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6. CONCURRENT DISORDERS

negative symptoms of schizophrenia (American Psychiatric Association,
1994; Markou, Kosten & Koob, 1998; Green et al., 1999; Ellenbroek & Cools,
2000). Together, these observations have led to several hypotheses that
attempt to explain the high incidence of psychostimulant use among
patients with schizophrenia. These hypotheses are not mutually exclusive
and parallel those postulated to explain the high incidence of tobacco
smoking among patients with schizophrenia. The commonalities in these
hypotheses are not surprising considering that cocaine and amphetamine
are psychomotor stimulant drugs, and nicotine is considered also to be a
relatively mild psychostimulant.

Hypotheses to explain the high rate of psychostimulant use among
patients with schizophrenia
The first hypothesis postulates that the high rate of psychostimulant use
among patients with schizophrenia reflects an attempt to reduce the
unpleasant side-effects of chronic neuroleptic treatment, including the motor
side-effects (Schneier & Siris, 1987; Robinson et al., 1991). The reasons for
this are likely to be the same as for nicotine. Briefly, since neuroleptic drugs
block dopamine, and excessive dopamine blockade results in motor and other
side-effects, the use of substances that increase dopamine function may
provide relief from such effects.
The second hypothesis postulates that administration of psychostimulants
ameliorates the cognitive deficits associated with schizophrenia (Cesarec
&Nyman, 1985; Krystal et al., 1999). Again, the mechanism of this effect is
likely to be through increasing mesolimbic and mesocortical dopamine
transmission; however, there is very little evidence in support of, or against,
these two hypotheses.
The third hypothesis postulates that administration of psychostimulants
ameliorates the negative symptoms of schizophrenia that are most resistant
to the majority of currently available antipsychotic treatments (Khantzian,
1985, 1997; Schneier & Siris, 1987; Dixon et al., 1990; Sevy et al., 1990;
Rosenthal, Hellerstein & Miner, 1994; Krystal et al., 1999). Experimental
studies over several decades in humans have clearly indicated that although
acute amphetamine administration exacerbates the positive symptoms of
schizophrenia, chronic administration diminishes the negative symptoms
(Angrist, Rotrosen & Gershon, 1980, 1982; Desai et al., 1984; Khantzian, 1985;
van Kammen & Boronow, 1988; LeDuc & Mittleman, 1995; Sanfilipo et al.,
1996; Krystal et al. 1999). Furthermore, patients with schizophrenia who use
psychostimulants exhibit less severe negative symptoms than patients who
do not (Dixon et al., 1991; Soni & Brownlee, 1991; Buckley et al., 1994; Lysaker
et al., 1994). Interestingly, clozapine, a neuroleptic drug that helps reduce
the negative symptoms of schizophrenia, reduced substance use, including
psychostimulant use, in more than 85% of the patients, and prevented re-
initiation of substance use (Zimmet et al., 2000).

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