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Titolo:
Relationship between plasma concentrations of clozapine and norclozapine and therapeutic response in patients with schizophrenia resistant to conventional neuroleptics
Autore:
Spina, E; Avenoso, A; Facciola, G; Scordo, MG; Ancione, M; Madia, AG; Ventimiglia, A; Perucca, E;
Indirizzi:
Univ Messina, Policlin Univ, Inst Pharmacol, I-98125 Messina, Italy Univ Messina Messina Italy I-98125 nst Pharmacol, I-98125 Messina, Italy Azienda USL 5, Ctr Mental Hlth, Messina, Italy Azienda USL 5 Messina Italy enda USL 5, Ctr Mental Hlth, Messina, Italy Villa Gerani Clin, Catania, Italy Villa Gerani Clin Catania ItalyVilla Gerani Clin, Catania, Italy Univ Pavia, Dept Internal Med, Clin Pharmacol Unit, I-27100 Pavia, Italy Univ Pavia Pavia Italy I-27100 Clin Pharmacol Unit, I-27100 Pavia, Italy
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 1, volume: 148, anno: 2000,
pagine: 83 - 89
Fonte:
ISI
Lingua:
ENG
Soggetto:
CLINICAL-RESPONSE;
Keywords:
clozapine; norclozapine; plasma concentration; schizophrenia; therapeutic drug monitoring;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Spina, E Univ Messina, Policlin Univ, Inst Pharmacol, Via Consolare Valeria, I-98125 Messina, Italy Univ Messina Via Consolare Valeria Messina ItalyI-98125 , Italy
Citazione:
E. Spina et al., "Relationship between plasma concentrations of clozapine and norclozapine and therapeutic response in patients with schizophrenia resistant to conventional neuroleptics", PSYCHOPHAR, 148(1), 2000, pp. 83-89

Abstract

Rationale: Monitoring plasma clozapine concentrations may play a useful role in the management of patients with schizophrenia, but information on therelationship between the plasma levels of the drug and response is still controversial. Objective: The purpose of this study was to assess the relationship between plasma concentrations of clozapine and its weakly active metabolite norclozapine and clinical response in patients with schizophrenia resistant to conventional neuroleptics. Methods: Forty-five patients, 35 males and ten females, aged 19-65 years, were given clozapine at a dosage up to 500 mg/day for 12 weeks. Steady-state plasma concentrations of clozapine and norclozapine were measured at week 12 by a specific HPLC assay. Psychopathological state was assessed at baseline and at week 12 by using the Brief Psychiatric Rating Scale, and patients were considered responders if theyshowed a greater than 20% reduction in total BPRS score compared with baseline and a final BPRS score of 35 or less. Results: Mean plasma clozapine concentrations were higher in responders (n=18) than in non-responders (n=27) (472+/-220 versus 328+/-128.ng/ml, P<0.01), whereas plasma norclozapine levels did not differ between the two groups (201+/-104 versus 156+/-64 ng/ml, NS). A significant positive correlation between plasma levels and percent decrease in total BPRS score was found for clozapine (r(s)=0.371, P<0.02), but not for norclozapine (r(s)=0.162, NS). A cutoff value at a clozapine concentration of about 350 ng/ml differentiated responders from non-responders with a sensitivity of 72% and a specificity of 70%. At a cutoff of 400 ng/ml, sensitivity was 67% and specificity 78%. The incidence of side effects was twice as high at clozapine concentrations above 350 ng/ml compared with lower concentrations (38% versus 17%). Conclusions: These results suggest that plasma clozapine levels are correlated with clinical effects, although there is considerable variability in the response achieved at any givendrug concentration. Because many patients respond well at plasma clozapineconcentrations in a low range, aiming initially at plasma clozapine concentrations of 350 ng/ml or greater would require in some patients use of unrealistically high dosages and imply an excessive risk of side effects. Increasing dosage to achieve plasma levels above 350-400 ng/ml may be especiallyindicated in patients without side effects who failed to exhibit amelioration of psychopathology at standard dosages or at lower drug concentrations.

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Documento generato il 21/01/20 alle ore 00:53:23