A multicenter, double-blind, randomized, controlled study of patients with treatment-resistant schizophrenia treated with yokukansan for 12 weeks.

Aim: We conducted a 12-week double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of yokukansan in patients with schizophrenia. Methods: Patients with schizophrenia resistant to antipsychotics whose Positive and Negative Syndrome Scale (PANSS) scores were stable within five points were enrolled and assigned to the yokukansan or placebo group. Fifty-three of the 61 consenting patients were allocated to the yokukansan (n = 27) and placebo (n = 26) groups. Results: The changes in total and positive PANSS scores at 12 weeks were significantly greater in the yokukansan group than in the placebo group. There were no significant changes in other psychiatric symptom rating scores in either group. Adverse reactions were reported in six of 27 patients (22.2%) in the yokukansan group and five of 26 patients (19.2%) in the placebo group, all of which were nonserious. Conclusion: Yokukansan is very safe and has clinical potential as a treatment for schizophrenia in combination with Western medicine.

Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a randomized, multicenter, double-blind, placebo-controlled trial.

Objectives. We aimed at evaluating both the efficacy and safety of TJ-54 (Yokukansan) in patients with treatment-resistant schizophrenia. This randomized, multicenter, double-blind, placebo-controlled study was conducted. Methods. One hundred and twenty antipsychotic-treated inpatients were included. Patients were randomized to adjuvant treatment with TJ-54 or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Results. TJ-54 showed a tendency of being superior to placebo in reduction total, positive, and general PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant in both per-protocol set (PPS) and intention-to-treat (ITT). However, in PPS analysis, compared to the placebo group, the TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores for lack of spontaneity and flow of conversation (TJ-54: -0.23 ± 0.08; placebo: -0.03 ± 0.08, P < 0.018), tension (TJ-54: -0.42 ± 0.09; placebo: -0.18 ± 0.09, P < 0.045), and poor impulse control (TJ-54: -0.39 ± 0.10; placebo: -0.07 ± 0.10, P < 0.037). Conclusions. The results of the present study indicate that TJ-54 showed a tendency of being superior to placebo in reduction PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant. However, compared to the placebo group, TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores.

Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled trial (a Positive and Negative Syndrome Scale, five-factor analysis).

BACKGROUND: Treating schizophrenia patients who fail to respond to antipsychotics is a major challenge, and the percentage of treatment-resistant patients is estimated to be 20-25 %. Recent studies indicate that yokukansan (YKS; D2 and 5HT1A partial agonist and 5HT2A and glutamate antagonist) to be safe and useful in treating behavioral and psychological symptoms associated with dementia and other neuropsychiatric conditions. We aimed at evaluating both the efficacy and safety of YKS in patients with treatment-resistant schizophrenia. METHODS: This randomized, multicenter, double-blind, placebo-controlled study was conducted between May 2010 and August 2012. One hundred twenty antipsychotic-treated inpatients from 34 psychiatric hospitals in Japan were included. Patients were randomized to adjuvant treatment with YKS 7.5 g/day or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) with five factors [excitement/hostility (P4, P7, G8, and G14), depression/anxiety (G1, G2, G3, G4, and G6), cognition (P2, N5, N7, G5, G10, G11, G12, G13, and G15], positive (P1, P3, P5, P6, and G9), and negative (N1, N2, N3, N4, N6, G7, and G16]]. Other assessments included, Clinical Global Impression-Severity (CGI-S), Global Assessment of Functioning (GAF), and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The primary efficacy outcome was the change in PANSS five-factor scores. The secondary outcomes were changes in the scores of CGI-S. The analysis was made on a modified intention to treat basis with the help of a last observation carried forward method. RESULTS: YKS showed a tendency of superiority to placebo in reducing total all PANSS five-factor scores in treatment-resistant schizophrenia, but the difference was not statistically significant in total, depression/anxiety, cognition, positive, and negative factors. However, compared to the placebo group, the YKS group showed statistically significant improvements in the PANSS excitement/hostility factor scores (p<0.05). No substantial side effects were recorded. CONCLUSION: The results of the present study indicate YKS to be a potential adjunctive treatment strategy for treatment-resistant schizophrenia, particularly to improve excitement/hostility symptoms.

Late-onset persistent visual hallucinations with epileptiform discharge.

We report the case of a 58-year-old female without a history of psychosis or epilepsy presenting with abrupt late-onset persistent visual hallucinations that had prominent epileptiform discharges with a diffuse sharp and slow wave complex on electroencephalography. Except for the visual hallucinations, other psychotic symptoms and epileptic seizures, such as disturbance of consciousness and convulsion, were not observed. The epileptiform discharge disappeared within 20 days after initiation of treatment with sodium valproate. Clinical improvement commenced after the electroencephalography improvement was complete. The cause remains obscure, but it was suggested that there were some organic factors in the aetiology of this late-onset visual hallucination.

