Discussion
We confirmed our hypothesis that recently withdrawn cocaine-dependent
schizophrenia patients who received risperidone had significantly
less cue-elicited craving on the intensity and depression items,
compared with the individuals who received the typical neuroleptics.
These individuals also had fewer relapses and study dropouts and
a greater reduction in PANSS Negative and Global scores by study
completion. One could hypothesize that the intensity of cue-elicited
craving and depression may play a role in priming patients for a
relapse. Others have found that depression is associated with increased
drug craving (25,26) and that atypical neuroleptics are useful for
treating depression because of their secondary action on the serotonin
system (27). The present research adds to the growing literature,
suggesting that atypical neuroleptics may be efficacious in the
treatment of cocaine addiction, particularly craving and depression,
which are common during protracted withdrawal. Interestingly, Farren
and others examined the acute effects of cocaine administration
and found that addicts who received clozapine had a diminished “expected
high” (28).
One could speculate that the dopamine abnormalities present in
individuals with schizophrenia may play a role in the high incidence
of cocaine use in this population. Also note, however, that individuals
with schizophrenia might abuse cocaine to self-medicate their symptoms
and decrease their EPS (29). In our sample, the individuals treated
with risperidone had a greater reduction in PANSS Negative and Global
scores, which are associated with schizophrenia, in addition to
decreased craving and relapses. Risperidone and other atypical neuroleptics
have the unique ability to regulate dopamine and serotonin systems,
which play a role in cocaine craving, while simultaneously managing
the negative symptoms and reducing the risk of EPS.
This class of medications appears to have numerous clinical advantages
over the typical neuroleptics in the treatment of schizophrenia,
including reduced risk for tardive dyskinesia and EPS, and greater
improvements in cognition (27). At this time, the choice of which
atypical antipsychotic to prescribe should be based on individual
clinical decisions, including side-effect profile. Future research
should include double-blind studies that compare typical with atypical
neuroleptics for decreasing craving and preventing drug relapses
in withdrawn cocaine-dependent schizophrenia subjects. We also need
to study atypical neuroleptics longitudinally to determine whether
they remain efficacious over time or whether the primary effect
is during protracted withdrawal.
Funding and Support
The authors wish to thank Janssen Research Foundation for funding
this investigator-initiated trial.
Acknowledgements
We also thank Dr Aron Starosta for his statistical consultation
and review of the manuscript. Portions of this research were presented
at the Annual Meeting of the American Psychiatric Association in
May 2000 in Chicago, Illinois; at the Annual Meeting of the College
on Problems and Drug Dependence June 2000 in San Juan, Port Rico;
and at the American College of Neuropsychopharmacology December
2001 in Waikoloa, Hawaii.
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Manuscript submitted September 2001, revised, and accepted
May 2002.
1 Research Faculty, Department of Veterans Affairs, VISN 3 Mental
Illness, Research, Education and Clinical Center, Lyons, New Jersey;
Assistant Professor of Psychiatry, Department of Psychiatry, University
of Medicine and Dentistry-Robert Wood Johnson Medical School, Piscataway,
New Jersey; Assistant Professor of Psychiatry, Department of Psychiatry,
University of Medicine Dentistry, New Jersey Medical School, Newark,
New Jersey.
2 Associate Clinical Director, Department of Veterans Affairs,
VISN 3 Mental Illness, Research, Education and Clinical Center,
Lyons, New Jersey; Associate Professor of Psychiatry, Department
of Psychiatry, University of Medicine and Dentistry-Robert Wood
Johnson Medical School, Piscataway, New Jersey; Associate Professor
of Psychiatry, Department of Psychiatry, University of Medicine
Dentistry, New Jersey Medical School, Newark, New Jersey.
3 New Jersey Site Coordinator, Department of Veterans Affairs,
VISN 3 Mental Illness, Research, Education and Clinical Center,
Lyons, New Jersey.
4 Research Faculty, Department of Veterans Affairs, VISN 3 Mental
Illness, Research, Education and Clinical Center, Lyons, New Jersey;
Assistant Professor of Psychiatry, Department of Psychiatry, University
of Medicine and Dentistry-Robert Wood Johnson Medical School, Piscataway,
New Jersey.
5 Research Faculty, Department of Veterans Affairs, VISN 3 Mental
Illness, Research, Education and Clinical Center, Lyons, New Jersey;
Assistant Professor of Psychiatry, Department of Psychiatry, University
of Medicine and Dentistry-Robert Wood Johnson Medical School, Piscataway,
New Jersey.
6 Associate Professor of Psychiatry, Department of Psychiatry,
University of Medicine and Dentistry-Robert Wood Johnson Medical
School, Newark, New Jersey.
Address for correspondence: Dr D Smelson, Department of Veterans
Affairs, New Jersey Health Care System, Lyons Campus, Mental Health
and Behavioral Sciences (Bldg. 143), 151 Knollcroft Road, Lyons,
NJ 07939-5000
e-mail: david.smelson@med.va.gov
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