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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

with bupropion having the highest efficacy overall, and fluoxetine (a selective
serotonin reuptake inhibitor) being most effective in people with depression.
The efficacy of antidepressant drugs, particularly bupropion and fluoxetine,
as anti-smoking agents supports the hypothesis that pre-existing depressive
symptomatology or depression associated with protracted nicotine
abstinence contributes to the perpetuation of substance dependence (West
et al., 1984; Glassman et al., 1990; Hughes et al., 1991; Hughes & Hatsukami,
1992; Parrott, 1993; West & Gossop, 1994; Markou, Kosten & Koob, 1998).
From most of the studies reviewed above, it is unclear whether individuals
who suffer from depressive symptomatology are more likely to initiate
smoking or whether depressive symptoms are induced or exacerbated by
long-term smoking and withdrawal from smoking (Markou, Kosten & Koob,
1998). Epidemiological data support both processes (Breslau, Kilbey
& Andreski, 1993, 1998), suggesting that smoking and depression share the
same neurobiological substrates (Breslau et al., 1998). Although the
mechanisms are not currently known, candidate neurotransmitter systems
are serotonin and dopamine, both of which may be dysregulated in
depression, and are increased by nicotine. The mesolimbic dopamine
pathway is strongly associated with reward and dependence (see Chapter 3),
but is also a candidate pathway that is dysregulated in depression (Nestler et
al., 2002).
Other clinical evidence that supports a linkage between smoking and
depression comes from a potential familial aggregation. It was shown that
dizygotic twin pairs, who share only about half of their genes, had an
intermediate level of association of smoking and depression, which fell
between that of the monozygotic twin pairs (which had a higher level) and
that of the general population (which had a lower level) (Kendler et al., 1993b).
These data are consistent with the hypothesis that common or shared genes
are a source of the association between depression and smoking.

Psychostimulant dependence and depression
Epidemiological data from the USA indicate that the lifetime rates of major
depression were 32% in cocaine users, and only 8–13% among non-cocaine
users (Robins et al., 1984; Regier et al., 1990; Robins & Reiger, 1991; Rounsaville
et al., 1991; Kessler et al., 1994). Similar to tobacco smoking, antidepressant
treatment of people with substance dependence results in greater
improvement in both mood and reduction in the use of psychostimulants in
those who also suffer from depression, than among those who do not.
Treatment with antidepressants appears to decrease cocaine use, as well
as depression. Treatment with the tricyclic antidepressant desmethyli-
mipramine resulted in a 90% reduction in cocaine use in users with
depression, while users who were not depressed showed a 50% reduction in
their use of cocaine (Ziedonis & Kosten, 1991). Similarly, 26% of cocaine users
with depression who were treated with imipramine (another tricyclic

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