Clinical Neuropsychopharmacology and Therapeutics
Online ISSN : 1884-8826
ISSN-L : 1884-8826
Volume 9
Displaying 1-7 of 7 articles from this issue
Letter to the Editor
Brief Report
  • Akifumi Nakamura, Kazuo Mihara, Goyo Nagai, Noboru Sakumoto, Tsuyoshi ...
    2018 Volume 9 Pages 3-6
    Published: March 14, 2018
    Released on J-STAGE: March 14, 2018

    Purpose: Marked elevations of serum creatine kinase (CK) activity in schizophrenia treated with atypical antipsychotics is regarded as a sign of neuroleptic malignant syndrome or rhabdomyolysis. It is suggested that atypical antipsychotics antagonize the 5-HT2A receptor in skeletal muscle, leading to changes in the sarcolemma which increases its permeability to CK. The 5-HT2A receptor gene (HTR2A) contains the T102C and His452Tyr polymorphisms, both of which affect the 5-HT2A receptor function. Meanwhile, the cytochromeP450 2D6 (CYP2D6), which shows a genetic polymorphism, may be involved in the development of CK elevation, because most antipsychotics are predominantly metabolized by this enzyme. This study aimed to investigate the relationship between the occurrence of CK elevation by atypical antipsychotics and these polymorphisms.

    Methods: The subjects were 15 Japanese schizophrenic patients who had developed CK elevation during the administration of atypical antipsychotics. The HTR2A T102C and His452Tyr, and CYP2D6 polymorphisms were determined by the polymerase chain reaction methods.

    Results: The allele frequencies of these polymorphisms were as follows: 102T, 40% vs. 102C=60%; His452, 100% vs. 452Tyr=0%; wild type for CYP2D6, 77% vs. *10=13% vs. *5=10%, respectively. Genotype patterns and allele frequency were nonspecific.

    Conclusions: These findings suggest that these genetic polymorphisms are not related to the development of CK elevation by atypical antipsychotics.

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Case Report
Original Contribution
  • Kensuke Yoshimura, Tasuku Hashimoto, Yasunori Sato, Aiko Sato, Takashi ...
    Article type: Original Contribution
    2018 Volume 9 Pages 20-28
    Published: September 28, 2018
    Released on J-STAGE: September 28, 2018

    Purpose: Pharmacological treatments with some anticonvulsants, including valproate, and lithium should be avoided where possible in childbearing-aged and pregnant women with epilepsy and bipolar disorder because they increase the risk of major congenital malformations. We surveilled real-world prescriptions of anticonvulsants and lithium in childbearing-aged female and male outpatients in Japan, using the first public National Insurance Claims Database of Japan.

    Methods: We performed a summary statistical analysis of the numbers of the most prescribed 11 anticonvulsants and lithium tablets in female and male outpatients aged 15-29 (younger childbearing age), 30-49 (older childbearing age), and >50 (non-childbearing age) years from April 2014 to March 2015. We determined the association between anticonvulsant or lithium use and sex at childbearing age, and the odds ratio (OR) and 95% confidence intervals (CIs) were estimated using logistic regression analysis.

    Results: Valproate (number of tablets = 273,135,937) was the most prescribed among the 12 investigated drugs, and 125,451,907 tablets were prescribed for women (younger, older, and non-childbearing ages, 19,296,528, 47,826,746, and 58,328,63, respectively), compared to 147,684,031 tablets for men (24,534,648, 57,229,981, and 65,919,402, respectively). Valproate prescription was only slightly lower in childbearing-aged women than in the same-aged men (i.e., 15-29 years of age, OR = 0.889 [95% CI, 0.888-0.890]; 30-49 years of age, OR = 0.944 [95% CI, 0.944-0.945]).

    Discussion: This study demonstrated valproate was highly prescribed for childbearing-aged women in Japan in 2014-2015. Physicians should prescribe valproate with considerable caution in girls and childbearing-aged women.

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