Dosage and duration of antipsychotic treatment in demented outpatients with agitation or psychosis

Background/PurposeThe USA Food and Drug Administration (FDA) issued warnings regarding the use of antipsychotics in patients with dementia in 2003 and 2005. We aimed to study the dose and duration of antipsychotic treatment in dementia, and to examine whether physicians' prescription behaviors changed after the FDA warnings.MethodsMedical charts of outpatients who had Alzheimer's disease, vascular dementia, or mixed dementia were reviewed. Patients must have achieved a clinically stable state for at least 4 weeks after receiving antipsychotic treatment for agitation or psychosis. Demographics, clinical correlates, and duration of antipsychotic treatment were compared among different antipsychotic groups. Because the quetiapine group had the largest sample size, the optimal dose and duration of quetiapine treatment were compared among three time periods (before 2003, 2003–2005, after 2005).ResultsStable state was achieved in 215 patients (80 had Alzheimer's disease, 117 vascular dementia, and 18 mixed dementia). Most patients (177) took quetiapine, 25 took risperidone, and 13 took sulpiride. The whole sample had a long total duration of antipsychotic treatment (median 525 days, mean 707 days). The median dose and total duration of antipsychotic treatment were 1.0mg/day and 238 days for risperidone, 100mg/day and 390 days for sulpiride, and 25mg/day and 611 days for quetiapine, respectively. The optimal dose and total duration of quetiapine treatment decreased significantly after FDA warning in 2005, although the duration remained long.ConclusionThe optimal doses of antipsychotics were not higher than those of western reports, but the total duration of antipsychotic treatment was quite long. Although our study suggests the prescription dosage and duration of antipsychotic treatment decreased significantly after FDA warning in 2005, the duration of treatment was still long. Given the serious safety concerns, more effort should be made to avoid unnecessary and prolonged prescription

Auditory Event-Related Potentials in Antipsychotic-Free Subjects With Ultra-High-Risk State and First-Episode Psychosis

Background: Auditory event-related potentials (ERPs) have been utilized to study defective information processing of patients with schizophrenia. To delineate the pathophysiological processes from pre-psychotic state to first-episode psychosis, a study on subjects from ultra-high-risk (UHR) state to first-episode psychosis, ideally in an antipsychotic-free condition, can add important information to our understanding.Methods: Patients with UHR state or at their first-episode psychosis (FEP) who were drug-naive or only have been temporarily treated with antipsychotics were assessed by auditory ERPs measurement, including P50/N100 (sensory gating) and duration mismatch negativity (MMN; deviance detection). A group of age-matched healthy subjects served as their controls.Results: A total of 42 patients (23 UHR and 19 FEP) and 120 control subjects were recruited, including 21 pure drug-naive and 21 with very short exposure to antipsychotics. Collapsing FEP and UHR as a patient group, they exhibited significant sensory deficits manifested as larger P50 S2 amplitude, larger N100 ratio, and smaller N100 difference, and significantly less deviance detection response revealed by MMN. Such differences were less significant when treating FEP and UHR separately for comparisons. Comparisons of ERP results between drug-naive subjects and antipsychotic-short-exposure subjects revealed no significant difference in any P50/N100 and MMN parameter.Conclusion: Our study is one of the few studies focused on drug-naive or minimally treated patients at pre- or early-psychotic states. Our results exhibited impaired performance in sensory gating and deviance detection shown by certain parameters. A longitudinal study with larger sample sizes will be helpful to provide more evidence to elucidate the role of antipsychotics on an individual’s neurophysiological performance at different stages of psychosis

Frequency Dependent Alterations in Regional Homogeneity of Baseline Brain Activity in Schizophrenia

Low frequency oscillations are essential in cognitive function impairment in schizophrenia. While functional connectivity can reveal the synchronization between distant brain regions, the regional abnormalities in task-independent baseline brain activity are less clear, especially in specific frequency bands. Here, we used a regional homogeneity (ReHo) method combined with resting-state functional magnetic resonance imaging to investigate low frequency spontaneous neural activity in the three different frequency bands (slow-5:0.01–0.027 Hz; slow-4:0.027–0.08 Hz; and typical band: 0.01–0.08 Hz) in 69 patients with schizophrenia and 62 healthy controls. Compared with controls, schizophrenia patients exhibited decreased ReHo in the precentral gyrus, middle occipital gyrus, and posterior insula, whereas increased ReHo in the medial prefrontal cortex and anterior insula. Significant differences in ReHo between the two bands were found in fusiform gyrus and superior frontal gyrus (slow-4> slow-5), and in basal ganglia, parahippocampus, and dorsal middle prefrontal gyrus (slow-5> slow-4). Importantly, we identified significant interaction between frequency bands and groups in the inferior occipital gyrus and caudate body. This study demonstrates that ReHo changes in schizophrenia are widespread and frequency dependent

Differentiation of Schizophrenia Patients from Healthy Subjects by Mismatch Negativity and Neuropsychological Tests

