1. Smoking Cessation in Women: Michele D. Levine, Ph.D Pittsburgh Mind-Body Center Summer Institute June 6, 2007

2. Overview Women and smoking Women and smoking Sex differences in smoking Sex differences in smoking Women's issues in cessation treatment Women's issues in cessation treatment

3. Women and Smoking 22% of American women smoke 22% of American women smoke 30% of young women report smoking within the past month 30% of young women report smoking within the past month

4. Women and Smoking The rate of smoking decline has been slower among women than men The rate of smoking decline has been slower among women than men Young women are more likely to initiate smoking than young men Young women are more likely to initiate smoking than young men Recent evidence suggests that women have greater difficulty quitting smoking than men do Recent evidence suggests that women have greater difficulty quitting smoking than men do

5. Women and Smoking There are many negative health consequences of smoking There are many negative health consequences of smoking Women suffer additional health consequences that do not affect men, and may be at higher risk for some smoking-related diseases Women suffer additional health consequences that do not affect men, and may be at higher risk for some smoking-related diseases

6. Here’s the Good News

7. Background 50% of ever smokers have now quit; and many smokers quit each year 50% of ever smokers have now quit; and many smokers quit each year Although many smokers quit with minimal intervention, clinic-based smoking cessation treatment accounts for approximately 10% of cessation Although many smokers quit with minimal intervention, clinic-based smoking cessation treatment accounts for approximately 10% of cessation

8. Sex Differences in Response to Nicotine

9. Women may be less responsive to reinforcing effects of nicotine Less self-administration of nicotine vs. placebo (Perkins et al. 1996, 1997; West et al. 2001) Less self-administration of nicotine vs. placebo (Perkins et al. 1996, 1997; West et al. 2001) Smaller difference in nicotine spray choice following nicotine patch pre-treatment (Perkins et al. 2001) Smaller difference in nicotine spray choice following nicotine patch pre-treatment (Perkins et al. 2001) Smaller difference in rewarding and reinforcing effects due to cigarette nicotine dose (Perkins et al. 2002) Smaller difference in rewarding and reinforcing effects due to cigarette nicotine dose (Perkins et al. 2002)

10. * Perkins et al. (1996) Exper Clin Psychopharmacology 4:157-165 Ad lib Spray Use in Men and Women

11. Why do women smoke?

12. Women obtain greater reinforcement than men from non-nicotine influences on smoking

13. Women may be more responsive to non-nicotine aspects of smoking Greater decrease in smoking reinforcement following removal of non-nicotine smoking stimuli (Perkins et al., 1994; 2001) Greater decrease in smoking reinforcement following removal of non-nicotine smoking stimuli (Perkins et al., 1994; 2001) More responsive to sensorimotor effects of smoking (Carpenter et al. 2005) More responsive to sensorimotor effects of smoking (Carpenter et al. 2005)

14. Clinical Implications If women’s smoking is less responsive to nicotine, then they should benefit less from nicotine replacement therapy (NRT) when trying to quit If women’s smoking is less responsive to nicotine, then they should benefit less from nicotine replacement therapy (NRT) when trying to quit If women’s smoking is more responsive to non- nicotine factors (e.g. cues), then they should benefit more from other approaches

15. Men and women (n=504) randomly assigned to one of four active NRT products to use in quit attempt West R, et al.,. (2001) Psychopharmacology, 153: 225-230 Sex Differences in Outcomes from NRT

16. Summary of Sex Differences Women appear to be less responsive to nicotine than men Women appear to obtain more reinforcement from the non-nicotine aspects of smoking Women are less responsive than men to most forms of nicotine replacement therapy Women may benefit from treatment approaches that address other factors or specific “women’s issues”

17. Women’s Issues in Cessation Treatment Pregnancy Pregnancy Postpartum Postpartum Weight Concerns Weight Concerns

18. Postpartum Smoking

19. An estimated 65% of women who quit during pregnancy will resume smoking by six months postpartum An estimated 65% of women who quit during pregnancy will resume smoking by six months postpartum 25% of women will relapse in the first month postpartum 25% of women will relapse in the first month postpartum There are numerous health consequences of postpartum smoking for both mother and child There are numerous health consequences of postpartum smoking for both mother and child

