clozapine and Leukocytosis

Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia. Despite its superior efficacy profile as compared with other antipsychotics, clozapine remains underutilized. Clozapine monitoring systems clearly describe the proposed management of clozapine-induced neutropenia; however, no specific mention is made of how to interpret neutrophilic leukocytosis, despite that being a relatively frequent finding. Prescribers unfamiliar with this molecule may misjudge its clinical significance, potentially leading to untimely treatment interruption. Here, we systematically review the literature on the risk of neutrophilic leukocytosis during clozapine treatment, and describe eight additional cases among our patient cohort.. We performed a systematic review of the literature on PubMed and Embase using the PRISMA 2020 guidelines, and selected all original reports describing either (1) the prevalence of neutrophilic leukocytosis during clozapine treatment, or (2) the clinical significance of neutrophilic leukocytosis. We described eight additional cases of neutrophilic leukocytosis during clozapine treatment while attending an outpatient psychiatric clinic.. Our research ultimately yielded the selection of 13 articles included in this systematic review. The case series highlighted the presence of stable and clinically unremarkable neutrophilia during a follow-up ranging from one to ten years.. Existing evidence indicates that leukocytosis associated with clozapine treatment can be considered as an asymptomatic and benign condition, suggesting that no change in clozapine treatment is needed upon its detection.

Topics: Antipsychotic Agents; Clozapine; Humans; Leukocytosis; Prevalence; Schizophrenia

A possible relationship between haematological adverse reactions and clozapine (CLZ) metabolism rate was studied. Sixteen chronic schizophrenic outpatients (mean age 34.62 years +/- 7.56 SD) were treated with CLZ, 75-600 mg/daily for 9 weeks. CLZ and norclozapine (NCLZ) plasma levels were determined weekly, contemporarily with blood cell counts. CLZ plasma levels ranged from 25 to 1270 ng/ml (mean 266.27 ng/ml +/- 197.44 SD), while NCLZ plasma levels ranged from 25 to 1280 ng/ml (mean 169.0 ng/ml +/- 127.94 SD). NCLZ/CLZ ratio ranged from 0.13 to 1.72 (mean 0.72 +/- 0.28 SD). Leukocyte count ranged from 5.2 to 18.8 10(9)/l (mean 9.37 10(9)/l +/- 2.94 SD) and neutrophil count ranged from 1.8 to 13.4 10(9)/l (mean 5.73 +/- 2.57 SD). No correlation was found between CLZ dosage and NCLZ plasma levels. Both CLZ and NCLZ plasma levels correlated positively with neutrophil count (CLZ: P = 0.001, r = 0.26; NCLZ: P = 0.01, r = 0.20). The correlation between NCLZ/CLZ plasma level ratio and neutrophil count was significantly negative (P = 0.002, r = 0.25). These preliminary data suggest that the NCLZ/CLZ ratio, as an index of CLZ metabolism, might be a possible risk factor associated with CLZ treatment.

Topics: Adult; Agranulocytosis; Antipsychotic Agents; Clozapine; Female; Humans; Leukocyte Count; Leukocytosis; Male; Middle Aged; Risk Factors; Schizophrenia

Neutropenia is a noteworthy side effect of clozapine, which might warrant this drugs' discontinuance for safety. Studies have revealed that the risk of neutropenia increases with concurrent administration of valproate, but the evidence was limited. Conversely, lithium may have an ameliorating effect on clozapine-induced neutropenia. This study explored the effects of valproate and lithium on white blood cell counts in patients treated with clozapine.. We retrospectively investigated the electronic medical records from one tertiary psychiatric hospital in Taiwan and enrolled patients discharged between January 1, 2006, and December 31, 2017, with clozapine prescriptions. We scrutinized their demographic data, medications, and hematological results at discharge and during follow-up outpatient clinic visits over the subsequent 3 years. Patients were classified into four groups: clozapine only (CLO), clozapine and valproate (CLO + VAL), clozapine and lithium (CLO + Li), and clozapine, valproate, and lithium (CLO + VAL + Li). We also identified hematological events (neutropenia or leukocytosis) of these patients during outpatient follow-ups.. Of the included 1084 patients, 55(5.1%) developed neutropenia. Concurrent valproate use (odds ratio [OR] = 3.49) and older age (p = .007) were identified as risk factors. Moreover, 453 (41.79%) patients developed leukocytosis. Younger age; male sex; and concurrent use of lithium (OR = 3.39, p < .001), clozapine daily dosage, and benzodiazepines were the risk factors for leukocytosis.. Concurrent valproate use and older age are associated with the development of neutropenia in patients treated with clozapine. Concurrent lithium usage, younger age, male sex, and concurrent benzodiazepine use might be related to leukocytosis.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Humans; Leukocytosis; Lithium; Male; Neutropenia; Retrospective Studies; Valproic Acid

Topics: Adult; Antipsychotic Agents; Biomarkers; Clozapine; Electrocardiography; Fever; Humans; Leukocytosis; Male; Myocarditis; Schizophrenia, Paranoid; Tachycardia; Ultrasonography

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.

