Kenichi Tsunoda

Reducing the dose of antipsychotic medications for those who had been treated with high-dose antipsychotic polypharmacy: an open study of dose reduction for chronic schizophrenia.

Antipsychotic medications are often used at higher than the recommended dose and sometimes in a combination regimen to treat schizophrenia. However, in general, high-dose therapies have been abandoned in recent clinical studies. In this study, dose reduction of antipsychotic medication was implemented for patients with chronic schizophrenia, most of whom (81%) had been treated with an antipsychotic high-dose polypharmacy regimen consisting of more than 1000 mg/day in total amount. The results show that merely reducing the amount of antipsychotic led to favourable outcome in 23 out of 41 cases (56%), with another 13 cases (32%) showing no change. Dose reduction ended in failure in only five subjects (12%). Overall, the amount as well as the number of antipsychotic medications was significantly reduced from 1984 mg to 812 mg per day (reductions of 59% and from 3.6 to 2.2, respectively; both P<0.0001). The Global Assessment of Functioning scale improved from 30.6 to 37.2, which reached significance (P<0.001). Accordingly, the Severity of Illness improved from 4.7 to 4.2, and was also significant (P<0.01). Dose reduction is an encouraging strategy to consider for those patients with schizophrenia who have chronically been treated with high-dose antipsychotic polypharmacy, even if judged unavoidable in the past.

Effects of discontinuing benzodiazepine-derivative hypnotics on postural sway and cognitive functions in the elderly.

Benzodiazepines (BZDs) have been reported to cause negative impacts on body stability and cognitive functions, which in turn could result in lethal incidents, including falls, especially in the elderly. This fact notwithstanding, no systematic trial has evaluated the feasibility and benefits of discontinuing BZD‐derivative hypnotics in this population, which was addressed in this study.

Dental conditions in inpatients with schizophrenia: A large-scale multi-site survey

BackgroundClinical relevance of dental caries is often underestimated in patients with schizophrenia. The objective of this study was to examine dental caries and to identify clinical and demographic variables associated with poor dental condition in patients with schizophrenia.MethodsInpatients with schizophrenia received a visual oral examination of their dental caries, using the decayed-missing-filled teeth (DMFT) index. This study was conducted in multiple sites in Japan, between October and December, 2010. A univariate general linear model was used to examine the effects of the following variables on the DMFT score: age, sex, smoking status, daily intake of sweets, dry mouth, frequency of daily tooth brushing, tremor, the Clinical Global Impression-Schizophrenia Overall severity score, and the Cumulative Illness Rating Scale for Geriatrics score.Results523 patients were included in this study (mean ± SD age = 55.6 ± 13.4 years; 297 men). A univariate general linear model showed significant effects of age group, smoking, frequency of daily tooth brushing, and tremor (all p’s < 0.001) on the DMFT score (Corrected Model: F(23, 483) = 3.55, p < 0.001, R2 = 0.42) . In other words, older age, smoking, tremor burden, and less frequent tooth brushing were associated with a greater DMFT score.ConclusionsGiven that poor dental condition has been related with an increased risk of physical co-morbidities, physicians should be aware of patients’ dental status, especially for aged smoking patients with schizophrenia. Furthermore, for schizophrenia patients who do not regularly brush their teeth or who exhibit tremor, it may be advisable for caregivers to encourage and help them to perform tooth brushing more frequently.

Effects of yoga therapy on postural stability in patients with schizophrenia-spectrum disorders: A single-blind randomized controlled trial

INTRODUCTION Postural instability is a serious concern in patients with schizophrenia-spectrum disorders since it is expected to increase the risk of falls that may lead to fractures. The impact of yoga therapy on postural stability has not been investigated. METHODS In this eight-week single-blind randomized controlled study with an eight-week follow-up, outpatients with schizophrenia or related psychotic disorder (ICD-10) were randomly assigned to either yoga therapy or a control group. In the yoga therapy group, the subjects received weekly sessions of 60-min yoga therapy for eight weeks in addition to their ongoing treatment. In the control group, the subjects received a weekly regular day-care program. The assessments that were performed at the baseline and endpoint included the Clinical Stabilometric Platform (CSP), anteflexion in standing. RESULTS Forty-nine patients participated in this study (32 men; mean ± SD age, 53.1 ± 12.3 years): yoga therapy group (n = 25) and control group (n = 24). In the yoga group, significant improvements were observed in a total length of trunk motion, the Romberg ratio, and anteflexion in standing at week 8 (mean ± SD: 63.9 ± 40.7-53.4 ± 26.2 cm, 1.6 ± 0.9-1.1 ± 0.6, and -8.7 ± 9.5 to -3.8 ± 12.4 cm, respectively) while there were no significant changes in the control group. However, those clinical gains returned to the baseline level at week 16. CONCLUSIONS The results confirmed the beneficial effects of the yoga therapy on postural stability in patients with schizophrenia. However, the therapeutic effects seemed transient, which warrants further investigations on strategies to sustain the improvements.

