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Article: Serum concentrations of clozapine and norclozapine in the prediction of relapse of patients with schizophrenia

TitleSerum concentrations of clozapine and norclozapine in the prediction of relapse of patients with schizophrenia
Authors
Issue Date2006
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/schres
Citation
Schizophrenia Research, 2006, v. 83 n. 2-3, p. 201-210 How to Cite?
AbstractSchizophrenic outpatients (n = 102) whose condition had stabilized with clozapine (CLZ) therapy and were being maintained on CLZ were followed for 1 year. Clinical status and concentrations of serum clozapine (CLZ) and its metabolite norclozapine (NCLZ) were evaluated periodically or when relapse occurred. Relapse was defined as a significant exacerbation of psychotic symptoms or hospitalization. Thirty-three patients relapsed and 69 did not. Relapse patients displayed significantly lower serum concentrations of CLZ and a sum of CLZ and NCLZ at endpoint than non-relapses (CLZ: 162 ng/ml vs. 237 ng/ml, p < 0.001; CLZ + NCLZ: 225 ng/ml vs. 301 ng/ml, p < 0.001). When all subjects were pooled together, a significant inverse correlation was observed between percent increase in the total score on the Brief Psychiatric Rating Scale (BPRS) from baseline and serum levels of CLZ alone (r = 0.404, p < 0.001) and the sum of CLZ and NCLZ (r = 0.364, p < 0.001). Relapses and non-relapses were well separated by a threshold CLZ serum concentration of 200 ng/ml with a sensitivity of 73% and a specificity of 80%. The threshold value represented about a 40% lower serum CLZ level than concentration achieved in acute treatment. Survival analysis showed a similarity of the relapse risk over time defined by the CLZ serum threshold and by symptomatic criteria. These results suggest that effective relapse prevention may require maintenance of patients at CLZ serum concentrations above 200 ng/ml and above 60% of the acute-phase level during long-term maintenance treatment of schizophrenia. © 2006 Elsevier B.V. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/179434
ISSN
2015 Impact Factor: 4.453
2015 SCImago Journal Rankings: 2.304
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXiang, YQen_US
dc.contributor.authorZhang, ZJen_US
dc.contributor.authorWeng, YZen_US
dc.contributor.authorZhai, YMen_US
dc.contributor.authorLi, WBen_US
dc.contributor.authorCai, ZJen_US
dc.contributor.authorTan, QRen_US
dc.contributor.authorWang, CYen_US
dc.date.accessioned2012-12-19T09:56:28Z-
dc.date.available2012-12-19T09:56:28Z-
dc.date.issued2006en_US
dc.identifier.citationSchizophrenia Research, 2006, v. 83 n. 2-3, p. 201-210en_US
dc.identifier.issn0920-9964en_US
dc.identifier.urihttp://hdl.handle.net/10722/179434-
dc.description.abstractSchizophrenic outpatients (n = 102) whose condition had stabilized with clozapine (CLZ) therapy and were being maintained on CLZ were followed for 1 year. Clinical status and concentrations of serum clozapine (CLZ) and its metabolite norclozapine (NCLZ) were evaluated periodically or when relapse occurred. Relapse was defined as a significant exacerbation of psychotic symptoms or hospitalization. Thirty-three patients relapsed and 69 did not. Relapse patients displayed significantly lower serum concentrations of CLZ and a sum of CLZ and NCLZ at endpoint than non-relapses (CLZ: 162 ng/ml vs. 237 ng/ml, p < 0.001; CLZ + NCLZ: 225 ng/ml vs. 301 ng/ml, p < 0.001). When all subjects were pooled together, a significant inverse correlation was observed between percent increase in the total score on the Brief Psychiatric Rating Scale (BPRS) from baseline and serum levels of CLZ alone (r = 0.404, p < 0.001) and the sum of CLZ and NCLZ (r = 0.364, p < 0.001). Relapses and non-relapses were well separated by a threshold CLZ serum concentration of 200 ng/ml with a sensitivity of 73% and a specificity of 80%. The threshold value represented about a 40% lower serum CLZ level than concentration achieved in acute treatment. Survival analysis showed a similarity of the relapse risk over time defined by the CLZ serum threshold and by symptomatic criteria. These results suggest that effective relapse prevention may require maintenance of patients at CLZ serum concentrations above 200 ng/ml and above 60% of the acute-phase level during long-term maintenance treatment of schizophrenia. © 2006 Elsevier B.V. All rights reserved.en_US
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/schresen_US
dc.relation.ispartofSchizophrenia Researchen_US
dc.subject.meshAdolescenten_US
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAnalysis Of Varianceen_US
dc.subject.meshAntipsychotic Agents - Blood - Therapeutic Useen_US
dc.subject.meshBrief Psychiatric Rating Scaleen_US
dc.subject.meshClozapine - Analogs & Derivatives - Blood - Therapeutic Useen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshFemaleen_US
dc.subject.meshFollow-Up Studiesen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshPredictive Value Of Testsen_US
dc.subject.meshProspective Studiesen_US
dc.subject.meshRecurrenceen_US
dc.subject.meshSchizophrenia - Blood - Drug Therapyen_US
dc.subject.meshStatistics As Topicen_US
dc.subject.meshTime Factorsen_US
dc.titleSerum concentrations of clozapine and norclozapine in the prediction of relapse of patients with schizophreniaen_US
dc.typeArticleen_US
dc.identifier.emailZhang, ZJ: zhangzj@hkucc.hku.hken_US
dc.identifier.authorityZhang, ZJ=rp01297en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.schres.2006.01.011en_US
dc.identifier.pmid16524698-
dc.identifier.scopuseid_2-s2.0-33646469840en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33646469840&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume83en_US
dc.identifier.issue2-3en_US
dc.identifier.spage201en_US
dc.identifier.epage210en_US
dc.identifier.isiWOS:000237012200010-
dc.publisher.placeNetherlandsen_US
dc.identifier.scopusauthoridXiang, YQ=35742320200en_US
dc.identifier.scopusauthoridZhang, ZJ=8061473900en_US
dc.identifier.scopusauthoridWeng, YZ=7103320159en_US
dc.identifier.scopusauthoridZhai, YM=7102983468en_US
dc.identifier.scopusauthoridLi, WB=36066834700en_US
dc.identifier.scopusauthoridCai, ZJ=7402902177en_US
dc.identifier.scopusauthoridTan, QR=7102120177en_US
dc.identifier.scopusauthoridWang, CY=35345843000en_US

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