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An exploratory study of the efficacy and safety of yokukansan for neuropsychiatric symptoms in patients with Parkinson’s disease

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

The present study examined the efficacy and safety of yokukansan (YKS) in neuropsychiatric symptoms in patients with Parkinson’s disease (PD) using the neuropsychiatric inventory (NPI). Twenty-five patients with PD (M:F 14:11; age 72 years) were enrolled and treated with YKS (7.5 g/day) for 12 weeks. The NPI was assessed at 0, 4, 8, 12 and 16 weeks. The patient’s motor function and progression were evaluated using the Unified PD Rating Scale part III (UPDRS-III) and Hoehn and Yahr scale, respectively. The serum potassium concentration (sK) and all adverse events were recorded. The median NPI total score significantly decreased from 12 points at baseline to 4.0 points at 12 weeks (p = 0.00003). Within each NPI subscale, significant improvements were observed in hallucinations, anxiety and apathy. These symptoms tended to worsen after the completion of YKS treatment. Delusions, agitation, depression, euphoria, disinhibition, aberrant motor activity tended to improve but irritability showed no change. The median NPI subtotal scores, positive symptoms (delusions–hallucinations–irritability) significantly decreased (p = 0.01660) and negative symptoms (anxiety–apathy) significantly decreased (p = 0.00391). Both UPDRS-III and the Hoehn and Yahr scale showed no significant change. sK decreased mildly from 4.26 ± 0.30 to 4.08 ± 0.33 mEq/L. Two patients showed hypokalemia lower than 3.5 mEq/L without any corresponding symptoms; two patients showed listlessness and one patient showed drug eruption. Each recovered after discontinuation of YKS. YKS improved neuropsychiatric symptoms associated with PD, including hallucinations, anxiety and apathy without severe adverse events and worsening of Parkinsonism.

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Acknowledgments

We would like to thank all subjects of this study and all relevant personnel at the clinical institutions where the study was carried out. We would also like to thank the following members of the YKS Parkinson’s Disease Study Group for their help in the enrollment of subjects: Dr. Asako Yoritaka at Juntendo University School of Medicine, Dr. Hisashi Yonezawa, Dr. Chigumi Otsuka and Dr. Masanori Mizuno at Iwate Medical University School of Medicine, Dr. Kazushi Takahashi at Keio University School of Medicine, Dr. Konosuke Iwamoto at Toho University Omori Medical Center, Dr. Shingo Konno at Toho University Ohashi Medical Center, and each of the clinical study supporters. We deeply thank Dr. Hiroshi Nagayama at Nippon Medical School for contributing to study supervision.

Conflict of interest

We have received funding for research expenses for this study including all tests costs, management fees and institutional review board (IRB) costs, from Tsumura & Co. (Tokyo, Japan), which has a role in for data collection, data management and maintenance, and data analysis tasks.

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Authors and Affiliations

  1. Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo, 113-8421, Japan

    Taku Hatano & Nobutaka Hattori

  2. Department of Neurology, Juntendo University Urayasu Hospital, Chiba, 279-0021, Japan

    Tadaaki Kawanabe

  3. Department of Neurology and Gerontology, Iwate Medical University School of Medicine, Iwate, 020-8505, Japan

    Yasuo Terayama

  4. Department of Neurology, Keio University School of Medicine, Tokyo, 160-8582, Japan

    Norihiro Suzuki

  5. Department of Neurology, Toho University Omori Medical Center, Tokyo, 143-8541, Japan

    Yasuo Iwasaki

  6. Department of Neurology, Toho University Ohashi Medical Center, Tokyo, 153-8515, Japan

    Toshiki Fujioka

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  1. Taku Hatano
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  2. Nobutaka Hattori
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  3. Tadaaki Kawanabe
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  4. Yasuo Terayama
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  5. Norihiro Suzuki
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  6. Yasuo Iwasaki
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  7. Toshiki Fujioka
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On behalf of the Yokukansan Parkinson’s Disease Study Group

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Correspondence to Nobutaka Hattori.

Additional information

Members of Yokukansan Parkinson’s Disease Study Group are listed in Acknowledgments.

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Hatano, T., Hattori, N., Kawanabe, T. et al. An exploratory study of the efficacy and safety of yokukansan for neuropsychiatric symptoms in patients with Parkinson’s disease. J Neural Transm 121, 275–281 (2014). https://doi.org/10.1007/s00702-013-1105-y

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  • DOI: https://doi.org/10.1007/s00702-013-1105-y

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