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

Objective: This randomized, observer-blind, controlled trial examined the efficacy and safety of the traditional Chinese herbal medicine Yi-Gan San (YGS, Yokukan-San in Japanese) in the improvement of behavioral and psychological symptoms of dementia (BPSD) and activities of daily living (ADL). Method: Fifty-two patients with mild-to-severe dementia (24 men and 28 women, mean ± SD age = 80.3 ± 9.0 years) according to DSM-IV criteria were investigated. Participants were randomly assigned to the YGS group (N = 27) or control (drug-free) group (N = 25) and treated for 4 weeks. The Neuropsychiatric Inventory (NPI) for the assessment of BPSD, the Mini-Mental State Examination (MMSE) for cognitive function, and the Barthel Index for ADL were administered at baseline and the end of the treatment. The frequency of extrapyramidal symptoms (EPS) and other adverse events was recorded. If patients showed insufficient response to treatment after 1 week, tiapride hydrochloride, a dopamine D₁ selective neuroleptic, was added to the regimen. Data were collected from January 2004 to March 2004. Results: All participants in both groups completed the trial. In the control group, 11 patients required treatment with tiapride hydrochloride. Significant improvements in mean ± SD NPI (from 37.9 ± 16.1 to 19.5 ± 15.6) and Barthel Index (from 56.4 ± 34.2 to 62.9 ± 35.2) scores were observed in the YGS group, but not in the control group. MMSE results were unchanged in both groups. EPS were not observed in either group, but dizziness and impaired postural sway were observed in 6 patients treated with tiapride hydrochloride. Conclusion: Yi-Gan San improves BPSD and ADL. Follow-up studies using a double-blinded, placebo-controlled design are recommended.