1. Depression and smoking: Treatments Lirio S. Covey, Ph.D. Columbia University New York State Psychiatric Institute New York, NY, U.S.A.

2. Depression is a risk factor for: Initiation of smoking Progression to dependence Failure to quit smoking Intense withdrawal symptoms Post-cessation depression

3. Initiation of smoking Smokers with depression are more likely to become smokers

4. Progression from experimentation to dependence In data from young adults, there is a higher likelihood of smoking developing to dependence among those with MDD.

5. Failure to stop smoking There has been some inconsistency in observations of effect of past MDD on smoking cessation.

6. Increased withdrawal symptoms Smokers with past major depression experience higher levels of withdrawal symptoms.

7. Nicotine withdrawal symptoms: intensity at week 1 after quit day p<.05 p<.0 1 Covey et al, Comp Psychiatry,1991 cravin g irritable anxiou s restles s appetit e concentr depresse d

8. Smokers with pasts depression are at risk of new MDD following a smoking cessation attempt The risk of a new episode may be independent of abstinence status. Simply making the effort may provoke the new depressive episode.

9. Incidence of major depressive episodes in 3-month follow-up of 126 abstinent smokers p=<.001, Covey et al, Am J Psychiatry, 1997

10. Incidence of major depressive episodes in 12 month clinical trial of 304 smokers Tsoh et al, Am J Psychiatry, 2000

11. Observations from an ongoing Smoking cessation trial 2001 – 2005

12. “Maintenance treatment for prevention of smoking relapse” Support: NIDA RO1#13490 Medication support from GSK

13. Study Design Aim: Efficacy of extended pharmacotherapy 8-week Open Rx 16-wk D/Blind Maintenance Zyban Nic patch Counseling Pbo + Pbo Pbo + Nic Gum Zyban + Pbo Gum Zyban + Nic Gum Rx-free Follow-up 9th mo. 12th mo. Phase I Phase II Phase III Successes

14. Phase 1: 8-week Open Rx Zyban-SR Nicotine patch Individual Counseling

15. STOP SMOKING and STAY QUIT! (212) 543-5905 Take part in research studies at no cost to you. Zyban, Nicotine Patch, Medical Exam, Counseling The Smoking Cessation Clinic at Columbia University Se requiere leer ingles.

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17. Study Sample: n= 588 Mean age = 41 years (s.d.=11) 52% Males, 48% Females 62% Caucasian 21% African-American 12% Hispanic 5% Asian 39% Married/with mate

18. Socio-demographic characteristics College - 51%, Graduate School – 28% Professional/Executive – 34% Technical/Administrative/Clerical – 45% Blue-collar – 21% < $29,000 – 23% $30,000-$50,000 – 37% $51,000 > - 40%

19. Smoking exposure at baseline Cigarettes smoked per day21.8 (14.1) Age first smoked 15.3( 3.7) Age smoked regularly17.5 (3.9) Carbon Monoxide 16.3 (8.5) Serum Cotinine 254.5 (121.1) Cotinine/cigarette ratio 13.2 (11.8) Fagerstrom Test Nicotine Dependence 5.2 (2.0)

20. Psychiatric History 21% Past Major Depression 14% Single 7% Recurrent 14% Past Alcohol Dependence

21. Dependence, and tobacco intake according to frequency of MDD No MDDS-MDDR-MDD Mean (s.d.)Mean (s.d.)Mean (s.d.) p Fagerstrom5.2 (2.1)5.2 (1.8)5.6 (1.8)N.S. Cigarettes/day21.5 (11.1) 24.9 (26.2)20.0 (7.1) 0.09 Cotinine259 (124)247 (110)221 ( 89)N.S. Times quit 3.5 (2.5) 3.9 (3.4) 4.3 (4.3) N.S. Age began smoking17.3 (4.1)17.4 (6.9)16.4 (5.8) N.S.

22. Smokers with depression are NOT so different from smokers without depression on smoking characteristics:

23. Psychological and Personality Variables by MDD history All p values = 0.000

24. MDD history and age of MDD onset S-MDDR-MDD Mean (s.d.)Mean (s.d.) p Age, years 33.4 (11.2)23.0 ( 9.6) 0.000

25. Other reported differences according to presence or absence of MDD history Less successful early quitting Higher rate of relapse to smoking

26. Implications for treatment Applying the 5 A’s. Ask Advice Assess Assist Arrange

27. ASK Among patients who are smokers, probe for depressive symptoms or depressive disorder (past or present) Among patients who present with depression, ask about smoking status

28. ADVISE For smokers who present with depression, in clear, strong, and personalized manner, give advise regarding harmful consequences of tobacco and benefits of stopping smoking.

29. ASSESS Depression Status Level of nicotine dependence Attitudes about stopping smoking

30. ASSESS Depression Status Current or past Single or recurrent (index of severity) Level of negative affect

31. ASSESS Level of nicotine dependence Fagerstrom Test for Nicotine Dependence DSM-IV nicotine dependence criteria Number of cigarettes smoked daily Carbon monoxide level Cotinine level

32. ASSESS Attitudes about stopping smoking Willing to stop? Motivation level? Confidence in ability to succeed

33. ASSIST Clinical support Knowledge and access to smoking cessation aids Self-help materials

34. ASSIST Clinical support Smokers with recurrent MDD are responsive to intensive counseling E.g. Cognitive behavioral therapy

35. ASSIST Nicotine gum (4 mg) reduced depressed mood during withdrawal Nicotine gum (4 mg) increased abstinence rate among smokers with MD

36. ASSIST Bupropion (Zyban) and Nortriptyline showed same short-term results regardless of MDD history Smith et al, 2004 - Zyban helpful for female smokers and those with MD history

37. EOT (Week 9) abstinence rates for 4 treatment groups by history of depression

38. ARRANGE Follow-up Prevent relapse to smoking - negative affect increases risk of smoking relapse Prevent relapse to depression - smokers with past MDD are at risk of experiencing a recurrence of depression

39. ARRANGE Schedule followup contact, preferably within first week after the quit date. Congratulate success View lapse as learning experience Anticipate challenges Assess medications Consider referral

40. Implications for cessation treatment Smokers with depression will: require more intensive interventions What works? Higher Nicotine Replacement dose Bupropion or Nortriptyline Clonidine Greater intensity of clinical support/counseling Longer follow-up/monitoring to identify psychiatric sequelae

41. Other Questions, no empirical evidence How to help depressed smokers who are currently depressed. How to help smokers with depression history being maintained on antidepressants.

42. Depression and smoking: Challenge to Psychiatry, General Medicine, and Public Health Depression-prone smokers require intensive treatments. In addition to pharmacotherapy: Psychologically trained therapists More frequent contacts Longer duration of treatment Are these costly treatments worthwhile?