Proton magnetic resonance spectroscopy (1H-MRS) of hippocampus, basal ganglia, and vermis of cerebellum in schizophrenia associated with idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome).

OBJECTIVE: Whether patients with schizophrenia-associated idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome, GS) have specific changes in brain metabolism was examined in this study. METHOD: This study applied proton magnetic resonance spectroscopy (1H-MRS) to the hippocampus, basal ganglia, and vermis of the cerebellum of schizophrenic patients with GS (n=15) or without GS (n=15), all diagnosed according to DSM-IV criteria, and healthy subjects (n=15). RESULTS: In the hippocampus, schizophrenic patients with GS showed a significant decrease of N-acetyl aspartate/creatine-phosphocreatinine (NAA/Cr) and myoinositol/creatine-phosphocreatinine (mI/Cr) ratios compared to healthy subjects and schizophrenic patients without GS, while schizophrenic patients without GS showed only a significant decrease of NAA/Cr compared to healthy subjects. In the basal ganglia, schizophrenic patients with GS showed a significant decrease of ml/Cr compared to schizophrenic patients without GS and healthy subjects, and schizophrenic patients with GS showed a significant decrease of NAA/Cr compared to healthy subjects. In the vermis of the cerebellum, schizophrenic patients with GS showed only a significant decrease of ml/Cr compared to healthy subjects, although schizophrenic patients without GS did not show a significant decrease of ml/Cr compared to healthy subjects. CONCLUSION: The findings suggest that schizophrenia with GS is a more severe sub-type with regard to brain metabolism.

Sleep disturbances and depression in the elderly in Japan.

UNLABELLED: The purpose of the present study was to evaluate the relationship between sleep disturbances and depression in the Japanese elderly. METHODS: These investigations in the Japanese elderly were carried out with the Geriatric Depression Scale, the Pittsburgh Sleep Quality Index, and questions on restless legs syndrome and nocturnal eating disorder. A total of 2023 people (male: 1008; female: 1015; average age: 74.2 +/- 6.3 years) were analyzed by chi2 test and simple and multiple logistic regression. The prevalence of sleep disturbance was 37.3% and that of depression was 31.3%. Female gender and/or older (> or =75 years) age were significantly associated with depression. Characteristics in depressive elderly were poor sleep efficiency, sleep disturbances due to difficulty of initiating sleep (DIS), breathing discomfort, coldness and pain, poor subjective sleep quality and lack of enthusiasm for activities. Sleep disturbances due to using the bathroom, breathing discomfort and coldness and long sleep latency were associated with depression in younger (65-74 years) men. Sleep disturbance due to DIS was associated with depression in older (> or =75 years) men. Sleep disturbance due to pain was associated with depression in younger and older women. Poor sleep efficiency was associated with depression in older women. Poor subjective sleep quality was associated with depression in younger and older men and younger women. Lack of enthusiasm was associated with depression in younger and older men and older women. Restless legs syndrome was statistically significantly associated with depression in younger men. It is concluded that sleep disturbance and depression among the Japanese elderly are closely related symptoms. The features of sleep disturbance with depression differed with sex and age.

Late onset anorexia nervosa: two case reports.

OBJECTIVE: Some patients develop an eating disorder at a late age. It is worth investigating why this syndrome develops at such widely different ages. METHODS: Two Japanese cases of late onset anorexia nervosa are reported. RESULTS: In these late onset cases, anorexia developed out of sadness over a loss such as bereavement, divorce, and fear or anxiety for the future. In addition, these two patients didn't demonstrate a fear of aging or of losing their attractiveness and sexuality, nor did they develop a dissociative disturbance based on an early traumatic history of sexual abuse in PTSD. CONCLUSION: Although the clinical features are similar, there appear to be differences between late onset and adolescent cases in psychological mechanisms.

Fluvoxamine for the treatment of depression and parkinsonism in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a parkinsonian-like disorder characterized by postural instability, rigidity, bradykinesia, supranuclear ocular palsy, dysarthria, dysphagia and dementia. There is no satisfactory treatment. A 68-year-old woman with initial progressive supranuclear palsy is described, who was generally apathetic, withdrawn, lacked spontaneity in speech and behavior, and suffered episodes of depression. Treatment with levodopa/carbidopa was ineffective in controlling her parkinsonism and depression, but these symptoms responded to fluvoxamine. This response may be related to fluvoxamine's putative effect on the serotonin system.