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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
90
80
70
60
50
40
30
20
10
0
Schiz
Mania
MDD
Anxiety
Controls
Early clinical studies: USA
Author, yr
Sample
Diagnoses
Hughes, 1986
Mental clinic
Outpatients vs
community
Bi-polar disorder,
Major Depression,
Anxiety, Schizophrenia
Glassman,
1988
Hall, 1989
Smoking
cessation pts
Smoking
cessation pts
Past Major Depression
Past Major Depression
Epidemiological studies: USA
Author, yr N
Lifetime Smoking
Quit Rate
Glassman 3213
1990
adults
MDD, Alcohol
Ab/Dep, Anxiety
MDD
Breslau
1991
MDD, Alcohol
----------
1007
Adults
/drug Dep, Anxiety
21-30 yrs
Covey
1993
2980
adults
Lasser
2000
4411
adults
MDD (males),
Alcohol/drug Dep,
GAD
Recurr MDD (f)
GAD (m)
Alcohol/drug,
Alcohol/drug,
Depression, Anxiety, GAD, Curr MD
ASP, Psychoses
Eversmoking by MDD hx and gender
St. Louis ECA (n=3213)
80
p<.001
p<.001
70
%
60
50
No MDD
MDD
40
30
20
10
0
Men
Glassman, et al, JAMA, 1990
Women
Odds ratios for psychiatric diagnoses by nicotine
dependence ,1200 adults, 21-30 yrs
5
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
Mild
Moderate
MDD
Anxiety
Breslau et al, 1992
Substance
Dep
Prevalence of Current Smoking
Lasser, JAMA, 2000
%
45
40
35
30
25
20
15
10
5
0
Major Depression
Alcohol
Dependence
Drug
Dependence
No Mental Illness
Smoking status and psychiatric lifetime diagnosis –
Odds Ratios relative to never smokers (Germany)
5
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
P<0.001
P<0.001
Substance Use
Affective
Disorders
P<0.001
P<0.05
Anxiety
Disorders
Somatoform
N=913, Lubeck, Germany John U et al, 2004, Drug Alc Dependence
Prevalence of current smoking according to
diagnosis: in-patient and out-patients, Paris, France
100
90
80
70
60
50
40
30
20
10
0
General
Population
Substance
Schizophrenia
Anxiety
Poirier M, et al, 2002, Prog in Neuro-Psychopharm Biol Psychiatry
Mood
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: Intensity
during Week 1 after quit day
4
MDD
No MDD
3.5
3
2.5
2
1.5
p<.05
1
p<.0
1
0.5
0
craving irritability
depressed
Covey et al, 1990
anxiety
restless-
appetite
difficulty
ness
increase
concentr
mood
Nicotine withdrawal symptoms: Frequency
during Week 1 after quit day.
MDD
No MDD
120
100
80
60
p<.03
40
20
0
craving
Covey et al, 1990
irritability
anxiety
restless- appetite
ness
increase
concentr
difficulty
depressive
mood
Nicotine withdrawal symptoms, MDD, and Anxiety,
Breslau et al, AJPsychiatry1992
40
35
30
25
MDD
Anxiety
Neither
20
15
10
5
0
Feel depressed
Drowsy
Trouble
Concentrating
Decreased
Heart Rate

Does smoking cessation provoke
new MDD?
New major depression within 3 months of
completing a 10-week cessation program
30 %
35
30
x2=14.19,
df=2, p<.001
25
%
16 %
20
15
10
5
2%
0
None
(n=91)
Covey et al, 1997
Single
(n=25)
Recurrent
(n=10)
Effect of cessation on new MDD,
Glassman et al, 2001
Incidence of major depressive episodes in
12 month clinical trial of 304 smokers
25
20
15
Abstainers
10
Nonabstainers
5
0
No MDD
Tsoh et al, Am J Psychiatry, 2000
MDD
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%
Age = 45.1
Race = 97% White
Education = 14.5 yrs.
Not smoking - 56
Smoking 121
 Does history of MDD influence cessation?
Quit rates by major depression hx among
subjects who received placebo (n=38)
50
40
%
30
20
10
0
Glassman et al, JAMA, 1988
No MDD (16)
MDD (22)
Quit rates by major depression hx
40
35
30
% 25
No MDD
MDD
20
15
10
5
0
Health Education Therapy
Hall et al, 1991
Cessation rate by MDD hx and gender in the
St. Louis ECA (n=1873)
40
35
% 30
p<.001
p<.001
25
No MDD
MDD
20
15
10
5
0
Men
Glassman, Helzer, Covey et al, 1990
Women
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
50
45
40
35
30
25
20
15
10
5
0
No MDD
MDD
Placebo-ST Placebo-LT Active-ST
Active-LT
Data from Covey et al, in press, NTR
Influence of Depression History on Acute
Cessation (Week 9) by Treatment
70
60
50
40
No Hx of MDD
Hx of MDD
30
20
10
0
Placebo
Nicotine
Patch
Bupropion
SR +/- Patch
Smith, Nicotine & Tobacco
Research 2003
Influence of Depression History on
One Year Cessation (Week 52) by Treatment
35
30
25
20
Bupropion
No Bup
15
10
5
0
No MDD
MDD Hx
Smith, Nicotine & Tobacco
Research 2003
Does depression lower
the quit rate? YES.
Cohort 1 (1952-1970)
16
14
12
%
Quit
10
8
6
4
%
Quit
2
0
Never depressed
Depressed
Does depression lower the
quit rate? YES.
Cohort 2 (1970-1992)
27
26
25
24
%
Quit
23
22
%
Quit
21
20
Never depressed
Depressed
 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 counseling
Haas et al, 2004, JCCP
60
50
40
No MDD
Single MDD
Recurr MDD
30
20
10
0
EOT
3 Mo FU
12 Mo FU
Single versus recurrent MDD:
End-of-treatment (short-term) quit rates
among smokers who received placebo or
clonidine
35
30
25
20
No MDD
Single MDD
Recurr MDD
15
10
5
0
Placebo
Covey et al, NTR, in press
Clonidine
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.