T. Iannaccone

Leucocytosis in clozapine-treated patients as predictor of loss of treatment response?

Anecdotal evidence tends to suggest clozapine treatment as a cause of leucocytosis in schizophrenic patients, however, no conclusive evidence is available on this topic. We report the clinical cases of two schizophrenic men who were diagnosed with clozapine-related leucocytosis. The clozapine treatment was performed at a dose between 200 and 400 mg/day. When leucocytosis appeared, there was a loss of response to clozapine in both patients. Clozapine-induced leucocytosis in schizophrenic patients could be correlated to occurrence of psychotic symptomatology.

Nor-clozapine Plasma Concentration/daily Clozapine Dose Ratio (Ncz/d): an Index of Response to Clozapine Treatment.

The present study investigated relationships between plasma concentrations of clozapine (CZ) and nor-clozapine (NCZ), clozapine metabolic index (NCZ/CZ), nor-clozapine plasma concentration/daily clozapine dose ratio (NCZ/D) and response to clozapine treatment in schizophrenic patients. Twelve treatment-resistant schizophrenic patients, recruited for this study, were treated with clozapine for six weeks. Our sample was composed by 4 males and 8 females aged 35-52 years recruited at the Department of Psychiatry, University of Naples SUN. The diagnosis of schizophrenia was established according to ICD-10 criteria (9 paranoid type and 3 residual type) and with history of illness from more than ten years, resistant to treatments with other typical and atypical antipsychotics. All the patients in this study were treated with clozapine, valproic acid, lorazepam or delorazepam. Patient health improvement was assessed before (T0) and after six weeks of clozapine therapy (T6), using the Brief Psychiatric Rating Scale (BPRS). Plasmatic clozapine and nor-clozapine concentrations were determined by high-performance liquid chromatography (HPLC). Analyses of variance (ANOVA) and χ 2 -test (SPSS 19) were used to find correlations between the different studied parameters and the BPRS scores. No significant correlations between CZ, NCZ, NCZ/CZ and clinical health improvement in BPRS scores among our schizophrenic patients were found; however, a significant correlation (p

Leukocytosis in Clozapine-treated Patients: a Sign of Loss of Response to the Antipsychotic

Anecdotal evidence tends to suggest clozapine as a cause of leukocytosis in schizophrenic patients, however no conclusive evidence is available on this topic so far. Moreover, transient and persistent clozapine-related leukocytosis has received little attention in the literature. We report two clinical cases of two men, respectively 23 and 34 years old, affected by schizophrenia, showing persecutory and reference delusions, auditory hallucinations and aggressive behaviour. Both had been treated for several years with first and second generation antipsychotics, all at therapeutic doses, reporting only occasional ameliorations. In both patients the previous treatment was gradually tapered down and then discontinued, and clozapine was gradually introduced, at a dose of 200 mg/die in the first patient, and of 400 mg/die in the second one. After ten years of clinical compensation and without any abnormality of blood cell count, leukocytosis appeared in both cases. WBC and ANC counts ranged between 12.56x10 3 and 22.26x10 x10 3 /mm 3 and between 8.57x10 3 and 17.67x10 3 /mm 3 , respectively. When leukocytosis appeared, there was loss of response to clozapine and, consequently, psychopatological decompensation in both patients. Therefore a daily clozapine dose of 350 mg in the first patient and of 650 mg in the second one was reached within two weeks. No clinical amelioration was observed, but an increase in the previous WBC count was shown. Medical and hematological consultations found no evidence of systemic or myeloproliferative illness. These two clinical cases suggest that the onset of leukocytosis in clozapine-treated patients could be associated to loss of response to the antipsychotic.

Cutaneous Reactions Carbamazepine-related, Dose and Time Independent, in Chronic Psychotic Patients

Anecdotal evidence suggests carbamazepine as treatment of impulsiveness in chronic psychotic patients. Several carbamazepine-related side effects have been reported in the literature and, among them, serious cutaneous reactions are the most frequent. Erythematous lesions onset, during the first carbamazepine introduction, suggest an idiosyncrasic nature of this reaction. We report here two clinical cases of two men, respectively 30 and 53 years old, affected by chronic psychosis, showing persecutory and reference delusions, auditory hallucinations and aggressive behaviour. Both were treated with carbamazepine (at a dose of 200 mg/day in the first patient, and of 400 mg/day in the second one), antipsychotics and benzodiazepines. After two weeks of carbamazepine treatment, a cutaneous reaction was shown in both cases: it was a papular and erythematous lesion, mainly spread on hands, feet and shoulders. Therefore, patients complained about pricking, fatigue and headache. Medical and allergological tests (Prick test, Patch test) were performed, but serum IgE levels were not reasonably related to an allergopathy; furthermore cutaneous tests were all negative. Carbamazepine treatment was discontinued and a steroidal i.m. therapy was performed for four days, with a gradual resolution of the symptoms. These two clinical cases suggest that cutaneous reactions carbamazepine-related could represent a serious side effect of this treatment. These reactions, dose and time independent are related to genic abnormalities involving alleles HLA-A31:01 e HLA-B15:02 (Genin et al., 2014). Pharmacogenetic studies to identify predictive factors of individual susceptibility to carbamazepine response are needed.