A case of improvement of clozapine-induced low leukocyte counts by adenine, cepharanthin and ninjin-yoei-to in a patient with treatment-resistant schizophrenia

Abstract Background Although clozapine is the optimal drug for patients with treatment-resistant schizophrenia, the drug has harmful adverse effects such as leukopenia. Adenine and cepharanthine are known to be effective for radiation- or drug-induced leukopenia. Furthermore, ninjin-yoei-to, a Chinese herbal medicine, augments the production of granulocyte-macrophage colony-stimulating factor. Thus, these drugs may be useful for clozapine-induced leukopenia. Case presentation A 21 years-old woman with schizophrenia was hospitalized for initiation of clozapine treatment. Despite concomitant use of adenine, cepharanthine, and lithium carbonate having activities of increasing leukocytes, a decrease in leukocyte counts occurred after the initiation of clozapine. Additional administration of ninjin-yoei-to increased leukocyte counts, which prevented the development of leukopenia. Conclusions This is the first case that concomitant use of adenine, cepharanthin, and ninjin-yoei-to exhibited the effectiveness of reversing the decrease in leukocytes caused by clozapine. Monitoring leukocyte counts and preventing leukopenia are essential for successful treatment with clozapine for refractory schizophrenia. These medicines may be a potential option for preventing clozapine-induced leukopenia.

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Utilization of G-CSF and GM-CSF as an alternative to discontinuation in clozapine-induced neutropenia or leukopenia: A case report and discussion

Mental Health Clinician ◽

10.9740/mhc.2018.09.250 ◽

2018 ◽

Vol 8 (5) ◽

pp. 250-255 ◽

Cited By ~ 1

Author(s):

Allison Karst ◽

Jonathan Lister

Keyword(s):

Case Report ◽

Treatment Resistant ◽

Colony Stimulating Factors ◽

Gm Csf ◽

Clozapine Treatment ◽

Increased Risk ◽

Proliferation And Differentiation ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

Abstract Clozapine remains the definitive gold standard for treatment-resistant schizophrenia despite limitations in use because of hematological abnormalities. Neutropenia or leukopenia are often treated with interruption of clozapine treatment, frequently resulting in clinical decompensation, hospitalization, increased burden to patient care, and increased risk of suicide. Colony-stimulating factors, including granulocyte colony-stimulating factors and granulocyte-macrophage colony-stimulating factors, are cytokines that stimulate proliferation and differentiation of myeloid precursor cells. Their use in the prevention and treatment of clozapine-associated neutropenia presents an alternative to clozapine discontinuation in certain cases. We present a case report of successful periodic granulocyte-macrophage colony-stimulating factor use with clozapine in a patient with treatment-resistant schizophrenia, as well as discussion of a practical approach to patients with possible clozapine-induced neutropenia or leukopenia.

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Safety of a Clozapine Trial Following Quetiapine-Induced Leukopenia: A Case Report

Current Drug Safety ◽

10.2174/1574886313666180807094654 ◽

2019 ◽

Vol 14 (1) ◽

pp. 80-83 ◽

Cited By ~ 3

Author(s):

Asma H. Almaghrebi

Keyword(s):

Treatment Options ◽

Young Female ◽

Similar Reaction ◽

Careful Monitoring ◽

Treatment Resistant ◽

Blood Cell Count ◽

Antipsychotic Medications ◽

Case Presentation ◽

Clozapine Treatment ◽

History Of

Background: The clozapine-derivative quetiapine has been shown in some cases to cause leukopenia and neutropenia. Case Presentation: We reported on a case of a young female diagnosed with treatment-resistant schizophrenia. After failed trials of three antipsychotic medications and despite a history of quetiapineinduced leukopenia, clozapine treatment was introduced due to the severity of the patient’s symptoms, the limited effective treatment options, and a lack of guidelines on this issue. Result: Over a ten-week period of clozapine treatment at 700 mg per day, the patient developed agranulocytosis. Her white blood cell count sharply dropped to 1.6 × 10<sup>9</sup> L, and her neutrophils decreased to 0.1 × 10<sup>9</sup> L. There had been no similar reaction to her previous medications (carbamazepine, risperidone, and haloperidol). Conclusion: The safety of clozapine in a patient who has previously experienced leukopenia and neutropenia with quetiapine requires further investigation. Increased attention should be paid to such cases. Careful monitoring and slow titration are advisable.

