Top

Published in:

01-03-2014 | 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

Authors: Taku Hatano, Nobutaka Hattori, Tadaaki Kawanabe, Yasuo Terayama, Norihiro Suzuki, Yasuo Iwasaki, Toshiki Fujioka, On behalf of the Yokukansan Parkinson’s Disease Study Group

Published in: Journal of Neural Transmission | Issue 3/2014

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.

Aarsland D, Larsen JP, Lim NG et al (1999) Range of neuropsychiatric disturbances in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 67(4):492–496PubMedCrossRef

Ballanger B, Strafella AP, van Eimeren T et al (2010) Serotonin 2A receptors and visual hallucinations in Parkinson disease. Arch Neurol 67(4):416–421PubMedCrossRef

Brandstädter D, Oertel WH (2002) Treatment of drug-induced psychosis with quetiapine and clozapine in Parkinson’s disease. Neurology 58(1):160–161PubMedCrossRef

Chaudhuri KR, Healy DG, Schapira AH, National Institute for Clinical Excellence (2006) Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol 5(3):235–245PubMedCrossRef

Conn JW, Rovner DR, Cohen EL (1968) Licorice-induced pseudoaldosteronism. Hypertension, hypokalemia, aldosteronopenia, and suppressed plasma renin activity. JAMA 205(7):492–496PubMedCrossRef

Cummings JL, Mega M, Gray K et al (1994) The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology 44(12):2308–2314PubMedCrossRef

Egashira N, Iwasaki K, Ishibashi A et al (2008) Repeated administration of yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry 32(6):1516–1520PubMedCrossRef

Fahn S, Elton RL, UPDRS Program Members (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Goldstein M, Calne DB (eds) Recent developments in Parkinson’s disease, vol 2. Macmillan Healthcare Information, Florham Park, pp 153–163 (293–304)

Fernandez HH, Friedman JH, Jacques C et al (1999) Quetiapine for the treatment of drug-induced psychosis in Parkinson’s disease. Mov Disord 14(3):484–487PubMedCrossRef

Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–198PubMedCrossRef

Fujioka T, Kawabe K, Kiyozuka T et al (2009) The effect of yokukansan on hallucinations in the patients with Parkinson disease treated with l-Dopa. Neurol Ther 26(1):55–59

Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17(5):427–442PubMedCrossRef

Iwasaki K, Satoh-Nakagawa T, Maruyama M et al (2005a) A randomized, observer-blind, controlled trial of the traditional Chinese medicine Yi-Gan San for improvement of behavioral and psychological symptoms and activities of daily living in dementia patients. J Clin Psychiatry 66(2):248–252PubMedCrossRef

Iwasaki K, Maruyama M, Tomita N et al (2005b) Effects of the traditional Chinese herbal medicine Yi-Gan San for cholinesterase inhibitor-resistant visual hallucinations and neuropsychiatric symptoms in patients with dementia with Lewy bodies. J Clin Psychiatry 66(12):1612–1613PubMedCrossRef

Iwasaki K, Kosaka K, Mori H et al (2011) Open label trial to evaluate the efficacy and safety of yokukansan, a traditional Asian medicine, in dementia with Lewy bodies. J Am Geriatr Soc 59(5):936–938PubMedCrossRef

Iwasaki K, Kosaka K, Mori H et al (2012) Improvement in delusions and hallucinations in patients with dementia with Lewy bodies upon administration of yokukansan, a traditional Japanese medicine. Psychogeriatrics 12(4):235–241PubMedCrossRef

Kawakami Z, Ikarashi Y, Kase Y (2010) Glycyrrhizin and its metabolite 18 beta-glycyrrhetinic acid in glycyrrhiza, a constituent herb of yokukansan, ameliorate thiamine deficiency-induced dysfunction of glutamate transport in cultured rat cortical astrocytes. Eur J Pharmacol 626(2–3):154–158PubMedCrossRef

Kawakami Z, Kanno H, Ikarashi Y et al (2011a) Yokukansan, a kampo medicine, protects against glutamate cytotoxicity due to oxidative stress in PC12 cells. J Ethnopharmacol 134(1):74–81PubMedCrossRef

Kawakami Z, Ikarashi Y, Kase Y (2011b) Isoliquiritigenin is a novel NMDA receptor antagonist in Kampo medicine yokukansan. Cell Mol Neurobiol 31(8):1203–1212PubMedCrossRef

Kawanabe T, Yoritaka A, Shimura H et al (2010) Successful treatment with yokukansan for behavioral and psychological symptoms of Parkinsonian dementia. Prog Neuropsychopharmacol Biol Psychiatry 34(2):284–287PubMedCrossRef

Merims D, Balas M, Peretz C et al (2006) Rater-blinded, prospective comparison: quetiapine versus clozapine for Parkinson’s disease psychosis. Clin Neuropharmacol 29(6):331–337PubMedCrossRef

Mizoguchi K, Tanaka Y, Tabira T (2010) Anxiolytic effect of a herbal medicine, yokukansan, in aged rats: involvement of serotonergic and dopaminergic transmissions in the prefrontal cortex. J Ethnopharmacol 127(1):70–76PubMedCrossRef

Papapetropoulos S, Mash DC (2005) Psychotic symptoms in Parkinson’s disease. From description to etiology. J Neurol 252(7):753–764PubMedCrossRef

Pollak P, Tison F, Rascol O et al (2004) Clozapine in drug induced psychosis in Parkinson’s disease: a randomised, placebo controlled study with open follow up. J Neurol Neurosurg Psychiatry 75(5):689–695PubMedCrossRef

Seppi K, Weintraub D, Coelho M et al (2011) The movement disorder society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord 26:S42–S80PubMedCrossRef

Takeda A, Tamano H, Itoh H et al (2008) Attenuation of abnormal glutamate release in zinc deficiency by zinc and yokukansan. Neurochem Int 53(6–8):230–235PubMedCrossRef

Terawaki K, Ikarashi Y, Sekiguchi K et al (2010) Partial agonistic effect of yokukansan on human recombinant serotonin 1A receptors expressed in the membranes of Chinese hamster ovary cells. J Ethnopharmacol 127(2):306–312PubMedCrossRef

Weintraub D, Stern MB (2005) Psychiatric complications in Parkinson disease. Am J Geriatr Psychiatry 13(10):844–851PubMedCrossRef

Title: An exploratory study of the efficacy and safety of yokukansan for neuropsychiatric symptoms in patients with Parkinson’s disease
Authors: Taku Hatano
Nobutaka Hattori
Tadaaki Kawanabe
Yasuo Terayama
Norihiro Suzuki
Yasuo Iwasaki
Toshiki Fujioka
On behalf of the Yokukansan Parkinson’s Disease Study Group
Publication date: 01-03-2014
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 3/2014
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-013-1105-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2014

Neuroimmunological function in parents of children suffering from cancer

Evidence for metaplasticity in the human visual cortex

Bacterial melanin increases electrical activity of neurons in Substantia Nigra pars compacta

Motor cortical inhibition in ADHD: modulation of the transcranial magnetic stimulation-evoked N100 in a response control task

Acute and chronic dose–response effect of methylphenidate on ventral tegmental area neurons correlated with animal behavior

TMEM106B and APOE polymorphisms interact to confer risk for late-onset Alzheimer’s disease in Han Chinese