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Clozapine Treatment in Patients With Prior Substance Abuse
Discussion
To our knowledge, this is one of the first studies that assessed the long-term outcome of recidivism in patients with a substance abuse history who were discharged on clozapine. Although the sample size is small and further studies are needed, our results suggest that treatment-resistant patients with schizophrenia and with a history of abuse who were discharged on clozapine may be no more likely to be rehospitalized than are NSA patients.
This study adds to the mounting evidence that SGAs may offer many benefits to prior SA patients that conventional agents do not offer. Response to traditional antipsychotics has been less favourable in patients who are dually diagnosed. This has not been seen with clozapine (4,11). Next, schizophrenia patients with comorbid substance abuse have been found to have a significantly higher risk of developing tardive dyskinesia (TD) while taking conventional antipsychotics (19). Third, compliance rates with SGAs are reported to be higher, compared with conventional agents. Most likely, a more tolerable side effect profile accounts for this difference; specifically, regarding extrapyramidal symptoms (13,20). Finally, SGAs may actually contribute to lower overall costs of illness treatment (21).
In our study, patients with a substance abuse history had total BPRS scores that were significantly lower in the SA patients upon discharge from the unit. Interestingly, prior to beginning clozapine, BPRS scores did not significantly differ between the SA and the NSA groups. SA patients, in fact, had a significantly greater improvement with clozapine on total BPRS scores prior to discharge (F1,42 = 4.73, P = 0.035). This finding is similar to the reports of others who also noted a comparable, if not favourable, response in SA patients vs NSA patients treated with clozapine (9,11). BPRS scores at baseline and magnitude of response during hospitalization were not correlated with the rate of rehospitalization. These results demonstrate that not only do patients with a substance abuse history have a better recovery potential, but they also maintain this benefit, which is similar to NSA patients on clozapine, for as long as 5 years following discharge.
A few limitations must be considered when interpreting our results. First, substance abuse, although defined and characterized by DSM-III-R criteria, often remains an ambiguous diagnosis. Although rigorous attempts were made to obtain accurate patient histories, this diagnosis may be under- reported. We found similar rates of rehospitalization between the SA and NSA groups, but the sample size is small. However, because the literature has little data in this population, we feel that these pilot data are a useful contribution. Clinical trials omit SA patients, and very few prospective trials exist that report effectiveness of SGAs in this population. Further, it is not an easy task to recruit large numbers of patients with stringently classified treatment-resistant schizophrenia into clinical trials.
In summary, patients with schizophrenia and with a history of substance abuse may have similar rates of rehospitalization over several years following discharge, compared with patients without any prior history of abuse. SGAs, specifically as seen here with clozapine, may offer many benefits to patients with dual diagnosis, compared with treatment with conventional agents. Patients with treatment-resistant schizophrenia who have extensive histories of drug and alcohol abuse should be expected to respond to and continue to benefit from clozapine treatment at comparable rates with patients who have never abused alcohol or drugs. Even so, little attention has been paid to this population, and more research is needed to replicate these preliminary findings.
Funding and Support
This work was completed at the Maryland Psychiatric Research Center, University of Maryland, Baltimore, Maryland. Support and funding for this work was, in part, by the Theodore and Vada Stanley Foundation and the National Institutes of Mental Health (NIMH) Intervention Research Center, Grant MH-40279.
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Manuscript received May 2002, revised, and accepted July 2002.
1. Assistant Professor of Psychiatry, School of Medicine, University of Maryland, Baltimore, Maryland.
2. Senior social worker, University of Maryland, Baltimore, Maryland.
3. Director, Treatment Research Unit, Maryland Psychiatric Research Center, Baltimore, Maryland; Associate Professor of Psychiatry, School of Medicine, Baltimore, Maryland.
Address for correspondence: Dr D Kelly, Maryland Psychiatric Research Center, Box 21247, Baltimore, MD 21228
e-mail: dkelly@mprc.umaryland.edu
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