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Differential activation of the endogenous leukotriene biosynthesis by two different preparations of granulocyte-macrophage colony-stimulating factor in healthy volunteers

Blood ◽

10.1182/blood.v81.8.2007.bloodjournal8182007 ◽

1993 ◽

Vol 81 (8) ◽

pp. 2007-2013 ◽

Cited By ~ 1

Author(s):

C Denzlinger ◽

W Tetzloff ◽

HH Gerhartz ◽

R Pokorny ◽

S Sagebiel ◽

...

Keyword(s):

Chinese Hamster ◽

Pharmacokinetic Parameters ◽

Colony Stimulating Factor ◽

Drug Induced ◽

E Coli ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

Results from in vitro investigations and recent data obtained in patients with drug-induced cytopenia or myelodysplasia suggest that leukotrienes may be involved in mediating some of the actions of granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, the possible role of leukotrienes was further characterized in 21 healthy individuals to avoid modification of response to GM-CSF by disease-specific variables. The effects of two different preparations of human recombinant GM-CSF, ie, glycosylated GM- CSF as expressed in a Chinese hamster ovary carcinoma (CHO) cell line and nonglycosylated GM-CSF obtained from Escherichia coli, were compared. GM-CSF was administered subcutaneously at a single dose of 0.7 nmol/kg body weight. Pharmacokinetic parameters and hematopoietic and adverse effects were monitored by blood analyses or physical examination, respectively. Leukotriene generation in vivo was evaluated by determination of leukotriene E4 and N-acetyl-leukotriene E4 in urine. After the injection of GM-CSF from E coli, serum concentrations increased and decreased more rapidly and reached a 2.3-fold higher maximum compared with GM-CSF from CHO. GM-CSF induced a biphasic change in leukocyte counts that proceeded considerably faster after the E coli preparation than after GM-CSF from CHO. The urinary leukotriene concentration increased 1.3- to 14-fold or 2.1- to 44-fold after the administration of GM-CSF from CHO or E coli, respectively. Urinary leukotriene concentrations correlated significantly with the maximum of basophil counts and correlated with the occurrence of some adverse reactions, ie, flu-like symptoms, bone pain, or dyspnoea. Our data confirm the conception that leukotrienes may play a significant role in GM-CSF action in vivo. They especially direct attention to the possible relevance of leukotrienes to untoward effects of GM-CSF treatment.

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Fatal Case of Vulvar Pyoderma Gangrenosum with Pulmonary Involvement: Case Presentation and Literature Review

Journal of Cutaneous Medicine and Surgery ◽

10.2310/7750.2014.13196 ◽

2014 ◽

Vol 18 (6) ◽

pp. 424-429 ◽

Cited By ~ 8

Author(s):

Joshua M. Mercer ◽

Paul Kuzel ◽

Muhammad N. Mahmood ◽

Alain Brassard

Keyword(s):

Literature Review ◽

Pyoderma Gangrenosum ◽

Rare Case ◽

Fatal Case ◽

Pulmonary Involvement ◽

Review Of The Literature ◽

Treatment Resistant ◽

Case Presentation ◽

First Case ◽

Systemic Therapies

Introduction: We report a case of a 61-year-old woman with locally destructive vulvar pyoderma gangrenosum (PG) with pulmonary involvement who was refractory to numerous systemic therapies and developed complications resulting in her demise. Objective: To report a rare case of treatment-resistant vulvar PG with pulmonary involvement that proved to be fatal. Methods: PubMed was used to search for other reports that discuss PG, or more specifically perigenital PG, with pulmonary involvement. Results and Conclusion: A thorough review of the literature revealed 33 cases of PG with pulmonary involvement, with only 4 involving the perigenital region. We report the second case of a female with vulvar PG and pulmonary involvement. In contrast to the first case described, our patient did not respond to systemic therapy, and, ultimately, her disease was fatal. It is hoped that with continued documentation of this rare and potentially lethal presentation of PG, physicians will determine more effective treatments.