20. Postpartum Smoking Relapse and Mood The experience of depressive symptoms and perceived stress are common during the postpartum period The experience of depressive symptoms and perceived stress are common during the postpartum period Concerns about shape and weight are common during the postpartum period Concerns about shape and weight are common during the postpartum period Depressive symptoms, stress and weight concerns have been related to smoking relapse Depressive symptoms, stress and weight concerns have been related to smoking relapse

21. Model of Postpartum Relapse Postpartum Period MOOD CHANGES INCREASE IN WEIGHT CONCERNS Increased Vulnerability Smoking Relapse Pregnancy Smoking Cessation  Postpartum hormonal changes  Baby blues  Stresses of young motherhood  Changes in role and self perception  Retention of pregnancy weight gain  Desire to return to pre-pregnancy weight  Change in perception of body shape Levine MD & Marcus, MD (2004), Archives of Women’s Mental Health, 7, 155-166.

22. Motivation for Postpartum Abstinence Women who relapse postpartum differ in reasons for quitting during pregnancy from those who remain abstinent Women who relapse postpartum differ in reasons for quitting during pregnancy from those who remain abstinent Motivation for the maintenance of smoking abstinence after childbirth may be an important, and potentially modifiable, predictor of women’s relapse to smoking postpartum Motivation for the maintenance of smoking abstinence after childbirth may be an important, and potentially modifiable, predictor of women’s relapse to smoking postpartum

23. Method Pregnant women (N = 119) who had recently quit smoking were recruited from obstetrical clinics Pregnant women (N = 119) who had recently quit smoking were recruited from obstetrical clinics Women completed assessments of motivation, depressive symptoms, perceived stress, and weight concerns in the third trimester of pregnancy Women completed assessments of motivation, depressive symptoms, perceived stress, and weight concerns in the third trimester of pregnancy

24. Results 65.6% of pregnant women were highly motivated to remain quit postpartum 65.6% of pregnant women were highly motivated to remain quit postpartum 74.0% felt confident in their ability to do so 74.0% felt confident in their ability to do so Self-efficacy for weight management was associated with motivation to maintain abstinence postpartum after controlling for mood and other variables that have been associated with postpartum smoking Self-efficacy for weight management was associated with motivation to maintain abstinence postpartum after controlling for mood and other variables that have been associated with postpartum smoking Levine MD, Marcus MD, et al., (2006). Weight concerns affect motivation to remain abstinent from smoking postpartum. Annals of Behavioral Medicine.

25. Predictors of postpartum relapse Among women who have completed the three- month postpartum assessments, 45% (36/80) have relapsed Among women who have completed the three- month postpartum assessments, 45% (36/80) have relapsed Relapse occurred 28.5 (±29.9) days after delivery Relapse occurred 28.5 (±29.9) days after delivery

26. Survival Curves by Weight Self-Efficacy 0255075100125150175 Number of days to relapse 0.0 0.2 0.4 0.6 0.8 1.0 Decreased ( n = 27) 0255075100125150175 Number of days to relapse 0.0 0.2 0.4 0.6 0.8 1.0 Increased (n = 16)

27. Weight Concerns and Smoking

28. Concerns about shape and weight are prevalent among women in general Concerns about shape and weight are prevalent among women in general For women smokers, these normative concerns may promote or maintain smoking behaviors For women smokers, these normative concerns may promote or maintain smoking behaviors

32. Smoking and Weight Concerns Individuals gain between 8-15 pounds upon quitting smoking Individuals gain between 8-15 pounds upon quitting smoking Women are more likely to be concerned about postcessation weight gain than are men Women are more likely to be concerned about postcessation weight gain than are men Women gain more weight than do men after quitting Women gain more weight than do men after quitting

33. Weight-concerned Smokers Weight-concerned women smokers gain between 10-15 pounds after quitting Weight-concerned women smokers gain between 10-15 pounds after quitting There is a considerable discrepancy between the amount of weight women expect to gain and the amount they are willing to tolerate There is a considerable discrepancy between the amount of weight women expect to gain and the amount they are willing to tolerate Expect to gain 17 lbs Expect to gain 17 lbs Less than 20% would tolerate greater than 5 lbs Less than 20% would tolerate greater than 5 lbs Levine, M.D., Perkins, K.A., & Marcus, M.D. (2001). Addictive Behaviors, 26, 749-756.

