993) Well tolerated UMass uses up to 42mg patch or patch plus GUM 21

22. 22

23. Smoking with NRT Relatively safe Harm Reduction Less reinforcing effects Not a distraction from quit attempts (Benowitz 1997, Hartman 1991, Slade 1995) 23

24. Concern about this is not supported by data. Joseph took a high risk cardiac group and put them on patch or placebo. 49% with active angina 40% with history of heart attack 35% with history of cardiac bypass No increase in cardiac events for the patient group 21% of the patients were not smoking at the end vs 9% of the placebo group. Jiminez-Ruiz put severe COPD patients on nicotine gum Most patients continued to smoke, though less. No adverse events attributed to nicotine. COPD (chronic obstructive pulmonary disease) got better (Joseph AM. NEJM 335:1792-8, 1996 & Jiminez-Ruiz. Respiration 69:452-6, 2002) Slide copied from OASAS. Smoking and NRT: IS THAT SAFE? 24

25. Conclusions Nicotine Replacement Therapy is being provided to assist tobacco users to become tobacco free. NRT is not a treatment in itself, but is intended to complement the other assessments and treatments provided. NRT works by reducing craving and withdrawal severity, enabling the patient to feel comfortable and able to concentrate on other psychosocial treatments. 25

26. Non-Nicotine Pharmacotherapy First-line non-nicotine medications -Bupropion (Zyban/Wellbutrin)** -Varenicline (Chantix)** Others (nortriptyline, clonidine) **FDA Approved for smoking cessation 26

27. Bupropion Hydrochloride Dopamine and norepinephrine (noradrenaline) effects Reduces cravings, withdrawal Improved abstinence rates in trials Less weight gain while using (Need to gain 100 pounds to diminish health benefit) Start 7-10 days prior to quit date Continue 7-12 weeks or longer ( > 6 months) 27

28. Bupropion Precautions Contraindicated: seizure disorder, eating disorders, electrolyte abnormalities, MAO use OK with SSRIs NOT dangerous to smoke while taking Monitor blood pressure Side effects: Insomnia (40%) 2nd dose early evening helps Dry mouth Headaches Rash 28

29. Bupropion Efficacy 29

30. Varenicline (Chantix) Action at ?4?2 nicotine receptor Partial agonist/antagonist Releases lower amounts of dopamine into brain than smoke Reduces withdrawal Not as addictive as smoke Blocks nicotine from binding to receptor Prevents reward of smoking

31. Varenicline (Chantix) Action at ?4?2 nicotine receptor Partial agonist/antagonist Releases lower amounts of dopamine into brain than smoke Reduces withdrawal Not as addictive as smoke Blocks nicotine from binding to receptor Prevents reward of smoking 31

32. Dosing Titrate dose from 0.5 mg daily to twice daily to 1 mg twice daily over 1 week Abstinence rates better vs. placebo and Bupropion at 1 year Optimal duration 12-24 weeks Most common side effect is nausea 32

33. Abstinence by medication use 33

34. Serious Mental Illness Reduced Cessation -Schizophrenia/Schizoaffective disorder -Bipolar disorder -PTSD -Alcohol use disorder 34

35. Smoking and Schizophrenia High prevalence of smoking (about 90%, OR = 5.9) Highly nicotine dependent (FTND = 7 or higher) Nicotine produces cognitive or other benefit Smoking ameliorates medication side effects (e.g., lower rates of neuroleptic-induced Parkinsonism) 35

36. Smoking and Schizophrenia (Continued) Smokers with schizophrenia take in more nicotine per cigarette than smokers without this disorder Higher levels of positive symptoms and decreased negative symptoms Ad libitum smoking increases after initiation of haloperidol SCZ tend to smoke less on clozapine 36

37. Neurobiology of Smoking and Schizophrenia Decreased low affinity and high affinity nAChRs Abnormal P50 responses are normalized Improved Spontaneous Pursuit Eye Movement and decreased Saccades with nicotine Improved cognition and attention 37

38. Smoking & Bipolar Disorder High prevalence of smoking: 61-80% Findings are inconsistent regarding the prevalence of smoking between bipolar disorder with and without psychotic features Bupropion is contraindicated Quit rates are comparable to general population and durable Quit rates enhanced with CBT 38

39. Smoking and Depression The prevalence of smoking: 37-60% Leads to more severe nicotine withdrawal symptoms - High risk for relapse in first week - Female > Male 30% risk of relapse to MDE after quitting if past history present Depressed smokers have higher suicide rates than depressed nonsmokers (Bruce, 1994; Lohr, 1992; Yassa, 1987) 39

40. Link Between MDD and Smoking 40

41. Smoking and Depression (Continued) NRT alone insufficient treatment for smokers with current and/or past MDD Combining NRT with non-NRT pharmacotherapy appear to be promising for smokers with depression (Ait-Daoud et al., 2006) CBT that emphasizes group cohesion and social support appears to be particularly effective for depressed smokers with or without alcohol dependence 41

42. Smoking and Anxiety D/O The prevalence of smoking: About 35-50% Smokers have greater anxiety and panic symptoms than non-smokers Heavy smoking in adolescent is associated with higher risk of developing Agoraphobia, GAD, and Panic Disorder PTSD: Increased risk for relapse in first two weeks of quit attempt Increased the risk of smoking and nicotine dependence lower rates for quitting smoking & remission from nicotine dependence Stopping smoking not associated with worsening of PTSD Bupropion tolerated and effective treatment 42

43. SSRIs and Smokers with Anxiety Disorder No benefit for smoking cessation Can reduce likelihood of emergent anxiety and panic during quit attempt Bupropion is not appropriate as only medication Can be combined with NRT/Bupuropion Can be combined with varnicline 43

44. Smoking and Alcohol Dependence High prevalence of smoking: 80-95% Two studies reporting similar outcomes of NRT in alcoholics compared with non-alcoholics (e.g., Grant et al., Alcohol, 2007) Tobacco dependence treatment does not cause abstinent alcoholics to relapse (Hughes & Callas, 2003) Smoking cessation reduces the risk of alcohol relapse (Sobell et al., 1995) 44

45. Smoking and Alcohol Dependence (Continued) Bupropion added to nicotine patch did not improve smoking outcomes Topiramate group was significantly more likely to become abstinent (OR = 4.46) compared with placebo group (Johnson et al., 2003) Topiramate group reported more weight loss compared with placebo group (44% vs. 18%) 45

46. 46

47. Benefits of Treating Tobacco Dependence in Mental Healthcare Settings Emerging evidence shows that morbidity is reduced May enhance abstinence from other substances Reduced financial burden Increased self-confidence 47

48. Conclusions Pharmacotherapy works and is relatively safe Many options now available Patients should be given accurate expectations (no magic bullet) 48