BPSD に対する抑肝散の効果 (140828) 抑肝散に関する RCT が結構たくさん出ている 実際 BPSD に関しては効果を実感する症例も あると思う いくつかの論文を読んでみた PECO P:BPSD in elderly patients with dementia(ninety inpatients with dementia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) E:flexibly dosed risperidone, yokukansan, or fluvoxamine. C: O:Primary outcome measures were Neuropsychiatric Inventory in Nursing Home Version total score and its items. Thiswas developed for use by professional caregivers. This instrument includes 12 neuropsychiatric symptoms: (1) delusions, (2) hallucinations, (3) agitation, (4) depression/dysphoria, (5) anxiety, (6) euphoria/elation, (7) apathy/indifference, (8) disinhibition, (9) irritability/lability, (10) aberrant motor behavior, (11) night-time disturbances, and (12) appetite/eating change. The caregiver was asked to rate the severity (1 = mild, 2= moderate, 3 = severe) and frequency (1 = occasionally; 2 = often, about once per week; 3 = frequently, several times per week but less than daily; 4 = very frequently, once or more per day or continuously) of the behavior 認知症の高齢患者に対して 抑肝散を投与すると risperidone や fluvoxamine を投与した場合と比 較して BPSD の評価スケールである NPI-NH が改善するかどうかを検討した研究であることが分か る 妥当か 抄録中に 8-week, rater-blinded, randomized などの項目が記載されている 本文には以下のような記 載があり 広義の ITT 解析が行われている Analyses of the primary and all secondary efficacy variables were performed on the
intent-to-treat population, which included all patients who received at least 1 dose of medication at baseline and had at least 1 postbaseline assessment of the primary efficacy variable, on a last-observation-carried-forward basis. 結果 NPI-NH は何れの群も改善傾向であったが差を認めなかった Mean Neuropsychiatric Inventory in Nursing Home Version total score decreased in all 3 drug groups, with no significant between-group differences. Mini-Mental State Examination and Functional Independence Measure scores did not change significantly. Drug-Induced Extra-Pyramidal Symptoms Scale scores did not change in the yokukansan and fluvoxamine groups, but increased significantly in the risperidone group. Risperidone, yokukansan, and fluvoxamine were equally effective in the treatment of BPSD in elderly patients. However, yokukansan or fluvoxamine for BPSD showed a more favorable profile in tolerability compared with risperidone. ( 参考文献 1 より引用 ) ( 参考文献 1 より引用 ) 別の論文も読んでみる PECO
P:patients with AD(Patients who had at least one symptom score of four or more on the Neuropsychiatric Inventory (NPI) subscales were enrolled in the study.) E:YKS-treated group (YKS/donepezil combination therapy group) C:non-YKS-treated group (donepezil monotherapy group). O:The subjects were evaluated twice at the start (Week 0) and completion (Week 4) of the study treatment in terms of NPI, Mini-Mental Status Examination (MMSE), Disability Assessment for Dementia (DAD), Zarit Burden Interview, and Self-rating Depression Scale (SDS). BPSD のある AD 患者に対して donepezil に加えて抑肝散を追加すると donepezil 単独治療を 行う場合と比較して 認知症評価の各種スケールが改善するかどうかを県とした研究であること が分かる 妥当か 抄録中に non-blinded, randomizedy や four-week study treatment period などの記載がある ま た 本文中には以下のような記載がある The efficacy analysis set (full analysis set: FAS) included all patients other than the above two excluded patients. 結果 併用群で NPI は低下していた MMSE など他の評価項目には有意差を認めなかった The NPI total score improved significantly more in the YKS-treated group than in the non-yks-treated group. In the NPI subscales of agitation/aggression and irritability/lability, the YKS-treated group showed significantly greater improvement than the non-yks-treated group, but no statistically significant improvement was seen with YKS in the other subscales. There were no significant differences between the YKS-treated group and the non-yks-treated group in MMSE, DAD, Zarit Burden Interview and SDS.
( 参考文献 2 より引用 ) もう一本読んでみる PECO P:106 patients diagnosed as having Alzheimer's disease (AD) (including mixed-type dementia) or dementia with Lewy bodies. E:TJ-54 treatment C:no treatment O:BPSD and cognitive functions were evaluated using the Neuropsychiatric Inventory (NPI) and the Mini-Mental State Examination (MMSE), respectively. Activities of daily living (ADL) were evaluated using Instrumental Activities of Daily Living (IADL) in outpatients and the Barthel Index in in-patients. AD 又はレビー小体型認知症と診断された患者に対して 抑肝散を投与すると 投与しない場合 と比較して 認知症の各種スケールが改善するかどうかを検討した研究であることが分かる 妥当か 抄録中に randomly assigned 4 wk などのキーワードが記載されている 広義の ITT 解析と言え
るかもしれないが periodⅡ になってくると除外が大きくなっているように思う The analysis set (full analysis set ; FAS) included all the enrolled subjects except those who did not return to the study site after their first visit (subjects with no available data) and those whose drug-taking compliance appeared to be poor. 結果 NPI スコアは抑肝散群で有意に改善していた MMSE など他の評価スコアは有意差なし For the safety evaluation, adverse events were investigated. Significant improvements in mean total NPI score associated with TJ-54 treatment were observed in both periods (Wilcoxon test, p=0.040 in period I and p=0.048 in period II). The mean NPI scores significantly improved during TJ-54 treatment in groups A and B (p=0.002 and p=0.007, respectively) but not during periods of no treatment. Among the NPI subscales, significant improvements were observed in delusions, hallucinations, agitation/aggression, depression, anxiety, and irritability/lability. ( 参考文献 3 より引用 ) 今後は認知症 BPSD は大きな問題になってくると思う 治療方法の選択肢が増えるという点で はいいことだと思う もちろん 薬剤の整理や便通の改善 生活上の工夫など 薬剤を検討する前 に注意するべき点は押さえておきたい
参考文献 1. Teranishi M, Kurita M, Nishino S, Takeyoshi K, Numata Y, Sato T, Tateno A, Okubo Y. Efficacy and tolerability of risperidone, yokukansan, and fluvoxamine for the treatment of behavioral and psychological symptoms of dementia: a blinded, randomized trial. J Clin Psychopharmacol. 2013 Oct;33(5):600-7. doi: 10.1097/JCP.0b013e31829798d5. PubMed PMID: 23948783. 2. Okahara K, Ishida Y, Hayashi Y, Inoue T, Tsuruta K, Takeuchi K, Yoshimuta H, Kiue K, Ninomiya Y, Kawano J, Yoshida K, Noda S, Tomita S, Fujimoto M, Hosomi J, Mitsuyama Y. Effects of Yokukansan on behavioral and psychological symptoms of dementia in regular treatment for Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Apr 16;34(3):532-6. doi: 10.1016/j.pnpbp.2010.02.013. Epub 2010 Feb 17. PubMed PMID: 20170698. 3. Mizukami K, Asada T, Kinoshita T, Tanaka K, Sonohara K, Nakai R, Yamaguchi K, Hanyu H, Kanaya K, Takao T, Okada M, Kudo S, Kotoku H, Iwakiri M, Kurita H, Miyamura T, Kawasaki Y, Omori K, Shiozaki K, Odawara T, Suzuki T, Yamada S, Nakamura Y, Toba K. A randomized cross-over study of a traditional Japanese medicine (kampo), yokukansan, in the treatment of the behavioural and psychological symptoms of dementia. Int J Neuropsychopharmacol. 2009 Mar;12(2):191-9. doi: 10.1017/S146114570800970X. Epub 2008 Dec 11. PubMed PMID: 19079814.