34. Weight-concerned Smokers Weight-concerned women are likelier than those without concerns to drop out of cessation treatment Weight-concerned women are likelier than those without concerns to drop out of cessation treatment Weight-concerned women have significantly poorer outcomes following a cessation attempt than do those without weight concerns Weight-concerned women have significantly poorer outcomes following a cessation attempt than do those without weight concerns

35. Weight Concerns and Smoking The addition of weight control interventions has not reliably improved smoking cessation outcomes The addition of weight control interventions has not reliably improved smoking cessation outcomes Concerns about shape and weight are prevalent among women in general Concerns about shape and weight are prevalent among women in general For smokers, maladaptive thoughts and beliefs about shape or weight may promote or maintain smoking For smokers, maladaptive thoughts and beliefs about shape or weight may promote or maintain smoking We reasoned that addressing women’s concerns about shape and weight, particularly those relating to the effects of smoking cessation, might improve cessation outcomes We reasoned that addressing women’s concerns about shape and weight, particularly those relating to the effects of smoking cessation, might improve cessation outcomes

36. The Women’s Smoking Cessation Project Research supported by NIDA DA04174 Ken Perkins, PI

37. Women’s Smoking Cessation Project The first women’s smoking cessation project was designed to compare two approaches to addressing women’s concern about postcessation weight gain The first women’s smoking cessation project was designed to compare two approaches to addressing women’s concern about postcessation weight gain We compared a cognitive behavioral program designed to reduce postcessation weight concerns and a behavioral weight control program to prevent postcessation weight gain with a standard cessation program We compared a cognitive behavioral program designed to reduce postcessation weight concerns and a behavioral weight control program to prevent postcessation weight gain with a standard cessation program Perkins, et al (2001). Cognitive-behavioral therapy to reduce weight concerns improves smoking cessation outcome in weight-concerned women. Journal of Consulting and Clinical Psychology, 69, 604-613.

38. Women’s Smoking Cessation Project All women received standard smoking cessation treatment plus one of three adjunctive treatments: All women received standard smoking cessation treatment plus one of three adjunctive treatments: 1. SOCIAL SUPPORT 2. WEIGHT CONTROL 3. WEIGHT CONCERNS (CBT)

39. SOCIAL SUPPORT ADJUNCT (Standard) Rationale: Smoking cessation alone requires considerable effort and it may be ineffective to deal with weight gain concerns at the same time Rationale: Smoking cessation alone requires considerable effort and it may be ineffective to deal with weight gain concerns at the same time Goal of Treatment: Target smoking cessation only without directly addressing weight concerns Goal of Treatment: Target smoking cessation only without directly addressing weight concerns

40. WEIGHT CONTROL ADJUNCT Rationale: Successful prevention of weight gain may help to improve cessation rates among weight concerned smokers Rationale: Successful prevention of weight gain may help to improve cessation rates among weight concerned smokers Goal of Treatment: Prevent actual weight gain by reducing calorie intake Goal of Treatment: Prevent actual weight gain by reducing calorie intake

41. WEIGHT CONCERNS ADJUNCT (CBT) Rationale: Average weight gain during smoking cessation is modest. Modifying women’s over- concern about shape and weight during smoking cessation may improve cessation rates Rationale: Average weight gain during smoking cessation is modest. Modifying women’s over- concern about shape and weight during smoking cessation may improve cessation rates Goal of Treatment: Reduce concern about weight gain and promote acceptance of modest weight gain Goal of Treatment: Reduce concern about weight gain and promote acceptance of modest weight gain

42. Weight Concerns Treatment Adapted from the cognitive behavioral treatment of eating disorders Adapted from the cognitive behavioral treatment of eating disorders Treatment Features Treatment Features Psychoeducation about smoking and weight gain Psychoeducation about smoking and weight gain Cognitive strategies to target irrational thoughts and beliefs about weight gain and smoking Cognitive strategies to target irrational thoughts and beliefs about weight gain and smoking Emphasis on moderation Emphasis on moderation

43. Smoking Cessation by Treatment Group % Abstinent Months postquit ** * * Compared to standard: ** p<.001 * p<.05

44. Weight Gain by Treatment Group Weight change (lb) Months postquit * * * ** Compared to Standard: ** p<.001 * p<.05 Weight change examined only among abstinent women only among abstinent women

45. Study 1 Conclusions A cognitive-behavioral treatment designed to reduce women’s concern about postcessation weight gain improved long-term smoking cessation outcome A cognitive-behavioral treatment designed to reduce women’s concern about postcessation weight gain improved long-term smoking cessation outcome This approach also attenuated postcessation weight gain among women who remained abstinent This approach also attenuated postcessation weight gain among women who remained abstinent

