Table 1: Clinical studies on the effects of YKS on PD-like symptoms in multiple neurological disorders.

SymptomParticipants (number)DesignInterventionComparisonOutcomeReference
PrimarySecondary

Sleep12 with AD and 1 with frontotemporal dementia (n= 13)Open-label trialYKS (5-7.5 g/day) for 8 weeksNoneImproved Sleep Disorder Inventory per NPIImproved wake after sleep onset and total NPI scores; 
No change in MMSE
[5]
5 with dementiaOpen-label trialYGS (2.5g) for 4 weeksNonePSG; total sleep time, sleep efficiency, stage 2 sleep ↑ and the number of arousals and periodic limb movements ↓; 
Improved PSQI
[6]
20 healthy adult malesDouble-blind trialYKSCH (7.5 g/day) for 3 daysAnchu-sanPSG; total sleep time, sleep efficiency, and stage 2 sleep ↑; 
Sleep latency and stage 3+4 sleep ↓
[7]
3 with rapid eye movement sleep 
behavior disorder
Case reportYGS (7.5 g/day) + clonazepam (0.5 mg/day)NoneSuppression of RBD[8]
YGS (7.5 g/day) + clonazepam (0.25 mg/day)
YGS(2.5 g/day)

25 with PDOpen-label trialYKS (7.5 g/day) for 12 weeksNoneNPI total score ↓; 
Improved subscale including hallucinations, anxiety, and apathy
No significant change in UPDRS part III and Hoehn–Yahr classification[2]
7 with PD 
7 with PDD 
(n=14)
Open-label trialYKS (7.5 g/day) for 4 weeksNoneNPI total score ↓; improved subscale including hallucinations 
MMSE improved slightly in PDD; 
No change in UPDRS III and ADL
[9]
90 with dementiaRandomized rater-blinded trialYKS (2.5-7.5 g/d) for 8 weeksRisperidone or fluvoxamineNPI-NH ↓No change in MMSE, FIM, and drug-induced Extra-Pyramidal Symptoms Scale[10]
103 with dementiaRandomized cross-over trialYKS (7.5 g) for 4 weeksNoneNPI total score ↓; improved subscale including delusions, hallucinations, agitation/aggression, depression, anxiety, and irritability/lability; 
No change in MMSE and ADL
[11]
5 with dementiaOpen-label trialYGS (2.5 g) for 4 weeksNoneNPI-NH total score ↓; improved subscale including delusions, 
hallucinations, agitation/aggression, anxiety, and irritability/lability; 
No change in MMSE
[6]
Neuropsychiatry52 with dementiaRandomized, observer-blind, controlled trialYGS (7.5 g/day) for 4 weeksDrug-freeNPI-NH total score ↓; improved subscale including hallucinations, agitation/aggression, irritability/lability and aberrant motor activity; 
Barthel index ↑; 
No change in MMSE
[12]
145 with ADRandomized double-blind placebo-controlled trialYKS (7.5 g/day) for 4 weeksPlacebo-controlNo significant difference in total NPI-Q scoresImproved NPI subscale including agitation/aggression and hallucinations; 
No change in MMSE
[13]
61 with ADRandomized, non-blinded, parallel-group comparison trialYKS (7.5 g/day) + donepezil for 4 weeksActive comparatorNPI total score ↓; improved subscale including agitation/aggression and irritability/lability; 
No significant difference in MMSE, DAD, ZBI, or SDS
[14]
29 with ADOpen-label trialYKS (7.5 g/day) for 4 weeksNoneNPI total score ↓Clinically decreased subscale including hallucinations, agitation, anxiety, irritability, and abnormal behaviors; 
No significant difference in MMSE, DAD, ZBI, or SDS
[15]
15 with ADRandomized controlled trialYKS(2.5 g) for 12 weeks + sulpiride (50 mg/day)ControlNPI total score ↓; 
No change in MMSE and ADL
[16]
13 with vascular dementiaOpen-label clinical trialYKS (7.5 g/day) for 4 weeksNoneNPI total score ↓; significantly improved subscale including agitation; 
No change in MMSE, ADL, DAD, or UPDRS
[17]
40 with schizophreniaOpen-label clinical trialYKS (2.5–7.5 g/day) for 4 weeksNoneSignificantly improved BPRS, CGI-S, and PANSS; 
Slightly decreased Simpson-Angus scale, Barnes Akathisia scale, and AIM
[18]

Cognition1 with schizophreniaCase reportYKS (5.0 g/day) for 3 monthsNoneMarkedly improved cognitive functions in daily life and BACS–J[19]

Pain10 with neuropathic painOpen-label clinical trialNoneMarkedly decreased VAS and PS[20]

Tardive dyskinesia22 with schizophreniaOpen-label trialYGS (7.5 g/day) for 12 weeksNoneSignificantly decreased AIMS total scores and all PANSS subscales; 
Substantial changes in CGI
[21]

NPI=neuropsychiatric inventory, MMSE=MINI-Mental State Examination, YGS=Yi-Gan San, PSG=polysomnography, ADL=the Barthel Index for activities of daily living, PDD=PD with dementia, NPI-NH=The Nursing Home version of Neuropsychiatric Inventory, PSQI=the Pittsburgh Sleep Quality Index, FIM=daily life function measured by Functional Independence Measure, DAD=Disability Assessment for Dementia, SDS=Self-rating Depression Scale, ZBI=Zarit Burden Interview, BPRS=psychiatric rating scale, CGI-S=clinical global impression scale-severity, PANSS=positive and negative syndrome scale, AIM=involuntary movement scale, BACS–J=Brief Assessment of Cognition in Schizophrenia, Japanese Version, VAS=visual analogue scale, and PS=pain score.