alexa Very Late-Onset Neutropenia in a Japanese Schizophrenia Patient Treated with Clozapine | Open Access Journals
ISSN: 2165-7920
Journal of Clinical Case Reports
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Very Late-Onset Neutropenia in a Japanese Schizophrenia Patient Treated with Clozapine

Reiji Yoshimura1*, Naoyuki Takashima1 and Jun Nakamura2,3

1Department of Psychiatry, University of Occupational and Environmental Health, Japan

2University of Occupational and Environmental Health, Japan

3Kitakyushu-Koga Hospital, Koga, Fukuoka, Japan

*Corresponding Author:
Reiji Yoshimura
Department of Psychiatry
University of Occupational and Environmental Health, Japan.
Tel: +81-93-691-7253
Fax: +81- 93-692-4894
Email: [email protected]

Received Date: March 29, 2017; Accepted Date: May 16, 2017; Published Date: May 21, 2017

Citation: Yoshimura R, Takashima N, Nakamura J (2017) Very Late-Onset Neutropenia in a Japanese Schizophrenia Patient Treated with Clozapine. J Clin Case Rep 7:956. doi: 10.4172/2165-7920.1000956

Copyright: © 2017 Yoshimura R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Clinical Case Reports

Abstract

We here reported a chronic schizophrenia patient who occurred neutropenia 13 years after starting clozapine. Thus, once clozapine is administered, the lifelong regular monitoring of the patient’s total WBC count should be done.

Keywords

Clozapine; Neutropenia; Late-onset

Case Report

The patient was a 46-year-old Japanese man who had met the DSMIV diagnosis of schizophrenia, disorganized-type, for the prior 30 years. He had been on antipsychotic regimens since being diagnosed when he was 16 years old. He had been treated with therapeutic doses of sulpiride, haloperidol, levomepromazine, risperidone, olanzapine, aripiprazole, or lithium on several occasions, after which the treatments were stopped due to inadequate treatment response. After that, clozapine was started during his eighth hospitalization in 33-year-old in which he was brought to the hospital for persistent auditory hallucinations, monologia, persecutory delusion aggressiveness, and psychomotor excitement.

After this admission, the clozapine dosage was titrated gradually up to 600 mg/day. The patient’s total leucocyte count at baseline was 10,000/mm3. After discharge from the hospital, he showed a prominent improvement in his clinical status, with no apparent psychotic symptoms, and he attended a day-care service. During the long follow-up period, his total leucocyte count range was between 5,380 and 11,290/mm3 with a daily 600 mg clozapine dosage. Twelve years after the start of that clozapine treatment, the patient’s total leucocyte count had gradually decreased to 2,255 mm3. We therefore added lithium carbonate (600 mg/day) to increase the leucocyte count. However, the total leucocyte count did not recover after the addition of lithium carbonate (2,460 mm3, 1,663 mm3, 1,584 mm3, 1,526 mm3). In 46-year-old (13 years later), the patient’s total leucocyte count had gradually declined to 1,330/ mm3, and the 600 mg/day clozapine was stopped at the same time. His auditory hallucination, persecutory delusion, irritability, psychomotor excitement were exacerbated after stopping clozapine. Olanzapine (20 mg/day) and levomepromazine (150 mg/day) were re-started; those symptoms were however not ameliorated. Physical symptoms associated with neutropenia including fever, anemia, bleeding, irritability, and hot flashes were not seen. Four weeks after the clozapine was discontinued, the patient’s total leucocyte count had recovered to 8,915/mm3. Written informed consent to have his case published was obtained from the patient.

Results and Discussion

We have reported the case of a patient who developed neutropenia a very long time after starting clozapine treatment, i.e., 13 years. The patient was asymptomatic when the neutropenia occurred. The problematic factor limiting the use of clozapine as a first-line agent in mentally ill patients is the risk of agranulocytosis. Clinicians should monitor a patient for neutropenia during the entire period of clozapine treatment. Although the greatest risk of developing this adverse reaction is during the initial 6-month exposure, clozapine-induced neutropenia may pose a risk after years of exposure [1-3]. The current product labeling for clozapine recommends the weekly determination of a patient’s total leucocyte count and granulocyte monitoring for the first 6 months of treatment, which may be decreased to biweekly monitoring based on the sudden and late onset of agranulocytosis in our patient in Japan according to the regulation of Clozaril Patient Monitoring Service. Several prior studies also found that neutropenia can occur many years after the start of clozapine treatment. Nongpiur et al. [2] reported a case of leucopenia that emerged after 11 years of continuous clozapine monotherapy. Taking these findings into account, it appears that the agranulocytosis occurs the lifelong for clozapine treatment. Our patient’s case indicates the necessity of the lifelong monitoring of the WBC count [4-7]. The mechanism responsible for neutrophil toxicity of clozapine is not fully elucidated. Genetic factors, as well as immunological and toxic mechanism may play an important role [8,9]. N-Desmethylclozapine and clozapine N-oxide are the known major metabolites of clozapine. In vitro studies demonstrated that those major metabolites, but not clozapine itself is toxic to neutrophils [10].

Most guidelines recommend stopping clozapine treatment when the level of neutrophils falls below 1500/mm3. In cases of neutropenia, the co-prescribing of lithium is supported by several reports [2,7]. The evidence regarding the efficacy of lithium for increasing the total leucocyte count is not robust. In the present case, the total leucocyte count was not recovered.

Conclusion

In conclusion, we treated a patient with very late-onset neutropenia induced by clozapine. Clinicians should pay attention to the risk of neutropenia even when a patient’s total leucocyte count remains constant over a long term. When clozapine is administered, the lifelong regular monitoring of the patient’s total WBC count should be done.

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

  • Global Experts Meeting on Case Reports
    Osaka, Japan October 09-11, 2017
  • 6th Global Experts Meeting on Medical Case Reports
    October 16-18, 2017 San Francisco, California, USA

Article Usage

  • Total views: 402
  • [From(publication date):
    May-2017 - Sep 21, 2017]
  • Breakdown by view type
  • HTML page views : 370
  • PDF downloads :32
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords