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6. CONCURRENT DISORDERS

Tobacco smoking and depression
There are several close links between major depressive disorder and tobacco
smoking. Studies have shown that up to 60% of heavy smokers have a history
of mental illness (Hughes et al., 1986; Glassman et al., 1988), and the
prevalence of major depressive disorder among smokers is twice that of non-
smokers (Glassman et al., 1990). Moreover, smokers who had a history of
clinical depression were half as likely to succeed in quitting smoking than
smokers without such a history (14% versus 28%) (Glassman et al., 1990).
Cessation of smoking results in an aversive withdrawal syndrome in
humans (Shiffman & Jarvik, 1976; Hughes et al., 1991), components of which
may be manifest for 1–10 weeks (Hughes, 1992). Depressed mood is one of the
core symptoms of the tobacco withdrawal syndrome that is experienced by a
large proportion of the people who attempt to quit smoking (Hughes et al.,
1984; West et al., 1984; Glassman et al., 1990; Hughes, 1992; Hughes
&Hatsukami, 1992; Glassman 1993; Parrott 1993; American Psychiatric
Association 1994; Hughes, Higgins & Bickel, 1994). The majority of researchers
in the field postulate self-medication of depressive symptoms with tobacco
smoking; this depressive symptomatology may have either pre-dated the
cigarette smoking or was induced by chronic cigarette smoking (Pomerleau,
Adkins & Pertschuk, 1978; Waal-Manning & de Hamel, 1978; Hughes et al., 1986;
Glassman, 1993; Markou, Kosten & Koob, 1998; Watkins, Koob & Markou, 2000).
The link between tobacco smoking, the tobacco abstinence syndrome and
depression is also supported by the fact that bupropion, an antidepressant
compound (Feighner et al., 1984; Caldecott-Hazard & Schneider, 1992) that
is a weak norepinephrine and dopamine reuptake inhibitor (Ascher et al.,
1995), and a nicotinic acetylcholine receptor antagonist (Fryer & Lukas, 1999;
Slemmer, Martin & Damaj, 2000), has been shown to be twice as effective as
placebo in clinical smoking cessation trials (Hurt et al., 1997; Jorenby et al.,
1999), and has been approved for this indication by the United States Food
and Drug Administration (FDA). Bupropion is the only non-nicotine based
therapy approved by the FDA as an antismoking agent. Trials have been
conducted also using the antidepressants fluoxetine, doxepin, and
moclobemide, a monoamine oxidase inhibitor (MAOI) (Robbins, 1993; Ferry
& Burchette, 1994; Dalack et al., 1995; Aubin, Tilikete & Barrucand, 1996).
These studies demonstrated modest effects of these antidepressants on
tobacco withdrawal symptoms. That is, patients treated with antidepressants
showed better abstinence rates than those treated with placebo at 4 weeks,
although relapse rates at 3 and 6 months remained high. Most interestingly,
however, patients with higher baseline depression remained abstinent for
longer periods of time than those with no depression when treated with the
antidepressant fluoxetine, although their mild depression could not be
considered clinically significant (Hitsman et al., 1999).
In conclusion, most antidepressant agents have some usefulness in
reducing relapse to smoking after the smoker with depression stops smoking,

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Chapter_6 181 19.1.2004, 11:48