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1. Clozapine treatment of a Japanese patient during pregnancy: Effect on fetal heart rate

Author

Shunya Aoki, Katsutoshi Takada, Tatsuru Sugama, Mitsugi Kimiwada, Tatsuya Hoshino, Takaoki Kaneko, Shintaro Obata, Yasuhiro Ota, Satoshi Toishi, Kaori Koike, Hirokazu Akada, Takahisa Saiga, and Shigeki Sato

Subjects
clozapine, drug monitoring, Japanese people, maternal‐fetal exchange, pregnancy, Therapeutics. Pharmacology, RM1-950, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract The current literature on the effects of clozapine on pregnancy is limited, and no cases of pregnant Japanese women have been reported. Decreased variability in the fetal heart rate due to clozapine exposure has been reported in countries other than Japan, but its association with serum concentrations of clozapine has not been documented. In this case, a 29‐year‐old Japanese primipara with treatment‐resistant schizophrenia taking clozapine 250 mg/day experienced pregnancy. The pregnancy progressed without complications. At 40 weeks and 2 days of gestation, the patient developed premature rupture of membranes, and decreased variability in the fetal heart rate and variable deceleration were observed, leading to an emergency cesarean section. The neonate had no congenital malformations, metabolic disorders, seizures, floppy infant syndrome, leukopenia, or neutropenia. Serum concentrations of clozapine and norclozapine (N‐desmethylclozapine), measured in the mother and in the neonate immediately after birth, suggested that clozapine and norclozapine were transported to the fetus during pregnancy. Based on these observations, the present case suggests that high fetal serum concentrations of clozapine and norclozapine may affect fetal heart rate. This case report concludes that, with careful monitoring, Japanese women taking clozapine can deliver successfully and emphasizes the importance of monitoring serum clozapine concentrations and fetal cardiac function throughout pregnancy, with particular attention to the later stages.

Published
2024
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2. The effectiveness of very slow switching to aripiprazole in schizophrenia patients with dopamine supersensitivity psychosis: a case series from an open study

Author

Hiroshi Yamanaka, Masaomi Iyo, Tsuyoshi Sasaki, Yasutaka Fujita, Takahisa Saiga, Takeshi Simoyama, Shingo Noda, Hitoshi Suzuki, Shigenori Tadokoro, Nobuhisa Kanahara, Satoshi Yanahashi, Masanori Honma, Naoya Komatsu, and Masayuki Takase

Subjects
Adult, Male, Psychosis, Pediatrics, medicine.medical_specialty, Dopamine, Aripiprazole, Psychoses, Substance-Induced, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Dopamine receptor D2, Medicine, Humans, Pharmacology (medical), business.industry, Middle Aged, medicine.disease, 030227 psychiatry, Blockade, Open study, Psychiatry and Mental health, Dopamine D2 Receptor Antagonists, Schizophrenia, Dopamine Agonists, business, 030217 neurology & neurosurgery, Psychopathology, medicine.drug, Antipsychotic Agents
Abstract

Dopamine supersensitivity psychosis (DSP) in patients with schizophrenia is induced by treatment with a high dosage of antipsychotics for a long time period, and it is characterized by unstable psychotic symptoms. The upregulation of dopamine D2 receptor (DRD2) provoked by antipsychotics underlies DSP. Aripiprazole does not cause an excessive blockade of DRD2 and is less likely to upregulate DRD2 by aripiprazole's dopamine partial agonistic profile. Aripiprazole; however, has a potential risk of inducing severe rebound psychosis in patients who have already developed dopamine supersensitivity. Recently, an animal model study suggested that aripiprazole could attenuate established dopamine supersensitivity. The present study was conducted to examine whether very slowly switching to aripiprazole could help patients with schizophrenia with dopamine supersensitivity while avoiding rebound psychosis. This study was a single-armed and open-labeled study in which patients were observed over a period of 2 years. Only 11 patients were ultimately recruited. Five patients were successfully switched to a sufficient dose of aripiprazole and completed the study protocol. These five patients did not present with severe DSP over the study period, but only one patient showed a large improvement in psychopathology. Five patients dropped out of the study, and one of these five showed a severe worsening of psychosis. The present study indicated that the introduction of aripiprazole in patients with DSP was difficult, but suggested that aripiprazole could contribute to attaining a stable state in psychosis if it was applied with careful observation.

Published
2020

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