BACKGROUND: Schizophrenia is a heterogeneous disorder with diverse presentations. The current and the proposed DSM-V diagnostic system remains phenomenologically based, despite the fact that several neurobiological and neuropsychological markers have been identified. A multivariate approach has better diagnostic utility than a single marker method. In this study, the mismatch negativity (MMN) deficit of schizophrenia was first replicated in a Han Chinese population, and then the MMN was combined with several neuropsychological measurements to differentiate schizophrenia patients from healthy subjects. METHODOLOGY/PRINCIPAL FINDINGS: 120 schizophrenia patients and 76 healthy controls were recruited. Each subject received examinations for duration MMN, Continuous Performance Test, Wisconsin Card Sorting Test, and Wechsler Adult Intelligence Scale Third Edition (WAIS-III). The MMN was compared between cases and controls, and important covariates were investigated. Schizophrenia patients had significantly reduced MMN amplitudes, and MMN decreased with increasing age in both patient and control groups. None of the neuropsychological indices correlated with MMN. Predictive multivariate logistic regression models using the MMN and neuropsychological measurements as predictors were developed. Four predictors, including MMN at electrode FCz and three scores from the WAIS-III (Arithmetic, Block Design, and Performance IQ) were retained in the final predictive model. The model performed well in differentiating patients from healthy subjects (percentage of concordant pairs: 90.5%). CONCLUSIONS/SIGNIFICANCE: MMN deficits were found in Han Chinese schizophrenia patients. The multivariate approach combining biomarkers from different modalities such as electrophysiology and neuropsychology had a better diagnostic utility

精神分裂症的臨床與精神病理

Schizophrenia has been the most noticeable major mental illness since 20( superscript th) century. It is a debilitating disorder with heterogeneous manifestations and high genetic hereditability, and with very large amount of research involved. On the one hand, it is an early-onset and chronic illness, with great impact on patients, families and the whole society; on the other, it is also a research paradigm for complex mental disorders. In this article, we review its prevalence, prognosis, psychopathological mechanisms, treatment and future prospect. It is hoped that, by integrating genetic, neuropathological and neuroimaging research, and cellular and animal models, the underlying mechanisms and biological markers of this disorder can be revealed and the goal of early treatment and prevention can be achieved

AMISULPRIDE與RISPERIDONE對精神分裂症病人之治療比較：雙盲前驅性研究

Background and Purpose: The atypical antipsychotics, amisulpride and risperidone, have different receptor affinity characteristics. Although the relative efficacy of both drugs compared to conventional antipsychotics is well established, it remains unclear how the efficacy of amisulpride compares with risperidone. There have been no controlled studies comparing amisulride to risperidone in Asian patients. The purpose of this study was to compare the efficacy and safety of amisulpride with that of risperidone in Taiwanese schizophrenic patients. Methods: Patients with productive positive symptoms (n=48) were enrolled into this double-blind, randomized pilot study for 6 weeks. Patients received either amisulpride (400-800 mg/day) or risperidone (4-8 mg/day).Positive and Negative Syndrome scale (PANSS), Clinical Global Impression (CGI), Social and Occupational Functioning Assessment Scale (SOFAS) , and patientsâ subjective responses to treatment were assessed during the trial period. Adverse events wee recorded at each follow-up visit. Results: At the end of the trial, the mean dosage was 630 + 134 mg/day and 6.88 + 1.54 mg/day for amisulpride and risperidone, respectively. There was no significant difference in the reduction of the PANSS total score ( amisulpride -24.1 versus risperidone -28.4, p = 0.999) , the PANSS positive subscale score (amisulpride -6.8 versus risperidone -8.3 , p = 0.467) , the PANSS negative subscale score (amisulpride -5.6 versus risperidone -6.4,p=0.999),or the CGI score between the two groups. The extrapyramidal symptom ratings, the improverment in the SOFAS (amisulpride 11.1 versus risperidone 10.0) and the subjective response ( amisulpride 82% versus risperidone 83%) were comparable. No serious adverse events were recorded in either treatment group. There was a statistically significant body weight gain in the risperidone group. In contrast, there was statistically, thought not clinically, significant reduction of blood pressure and heart rate in the amisulpride group. Conclusions: This study suggests that amisulpride is as effective as risperidone in the treatment of patients with schizophrenia. Both drugs were well tolerated, but had different side effect profiles

Fast Versus Slow Strategy of Switching Patients With Schizophrenia to Aripiprazole From Other Antipsychotics

This study aimed to compare strategies differing in the speed of switching schizophrenic patients to aripiprazole from other antipsychotic agents, with dual administration for 2 weeks and then tapering off the current antipsychotic in fast (within 1 week) versus slow (within 4 weeks) strategies. This 8-week, open-label, randomized, parallel study assigned patients with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia or schizoaffective disorder to either the fast-switching (n = 38) or slow-switching (n = 41) group. Efficacy assessments at 5 time points included Positive and Negative Syndrome Scale and Clinical Global Impression scale. Safety assessments included extrapyramidal symptoms, metabolic profile, serum prolactin level, QTc interval, and adverse events. Drug concentrations and cytochrome P450 CYP2D6 and CYP3A4 genotypes were also measured. The fast- and slow-switching groups were comparable in demographical and clinical features at baseline and dropout rate. In the intention-to-treat analysis using mixed-effects models, there were significant within-group decreases over time in the Positive and Negative Syndrome Scale total scores (P = 0.03) and its subscores except for positive subscores, whereas no between-group differences were found. A reduction in body weight (P = 0.01) and lower levels of total cholesterol (P = 0.03), triglycerides (P = 0.03), and prolactin (P = 0.01) were noted in both groups but no increase in extrapyramidal symptoms or prolongation of QTc. The blood concentrations of aripiprazole in all patients were in a therapeutic range at day 56, with CYP2D6*10 polymorphisms being associated with aripiprazole concentrations. In conclusion, there is no significant difference between the fast- and slow-switching strategy in terms of improvements in clinical symptoms and metabolic profile in this 8-week study