Randomized double-blind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease.

Aim Yokukansan ( YKS), a traditional herbal medicine, has been used to treat behavioral and psychological symptoms of dementia ( BPSD). The present study is the first double-blind, randomized, placebo-controlled trial to determine the efficacy and safety of YKS for the treatment of BPSD in Alzheimer's disease ( AD). Methods A total of 22 sites consisting of clinics, hospitals and nursing homes participated. A total of 145 patients with AD were randomized. Active YKS (7.5 g/day) and placebo were supplied to 75 and 70 participants, respectively. The primary outcome measure was the 4-week change in total score of the Neuropsychiatric Inventory Brief Questionnaire Form ( NPI-Q), an instrument that evaluates BPSD. Secondary outcome measures included 12-week changes in NPI-Q scores, changes in NPI-Q subcategory scores and total scores of the Mini-Mental-State Examination. Results Four-week changes in NPI- Q total scores did not differ significantly between the treatment and placebo groups. There were also no significant differences between groups in 12-week changes in total NPI- Q scores, NPI- Q subcategory scores or total Mini-Mental-State Examination scores. However, a subgroup with fewer than 20 points on the Mini-Mental-State Examination at baseline showed a greater decrease in 'agitation/aggression' score in the YKS group than in the placebo group ( P = 0.007). No serious adverse effects were observed during the study. Conclusions Our data did not reach statistical significance regarding the efficacy of YKS against BPSD; however, YKS improves some symptoms including 'agitation/aggression' and 'hallucinations' with low frequencies of adverse events. Geriatr Gerontol Int 2017; 17: 211-218