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Circadian rhythm of neutrophil counts and granulocyte macrophage-colony stimulating factor (GM-CSF) under clozapine treatment: A case report

The World Journal of Biological Psychiatry ◽

10.3109/15622970902806132 ◽

2010 ◽

Vol 11 (2-2) ◽

pp. 511-513 ◽

Cited By ~ 2

Author(s):

Stefano Ferrea ◽

Karin Fehsel ◽

Joachim Cordes ◽

Christian Luckhaus

Keyword(s):

Circadian Rhythm ◽

Case Report ◽

Colony Stimulating Factor ◽

Gm Csf ◽

Clozapine Treatment ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

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Plasma macrophage colony-stimulating factor levels during cardiopulmonary bypass with extracorporeal circulation

Mediators of Inflammation ◽

10.1155/s0962935196000518 ◽

1996 ◽

Vol 5 (5) ◽

pp. 358-361

Author(s):

Y. Denizot ◽

P. Fixe ◽

E. Cornu ◽

N. Nathan

Keyword(s):

Cardiopulmonary Bypass ◽

Extracorporeal Circulation ◽

Inflammatory Process ◽

Protein A ◽

Colony Stimulating Factor ◽

Leukocyte Counts ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Different Origins ◽

Stimulating Factor

Leukocytosis and thrombocytopenia occur during cardiopulmonary bypass (CPB) with extracorporeal circulation (ECC). Elevated circulating concentrations of macrophage colony-stimulating factor (M-CSF) are reported during thrombocytopenia and leukopenia of different origins. We have assessed M-CSF concentrations in 40 patients undergoing CPB with ECC. Plasma M-CSF concentrations were stable during ECC and increased at the 6th (7.3 ± 0.7 IU/μg protein) and 24th (8.6 ± 0.8 IU/μg protein) postoperative hour compared with pre-ECC values (4.9 ± 0.5 IU/μg protein). A deep thrombocytopenia was found during ECC and until the 24th postoperative hour. A drop of leukocyte counts was found during ECC followed by an increase after ECC weaning. While no correlation was found between M-CSF concentrations and the leukocyte counts, M-CSF values were positively correlated with platelet counts only before and during ECC. Thus, M-CSF is not implicated in the thrombocytopenia and the leukopenia generated during CPB with ECC. However the elevated levels of M-CSFa few hours after the end of ECC might play a role in the inflammatory process often observed after CPB.

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Hydromorphone-induced chorea as an atypical presentation of opioid neurotoxicity: A case report and review of the literature

Palliative Medicine ◽

10.1177/0269216318786861 ◽

2018 ◽

Vol 32 (9) ◽

pp. 1529-1532 ◽

Cited By ~ 1

Author(s):

Emily J Martin ◽

Christina L Vaughan ◽

Rabia Atayee ◽

Jeremy M Hirst ◽

Kaitlyn O’Donnell ◽

...

Keyword(s):

Cutaneous Lesion ◽

Cutaneous Lesions ◽

Drug Induced ◽

Case Presentation ◽

Opioid Dose ◽

First Case ◽

Severe Postoperative Pain ◽

History Of ◽

Case Outcome ◽

Primary Cutaneous Lymphoma

Background: While opioid-induced myoclonus is well described, there are limited reports of opioid-induced chorea. Here we present the first case of chorea as a manifestation of opioid neurotoxicity due to hydromorphone. Case presentation: A 20-year-old woman presenting with fevers and cutaneous lesions was diagnosed with hemophagocytic lymphohistiocytosis secondary to primary cutaneous lymphoma. Surgical resection of a cutaneous lesion was complicated by severe postoperative pain requiring rapid opioid dose escalation. Seven days after hydromorphone was initiated, she developed positive myoclonus, hallucinations, delirium, and involuntary, flowing movements consistent with chorea. She had no personal or family history of nervous system disorders and was not taking any medications associated with drug-induced chorea. Case management: The remainder of her neurologic examination was unremarkable. Her renal function was normal and no etiology was found on neuroimaging or laboratory workup. Hydromorphone was discontinued and pain control was achieved with fentanyl. Case outcome: The patient’s neurotoxic symptoms including chorea resolved within 72 h of hydromorphone discontinuation. Conclusion: Further studies are needed to determine which patients have a unique sensitivity to opioids predisposing them to chorea. Clinicians should be aware that chorea may be a sign of such toxicity so that rapid corrective action can be taken.

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