Bunta Yoshimura

Is quetiapine suitable for treatment of acute schizophrenia with catatonic stupor? A case series of 39 patients

Purpose We aimed to determine which antipsychotic is most effective for the treatment of acute schizophrenia with catatonic stupor. Patients and methods Data were obtained from the medical records of 450 patients with the diagnosis of schizophrenia, who had received acute psychiatric inpatient treatment between January 2008 and December 2010 at our hospital. Among them, 39 patients (8.7%) met the definition of catatonic stupor during hospitalization. The diagnoses of schizophrenia in all 39 patients were reconfirmed during the maintenance phase. We retrospectively reviewed the medical records of these 39 patients to investigate which antipsychotics were chosen for treatment during the period from admission to recovery from catatonia, at the time of discharge, and 12 and 30 months after discharge. Results As compared to other antipsychotics, it was found out that use of quetiapine had better outcomes and hence was used more often. A total of 61.5% of patients were on quetiapine at the time of recovery from catatonia and 51.3% of patients were on quetiapine at the time of discharge as compared to only 17.9% of patients on quetiapine on admission. However, at 12 and 30 months after discharge, the rates had decreased to 38.4% and 25.6%. Similarly, of 29 patients who were not administered electroconvulsive therapy, quetiapine was used at significantly higher rates at the time of recovery from catatonia (48.3%) than at the time of admission (17.2%). All 39 patients had received an antipsychotic as the first-line treatment and some antipsychotics might have contributed to the development of catatonia. Conclusion This study suggests that quetiapine is a promising agent for the treatment of schizophrenia with catatonic stupor during the acute phase.

Correlation between delay in initiating clozapine and symptomatic improvement

The correlation between long duration of untreated psychosis (DUP) and poor outcome in first-episode schizophrenia (FES) has been systematically shown (Marshall et al., 2005; Perkins et al., 2005; Penttilä et al., 2014). However, the effect of the delay in initiating clozapine (DIC) on treatment-resistant schizophrenia (TRS) remains unclear. We conducted a retrospective chart review to investigate the correlation between DIC and symptomatic improvement of TRS. We collected data using a retrospective, observational review of charts of 105 Japanese patients (continuous sampling) with the diagnosis of treatment-resistant schizophrenia, based on the International Classification of Diseases, Tenth Revision, and treated with clozapine at the Okayama Psychiatric Medical Center. Patients who started on clozapine between 1 January 2010 and 28 February 2015 and remained on clozapine for a period of at least three months were included. Clinical ratings, routinely administered by each attending physician at baseline, months 1, 3, 6, 12, 18, and 24, then yearly thereafter, included the 18item Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham, 1962), with each item rated from 1 (not present) to 7 (extremely severe), and the Clinical Global Impressions-improvement scale (CGI-I) (Guy, 1976). We defined DIC as the time from onset/relapse of a treatment-resistant psychotic episode to initiating clozapine, and the duration of illness (DOI) as the time fromonset of first-episode psychotic episode to initiating clozapine. Antipsychotic treatment-resistance was defined as a history of at least two failed trials of 600 mg of chlorpromazine equivalents for at least four weeks. We defined the improvement in BPRS total score as ([BPRS total score at baseline]− [BPRS total score at last observation] / [BPRS total score at baseline]− 18) × 100 (%), and the improvement in BPRS psychosis score as ([BPRS psychosis score at baseline] − [BPRS-psychosis score at last observation] / [BPRS psychosis score at baseline] − 4) × 100 (%). The Institutional Review Board of the Okayama Psychiatric Medical Center approved this study. Informed consent was not required. The correlations between improvement in BPRS total/psychosis scores at last observation andDIC/DOIwere analyzed using Spearmans rank correlation coefficient. Statistical analyses were done using IBM SPSS Statistics 22. The level of significance was set at two-tailed p b 0.05. As the result of exclusion of 15 patients who discontinued treatment with clozapine less than three months for the following reasons: side

The critical treatment window of clozapine in treatment-resistant schizophrenia: Secondary analysis of an observational study

Previous studies have suggested that a delay in initiating clozapine is one of the predictors of outcomes in treatment-resistant schizophrenia (TRS). However, whether there is a critical treatment window of clozapine in TRS and the duration of that window remain unclear. We conducted a secondary analysis of a previously published observational study using a retrospective chart review of 105 patients with TRS who were treated with clozapine. We included 90 patients who remained on clozapine for at least 3 months. The delay in initiating clozapine was an independent contributor to symptomatic improvement based on treatment with clozapine by multiple linear regression analysis. A receiver operating characteristic curve analysis (area under the curve: 0.78) confirmed 2.8 years was the best predictive cut-off value of delay in initiating clozapine for responses in patients treated with clozapine (sensitivity: 0.66, specificity: 0.84). In patients with a delay in initiating clozapine of ≤2.8 years and a delay in initiating clozapine of >2.8 years, the response rates were 81.6% and 30.8% (risk ratio=2.65; 95% confidence interval, 1.80, 3.63), respectively. Clinicians should reduce the delay in initiating clozapine to less than 3 years to improve symptomatic outcomes in TRS and to prevent clozapine-resistant schizophrenia.

