V. Prisco

Clozapine versus other antipsychotics during the first 18 weeks of treatment: A retrospective study on risk factor increase of blood dyscrasias

Blood dyscrasias excluding agranulocytosis received limited attention in antipsychotic-treated patients during the first 18 weeks of therapy, although severe clinical conditions have been reported in a few cases. We extracted data records of 285 Caucasian patients after 18 weeks of antipsychotic treatments to investigate risk factors of blood dyscrasias. We observed a higher risk to develop both transient and persistent anemia, neutrophilia and eosinophilia in clozapine-treated patients, whereas in those treated with other atypical antipsychotics when compared to a reference group under typical antipsychotics, emerged an increased risk for transient neutrophilia and eosinophilia. Male patients revealed a higher risk of persistent eosinophilia, neutrophilia, and leukocytosis. Concomitant treatments with mood stabilizers or benzodiazepines proved to be risk factors for transient anemia, antidepressants for transient eosinophilia. Severe complications emerged in 3 cases of agranulocytosis. Cross-tabulation analysis showed a higher probability of a poor response in clozapine-treated patients with persistent anemia and a positive with persistent neutrophilia and eosinophilia. Our data evidenced that emerging blood dyscrasias were not associated with critical adverse effects, and only agranulocytosis required a treatment interruption. Other atypical antipsychotics might represent a viable alternative to potentially harmful clozapine and typical antipsychotics at the onset of life-threatening haematological alterations.

Olanzapine Is Faster than Haloperidol in Inducing Metabolic Abnormalities in Schizophrenic and Bipolar Patients

The effects of olanzapine and haloperidol on metabolic parameters in bipolar patients have been evaluated much less comprehensively than in schizophrenic patients. Therefore, in this study, medical records of 343 schizophrenic and bipolar patients treated with haloperidol or olanzapine for 1 year were retrospectively reviewed and metabolic outcomes were evaluated. After 12 months of follow-up, 25.9% of patients showed ≥3 metabolic abnormalities with a point prevalence of 27.2% in the bipolar and 24.9% in the schizophrenic group: 22.0% of the schizophrenic patients treated with haloperidol and 29.8% of those treated with olanzapine achieved ≥3 metabolic alterations; in bipolar patients, these percentages were 15.8% of those treated with haloperidol and 37.8% of those treated with olanzapine (p < 0.0001). Significant changes were reported over time in fasting glucose, triglycerides and cholesterol blood levels, systolic and diastolic blood pressure, body weight, and BMI. Overall, a significant number of schizophrenic and bipolar patients treated with olanzapine showed ≥3 metabolic alterations in the first month of treatment when compared to those treated with haloperidol. Moreover, the number of olanzapine-treated patients developing metabolic changes in the first month was significantly higher in both diagnostic groups when compared to those who reached metabolic abnormal values in the subsequent 11 months. These data suggest that both antipsychotics could increase the metabolic risk in schizophrenic and bipolar patients with a higher prevalence in olanzapine-treated patients. On the other hand, olanzapine-treated patients seem to achieve metabolic abnormalities faster than haloperidol-treated subjects in both diagnostic groups.

Brain natriuretic peptide as a biomarker of asymptomatic clozapine-related heart dysfunction: a criterion for a more cautious administration.

Clozapine-related pericarditis is a rare side effect of the drug. We reported the clinical cases of two women, aged 22 and 28 years, affected by schizophrenia with pericarditis symptoms related to clozapine treatment of 200 mg/day. Clozapine was discontinued in both patients, resulting in normalization of the ECG changes, and echocardiography confirmed the progressive disappearance of the pericardial effusion. Interestingly, while inflammatory indices and pro-brain natriuretic peptide (pro-BNP) plasma levels were high in both patients, only one of them showed tachycardia, subjective chest pain, shortness of breath and dyspnea, with a clinical symptomatology suggesting a cardiac involvement. BNP is a vasoactive peptide synthetized by the ventricular myocardium which splits in two fragments: BNP and the N-terminal (pro-BNP). Both are considered valuable biomarkers in clinical practice for the prediction of disease state and prognosis in patients with suspected heart failure. Pro-BNP acts as a key regulator in the homeostasis of water and salt excretion and in the maintenance of blood pressure, mainly by inhibiting the renin-angiotensin-aldosterone axis and blocking the sympathetic nervous activity. In our cases, pro-BNP plasma levels proved to be a profitable way to identify subjects with asymptomatic cardiac impairment who could benefit from a therapy preventing progression to heart failure.

Antipsychotic Treatment and Metabolic Syndrome: a Comparison Between Schizophrenic and Bipolar Patients

Only few studies have compared the effects of Typical and Atypical Antipsychotics on Metabolic Syndrome (MS) onset. The present study examined the impact of antipsychotic treatment on MS in schizophrenic and bipolar patients. Medical records of 535 patients who completed a 1-year treatment with haloperidol, olanzapine, risperidone, paliperidone, quetiapine, aripiprazole, clozapine were retrospectively reviewed, and metabolic outcomes were evaluated. MS was diagnosed according to ATP III criteria. The mean daily dose of each antispychotic was calculated in haloperidol equivalents (Eq). Schizophrenic patients were treated with a higher daily antipsychotic dose than bipolar ones (5.9 mg /die ± 4.2 mg/die vs 4.9 mg/die ± 4.0 mg/die, p

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.

EPA-0283 – Olanzapine is faster than haloperidol in inducing metabolic syndrome in schizophrenics but not in bipolar patients

Metabolic profile of olanzapine as compared to haloperidol has been evaluated much less comprehensively in bipolar than in schizophrenic patients. Medical records of 343 patients who completed a 3-year treatment with haloperidol or olanzapine were retrospectively reviewed, and metabolic outcomes were evaluated. Twenty-three percent of patients fulfilled MetS criteria with a point prevalence of 25.3% in bipolar and 21.2% in schizophrenic group; 20.3% of schizophrenics treated with haloperidol and 22.4% of those treated with olanzapine developed MetS, which was detected, instead, in 17.1% of haloperidol-treated bipolar patients and 32.9% of those treated with olanzapine. Significant changes were detected overtime in fasting cholesterol, systolic BP, BW and BMI; some of these parameters at the 3-year follow-up presented more severe changes with olanzapine than haloperidol in both diagnostic groups. Overall, a significant number of subjects fulfilled MetS criteria in the first month of treatment, but only in schizophrenics olanzapine was faster than haloperidol in inducing such an effect. These data suggest that haloperidol and olanzapine increase the risk for MetS in both schizophrenic and bipolar patients with a higher prevalence for olanzapine only in bipolar patients. Morever, as compared to haloperidol, olanzapine has a faster dismetabolic action in schizophrenic but not in bipolar patients.

EPA-0282 – Clozapine treatment and other atypical and typical antipsychotics: incidence and course of blood dyscrasias during the first eighteen weeks of treatment

Blood dyscrasias induced by clozapine treatment and other Typical and Atypical Antipsychotics have received little attention. The aim of the present study was to shed more light on the incidence and course of clozapine-induced blood dyscrasias that occour during the first eighteen weeks of treatment compared to dyscrasias induced by other Typical and Atypical Antipsychotics. The study included 135 clozapine-treated patients (M 75 and F 60), 75 patients treated with other Atypical (M 35 and F 40), and 75 treated with Typical (M 39 and F 36). Persistent eosinophilia appeared in 36.8% of clozapine-treated patients, in 4%, (p