Yi-Gan San as Adjunctive Therapy for Treatment-Resistant Schizophrenia: An Open-Label Study

Department of Psychiatry, Shimane University School of Medicine, Izumo, Japan.
Clinical neuropharmacology (Impact Factor: 2.01). 01/2009; 32(1):6-9. DOI: 10.1097/WNF.0b013e31817e08c3
Source: PubMed


Recent studies indicate that the traditional Japanese herbal medicine yi-gan san (YGS; yokukan-san in Japanese) may be safe and useful in treating behavioral and psychological symptoms in patients with dementia and borderline personality disorder. We aimed at evaluating both the efficacy and safety of YGS in patients with treatment-resistant schizophrenia.
Thirty-four patients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (YGS-free) group (n = 25) and treated in a 4-week open-label study with YGS at an average daily dosage of 6.7 +/- 2.5 g (range, 2.5-7.5 g). Psychometric instruments used to assess efficacy included the Positive and Negative Syndrome Scale for Schizophrenia and the Drug-Induced Extrapyramidal Symptom Scale.
A significant decrease was observed at 2 weeks and at 4 weeks in each Positive and Negative Syndrome Scale for Schizophrenia subscale score in the YGS group, but this was not observed in the control group. However, the Drug-Induced Extrapyramidal Symptom Scale total score did not change in both groups.
In this open-label pilot study, patients treated with YGS showed a statistically significant reduction on clinician-rated scales. The present findings suggest that an adjunction of YGS might be effective for treatment-resistant schizophrenia.

