Yi-gan san as adjunctive therapy for treatment-resistant schizophrenia: an open-label study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Hyperbilirubinemia-related behavioral and neuropathological changes in rats: a possible schizophrenia animal model.

BACKGROUND: Patients with schizophrenia show a significantly higher frequency of hyperbilirubinemia than patients suffering from other psychiatric disorders and the general healthy population. We examined the hyperbilirubinemia on behavioral and neuropathological changes in rats as a possible animal model of schizophrenia. METHODS: Gunn rats with severe hyperbilirubinemia (j/j), Gunn rats without severe hyperbilirubinemia (+/j), and Wistar rats were examined by open-field, social interaction, and prepulse inhibition tests. TUNEL, AgNOR and Ki-67 were also assayed on paraffin-embedded brain sections of these rats. RESULTS: Compared to Wistar rats, both Gunn j/j and +/j rats showed hyperlocomotion, high sniffing scores, and low defecation scores. They showed significantly more aggressive behaviors and impaired prepulse inhibition. The numbers of Ki-67-labeled cells and AgNOR were lower and the number of TUNEL-positive cells was higher than that of Wistar rats. CONCLUSIONS: These results might support the neurodevelopmental hypothesis of schizophrenia. Both Gunn j/j and +/j rats may be a useful animal model and provide clues to the role of hyperbilirubinemia in schizophrenia.

Yi-gan san for the treatment of neuroleptic-induced tardive dyskinesia: an open-label study.

BACKGROUND: Recent studies indicate that the traditional Japanese herbal medicine yi-gan san (YGS, yokukan-san in Japanese), a serotonin modulator, may be safe and useful in treating behavioral and psychological symptoms in dementia and borderline personality disorder patients. The authors examined the efficacy, tolerability, and safety of YGS in patients with tardive dyskinesia. METHODS: Twenty-two patients with schizophrenia who had neuroleptic-induced tardive dyskinesia were given 7.5 g/day of YGS for 12 weeks in an open-label study. RESULTS: Administration of YGS resulted in a statistically significant improvement in tardive dyskinesia and psychotic symptoms. CONCLUSIONS: YGS may be an effective and safe therapy to control tardive dyskinesia and psychosis in patients with schizophrenia, that should be further tested in double-blind, placebo-controlled trials.

Yi-gan san for the treatment of borderline personality disorder: an open-label study.

BACKGROUND: Numerous medications have been tested on patients with borderline personality disorder (BPD). Although many of these medications have been demonstrated to be useful, no clear main treatment for BPD has emerged. Despite the efficacy of some of the medicines, acceptability and side effects have proven to be barriers to their use. Recent studies indicate that the traditional Chinese herbal medicine yi-gan san (YGS, yokukan-san in Japanese) may be safe and useful in treating behavioral and psychological symptoms in dementia patients. We aimed at evaluating both efficacy and safety of yi-gan san in patients with well-defined BPD. METHODS: Twenty female outpatients diagnosed with BPD according to DSM-IV criteria and the revised Diagnostic Interview for Borderlines completed a 12-week open-label study with yi-gan san at an average daily dosage of 6.4+/-1.9 g (2.5-7.5 g). Psychometric instruments to assess efficacy included the Brief Psychiatric Rating Scale (BPRS), Hamilton Rating Scales for Depression (HAM-D), Global Assessment of Functioning (GAF), Clinical Global Impression Scale (CGI), and Aggression Questionnaire (AQ). RESULTS: Most psychometric scale scores exhibited a highly significant improvement (total BPRS; BPRS somatic concern, anxiety, tension, depressive mood, hostility, suspiciousness, motor retardation, uncooperativeness, and excitement subscale; CGI; GAF; AQ) over time. CONCLUSIONS: In this open-label pilot study, patients treated with YGS showed statistically significant reduction on self-rated and clinician-rated scales. The present findings suggest that yi-gan san might be effective for the treatment of a number of BPD symptoms, including low mood, impulsivity, and aggression.

Influence of sevelamer on mineral metabolism and hyperparathyroidism in Japanese hemodialysis patients.

In June 2003, sevelamer hydrochloride became widely available in Japan and was expected to control hyperphosphatemia in hemodialysis patients without inducing hypercalcemia. To evaluate the impact of sevelamer therapy on mineral metabolism, we recruited 954 hemodialysis patients from 21 renal units just before the general release of sevelamer in Japan. The serum calcium, phosphate, and parathyroid hormone levels determined on enrollment were compared with those later measured in June 2004. Sevelamer was prescribed for 169 of the 859 patients for whom data were available in 2004. The mean calcium level, phosphate level, and calcium x phosphate product were all significantly reduced during the 12-month study period, but the intact parathyroid hormone (iPTH) level did not change. As a result, the percentage of patients who achieved a calcium x phosphate product of <55 mg(2)/dL(2) was significantly increased, but there were no changes in that of patients who achieved the target ranges for phosphate (3.5-5.5 mg/dL) or iPTH (150-300 pg/mL). Among sevelamer-treated patients, iPTH significantly increased, and this change was more marked in the patients with an initial iPTH level <150 pg/mL. Sevelamer was useful for reducing the serum calcium level and calcium x phosphate product, but hyperphosphatemia and hyperparathyroidism were not improved in our study population at 12 months after the release of sevelamer. A decrease in the calcium load might result in the exacerbation of hyperparathyroidism. However, among patients with relative hypoparathyroidism, sevelamer therapy may be beneficial for the prevention of adynamic bone disease.