PURPOSE: Patients with AD commonly exhibit behavioral and psychological symptoms of dementia (BPSD). This study is aimed to compare the efficacy of yokukansan (YKS) and risperidone (RIS) on BPSD in patients with severe Alzheimer’s disease (AD). METHODS: Thirty eight inpatients with AD were investigated. Patients were randomly as-signed to the YKS group (N = 18) or the RIS group (N = 20) and treated for 4 weeks. The primary outcomes were changes in the scores on the Neuropsychiatric Inventory (NPI), the Mini-Mental State Examination (MMSE), the Bar-thel Index, and the Cohen-Mansfield Agitation Inventory (CMAI). The frequency of extrapyramidal symptoms (EPS) and other adverse events were recorded at every visit. RESULTS: All participants in both groups completed the trial. The Barthel Index did not significantly change either in the RIS group or the YKS group. The MMSE scores did not change either in the RIS group or the YKS group. Significant improvements in mean total NPI and CMAI scores showed in both groups. Between the YKS and the RIS groups, there were no significant differences in the NPI or the CMAI scores. EPS and other serious adverse effects were not observed in either group. CONCLUSIONS: In this 4-week trial, YKS treatment significantly improved BPSD in the patients with severe AD. The present study suggests that YKS is as effective as RIS on BPSD with severe AD.
 R. Howard, C. Ballard , J. O’Brien, A. Burns and UK and Ireland Group for Optimization of Management in dementia, “Guidelines for the Management of Agitation in Dementia,” International Journal of Geriatric Psychiatry, Vol. 16, No. 7, 2001, pp. 714-717.
 P. E. Lee, S. S. Gill, M. Freedman , S. E. Bronskill, M. P. Hillmer and P. A. Rochon, “Atypical Antipsychotic Drugs in the Treatment of Behavioral and Psychological Symptoms of Dementia: Systematic Review,” British Medical Journal, Vol. 329, No. 10, 2004, pp. 7457-7475.
 L. S. Schneider, P. N. Tariot, K. S. Dagerman , S. M. Davis, J. K .Hsiao, M. S. Ismail, B. D. Lebowitz, C. G. Lyketsos, J. M. Ryan, T. S. Stroup, D. L. Sultzer, D. Weintraub, J. A. Lieberman and CATIE-AD Study Group, “Effectiveness of Atypical Antipsychotics Drugs in Pa- tients with Alzheimer’s Disease,” The New England Journal of Medicine, Vol. 355, No. 15, 2006, pp. 1525 -1538.
 P. Rocca, F. Marino, C. Montemagni, D. Perrone and F. Bogetto, “Risperidone, Olanzapine and Quetiapine in the Treatment of Behavioral and Psychological Symptoms in Patients with Alzheimer’s Disease: Preliminary Finding from a Naturalistic, Retrospective Study,” Psychiatry Clinical Neuroscience, Vol. 61, No. 6, 2007, pp. 622-629.
 P. P. De Deyn, K. Rabheru, A. Rasmussen, J. P. Bocks- berger, P. L. Dautzenberg, S. Eriksson and B. A. Lawlor, “A Randomized Trial of Risperidone, Placebo, and Halo- peridol for Behavioral Symptoms of Dementia,” Neu- rology, Vol. 53, No. 5, 1999, pp. 946-595.
 I. R. Katz, D. V. Jeste, J. E. Mintzer, C. Clyde, J. Napolitano and M. Brecher, “Comparison of Risperidone and Placebo for Psychosis and Behavioral Disturbances Associated with Dementia: A Randomized, Double-Blind Trial,” Journal of Clinical Psychiatry, Vol. 60, No. 2, 1999, pp. 107-115. doi:10.4088/JCP.v60n0207
 P. P. De Deyn and I. R. Katz, “Control of Aggression and Agitation in Patients with Dementia: Efficacy and Safety of Risperidone,” International Journal of Geriatric Psychiatry, Vol. 15, No. 1, 2000, pp. 514-522.
 D. Paleacu, Y. Barak, I. Mirecky and D. Mazeh, “Quetiapine Treatment for Behavioural and Psychological Symptoms of Dementia in Alzheimer’s Disease Patients: A 6-Week, Double-Blind, Placebo-Controlled Study,” International Journal of Geriatric Psychiatry, Vol. 23, No. 4, 2008, pp. 393-400. doi:10.1002/gps.1892
 K. Iwasaki, T. Satoh-Nakagawa, M. Maruyama, Y. Monma, M. Nemoto, N. Tomita, H. Tanji, H. Fujiwara, T. Seki, M. Fujii, H. Arai and H. Sasaki, “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,” Journal of Clinical Psychiatry, Vol. 66, No. 2, 2005, pp. 248-252.
