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. 2020 Jul 15;7:86. doi: 10.3389/fnut.2020.00086

Table 4.

RCT of Kampo medicine for symptoms of dementia.

References Study design Subjects (n) Age, years (mean ± SD) Disease/symptom Kampo formulation Comparator Outcome Adverse event related with Kampo
Shimada et al. (75) RCT 57 78.9 ± 7.6 VD and subarachnoid hemorrhage CTS Placebo The scores of cognitive dysfunction (Hasegawa's Dementia Scale-Revised), the global improvement rating, utility rating, global rating for subjective symptoms, subjective symptoms (shoulder stiffness and palpations), global rating for psychiatric symptoms, psychiatric symptoms (decline in interest in television or books, lack of facial expression), and ADL were decreased after 12-week administration of CTS compared to placebo. 1 liver dysfunction in 1 case
Terasawa et al. (76) DB-RCT 139 76.6 ± 8.4 VD CTS Placebo The global improvement rating, global rating for subjective symptoms, psychiatric symptoms (decline in simple arithmetic ability, global intellectual ability, sleep disturbance, hallucination, and delusion), and ADL were alleviated after 12-week administration of CTS compared to placebo. Urtic aria in one, diarrhea in one, appetite, in one loss, oral bitterness in one, and liver dysfunction in one case (no information of intervention group)
Suzuki et al. (78) DB-RCT 30 84.4 ± 6.3 AD and VD CTS/GJG Placebo CTS improved the scores of cognitive dysfunction (MMSE), and ADL, compared to placebo. N/A
Iwasaki et al. (79) DB-RCT 33 84.4 ± 7.8 Mixed dementia and AD HJG Placebo Cognitive dysfunction (MMSE), and ADL were improved after treatment of HJG compared to placebo. No
Maruyama et al. (77) Observer blind RCT 38 73.7 ± 5.6 74.6 ± 3.9 AD Kamiuntanto add to donepezil Donepezil Kamiuntanto added to donepezil improved the scores of MMSE, and Alzheimer's Disease Assessment Scale, compared to donepezil alone. No
Higashi et al. (81) RCT 75 82.8 ± 8.1 84.2 ± 6.4 86.1 ± 5.0 AD KHT/GJG No treatment The scores of MMSE improved only in the KHT treatment group. The orientation and attention subscale scores of the MMSE improved significantly in the KHT-treatment group. N/A
Iwasaki et al. (82) Observer blind RCT 52 80.3 ± 9.0 AD, VD, mixed dementia and DLB YKS No treatment Four-week administration of YKS significantly improved BPSD, especially in hallucinations, agitation/aggression, irritability/lability, and aberrant motor activity, and ADL. No
Mizukami et al. (83) RCT- cross over N = 88 78.7 ± 5.4 AD and DLB YKS No treatment BPSD, especially in agitation/aggression and irritability/lability subscale scores, were improved after treatment of YKS. Gastrointestinal distress in 3 cases
Monji et al. (84) RCT N = 15 80.2 ± 4.0 AD YKS add to sulpiride Sulpiride The average dose of sulpiride tened to be less in the YKS treatment group than the control group. Hypokalemia in 2 cases
Okahara et al. (85) RCT N = 61 76.1 ± 8.1 77.1 ± 6.8 AD YKS add to donepezil Donepezil The scores of BPSD decreased in the YKS treatment group. The subscale score of agitation and irritability decreased significantly. N/A
Teranishi et al. (86) Rater blind RCT N = 76 83.5 ± 5.8 80.7 ± 8.8 83.2 ± 5.4 AD, VD, and DLB YKS Risperidone/fluvoxamine The three intervention significantly alleviated BPSD. The adverse events were more frequent in the risperidone-treatment group. No
Fukuhara et al. (87) DB-RCT N = 145 78.3 ± 5.4 78.5 ± 5.1 AD YKS Placebo The BPSD scores did not change in both YKS and placebo intervention. The subgroup scoring below 20 points on the MMSE at baseline showed a greater improvement in BPSD, especially in agitation/aggregation in the YKS-treatment group, compared to the placebo group. In the subgroup younger than 74 years of age, a significant decrease in the score for agitation/aggression was shown in the YKS-treatment group. Hypokalemia in 3 cases

VD, Vascular dementia; CTS, chotosan; ADL, activity of daily living; AD, Alzheimer's disease; GJG, goshajinkigan; HJG hachimijiogan; MMSE, Mini-Mental State Examination; KHT, kihito; DLB, dementia with Lewy body; YKS, yokukansan; BPSD, behavioral and psychological symptoms of dementia; N/A, not assigned; SD, standard deviaton.