Anti-NMDA Receptor Antibody Positivity and Presentations Without Seizure, Involuntary Movement, Hypoventilation, or Tumor: A Systematic Review of the Literature

Patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis may remain undiagnosed and untreated with immunotherapy. To investigate specific features and responses to immunotherapy of atypical anti-NMDAR antibody positivity patients, the authors reviewed and evaluated previous case reports/series including patients without seizure, involuntary movement, hypoventilation, or tumor. Of 22 patients identified, 21 responded to immunotherapy. Two patients had neurological/motor symptoms with few/no psychiatric/cognitive symptoms, and eight had both. Twelve patients presented with psychiatric/cognitive symptoms with few/no neurological/motor symptoms, and ≥1 had memory impairment, catatonia, abnormal MRI or electroencephalogram results. The authors recommend lumbar puncture and examination of anti-NMDAR antibodies for patients with these features.

Algorithm-based pharmacotherapy for first-episode schizophrenia involuntarily hospitalized: A retrospective analysis of real-world practice

Little is known about the clinical outcomes of severely ill patients with first‐episode schizophrenia spectrum disorders (FES) who are considered to lack the capacity to consent to clinical trials. We investigated the feasibility of an algorithm‐based pharmacotherapy (ABP) and clinical outcomes of patients with FES involuntarily hospitalized and treated with ABP.

Optimal Dosing of Risperidone and Olanzapine in the Maintenance Treatment for Patients With Schizophrenia and Related Psychotic Disorders: A Retrospective Multicenter Study

Objectives This study aims to determine the optimal tolerability dose ranges of risperidone (RIS) and olanzapine (OLZ) administered during schizophrenia maintenance phase. Methods Two-year continuation rates of prescription at discharge were examined using a retrospective cohort study method. Adult patients with schizophrenia and related psychotic disorders, receiving antipsychotic monotherapy with RIS or OLZ at discharge, were included. The primary outcome measures were the time to treatment discontinuation and 2-year continuation rates at 4 modal dose ranges of each drug. We estimated the optimal tolerability dose ranges by comparing the continuation rates at various modal doses. Results Of 648 patients, 344 received RIS and 304 received OLZ. The RIS 2-year continuation rates at 4 daily modal dose ranges were significantly different (0.5–2.5 mg: 46.0%, 3.0–5.0 mg: 40.0%, 5.5–7.5 mg: 30.0%, and 8.0–10.0 mg: 28.0%), with the difference favoring RIS at lower doses (0.5–5.0 mg) more than higher doses (5.5–10.0 mg). In contrast, there were no significant differences among OLZ 4 modal dose ranges (2.5–7.5 mg: 49.1%, 10.0–15.0 mg: 42.6%, 17.5–22.5 mg: 40.9%, and 25.0–30.0 mg: 39.0%). The time to treatment discontinuation significantly favored OLZ over RIS. However, it did not significantly differ between RIS and OLZ at lower doses. Conclusions It is suggested that the optimal tolerability dose range during maintenance treatment is 0.5 to 5.0 mg/d for RIS and 2.5 to 30 mg/d for OLZ, and that RIS at lower doses is comparable with OLZ at lower doses.

Hospitalization Risk Before and After Discontinuation of Long-Acting Injectable Antipsychotics.

