Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled trial (a Positive and Negative Syndrome Scale, five-factor analysis)

Miyaoka, Tsuyoshi; Furuya, Motohide; Horiguchi, Jun; Wake, Rei; Hashioka, Sadayuki; Tohyama, Masaya; Mori, Norio; Minabe, Yoshio; Iyo, Masaomi; Ueno, Shyuichi; Ezoe, Sachiko; Murotani, Kenta; Hoshino, Shunichi; Seno, Haruo

doi:10.1007/s00213-014-3645-8

Cited by 16 publications

(18 citation statements)

References 45 publications

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“…Yokukansan has been used to treat various diseases such as Alzheimer's disease and schizophrenia [6][7][8][9][10]. However, whether or not yokukansan is able to reduce demyelination in the CNS remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Inflammatory cytokines and pro-oxidant molecules cause irreversible damage in demyelination in the CNS [2,4]. It is possible that yokukansan reduces these inflammatory responses without serious adverse effects [6][7][8][9][10]. Moreover, yokukansan might also promote maturation of oligodendrocytes during the remyelination phase [34].…”

Section: Discussionmentioning

confidence: 99%

“…Yokukansan, a traditional Japanese herbal medicine, has been reported to have various ameliorative effects on the neurological symptoms of patients with Alzheimer's disease or schizophrenia [6][7][8][9][10]. In both diseases, activated microglia were observed [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Yokukansan Reduces Cuprizone-Induced Demyelination in the Corpus Callosum Through Anti-inflammatory Effects on Microglia

et al. 2017

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Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). The release of inflammatory cytokines and pro-oxidant molecules from microglia has been shown to play a key role in the pathology of MS. Thus, suppression of microglial cell activation is an attractive therapeutic option. Yokukansan, a traditional Japanese herbal medicine, has been shown to suppress microglial activity in the CNS. However, whether or not yokukansan reduces demyelination observed in the CNS during MS remains unknown. In this study, female C57BL/6 mice were fed a diet containing 0.2% cuprizone (bis-cyclohexanone oxaldihydrazone) to induce demyelination in the corpus callosum. We investigated whether or not yokukansan reduces cuprizone-induced demyelination using immunohistochemical analyses. Furthermore, we examined the in vitro anti-inflammatory effects of yokukansan on LPS-stimulated BV2 cells, a murine microglial cell line. Luxol fast blue staining and immunostaining for myelin basic protein demonstrated that yokukansan reduces demyelination of the corpora callosa of cuprizone-fed mice. In addition, yokukansan significantly decreased the number of activated microglial cells in the corpora callosa of cuprizone-fed mice. Furthermore, treatment with 500 μg/ml yokukansan suppressed the expression of interleukin-1β and inducible nitric-oxide synthase mRNA and protein in LPS-stimulated BV2 cells. These findings suggest that yokukansan reduces demyelination owing to anti-inflammatory effects on microglia. As yokukansan has few adverse effects, yokukansan has the potential to be a novel option to treat MS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Yokukansan Reduces Cuprizone-Induced Demyelination in the Corpus Callosum Through Anti-inflammatory Effects on Microglia

et al. 2017

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“…The sum of enrolled participants was 1725 among the 14 included studies (868 participants in the treatment group and 857 in the control group) 17 – 30 , there were no observed significant differences in terms of gender, age and other demographic information. One study included Japanese patients 18 while the remaining research subjects were all Chinese. Regarding specific selection of the treatment periods, one study reported changes after 16 weeks 25 , 8 studies were limited to 12 weeks 19 , 21 , 23 , 26 – 30 , 4 studies were limited to 8 weeks 17 , 20 , 22 , 24 and one study only identified changes after 4 weeks 18 .…”

Section: Resultsmentioning

confidence: 99%

Effectiveness of Traditional Chinese Medicineas as an Adjunct Therapy for Refractory Schizophrenia: A Systematic Review and Meta Analysis

Wei

Lin

Zhang

et al. 2018

Sci Rep

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Although recent studies focused on traditional Chinese medicine (TCM) for the treatment of refractory schizophrenia have reported that it may be beneficial, there is still lack of convincing evidence and critical meta-analytic work regarding its effectiveness as an adjunctive therapy. Therefore, we performed a meta-analysis to investigate the effectiveness of TCM in combination with antipsychotics for refractory schizophrenia. Fourteen articles involving 1725 patients published as of December 2016 were included which compared antipsychotic therapies to either TCM alone, or TCM as an adjunctive therapy. TCM was observed to have beneficial effects on aspects of the Positive and Negative Syndrome Scale (PANSS) including total score changes and negative score changes, as well as clinical effects estimated with PANSS or the Brief Psychiatric Rating Scale (BPRS). The changes in extrapyramidal side effects (RSESE) scores from baseline to the end of the treatment period were similar in two groups of related trials. TCM was also reported to mitigate some anti-psychotic related side-effects and overall, TCM adjuvant therapy was generally safe and well tolerated. While, the results indicated the potential utility of TCM as an alternative adjunctive therapeutic for refractory schizophrenia treatment, there remains a need for further high-quality studies.

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“…In that book, it is suggested to give yokukansan to both mothers and children simultaneously to treat night crying. Currently, yokukansan is widely prescribed for a wide age range in Japan because of its potent effects on the symptoms of a variety of important disorders such as neurosis, insomnia, dementia, schizophrenia, and post‐partum depression (PPD) .…”

Section: Introductionmentioning

confidence: 99%

Effect of maternal yokukansan treatment on somatosensory map formation in the cerebral cortex of newborn mouse pups

Mishima

Shinmyo

Kawasaki

et al. 2018

Traditional & Kampo Medicine

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Aim: The effectiveness of traditional Japanese herbal medicine (kampo) is gradually attracting worldwide attention. Although yokukansan has been shown to be clinically effective in suppressing maternal post-partum depression, the safety of maternal yokukansan treatment in newborn infants has not been fully established. Methods: Herein we examined the effect of maternal yokukansan treatment on neuronal circuit formation using somatosensory maps in the cerebral cortex of the newborn mouse brain. Results: Somatosensory maps in newborn mouse pups were formed normally at postnatal day (P)5, even though yokukansan was given to lactating mouse dams. Paroxetine injected into pups strongly inhibited somatosensory map formation in mouse pups at P5, whereas paroxetine injected into lactating dams did not inhibit somatosensory map formation in pups. Yokukansan also did not affect the timing of somatosensory map formation in mouse pups at P3 and P4. Conclusion: Maternal yokukansan treatment does not have apparent adverse effects on somatosensory map formation in the brain of mouse pups.

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Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled trial (a Positive and Negative Syndrome Scale, five-factor analysis)

Abstract: The results of the present study indicate YKS to be a potential adjunctive treatment strategy for treatment-resistant schizophrenia, particularly to improve excitement/hostility symptoms.

Cited by 16 publications

References 45 publications

Yokukansan Reduces Cuprizone-Induced Demyelination in the Corpus Callosum Through Anti-inflammatory Effects on Microglia

Yokukansan Reduces Cuprizone-Induced Demyelination in the Corpus Callosum Through Anti-inflammatory Effects on Microglia

Effectiveness of Traditional Chinese Medicineas as an Adjunct Therapy for Refractory Schizophrenia: A Systematic Review and Meta Analysis

Effect of maternal yokukansan treatment on somatosensory map formation in the cerebral cortex of newborn mouse pups

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