Tobacco Use and Depression: Myths or Realities

Lirio S. Covey, Ph.D.Columbia University

New York State Psychiatric Institute

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

Prevalence of smoking: Psychiatric outpatients and population–based controls,

Hughes et al, 1986

0102030405060708090

Schiz Mania MDD Anxiety Controls

Early clinical studies: USA

Author, yr Sample DiagnosesHughes, 1986 Mental clinic

Outpatients vs community

Bi-polar disorder, Major Depression, Anxiety, Schizophrenia

Glassman, 1988

Smoking cessation pts

Past Major Depression

Hall, 1989 Smoking cessation pts

Past Major Depression

Epidemiological studies: USAAuthor, yr N Lifetime Smoking Quit Rate

Glassman1990

3213adults

MDD, Alcohol Ab/Dep, Anxiety

MDD

Breslau1991

1007Adults21-30 yrs

MDD, Alcohol /drug Dep, Anxiety

----------

Covey1993

2980adults

MDD (males), Alcohol/drug Dep, GAD

Recurr MDD (f)GAD (m)

Lasser2000

4411adults

Alcohol/drug, Depression, Anxiety, ASP, Psychoses

Alcohol/drug,GAD, Curr MD

Eversmoking by MDD hx and genderSt. Louis ECA (n=3213)

010203040506070

80

Men Women

No MDDMDD

%

p<.001 p<.001

Glassman, et al, JAMA, 1990

Odds ratios for psychiatric diagnoses by nicotine dependence ,1200 adults, 21-30 yrs

00.5

11.5

22.5

33.5

44.5

5

MildModerate

MDD Anxiety Substance Dep

Breslau et al, 1992

Prevalence of Current SmokingLasser, JAMA, 2000

05

1015202530354045

Major Depression AlcoholDependence

Drug Dependence

No Mental Illness

%

Smoking status and psychiatric lifetime diagnosis – Odds Ratios relative to never smokers (Germany)

00.5

11.5

22.5

33.5

44.5

5

Substance Use AffectiveDisorders

AnxietyDisorders

Somatoform

N=913, Lubeck, Germany John U et al, 2004, Drug Alc Dependence

P<0.001

P<0.001P<0.001 P<0.05

Prevalence of current smoking according to diagnosis: in-patient and out-patients, Paris, France

0102030405060708090

100

Poirier M, et al, 2002, Prog in Neuro-Psychopharm Biol Psychiatry

General Substance Schizophrenia Anxiety Mood Population

Association between MDD

and Tobacco Use.

What Else Do We Know?

Significant association between MDD and tobacco use.

Observed in multiple studies, in clinical and community samples, across age groups, several nationalities.

Smokers with MDD history have more withdrawal symptoms.

Seen in clinical and community based studies.

Nicotine withdrawal symptoms: Intensityduring Week 1 after quit day

0

0.5

1

1.5

2

2.5

3

3.5

4

MDDNo MDD

p<.05

p<.01

craving irritability anxiety restless- appetite difficulty depressed ness increase concentr moodCovey et al, 1990

Nicotine withdrawal symptoms: Frequency during Week 1 after quit day.

0

20

40

60

80

100

120 MDDNo MDD

craving irritability anxiety restless- appetite concentr depressive ness increase difficulty mood

p<.03

Covey et al, 1990

Nicotine withdrawal symptoms, MDD, and Anxiety, Breslau et al, AJPsychiatry1992

0

5

10

15

20

25

30

35

40

MDDAnxietyNeither

Feel depressed Drowsy Trouble Decreased Concentrating Heart Rate

Does smoking cessation provoke new MDD?

New major depression within 3 months of completing a 10-week cessation program

0

5

10

15

20

25

30

35

None Single Recurrent

%

(n=91) (n=25) (n=10)

2 %

16 %

30 %x2=14.19, df=2, p<.001

Covey et al, 1997

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

Incidence of major depressive episodes in 12 month clinical trial of 304 smokers

0

5

10

15

20

25

No MDD MDD

Abstainers

Nonabstainers

Tsoh et al, Am J Psychiatry, 2000

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 - 56Age = 45.1 Smoking - 121Race = 97% WhiteEducation = 14.5 yrs.

Does history of MDD influence cessation?

Quit rates by major depression hx among subjects who received placebo (n=38)

0

10

20

30

40

50

No MDD (16)MDD (22)

%

Glassman et al, JAMA, 1988

Quit rates by major depression hx

05

10152025303540

No MDDMDD

Health Education Therapy

%

Hall et al, 1991

Cessation rate by MDD hx and gender in the St. Louis ECA (n=1873)

05

101520253035

40

Men Women

No MDDMDD

% p<.001p<.001

Glassman, Helzer, Covey et al, 1990

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

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

Odds ratios: effect of past Major Depression versus no MDD on smoking cessation

Placebo Active

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

Combined quit rates in 8 studies on effect of past MDD on smoking cessation

05

101520253035404550

Placebo-ST Placebo-LT Active-ST Active-LT

No MDDMDD

Data from Covey et al, in press, NTR

Influence of Depression History on Acute Cessation (Week 9) by Treatment

0

10

20

30

40

50

60

70

Placebo NicotinePatch

BupropionSR +/- Patch

No Hx of MDDHx of MDD

Smith, Nicotine & Tobacco Research 2003

Influence of Depression History on One Year Cessation (Week 52) by Treatment

0

5

10

15

20

25

30

35

No MDD MDD Hx

BupropionNo Bup

Smith, Nicotine & Tobacco Research 2003

Does depression lower the quit rate? YES.

Cohort 1 (1952-1970)

0

2

4

6

8

10

12

14

16

Never depressed Depressed

%Quit

%Quit

Does depression lower thequit rate? YES.Cohort 2 (1970-1992)

20

21

22

23

24

25

26

27

Never depressed Depressed

%Quit

%Quit

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.

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?

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

Single versus Recurrent MDD:Quit rates among smokers who received

standard cessation counselingHaas et al, 2004, JCCP

0

10

20

30

40

50

60

EOT 3 Mo FU 12 Mo FU

No MDDSingle MDDRecurr MDD

Single versus recurrent MDD:End-of-treatment (short-term) quit rates among smokers who received placebo or

clonidine

0

5

10

15

20

25

30

35

Placebo Clonidine

No MDDSingle MDDRecurr MDD

Covey et al, NTR, in press

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?

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.