1. Tobacco Use and Depression: Myths or Realities Lirio S. Covey, Ph.D. Columbia University New York State Psychiatric Institute

2.  Substantial co-morbidity between mental illness and nicotine dependence  Multiple mental disorders are involved: Depression (Unipolar, bipolar) Anxiety disorders (GAD, phobias, OCD, PTSD) Alcohol and drug dependence Schizophrenia Antisocial personality disorder Conduct disorder and ADHD

3. Prevalence of smoking: Psychiatric outpatients and population–based controls, Hughes et al, 1986

4. Early clinical studies: USA Author, yrSampleDiagnoses Hughes, 1986Mental clinic Outpatients vs community Bi-polar disorder, Major Depression, Anxiety, Schizophrenia Glassman, 1988 Smoking cessation pts Past Major Depression Hall, 1989Smoking cessation pts Past Major Depression

5. Epidemiological studies: USA Author, yrNLifetime SmokingQuit Rate Glassman 1990 3213 adults MDD, Alcohol Ab/Dep, Anxiety MDD Breslau 1991 1007 Adults 21-30 yrs MDD, Alcohol /drug Dep, Anxiety ---------- Covey 1993 2980 adults MDD (males), Alcohol/drug Dep, GAD Recurr MDD (f) GAD (m) Lasser 2000 4411 adults Alcohol/drug, Depression, Anxiety, ASP, Psychoses Alcohol/drug, GAD, Curr MD

6. Eversmoking by MDD hx and gender St. Louis ECA (n=3213) % p<.001 Glassman, et al, JAMA, 1990

7. Odds ratios for psychiatric diagnoses by nicotine dependence,1200 adults, 21-30 yrs MDDAnxiety Substance Dep Breslau et al, 1992

8. Prevalence of Current Smoking Lasser, JAMA, 2000 %

9. Smoking status and psychiatric lifetime diagnosis – Odds Ratios relative to never smokers (Germany) N=913, Lubeck, Germany John U et al, 2004, Drug Alc Dependence P<0.001 P<0.05

10. Prevalence of current smoking according to diagnosis: in-patient and out-patients, Paris, France Poirier M, et al, 2002, Prog in Neuro-Psychopharm Biol Psychiatry General Substance Schizophrenia Anxiety Mood Population

11. Association between MDD and Tobacco Use. What Else Do We Know?

12.  Significant association between MDD and tobacco use. Observed in multiple studies, in clinical and community samples, across age groups, several nationalities.

13.  Smokers with MDD history have more withdrawal symptoms.  Seen in clinical and community based studies.

14. Nicotine withdrawal symptoms: Intensity during Week 1 after quit day p<.05 p<.0 1 craving irritability anxiety restless- appetite difficulty depressed ness increase concentr mood Covey et al, 1990

15. Nicotine withdrawal symptoms: Frequency during Week 1 after quit day. craving irritability anxiety restless- appetite concentr depressive ness increase difficulty mood p<.03 Covey et al, 1990

16. Nicotine withdrawal symptoms, MDD, and Anxiety, Breslau et al, AJPsychiatry1992 Feel depressed Drowsy Trouble Decreased Concentrating Heart Rate

17.  Does smoking cessation provoke new MDD?

18. New major depression within 3 months of completing a 10-week cessation program % (n=91) (n=25) (n=10) 2 % 16 % 30 % x 2 =14.19, df=2, p<.001 Covey et al, 1997

19. Effect of cessation on new MDD, Glassman et al, 2001

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

21. Incidence of MDD after Cessation Treatment Kahler et al, J Ab Psychol, 2002 Somewhat more new depression episodes among abstainers, but the observation was not statistically significant (RR =.53, p =.18). Women = 59.8%Not smoking - 56 Age = 45.1Smoking - 121 Race = 97% White Education = 14.5 yrs.

22.  Does history of MDD influence cessation?

23. Quit rates by major depression hx among subjects who received placebo (n=38) % Glassman et al, JAMA, 1988

24. Quit rates by major depression hx Health Education Therapy % Hall et al, 1991

25. Cessation rate by MDD hx and gender in the St. Louis ECA (n=1873) % p<.001 Glassman, Helzer, Covey et al, 1990

26. Figure 1. Effect size estimates for short-term abstinence (≤ 3 months) weighted by sample sizes. Hitsman et al, JCCP, 2003

27. Figure 2. Effect size estimates for long-term abstinence (≥ 6 months) weighted by sample sizes. Hitsman et al, JCCP, 2003

28. Odds ratios: effect of past Major Depression versus no MDD on smoking cessation PlaceboActive Short-term (< 3 Mos) 0.76 (0.5-1.2) 0.87 (0.7-1.1) Long-term (>3 Mos) 0.75 (0.4-1.3) 0.94 (0.7-1.2) Covey et al, in press, Nic Tob Research

29. Combined quit rates in 8 studies on effect of past MDD on smoking cessation Data from Covey et al, in press, NTR

30. Influence of Depression History on Acute Cessation (Week 9) by Treatment Smith, Nicotine & Tobacco Research 2003

31. Influence of Depression History on One Year Cessation (Week 52) by Treatment Smith, Nicotine & Tobacco Research 2003

32. Does depression lower the quit rate? YES. Cohort 1 (1952-1970) % Quit % Quit

33. Does depression lower the quit rate? YES. Cohort 2 (1970-1992) % Quit % Quit

34.  Does history of MDD influence cessation?  Meta-analysis studies have not supported a significant effect of history of MDD on smoking cessation.  Data from a prospective study (Murphy et al, 2004) are not supportive of a negative association.  Further work is needed to understand the reasons for the inconsistencies among individual studies.

35. Could variations in the nature of major depression, not simply presence or absence of major depression, explain the inconsistent findings regarding its effect on cessation?

36. Some variations in features of major depression Frequency of episodes –Single episode –Multiple episodes (2 or more) Age of onset Level of depressed mood, anxiety, or other negative psychological symptom Genetic variations

37. Single versus Recurrent MDD: Quit rates among smokers who received standard cessation counseling Haas et al, 2004, JCCP

38. Single versus recurrent MDD: End-of-treatment (short-term) quit rates among smokers who received placebo or clonidine Covey et al, NTR, in press

39. Since smokers with single or recurrent MDD manifest different cessation outcomes, are there differences between individuals with recurrent and single type of major depression that influence nicotine dependence and smoking cessation outcome?

40. Summary: Depression and Smoking  Significant association observed among multiple studies.  Smokers with MDD history have worse withdrawal symptoms.  Whether smoking cessation provokes new MDD is unclear.  Does history of MDD influence cessation?  Meta-analyses suggest no overall influence.  There is a need to examine variations in the nature of major depressive disorder. For example, studies comparing smokers with Single or Recurrent MDD may provide an answer.