An Exploratory Study of the Efficacy and Safety of Yokukansan for Neuropsychiatric Symptoms in Patients with Parkinson's Disease

Overview

Journal J Neural Transm (Vienna)

Specialties Neurology
Physiology

Date 2013 Oct 31

PMID 24169925

Citations 14

Authors

Taku Hatano

Nobutaka Hattori

Tadaaki Kawanabe

Yasuo Terayama

Norihiro Suzuki

Yasuo Iwasaki

Toshiki Fujioka

Affiliations

Soon will be listed here.

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.

Citing Articles

Effective use of for Caucasian patient with panic disorder: A case report.

Ohsako N, Kimura H PCN Rep. 2024; 3(3):e231.

PMID: 39081394 PMC: 11286702. DOI: 10.1002/pcn5.231.

Predictive Analysis of Yi-Gai-San's Multifaceted Mechanisms for Tremor-dominant Parkinson's Disease Network Pharmacology and Molecular Docking Validation.

Lin C, Wu L, Tsai F Curr Med Chem. 2024; 31(36):5989-6012.

PMID: 38879763 PMC: 11475103. DOI: 10.2174/0109298673291838240311075415.

Effectiveness and safety of herbal medicine Ukgansan for clinical symptoms in Parkinson's disease: A pilot, randomized, assessor-blinded clinical trial.

Jin C, Cho K, Kwon S, Lee H, Kim T, Jung W Front Neurol. 2022; 13:1025269.

PMID: 36438946 PMC: 9685812. DOI: 10.3389/fneur.2022.1025269.

Ukgansan Protects Dopaminergic Neurons against MPTP-Induced Neurotoxicity via the Nurr1 Signaling Pathway.

Chae I, Jang J, Seol I, Kim Y, Park G, Yoo H Evid Based Complement Alternat Med. 2022; 2022:7393557.

PMID: 36193151 PMC: 9526663. DOI: 10.1155/2022/7393557.

Apathy in Parkinson's Disease: Defining the Park Apathy Subtype.

De Waele S, Cras P, Crosiers D Brain Sci. 2022; 12(7).

PMID: 35884730 PMC: 9313138. DOI: 10.3390/brainsci12070923.

References

HOEHN M, Yahr M . Parkinsonism: onset, progression and mortality. Neurology. 1967; 17(5):427-42. DOI: 10.1212/wnl.17.5.427. View

Terawaki K, Ikarashi Y, Sekiguchi K, Nakai Y, Kase Y . Partial agonistic effect of yokukansan on human recombinant serotonin 1A receptors expressed in the membranes of Chinese hamster ovary cells. J Ethnopharmacol. 2009; 127(2):306-12. DOI: 10.1016/j.jep.2009.11.003. View

Iwasaki K, Satoh-Nakagawa T, Maruyama M, Monma Y, Nemoto M, Tomita N . 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. 2005; 66(2):248-52. DOI: 10.4088/jcp.v66n0214. View

Brandstadter D, Oertel W . Treatment of drug-induced psychosis with quetiapine and clozapine in Parkinson's disease. Neurology. 2002; 58(1):160-1. DOI: 10.1212/wnl.58.1.160-a. View

Ballanger B, Strafella A, van Eimeren T, Zurowski M, Rusjan P, Houle S . Serotonin 2A receptors and visual hallucinations in Parkinson disease. Arch Neurol. 2010; 67(4):416-21. DOI: 10.1001/archneurol.2010.35. View

Chaudhuri K, Healy D, Schapira A . Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol. 2006; 5(3):235-45. DOI: 10.1016/S1474-4422(06)70373-8. View

Papapetropoulos S, Mash D . Psychotic symptoms in Parkinson's disease. From description to etiology. J Neurol. 2005; 252(7):753-64. DOI: 10.1007/s00415-005-0918-5. View

Iwasaki K, Kosaka K, Mori H, Okitsu R, Furukawa K, Manabe Y . Improvement in delusions and hallucinations in patients with dementia with Lewy bodies upon administration of yokukansan, a traditional Japanese medicine. Psychogeriatrics. 2013; 12(4):235-41. DOI: 10.1111/j.1479-8301.2012.00413.x. View

Iwasaki K, Maruyama M, Tomita N, Furukawa K, Nemoto M, Fujiwara H . 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. 2006; 66(12):1612-3. DOI: 10.4088/jcp.v66n1219a. View

10.

Takeda A, Tamano H, Itoh H, Oku N . Attenuation of abnormal glutamate release in zinc deficiency by zinc and Yokukansan. Neurochem Int. 2008; 53(6-8):230-5. DOI: 10.1016/j.neuint.2008.07.009. View

11.

Pollak P, Tison F, Rascol O, Destee A, Pere J, Senard J . Clozapine in drug induced psychosis in Parkinson's disease: a randomised, placebo controlled study with open follow up. J Neurol Neurosurg Psychiatry. 2004; 75(5):689-95. PMC: 1763590. DOI: 10.1136/jnnp.2003.029868. View

12.

Folstein M, Folstein S, McHugh P . "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3):189-98. DOI: 10.1016/0022-3956(75)90026-6. View

13.

Kawakami Z, Ikarashi Y, Kase Y . 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. 2009; 626(2-3):154-8. DOI: 10.1016/j.ejphar.2009.09.046. View

14.

Egashira N, Iwasaki K, Ishibashi A, Hayakawa K, Okuno R, Abe M . 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. 2008; 32(6):1516-20. DOI: 10.1016/j.pnpbp.2008.05.010. View

15.

Kawakami Z, Kanno H, Ikarashi Y, Kase Y . Yokukansan, a kampo medicine, protects against glutamate cytotoxicity due to oxidative stress in PC12 cells. J Ethnopharmacol. 2010; 134(1):74-81. DOI: 10.1016/j.jep.2010.11.063. View

16.

Mizoguchi K, Tanaka Y, Tabira T . Anxiolytic effect of a herbal medicine, yokukansan, in aged rats: involvement of serotonergic and dopaminergic transmissions in the prefrontal cortex. J Ethnopharmacol. 2009; 127(1):70-6. DOI: 10.1016/j.jep.2009.09.048. View

17.

Kawanabe T, Yoritaka A, Shimura H, Oizumi H, Tanaka S, Hattori N . Successful treatment with Yokukansan for behavioral and psychological symptoms of Parkinsonian dementia. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 34(2):284-7. DOI: 10.1016/j.pnpbp.2009.11.019. View

18.

Kawakami Z, Ikarashi Y, Kase Y . Isoliquiritigenin is a novel NMDA receptor antagonist in kampo medicine yokukansan. Cell Mol Neurobiol. 2011; 31(8):1203-12. PMC: 11498536. DOI: 10.1007/s10571-011-9722-1. View

19.

Cummings J, Mega M, Gray K, Carusi D, Gornbein J . The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994; 44(12):2308-14. DOI: 10.1212/wnl.44.12.2308. View

20.

CONN J, ROVNER D, Cohen E . Licorice-induced pseudoaldosteronism. Hypertension, hypokalemia, aldosteronopenia, and suppressed plasma renin activity. JAMA. 1968; 205(7):492-6. DOI: 10.1001/jama.205.7.492. View