Predicting plasma concentration of risperidone associated with dosage change: A population pharmacokinetic study

Background Due to high interindividual variability in peripheral pharmacokinetic parameters, dosing of antipsychotics relies on clinical trial and error. This blind process of upward or downward clinical dose titration carries a risk of relapse and adverse effects in the treatment of schizophrenia. Using population pharmacokinetic methods, the authors therefore sought to predict plasma concentrations of risperidone (RIS) plus 9-hydroxyrisperidone (9-OH-RIS) before a dosage change. Methods Two plasma samples were collected at 2 separate given time points for the measurement of RIS and 9-OH-RIS concentrations from 50 patients with schizophrenia or schizoaffective disorder maintained on risperidone (mean ± SD age = 56 ± 15 years; 39 men). After an oral risperidone dose adjustment, a third sample was collected. The plasma concentration of the third sample was individually predicted in a blinded fashion with the 2 baseline plasma concentrations before dose adjustment and clinical and demographic information, using the mixed-effects model with NONMEM that was derived from the data of the Clinical Antipsychotic Trials in Intervention Effectiveness study. Results The mean (95% confidence interval) prediction errors (in ng/mL) were as low as 0.0 (−1.3 to 1.4) for RIS and 1.0 (−1.1 to 3.0) for 9-OH-RIS. The observed and predicted concentrations of RIS and 9-OH-RIS were highly correlated (r = 0.96, P < 0.0001 and r = 0.92, P < 0.0001, respectively). Conclusions Antipsychotic plasma concentrations can be predicted before risperidone dose adjustment. In light of the known relationship between plasma drug concentration, dopamine D2 receptor occupancy, and clinical effects, our results confirm that individualized dosing with the measurement of antipsychotic plasma concentrations has the potential for bedside clinical application.

Survey of benzodiazepine and antidepressant use in outpatients with mood disorders in Japan

Data on benzodiazepine use in mood disorders are still limited, especially among seniors. A cross‐sectional review of psychotropic prescriptions in 948 outpatients with mood disorders (405 male; mean ± SD age, 52 ± 17 years; age range, 16– 91 years) was conducted in Japan. The use of benzodiazepine‐derivative anxiolytics was approximately 60% in all decades, including older patients, without a group difference. The frequent use of benzodiazepines is a cause for concern because they are not preferred treatment, given their well‐known adverse effects especially in the elderly.

Relationships between global assessment of functioning and other rating scales in clinical trials for schizophrenia

The relationship between the Global Assessment of Functioning (GAF) with other scales in schizophrenia has rarely been investigated. A systematic literature search was conducted to identify articles that reported the GAF score together with scores in the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) or Brief Psychiatric Rating Scale (BPRS), using MEDLINE, EMBASE and PsycINFO, with keywords of schizophrenia, clinical trial and global assessment of functioning (last search 30 June 2013). Correlational analyses with weighting by the study participant numbers across these rating scales were performed. In 40 clinical trials (n=8000) that reported cross-sectional data on the GAF and PANSS, a significant but modest correlation was noted (Pearson׳s r=-0.401, p<0.0001). Furthermore, a correlation between the GAF and CGI-severity (CGI-S) at study baseline in 38 studies (n=11,315) was robust (r=-0.893, p<0.0001). In longitudinal studies, changes in the GAF scores were negatively correlated with those in the PANSS as well as CGI-S scores (p<0.0001 for both). Data on the BPRS were all statistically significant although relatively scarce. While optimal degree of concordance is undetermined among psychiatric scales that are presumed to be measuring different but overlapping constructs, this study found significant correlations in the GAF and CGI-S or PANSS, both cross-sectionally and longitudinally. The GAF-CGI-S relationship was especially tighter, making it a reliable clinical indicator.