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    • "Gastrointestinal complaints have been reported in the elderly5,11,13 and the non-elderly;17–19,33,34 however, these complaints are mild and transient. Mild elevation of blood liver enzymes was observed in one case.9 "
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    ABSTRACT: Japanese traditional herbal medicine (Kampo) has its origins in traditional Chinese medicine (TCM). It was introduced to Japan in the middle of the sixth century and has evolved over the past 1,400 years after combining with Japan's original folk remedies. While it retains some similarities to TCM, Kampo has evolved in Japan, resulting in a system of medicine that has many differences from TCM. Kampo medicine is considered to be very safe; in Japan, Kampo herbal formulas are manufactured by licensed pharmaceutical companies, prescribed by Western-trained medical doctors (usually as a freeze-dried extract), and have quality control standards similar to those of prescription drugs. The present study examined Yokukan-san (Yi-Gan San in TCM), a Kampo formula that has been used empirically in Japan for more than 400 years. Accumulating clinical trials have demonstrated Yokukan-san's efficacy in treating patients with behavioral and psychological symptoms of dementia, which has resulted in the Japanese Society of Neurology listing it in the Japanese Guidelines for the Management of Dementia 2010. Efficacy in other diseases and conditions, such as sleep disorders, tardive dyskinesia, aggression, and impulsivity has also been reported. This article reviews both clinical and basic studies of Yokukan-san, with the goal of clarifying its clinical indications.
    Neuropsychiatric Disease and Treatment 09/2014; 10:1727-42. DOI:10.2147/NDT.S65257 · 1.74 Impact Factor
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    • "Yokukan-san (also called “yoku-kan-san,” “yokukansan,” and “yi-gan-san”; Tsumura and Company, Tokyo, Japan), a Japanese traditional herbal (Kampo) prescription, has recently gathered increasing attention in the field of psychiatry due to accumulating reports showing its remarkable efficacy in treating behavioral and psychological symptoms of dementia (BPSD), as reviewed in 2010.1 In addition, various therapeutic effects of yokukan-san have been reported in the treatment of other symptoms such as those of treatment-resistant schizophrenia,2 tardive dyskinesia,3 borderline personality disorder,4 and Huntington’s disease.5 Today, such differing uses of yokukan-san are consistent with the uses of yokukan-san described in classic medical books. Yokukan-san has been utilized for more than 400 years, since before the establishment of conventional medicine, based on Kampo-specific indications. "
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    ABSTRACT: Yokukan-san, a Japanese traditional herbal (Kampo) prescription, has recently gathered increasing attention due to accumulating reports showing its remarkable efficacy in treating a wide variety of diseases refractory to conventional medicine as well as the behavioral and psychological symptoms of dementia. As yokukan-san has become broadly integrated with conventional medicine, augmentation therapy with other Kampo prescriptions has become necessary when the yokukan-san has been only partially efficacious. In this paper, we report three cases in which the addition of orengedoku-to, another Kampo formula, to yokukan-san was remarkably effective. Case 1 was an 85-year-old man with Alzheimer-type dementia who had become aggressive during the past 2 years. Three milligrams of aripiprazole completely suppressed his problematic behaviors but had to be stopped because of extrapyramidal symptoms. In the second case, a 44-year-old man with methamphetamine-induced psychosis had suffered from serious tardive dystonia for 2 years. No conventional approach had improved his tardive dystonia. The third case was a 29-year-old engineer who often failed to resist aggressive impulses and was diagnosed with intermittent explosive disorder. He was prescribed 5 mg of olanzapine, which did not suppress his extraordinary anger and caused somnolence even though the dose was low. Yokukan-san was complementarily added to the patients' regular medication and exerted a definitive but partial effect in all cases. The addition of orengedoku-to to yokukan-san exerted the same efficacy as aripiprazole in controlling aggressiveness in Case 1, improved the tardive dystonia by 80% in Case 2, and was completely effective in controlling the patient's aggressive impulses in Case 3. Together with empirical evidence demonstrating the effectiveness of both yokukansan and orengedoku-to in reducing irritability, impulsivity, and aggression, these three cases suggest that orengedoku-to augmentation can be an effective option in cases that are partially responsive to yokukan-san treatment.
    Neuropsychiatric Disease and Treatment 01/2013; 9(1):151-5. DOI:10.2147/NDT.S38318 · 1.74 Impact Factor
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    • "Although highly speculative, these positive changes in socialization may be due to TJ-54’s mechanism of action as a partial 5-HT1A agonist [25]. A putative association has been hypothesized between partial agonism at 5-HT1A receptors and improvements in anxiety and depression, as well as the negative symptoms of schizophrenia [24]. Thus, it is possible that TJ-54 targets these symptoms, thereby potentially resulting in subjects’ increased ability and/or interest in interacting with others. "
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    ABSTRACT: Background Numerous medications have been tested on patients with pervasive developmental disorder not otherwise specified (PDD-NOS) and Asperger’s disorder. Although many of these medications have been demonstrated to be useful, no clear primary treatment for PDD-NOS and Asperger’s disorder has emerged. Despite the efficacy of some of the medicines, the acceptability and side effects have proven to be barriers to their use. Recent studies indicate that the traditional Japanese herbal medicine yokukansan (TJ-54) may be safe and useful in treating behavioral and psychological symptoms in dementia and some neuropsychiatric disorders. We aimed at evaluating both the efficacy and safety of TJ-54 in patients with well-defined PDD-NOS and Asperger’s disorder. Methods This was a 12-week prospective, open-label investigation of TJ-54 in 40 children, adolescents, and adults diagnosed with PDD-NOS or Asperger’s disorder. Primary outcome measures included the Clinical Global Impressions-Severity of Illness Scale (CGI-S) and the Aberrant Behavior Checklist-Iritability subscale score (ABC-I). Results Forty subjects, ages 8–40 years (mean 22.7 ± 7.3 years) received a mean final TJ-54 dosage of 6.4 ± 1.3 g/day (range 2.5-7.5 g/day). Full-scale intelligence quotient (IQ) scores ranged from 70 to 110 (mean 88.9 ± 13.2). Thirty-six (90%) of 40 subjects showed fewer interfering symptoms of irritability, including aggression, self-injury, and tantrums, with a final CGI-S of 1 or 2 (normal, not at all ill or borderline mentally ill) and a 80% or greater improvement on the ABC-I. The mean CGI-S score at baseline was 6.8 ± 0.8 whereas scores at end point was 1.9 ± 0.1 (< 0.0001). ABC-I scores ranged from 11 to 29 (mean 17.4 ± 3.66) at baseline, whereas scores at week 12 ranged from 0 to 5 (mean 0.93 ± 0.97) (p <0.0001). TJ-54 was well tolerated. No subject exited the study due to a drug-related adverse event. Conclusions These preliminary data suggest that TJ-54 may be effective and well tolerated for treatment of severe irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech in patients with PDD-NOS or Asperger’s disorder. However, given the characteristics of this trial, the present findings should be taken cautiously, and larger-scale placebo-controlled studies are needed to elucidate the efficacy and tolerability of TJ-54 in this understudied population.
    BMC Psychiatry 11/2012; 12(1). DOI:10.1186/1471-244X-12-215 · 2.21 Impact Factor
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