Topics: Adult; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Humans; Leukocytosis; Male; Predictive Value of Tests; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Child; Clozapine; Female; Fever; Humans; Leukocytosis; National Institute of Mental Health (U.S.); Schizophrenia; United States

Clozapine is an important second-generation antipsychotic that is reserved for patients with refractory schizophrenia. Unfortunately, clozapine is also associated with a number of adverse effects, with agranulocytosis being one of the chief concerns. Interestingly, patients who receive clozapine treatment may occasionally experience elevations in their total white blood cell count (WBC). In some of these patients, the leukocytosis may be persistent. We report the case of a patient with refractory schizophrenia who is treated with clozapine and who experienced chronic leukocytosis. A brief review of the literature addressing clozapine-associated leukocytosis follows the case report.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Clozapine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Leukocyte Count; Leukocytosis; Male; Schizophrenia, Paranoid

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Leukocyte Count; Leukocytosis; Lithium Carbonate; Male; Neutrophils; Psychotic Disorders; Reference Values

Topics: Adult; Antipsychotic Agents; Chronic Disease; Clozapine; Humans; Leukocytosis; Male; Middle Aged; Retrospective Studies

Clozapine is a dibenzodiazepine derivative that is more effective than standard neuroleptic drugs in refractory schizophrenic patients, but its introduction in some countries was delayed by its propensity to cause blood dyscrasias. However, over the last ten years, different reports have clearly demonstrated that agranulocytosis and neutropenia can be easily prevented by means of strict hematologic surveillance. This article reviews the results of the first five years of the Italian Clozapine Monitoring System (ICLOS).. The hematologic parameters of 2,404 patients registered between 1995 and 1999 were collected in a central database, before the patients began clozapine-treatment, weekly for the first 18 weeks, and then monthly throughout the duration of therapy. On the basis of conventional criteria, different risk levels have been identified with total leukocyte <3. 0x10(9)/L and/or an absolute neutrophil count <1.5x10(9)/L leading to immediate discontinuation of the drug.. The analysis shows that 0.9% of the patients developed neutropenia and 0.7% agranulocytosis, mainly during the first 18 weeks of clozapine treatment. Drug discontinuation led to the normalization of hematologic parameters in all cases, and the use of growth factors reduced the risk of infectious complications. Transient leukocytosis and eosinophilia were also observed but these did not have any serious clinical effects.. The ICLOS study confirms that regular hematologic monitoring is highly effective in minimizing the incidence of clozapine-associated blood dyscrasias. The lower than initially expected rates of agranulocytosis and associated deaths are encouraging in view of the benefits of this drug in treatment-resistant schizophrenia and other neurologic disorders.

Topics: Adult; Agranulocytosis; Antipsychotic Agents; Clozapine; Eosinophilia; Female; GABA Antagonists; Granulocyte Colony-Stimulating Factor; Humans; Incidence; Italy; Leukocytosis; Male; Middle Aged; Neutropenia; Paraproteinemias; Retrospective Studies; Risk Factors; Schizophrenia; Serotonin Antagonists; Thrombocytopenia

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Leukocytosis; Male; Schizophrenia

Topics: Antipsychotic Agents; Clozapine; Humans; Leukocytosis; Male; Middle Aged; Schizophrenia

Topics: Adult; Clozapine; Drug Administration Schedule; Drug Monitoring; Female; Hospitals, Psychiatric; Humans; Leukocytosis; Male; Middle Aged; Schizophrenia

The aim of the study was to shed more light on the incidence and course of clozapine-induced transient white blood count (WBC) disorders.. In an analysis of our clozapine drug monitoring program, we evaluated the data of 68 patients receiving clozapine for the first time. Incidence rates were calculated by actuarial life table analysis. The potential influence of sex, age, dose, and plasma level was evaluated using discriminant analysis.. Two patients developed progressive neutropenia, leading to agranulocytosis in one case. We also found the following transient hematologic dysfunctions: neutropenia (22.0%), eosinophilia (61.7%), and leukocytosis (40.9%). One patient showed chronic leukocytosis. Additionally, minor changes in the number of lymphocytes, monocytes, and basophilic granulocytes were detected in the study population.. Hematologic side effects are frequently induced by the atypical antipsychotic clozapine. Next to agranulocytosis, a progressive and potentially lethal hematologic adverse effect, most of the WBC disorders are transient and appear to be harmless.

Topics: Actuarial Analysis; Adult; Agranulocytosis; Austria; Clozapine; Drug Monitoring; Eosinophilia; Female; Humans; Incidence; Leukocytosis; Male; Neutropenia; Prevalence; Prospective Studies; Schizophrenia

Topics: Amitriptyline; Anti-Anxiety Agents; Benzodiazepines; Clozapine; Depressive Disorder; Humans; Leukocytosis; Male; Middle Aged; Neutrophils; Smoking; Stress, Psychological

Topics: Clozapine; Humans; Leukocytosis; Male; Middle Aged; Monocytes; Parkinson Disease; Time Factors

Topics: Adult; Clozapine; Eosinophilia; Humans; Leukocytosis; Male; Recurrence; Schizophrenia

The main side effects of 7921 hospitalized patients taken clozapine from July in 1980 to October in 1988 were investigated. In these cases, there were 600 patients with the main side effects caused by clozapine. They included 312 patients with leukocytosis (52.0%), 114 patients with leukopenia (19.0%), (included 16 patients with agranulocytosis), 53 patients with EEG abnormal (8.9%), 35 patients with fever (5.9%), 32 patients with EKG abnormal (5.3%), 14 patients with rash (2.3%), 12 patients with epileptic seizure (2.0%), 11 patients with posture hypotension (1.8%), 8 patients with paralytic intestinal obstruction (1.3%), 6 patients with SGPT raised (1.0%) and 3 patients with conscious disturbances (0.5%). The causes and treatments of the main side effects mentioned above were discussed.

Topics: Adolescent; Adult; Aged; Child; Clozapine; Electroencephalography; Epilepsy; Female; Humans; Intestinal Pseudo-Obstruction; Leukocytosis; Leukopenia; Male; Middle Aged