 H. Shinno, E. Utani, S. Okazaki, T. Kawamukai, H. Yasuda, T. Inagaki, Y. Inami and J. Horiguchi, “Successful Treatment with Yi-Gan San for Psychosis and Sleep Disturbances in a Patient with Dementia with Lewy Bodies,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, Vol. 31, No. 7, 2007, pp. 1543-1545. doi:10.1016/j.pnpbp.2007.07.002
 K. Mizumaki, “Kampo Therapy as an Alternative to Pharmacotherapy Using Antipsychotic Medicines for Behavioral and Psychological Symptoms of Dementia (BPSD),” Psychogeriatrics, Vol. 8, No. 3, 2008, pp. 137-141. doi:10.1111/j.1479-8301.2008.00242.x
 H. Shinno, Y. Inami, T. Inagaki, Y. Nakamura and J. Horiguchi, “Effect of Yi-Gan San on Psychiatric Symptoms and Sleep Structure at Patients with Behavioral and Psychological Symptoms of Dementia,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, Vol. 32, No. 3, 2008, pp. 881-885.
 K. Mizukami, T. Asada, T. Kinoshita, K. Tanaka, K. Sonohara, R. Nakai, K. Yamaguchi, H. Hanyu, K. Kanaya, T. Takao, M. Okada, S. Kudo, H. Kotoku, M. Iwaskiri, H. Kurita, T. Miyamura, Y. Kawasaki, K. Omori, K. Shiozaki, T. Odawara, T. Suzuki, S. Yamada, Y. Nakamura and K. Toba, “A Randomized Cross-over Study of a Traditional Japanese Medicine (Kampo), Yokukansan, in the Treatment of the Behavioral and Psychological Symptoms of Dementia,” International Journal of Neuropsychopharmacoly, Vol. 12, No. 2,
 M. F. Folstein, S. E. Folstein and P. R. McHugh, “Mini Mental State: A Practical Method for Grading the Cognitive State of Patients for the Clinician,” Journal of Psychiatric Research, Vol. 12, No. 3, 1975, pp. 189-198.
 G. Mckhann, D. Drachman, M. Folstein, R. Katzman, D. Price and E. M. Stadlan, “Clinical Diagnosis of Al- zheimer’s Disease: Report of the NINCDS-ADRDA Work Group under the Auspices of the Department of Health and Human Services Task Force on Alzheimer’s Disease,” Neurology, Vol. 34, No. 7, 1984, pp. 939-944.
 J. L. Cummings, M. Mega, K. Gray, S. Rosenberg- Thompson, D. A. Carusiand and J. Gornbein, “The Neu- ropsychiatric Inventory: Comprehensive Assessment of Psychopathology in Dementia,” Neurology, Vol. 44, No. 12, 1994, pp. 2308-2314.
 H. Fujisawa, K. Iwasaki, K. Furukawa, T. Seki, M. He, M. Maruyama, N. Tomita, Y. Kudo, M. Higuchi, T. C. Saido, S. Maeda, A. Takashima, M. Hara, Y. Ohizumi and H. Arai, “Uncaria Rhynochophylla, a Chinese Medical Herb, Has Potent Anti-Aggregation Effects on Alzheimer’S Beta-Amyloid Proteins,” Journal of Neuroscience Research, Vol. 84, No. 2, 2006, pp. 427-433.
 M. Tateno, W. Ukai, T. Ono, S. Saito, E. Hashimoto and T. Saito, “Neuroprotective Effects of Yi-Gan San against Beta Amyloid-Induced Cytotoxicity on Rat Cortical Neurons,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, Vol. 32, No. 7, 2008, pp. 1704-1707. doi:10.1016/j.pnpbp.2008.07.006
 A. Takeda, H. Itoh, H. Tamano, M. Yuzurihara and N. Oku, “Suppressive Effects of Yokukansan on Excessive Release of Glutamate and Aspartate in Hippocampus of Zinc-Deficient Rats,” Nutritional Neuroscience, Vol. 11, No. 1, 2008, pp. 41-46. doi:10.1179/147683008X301414
 N. Egashira, K. Iwasaki, A. Ishibashi, K. Hayakawa, R. Okuno, M. Abe, N. Uchida, K. Mishima, K. Takasaki, R. Nishimura, R. Oishi and M. Fujiwara, “Repeated Administration of Yokukansan Inhibits DOI-Induced Head-Twitch Response and Decreases Expression of 5-Hydroxy-Truptamine (5-HT)2A Receptors in the Pre- Frontal Cortex,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, Vol. 32, No. 6, 2008, pp. 1516-1520. doi:10.1016/j.pnpbp.2008.05.010
 M. Tabuchi, T. Yamaguchi, S. Iizuka, S. Imamura, Y. Ikarashi and Y. Kase, “Ameliorative Effects of Yoku- Kansan, a Traditional Japanese Medicine, on Learning and Non-Cognitive Disturbances in the Tg2576 Mouse Model of Alzheimer’s Disease,” Journal of Ethno- pharmacology, Vol. 122, No. 1, 2009, pp. 157-162.