Clinical and demographic characteristics associated with postural instability in patients with schizophrenia.

As people with schizophrenia grow older, prevention of falls in this older population has become a public health priority. It is therefore critically important to identify risk factors to effectively prevent falls. For this purpose, the degree of postural sway can serve as a convenient index of risk assessment. The objective of this study was to find clinical and demographic characteristics associated with postural instability. Inpatients and outpatients with schizophrenia or related psychosis were recruited at 2 hospitals in Japan. The clinical stabilometric platform, which measured a range of the trunk motion, and extrapyramidal side effects were evaluated between 9 and 11 a.m. Four hundred two subjects were enrolled (age: mean, 55.5 [SD, 14.4] years). A univariate general linear model showed that the use of antipsychotic drugs with a chlorpromazine equivalent of 10 or greater, being overweight, and inpatient treatment setting were associated with a greater degree of the range of postural sway. Another general linear model, including a subgroup of 300 subjects who did not present any extrapyramidal side effects, not only consolidated these findings, but also revealed a great degree of postural sway in older subjects. In addition, quetiapine was found to be associated with a greater range of postural sway among atypical antipsychotics. Schizophrenia patients generally showed a greater degree of postural instability, compared with the reference data of healthy people. These findings highlight truncal instability as a risk factor of falls in patients with schizophrenia, especially when they are overweight, old, and/or receiving antipsychotics with a chlorpromazine equivalent of 10 or greater, including quetiapine.

Oversight of constipation in inpatients with schizophrenia: a cross-sectional study☆ , ☆☆ ,★,★★

OBJECTIVE Constipation is often overlooked in patients with schizophrenia. We examined their awareness of constipation and whether they reported it to their psychiatrists. METHOD Five hundred three inpatients with schizophrenia (International Classification of Diseases, 10th Revision) were interviewed about their recent bowel movements and evaluated for the diagnostic criteria for functional constipation. If constipation was present, patients were asked if they were aware of it and had reported it to their psychiatrists in charge. Additionally, their global psychopathology and functioning were assessed using the Clinical Global Impression-Schizophrenia (CGI-SCH) and the Global Assessment of Functioning (GAF), respectively. RESULTS The criteria for constipation were met by 184 patients (36.6%); of these patients, only 56.0% (103/184) were aware of it. Moreover, only 34 of the constipated patients (18.5%) reported its presence to their psychiatrists. No significant differences were found in the CGI-SCH overall severity or subscale scores or in the GAF scores between those patients who reported and those who failed to report constipation. CONCLUSIONS The present study demonstrated that constipation was neither recognized nor reported to psychiatrists by a significant percentage of the patients. These findings underscore the importance of greater vigilance and active evaluation of constipation in patients with schizophrenia for appropriate clinical management.

Postural sway and flexibility in patients with schizophrenia-spectrum disorders: A cross-sectional study

Coordinated bodily balance is necessary to prevent falls, where postural sway and/or body inflexibility should be relevant. We aimed to assess postural sway and flexibility in patients with schizophrenia and identify clinical characteristics. Postural sway (length and range of trunk motion, and Romberg ratio) and flexibility (anteflexion in sitting) were measured in schizophrenia. The Positive and Negative Syndrome Scale (PANSS) and the Drug Induced Extrapyramidal Symptoms Scale (DIEPSS) were used for the assessment of psychopathology and extrapyramidal symptoms, respectively. Characteristics associated with postural sway and flexibility were examined with regression analysis. A total of 100 patients (68 men, mean ± S.D. age: 49.3 ± 13.8 years, PANSS score: 83.4 ± 15.1, DIEPSS score: 2.2 ± 2.2) participated in this study. The anteflexion in sitting was not significantly correlated with length of trunk motion, range of trunk motion, or Romberg ratio. Postural instability was associated with higher DIEPSS overall severity score and PANSS positive symptoms. A significant correlation was also found between less flexibility and increased PANSS negative symptoms. In conclusion, flexibility and postural stability might be regarded as separate elements of physical fitness in schizophrenia. Prospective exercise intervention would be worthy of investigation to enhance postural stability and flexibility in an effort to prevent falls.