To the Editors: A previous meta-analysis of mirror-image studies investigating hospitalization risk before and after initiation of long-acting injectable antipsychotics (LAI) showed that treatment with LAI avoids hospitalization in the treatment of schizophrenia. To our knowledge, there is no evidence of hospitalization risk before and after discontinuation of LAI. This study used mirror-image analysis to investigate changes in the hospitalization risk, number of hospitalizations, and hospitalization days in a real-world practice for patients with psychotic disorders 6 months before and 6 months after discontinuation of LAI. We collected data using a retrospective, observational review of charts of 517 patients with schizophrenia, schizoaffective disorder, or psychotic bipolar affective disorder (ICD-10) treated with LAI at least once between 1 April 2012 and 31 March 2015 at Okayama Psychiatric Medical Center in Japan. The LAI used for 517 patients were 165 haloperidol decanoate, 148 fluphenazine decanoate, 98 risperidone long-acting injection (RLAI), and 106 paliperidone palmitate (PP). Patients who were treated with LAI 6 months or more, but discontinued it and did not reinitiate it for a period of at least 6 months on April 30, 2015, were included. If treatment with LAI was discontinued during hospitalization, we defined the day of discharge as the start of the postdiscontinuation period. Patients who remained in hospital for the entire prediscontinuation period were excluded. The Institutional Review Board of Okayama Psychiatric Medical Center approved this study. Informed consent was not required. Continuous variables were analyzed using the paired t test; categorical variables were analyzed using the χ test. The 2-tailed P value less than 0.05 was considered statistically significant. A total of 110 patients met the selection criteria. However, 36 patients (33%; due to changing hospital, N = 18; death, N = 12; imprisonment, N = 2; unknown, N = 4) became lost to follow-up simultaneously with discontinuation of LAI. We therefore analyzed 74 patients (schizophrenia, N = 62; schizoaffective disorder, N = 10; and psychotic bipolar affective disorder, N = 2), including 43 men (58%) and

Effects of the antipsychotics haloperidol, clozapine, and aripiprazole on the dendritic spine

Three types of antipsychotics, typical (e.g. haloperidol), atypical (e.g. clozapine), and dopamine partial agonist (e.g. aripiprazole), are administered for treatment of schizophrenia. These antipsychotics have different efficacy and side-effect profiles. We investigated whether aripiprazole, clozapine, and haloperidol differentially regulate the dendritic spine through the AKT-GSK-3 beta cascade. Dissociated cortical neurons from Sprague-Dawley rats were prepared and cultured for 28 days. Aripiprazole, clozapine, or haloperidol was administered to the rat cortical neurons. The levels of PSD95 protein and AKT-GSK-3 beta cascade-related proteins were investigated by Western blot. The number of spines and PSD95 puncta were investigated by immunofluorescence cell staining. Aripiprazole (1 µM or 10 µM) and clozapine (1 µM) increased the levels of PSD95 protein, the number of spines, phosphorylated Akt Thr308 and Ser473, and phosphorylated GSK-3 beta Ser9. On the other hand, haloperidol (1 µM or 10 µM) or an inappropriate concentration of clozapine (10 µM) decreased them. A GSK inhibitor also increased the levels of PSD-95 protein and caused the same morphology. Aripiprazole, clozapine, and haloperidol differentially regulate the dendritic spine, and this effect may occur through the AKT-GSK-3 beta cascade. Selection and appropriate dose of these antipsychotics may be important for the protection of dendritic spines in patients with schizophrenia.

Predictors of remission during acute treatment of first-episode schizophrenia patients involuntarily hospitalized and treated with algorithm-based pharmacotherapy: Secondary analysis of an observational study

AIM Early clinical response predicts symptomatic remission and recovery in the maintenance treatment phase of first-episode schizophrenia (FES). However, little is known about predictors of symptomatic remission during acute treatment of severely ill patients with FES. Here, we conducted a secondary analysis of our retrospective observational study, which examined response, remission and treatment-resistance rates in seriously ill patients with FES spectrum disorders involuntarily hospitalized and treated with algorithm-based pharmacotherapy. METHODS We performed a retrospective chart review of 131 involuntarily admitted patients with schizophrenia or schizoaffective disorder. Our algorithm aimed to delay olanzapine treatment, standardize medications and suggest initiation of clozapine after failure of third-line antipsychotic treatment. The duration of each adequate antipsychotic treatment at an optimal dosage was 4 weeks or more. Remission was defined using the symptom-severity component of consensus remission criteria. A logistic regression model was applied to identify significant predictors of remission at discharge. RESULTS Overall, 74 patients (56%) were in remission at discharge. Non-remitters were hampered from becoming remitters mainly by the presence of negative symptoms. There were no differences in first-line antipsychotics, dosage of antipsychotics at time of response and adherence rates to algorithm-based pharmacotherapy between remitters and non-remitters. Shorter duration of untreated psychosis, favourable early response and less negative symptoms at baseline were identified as independent predictors of remission at discharge. CONCLUSIONS The importance of early intervention and specific and adequate treatments of negative symptoms is highlighted.