Efficacy and Tolerability of Risperidone, Yokukansan, and Fluvoxamine for the Treatment of Behavioral and Psychological Symptoms of Dementia

Abstract

The descriptive term behavioral and psychological symptoms of dementia (BPSD) is used to cover a range of noncognitive disturbances including anxiety, depression, irritability, aggression, agitation, eating disorders, and inappropriate social or sexual behaviors. Behavioral and psychological symptoms of dementia are seen in about 90% of patients with dementia. We aimed to compare the efficacy and tolerability of risperidone, yokukansan, and fluvoxamine used for BPSD in elderly patients with dementia. Ninety inpatients with dementia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria were investigated in Sato Hospital, Koutokukai. We conducted an 8-week, rater-blinded, randomized trial, administering flexibly dosed risperidone, yokukansan, or fluvoxamine. Primary outcome measures were Neuropsychiatric Inventory in Nursing Home Version total score and its items. Secondary outcome measures were cognitive function measured by Mini-Mental State Examination and daily life function measured by Functional Independence Measure (FIM). Neurological adverse effects were measured by the Drug-Induced Extra-Pyramidal Symptoms Scale. At the end of the study, we analyzed 76 patients (92.7%). 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. This trial is registered at UMIN Clinical Trials Registry (identifier: UMIN000006146).

Yokukan-san: a review of the evidence for use of this Kampo herbal formula in dementia and psychiatric conditions

“…One good example of Ibyodochi is YKS, a single prescription that is reported to be effective in treating many different diseases such as dementia,1–14 sleep disorders,15,16 tardive dyskinesia,17 borderline personality disorder,18 and schizophrenia-related diseases 19,20. On the other hand, different herbal formulas may also be used to treat the same disease (called “Dobyoichi” in Kampo).…”

“…YKS has attracted attention in the field of psychiatry due to reports of its efficacy in patients with dementia 1–14. In addition, therapeutic effects of YKS have been reported in the treatment of sleep disorders,15,16 tardive dyskinesia,17 borderline personality disorder,18 and schizophrenia-related diseases 19,20.…”

What is the therapeutic value of antidepressants in dementia? A narrative review

“…Despite anxiety being common in dementia (Badrakalimuthu and Tarbuck, ) and previous recommendations to use antidepressants in its treatment (Sink et al , ), few RCTs have investigated the effects of antidepressants on anxiety in dementia. In four trials, treatment had no significant effect on anxiety score over placebo (Lebert et al , ; Teranishi et al , ; Nyth et al , ; Nyth and Gottfries, ). In all four trials, anxiety was only measured by using a subscale of a broader assessment tool.…”

Treatment of Dementia-related Symptoms with Japanese Traditional Medicine (Kampo): A Review of Clinical Studies

“…In fact, since 2010, YKS has been listed alongside modern conventional medicine in the Japanese Guidelines for the Management of Dementia by the Japanese Society of Neurology (http://www.neurology-jp.org/guidelinem/nintisyo.html). YKS has a different therapeutic mechanism from that of anti-psychotic agents and improves BPSD and activities of daily living (ADL) without impairing cognitive function or causing extrapyramidal symptoms, which is its greatest advantage in the treatment of elderly patients [5][6][7][8][9][10]. Interestingly, YKS used to be a TCM medicine for symptoms in children such as night cry and sleep terrors.…”

“…Interestingly, YKS used to be a TCM medicine for symptoms in children such as night cry and sleep terrors. Meanwhile, starting in 2005, 5 RCTs have provided support for YKS's efficacy in treating dementia-related symptoms [5,[7][8][9][10] and YKS is now used widely for various symptoms in elderly patients as well as in children in Japan.…”