NEUROLOGY AND PRECLINICAL NEUROLOGICAL STUDIES - ORIGINAL ARTICLE An exploratory study of the efficacy and safety of yokukansan for neuropsychiatric symptoms in patients with Parkinson’s disease Taku Hatano • Nobutaka Hattori • Tadaaki Kawanabe • Yasuo Terayama • Norihiro Suzuki • Yasuo Iwasaki • Toshiki Fujioka • On behalf of the Yokukansan Parkinson’s Disease Study Group Received: 25 May 2013 / Accepted: 15 October 2013 Ó Springer-Verlag Wien 2013 Abstract The present study examined the efficacy and safety of yokukansan (YKS) in neuropsychiatric symptoms in patients with Parkinson’s disease (PD) using the neu- ropsychiatric 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 base- line 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. Delu- sions, agitation, depression, euphoria, disinhibition, aber- rant 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 symp- toms (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. Keywords Parkinson’s disease Á Neuropsychiatric symptoms Á Yokukansan (YKS) Á Neuropsychiatric inventory (NPI) Introduction Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor dysfunctions such as, resting tremor, rigidity, akinesia and postural instability. PD patients usually experience distress related to not only motor dysfunction but also non-motor symptoms, such as hallucination, depression, anxiety, apathy, fatigue and autonomic dysfunctions, which Members of Yokukansan Parkinson’s Disease Study Group are listed in Acknowledgments. T. Hatano Á N. Hattori (&) Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan e-mail: nhattori@juntendo.ac.jp T. Kawanabe Department of Neurology, Juntendo University Urayasu Hospital, Chiba 279-0021, Japan Y. Terayama Department of Neurology and Gerontology, Iwate Medical University School of Medicine, Iwate 020-8505, Japan N. Suzuki Department of Neurology, Keio University School of Medicine, Tokyo 160-8582, Japan Y. Iwasaki Department of Neurology, Toho University Omori Medical Center, Tokyo 143-8541, Japan T. Fujioka Department of Neurology, Toho University Ohashi Medical Center, Tokyo 153-8515, Japan 123 J Neural Transm DOI 10.1007/s00702-013-1105-y