Yokukansan improves behavioral and psychological symptoms of dementia by suppressing dopaminergic function

Abstract

Although three drugs, risperidone, yokukansan, and fluvoxamine, have shown equal efficacy in treating behavioral and psychological symptoms of dementia (BPSD) in our previous study, their mechanisms of action are different from one another. Monoamines have attracted attention for their key roles in mediating several behavioral symptoms or psychological symptoms through synaptic signaling. We aimed to clarify the monoamines changed by treatment with each drug in patients with BPSD. The main purpose of this study was to determine whether plasma levels of catecholamine metabolites are correlated with pharmacological treatments. This was an 8-week, rater-blinded, randomized, flexible-dose, triple-group trial. In total, 90 subjects were recruited and subsequently three different drugs were allocated to 82 inpatients with BPSD. We examined BPSD data from patients who completed 8 weeks of treatment. Eventually, we analyzed 42 patients (yokukansan: 17; risperidone: 9; fluvoxamine: 16). Homovanillic acid, a metabolite of dopamine, and 3-methoxy-4-hydroxyphenylglycol, a metabolite of noradrenaline, in their plasma were analyzed by high-performance liquid chromatography with electrochemical detection. All three drugs showed equal significant efficacy between baseline and study endpoint. By contrast, biomarkers showed mutually different changes. Patients in the yokukansan group had significantly decreased plasma homovanillic acid levels from baseline. Conversely, patients in the risperidone and fluvoxamine groups exhibited no significant changes in plasma homovanillic acid levels from baseline. Yokukansan contains geissoschizine methyl ether, which is known to have a partial agonist effect on dopamine D2 receptors. An improvement in BPSD condition with the intake of yokukansan is suggested to occur through a suppressed dopaminergic function, which is similar to the effect of aripiprazole.

Decreased Behavioral Abnormalities After Treatment with Combined Donepezil and Yokukansankachimpihange in Alzheimer Disease: An Observational Study. The Osaki-Tajiri Project

“…In contrast to the hypothesis introduced by the previous finding of yokukansan [ 11 ], yokukansankachimpihange did not improve “active symptoms”, as shown by the non-significant effects revealed here on subscales A (Paranoid and Delusional Ideation), B (Hallucinations), C (Activity Disturbances), and D (Aggressiveness).…”

“…Yokukansan is one of the traditional herbal medicines (Kampo medicine in Japan) that is commonly used for the treatment of BPSD [ 10 ], and some neuropharmacological actions have been reported [ 11 ]. A recent systematic review [ 12 ] described five RCTs with 381 patients, versus controls, that reported that yokukansan significantly decreased BPSD total scores, as well as the BPSD subscale of “active symptoms”, i.e., delusions, hallucinations, and agitation/aggression.…”

A National Survey on the Clinical Practice Patterns of Korean Medicine Doctors for Attention Deficit Hyperactivity Disorder (ADHD) in Children and Adolescents

“…Since modified forms are widely used in combination, the questionnaire in this study included a modified form in response to Ondam-tang. Eokgan-san has been prescribed for restlessness and agitation in children and has been reported to improve the behavioral and psychological symptoms of dementia [ 45 , 46 ] and Tourette’s syndrome symptoms in children and adolescents for a short period of time [ 47 ]. Sihogayonggolmororyeo-tang (written as Chaihu Jia Longgu Muli decoction in Chinese) has been reported to have an antiepileptic effect in an experimental study on rats [ 48 ], and in an SR, it was found to be more effective than conventional medicine in the treatment of post-stroke depression [ 49 ] and insomnia [ 50 ].…”

Herbal Medicine for Behavioral and Psychological Symptoms of Dementia: A Systematic Review and Meta-Analysis

“…Moreover, there are safety issues associated with HM, such as lack of safety monitoring and potential interactions with conventional pharmaceuticals ( Ekor, 2014 ). Fortunately, for some standardized HMs, such as Yokukansan, underlying therapeutic mechanisms for dementia ( Takeyoshi et al, 2016 ), potential interactions with conventional medications ( Soraoka et al, 2016 ) and safety issues have been documented ( Shimada et al, 2017 ). Similarly, a database of some potential herb-drug interactions relevant to the management of cognitive impairment has been recently developed.…”