Increase in white cell and neutrophil counts during the first eighteen weeks of treatment with clozapine in patients admitted to a long-term psychiatric care inpatient unit

Capllonch-Carrión, Adrián; Pablo, Silvia de; Torre, A. de la; Morales, Ignacio

doi:10.1016/j.rpsmen.2018.02.007

Cited by 3 publications

(5 citation statements)

References 7 publications

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“…This is because, unlike these drugs, lithium carbonate has the opposite effect, leading to leukocytosis and an improvement in neutropenia and leukopenia (14). Regarding neutropenia, the simultaneous administration of lithium is supported by published studies (13,15).…”

Section: Discussionmentioning

confidence: 99%

“…Potential mechanisms that may predispose to leukopenia and neutropenia include direct toxic effects upon the bone marrow, the formation of antibodies against hematopoietic precursors, or involvement in the peripheral destruction of cells (12). To reduce this risk, monitoring the number of WBC and treatment decisions, including early administration of growth factors or lithium, may be useful (13). This is because, unlike these drugs, lithium carbonate has the opposite effect, leading to leukocytosis and an improvement in neutropenia and leukopenia (14).…”

Section: Discussionmentioning

confidence: 99%

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The effect of lithium on clozapine-induced neutropenia reduction in refractory schizoaffective disorder

Rezaei Kheirabadi,

Naderi,

Karami

2023

J Shahrekord Univ Med Sci

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Resistant schizoaffective disorder has persistent psychotic symptoms and intermittent mood swings. A satisfying method for treating these patients is the use of the antipsychotic drug clozapine, but its use is limited due to significant side effects such as leukopenia and neutropenia. Lithium carbonate is another psychiatric drug that reduces these side effects. We hypothesized that lithium, along with clozapine, in addition to controlling side effects, could have a dual effect on mood episodes in schizoaffective disorder, and used it in a chronic case. The patient was a 48-year-old man with a 20-year history of the disease. Therefore, the use of lithium along with clozapine is recommended in refractory schizoaffective patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The effect of lithium on clozapine-induced neutropenia reduction in refractory schizoaffective disorder

Rezaei Kheirabadi,

Naderi,

Karami

2023

J Shahrekord Univ Med Sci

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“…In contrast to haloperidol, which seems to show only rare hematological effects, it is known that clozapine induces dyscrasias of leukocytes [ 58 ] and erythrocytes [ 7 ] in humans, and chronic liver injury in mice [ 59 ] and rats [ 28 , 29 ]. There is growing evidence that clozapine medication is associated with severe drug-induced hepatic injury in patients [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome

Bouvier

Fehsel

Schmitt

et al. 2022

BMC Pharmacol Toxicol

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Background Patients with liver diseases often have some form of anemia. Hematological dyscrasias are known side effects of antipsychotic drug medication and the occurrence of agranulocytosis under clozapine is well described. However, the sex-dependent impact of clozapine and haloperidol on erythrocytes and symptoms like anemia, and its association with hepatic iron metabolism has not yet been completely clarified. Therefore, in the present study, we investigated the effect of both antipsychotic drugs on blood parameters and iron metabolism in the liver of male and female Sprague Dawley rats. Methods After puberty, rats were treated orally with haloperidol or clozapine for 12 weeks. Blood count parameters, serum ferritin, and liver transferrin bound iron were determined by automated counter. Hemosiderin (Fe3+) was detected in liver sections by Perl’s Prussian blue staining. Liver hemoxygenase (HO-1), 5’aminolevulinate synthase (ALAS1), hepcidin, heme-regulated inhibitor (HRI), cytochrome P4501A1 (CYP1A1) and 1A2 (CYP1A2) were determined by Western blotting. Results We found anemia with decreased erythrocyte counts, associated with lower hemoglobin and hematocrit, in females with haloperidol treatment. Males with clozapine medication showed reduced hemoglobin and increased red cell distribution width (RDW) without changes in erythrocyte numbers. High levels of hepatic hemosiderin were found in the female clozapine and haloperidol medicated groups. Liver HRI was significantly elevated in male clozapine medicated rats. CYP1A2 was significantly reduced in clozapine medicated females. Conclusions The characteristics of anemia under haloperidol and clozapine medication depend on the administered antipsychotic drug and on sex. We suggest that anemia in rats under antipsychotic drug medication is a sign of an underlying liver injury induced by the drugs. Changing hepatic iron metabolism under clozapine and haloperidol may help to reduce these effects of liver diseases.

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“…Increased release of cytokines such as TNF-α, IL-2, IL-6, and G-CSF instead indirectly induces the expression of anti-apoptotic proteins, capable of promoting the differentiation and maturation of myelocytes. In this setting, leukocytosis ensues from the preponderance of anti-apoptotic factors, tipping the scale in favor of an increased total leukocyte count, and in particular in the neutrophil count [ 25 , 51 , 52 ]. An additional hypothesis involves the inflammatory response mediated by clozapine itself on blood cells, which appears particularly evident during the first month of treatment [ 25 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

“…During a two-year period, his leukocyte count fluctuated from a minimum of 10,000 units/mm 3 to a maximum of 28,000 units/mm 3 [ 27 ]. Capllonch and coauthors reported on a cohort of 55 women treated with clozapine presenting higher leukocyte and neutrophil levels after the first three to four weeks of treatment, with persistent elevations from the baseline observed during the 18-week follow-up [ 51 ]. In a case series, Prisco et al proposed neutrophilic leukocytosis as a possible predictor of resistance to clozapine treatment [ 56 ], in accordance with previous reports [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Leukocytosis Associated with Clozapine Treatment: A Case Series and Systematic Review of the Literature

et al. 2021

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Background and Objectives: 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. Materials and Methods: 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. Results: 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. Conclusions: 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.

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Increase in white cell and neutrophil counts during the first eighteen weeks of treatment with clozapine in patients admitted to a long-term psychiatric care inpatient unit

Cited by 3 publications

References 7 publications

The effect of lithium on clozapine-induced neutropenia reduction in refractory schizoaffective disorder

The effect of lithium on clozapine-induced neutropenia reduction in refractory schizoaffective disorder

Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome

Leukocytosis Associated with Clozapine Treatment: A Case Series and Systematic Review of the Literature

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