Safety profile of clozapine: Analysis using national registry data in Japan

Funahashi

et al. 2023

Neuropsychopharm Rep

Background The optimal treatment strategy for patients with treatment‐resistant schizophrenia (TRS) associated with 22q11.2 deletion syndrome (DS) remains a subject of debate. Case Presentation We present the case of a 40‐year‐old female patient diagnosed with TRS and 22q11.2DS who was effectively treated with clozapine. She was diagnosed with schizophrenia and mild intellectual disability during her adolescence; despite being hospitalized for a period of 10 years beginning in her 30s, she continued to exhibit symptoms of impulsivity, and explosive behavior, requiring periods of isolation. We ultimately decided to switch her medication to clozapine, which was administered with caution and gradually titrated upward, with no discernable adverse effects, resulting in a marked improvement in her symptoms and obviated the need for isolation. Subsequently, the patient's history of congenital heart disease and facial abnormalities prompted initial suspicions of a 22q11.2DS diagnosis, which was subsequently confirmed through genetic testing. Conclusion Clozapine may serve as an efficacious pharmacological intervention for TRS patients with 22q11.2DS, including those of Asian descent.

Section: Discussionmentioning

confidence: 99%

A case study of the utilization of clozapine treatment for treatment‐resistant schizophrenia associated with 22q11.2 deletion syndrome

Funahashi

et al. 2023

Neuropsychopharm Rep

Drugs - Real World Outcomes

“…We requested use of the database, but were denied access. Some studies by researchers or psychiatrists who had access to the database have been reported [ 14 – 16 ]. Clozapine was launched in Japan in 2009, and the number of patients in the database was approximately 8,000 by January 2020 [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Some studies by researchers or psychiatrists who had access to the database have been reported [ 14 – 16 ]. Clozapine was launched in Japan in 2009, and the number of patients in the database was approximately 8,000 by January 2020 [ 16 ]. In the database, neutropenia/leukopenia, seizure, gastrointestinal disorders, and cardiac disorders developed in 411, 21, 73, and 41 patients, respectively [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Clozapine was launched in Japan in 2009, and the number of patients in the database was approximately 8,000 by January 2020 [ 16 ]. In the database, neutropenia/leukopenia, seizure, gastrointestinal disorders, and cardiac disorders developed in 411, 21, 73, and 41 patients, respectively [ 16 ]. Using this database to identify risk factors for each side effect is likely to take time.…”

Section: Discussionmentioning

confidence: 99%

“…The reporting of other adverse drug events may reduce the reported frequency of the target adverse drug event. Clozapine-induced myocarditis develops within 3 weeks of the initiation of treatment [ 24 ], and this time to onset is shorter than that of other side effects [ 16 ]. Accordingly, reports on noninfectious myocarditis/pericarditis in clozapine-treated patients are expected to be insensitive to other adverse events.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Data Mining for Risks of Clozapine Side Effects, Including Neutropenia, Associated with Lithium Carbonate Administration: Analysis Using the Japanese Adverse Drug Event Report Database

Uwai

Nabekura

2023

Background and Objective Clozapine use is associated with development of neutropenia, and lithium carbonate may be co-administered to reduce this risk; however, this has not yet been adequately investigated. The present study examined whether lithium administration is associated with the risks of clozapine side effects, including neutropenia. Methods Data on patients taking clozapine, extracted from the Japanese Adverse Drug Event Report (JADER) database, were analyzed. Patients who developed clozapine side effects were identified by the Standardized Medical Dictionary for Regulatory Activities Queries. The relationship between the use of lithium and risk of clozapine side effects was examined using logistic regression analysis. Results The use of lithium was reported in 530 out of 2,453 clozapine users. Hematopoietic leukopenia, convulsion, and noninfectious myocarditis/pericarditis developed in 109, 87, and seven lithium-treated patients, and in 335, 173, and 62 untreated patients, respectively. Univariate analysis showed no relationship between lithium administration and the risks of hematopoietic leukopenia (adjusted odds ratio (aOR) 1.11; 95% confidence interval (CI) 0.98–1.25), and the association with the risks of convulsion (aOR 1.41; 95% CI 1.23–1.62) and noninfectious myocarditis/pericarditis (aOR 0.63; 95% CI 0.43–0.94). Multivariate analysis revealed that lithium use was independently associated with the risks of convulsion (aOR 1.40; 95% CI 1.21–1.60) and noninfectious myocarditis/pericarditis (aOR 0.62; 95% CI 0.41–0.91). Conclusion The risks of seizure and myocarditis, but not of neutropenia, in clozapine-treated patients may be altered by lithium. Although the JADER database is based on spontaneous reporting, the present results warrant further study.

Recurrent reactive hypoglycemia due to clozapine‐induced glucose intolerance: A case report

Kawai,

Watanabe,

Ebihara

et al. 2023

PCN Reports

BackgroundAlthough diabetes is one of the most common side effects of clozapine, a medication for the treatment of schizophrenia, to the best of our knowledge no study exists on clozapine‐induced glucose intolerance or hypoglycemia in patients with schizophrenia.Case PresentationWe report a case of schizophrenia with repeated reactive hypoglycemia due to abnormal glucose tolerance during clozapine treatment. During clozapine administration in patients with schizophrenia, it is necessary to monitor physical and psychiatric symptoms due to reactive hypoglycemia and hyperglycemia. If abnormal glucose tolerance is a concern, it should be promptly detected using blood or oral glucose tolerance tests.ConclusionEarly intervention for impaired glucose tolerance may prevent clozapine discontinuation due to diabetes or hyperglycemia.