46. Study Conclusions Although the weight concerns treatment helped women who are concerned about postcessation weight gain to quit smoking, the overall cessation rates are low Although the weight concerns treatment helped women who are concerned about postcessation weight gain to quit smoking, the overall cessation rates are low Rates of abstinence decline sharply at the conclusion of treatment Rates of abstinence decline sharply at the conclusion of treatment

47. The Women’s Smoking Cessation Project II: “The Zyban Study”

48. Women’s Smoking Cessation Project II Rationale for bupropion Rationale for bupropion Nicotine replacement may be a less desirable choice for women Nicotine replacement may be a less desirable choice for women It may attenuate post cessation weight gain It may attenuate post cessation weight gain It may relieve negative mood It may relieve negative mood Thus, the goal of the current investigation was to determine whether the addition of bupropion would enhance the efficacy of our CBT for weight concerns program Thus, the goal of the current investigation was to determine whether the addition of bupropion would enhance the efficacy of our CBT for weight concerns program

49. Weight Concerns and Depression Depression history may pose a particular problem for weight-concerned women smokers Depression history may pose a particular problem for weight-concerned women smokers Weight-concerned individuals may be more likely to gain weight during episodes of depression Weight-concerned individuals may be more likely to gain weight during episodes of depression Depression history has been associated with postcessation weight gain Depression history has been associated with postcessation weight gain

50. Hypotheses 1.The addition of bupropion to CBT for weight concerns (WC) would increase cessation rates (i.e., WC+B vs WC+P) (i.e., WC+B vs WC+P) 2.The addition of CBT for weight concerns to bupropion would increase cessation rates (i.e., WC+B vs SS+B)

51. Participant Characteristics (N = 349) M(SD) Age42.0(10.1) Body Mass Index27.3(5.5) Cigarettes/Day20.7(8.4) Weight Concerns (0-100)73.2(25.8) Years Smoking25.5(5.2) Fagerstrom Nicotine Dependence5.2(2.2) Beck Depression Inventory4.7(5.4) % African American13.4 % Some College85.2

52. Study Design Overview

53. Rates of abstinence: Bupropion vs. Placebo *** p <.0001 ** p <.004 *** ** *** **

54. Hypothesis 1: Abstinence rates in WC+B vs WC+P *** ** *** *** p <.0001 ** p =.004

55. Hypothesis 2: Abstinence Rates: WC+B vs SS+B ** * † ** p =.004 * p =.05 † p =.057

56. Summary Bupropion enhanced cessation rates among women receiving a CBT treatment for weight concerns Bupropion enhanced cessation rates among women receiving a CBT treatment for weight concerns Addressing women’s concerns about postcessation weight gain enhanced smoking cessation rates in comparison to bupropion and a standard cessation program among weight concerned smokers Addressing women’s concerns about postcessation weight gain enhanced smoking cessation rates in comparison to bupropion and a standard cessation program among weight concerned smokers

57. Conclusions Cognitive behavioral treatment to ameliorate weight concerns may enhance the efficacy of bupropion Cognitive behavioral treatment to ameliorate weight concerns may enhance the efficacy of bupropion It may be that the weight attenuating effects of bupropion complement the CBT treatment It may be that the weight attenuating effects of bupropion complement the CBT treatment Treatments designed to address women’s issues may improve smoking cessation rates Treatments designed to address women’s issues may improve smoking cessation rates

58. Acknowledgments Kenneth A. Perkins, Ph.D Marsha D. Marcus, Ph.D. Nicole Beagle, M.S.W. Melissa A. Kalarchian, Ph.D. Donielle Mesko, B.A. Julie Mossing, B.A. Rebecca M. Ringham, Ph.D. Jennifer Slane, B.A. Meghan Wisinski, B.A.. Research supported by NIH Grants: Pilot funding from Pittsburgh Mind Body Center Pilot funding from Pittsburgh Mind Body Center R01 DA04174 (PI: Marcus, Co-PI: Perkins) R01 DA04174 (PI: Marcus, Co-PI: Perkins) K01 DA15396 (PI: Levine) K01 DA15396 (PI: Levine) GlaxoSmithKline provided study medication

59. THANK YOU!