Serum concentrations of clozapine and norclozapine in the prediction of relapse of patients with schizophrenia.
Schizophrenic 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.
Xiang
Ying-Qiang
YQ
Laboratory of Clinical Psychopharmacology, Beijing Anding Hospital, Capital University of Medical Sciences, 5 Ankang Lane, Deshengmenwai Avenue, Xicheng District, Beijing 100088, China.
Zhang
Zhang-Jin
ZJ
Weng
Yong-Zhen
YZ
Zhai
Yi-Min
YM
Li
Wen-Biao
WB
Cai
Zhuo-Ji
ZJ
Tan
Qing-Rong
QR
Wang
Chuan-Yue
CY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use; D010054:Brief Psychiatric Rating Scale; D003024:Clozapine / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D013223:Statistics as Topic; D013997:Time Factors
D014150:Antipsychotic Agents; C058272:norclozapine; D003024:Clozapine