Among the Severely Mentally Ill, Who Responds to Ziprasidone?

So far, demographic variables have not consistently been found to predict clinical response to antipsychotics. This study examines some differences in response to ziprasidone, which has been shown to be effective, with a better metabolic side effect profile, but was little used in New York State Hospitals. The aim was to study state hospital patients switched to ziprasidone. The results led to questions about different responses in different groups. Subjects from state hospitals who needed a change of antipsychotic participated in this open-label, 8-week trial of up to 240-mg ziprasidone. Analyses included comparisons of the very different results from two sites. Of the 36 study subjects, 12 terminated early. The 17 outpatients from Buffalo, who were older and on lower doses of antipsychotics pre-study, improved significantly. The 19 inpatients from the Bronx, overall younger and on higher pre-study doses, barely changed. Improvements in PANSS total score were significantly associated with older age, greater baseline severity, and lower doses of antipsychotics pre-study. The subjects improved on metabolic parameters. The results suggest that ziprasidone may be just as effective as previous antipsychotics taken by these severely mentally ill patients, and with fewer metabolic side effects. Note: The study described here includes a dosage of ziprasidone that has not been approved by the U.S. Food and Drug Administration (FDA). The FDA has approved daily doses of ziprasidone no greater than 100 mg PO bid.

Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder.

CONTEXT: Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance. OBJECTIVE: To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder. DESIGN AND SETTING: Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36). MAIN OUTCOME MEASURES: Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS). RESULTS: Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales. CONCLUSIONS: Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.

Among the severely mentally ill, who responds to ziprasidone?

So far, demographic variables have not consistently been found to predict clinical response to antipsychotics. This study examines some differences in response to ziprasidone, which has been shown to be effective, with a better metabolic side effect profile, but was little used in New York State Hospitals. The aim was to study state hospital patients switched to ziprasidone. The results led to questions about different responses in different groups. Subjects from state hospitals who needed a change of antipsychotic participated in this openlabel 8 week trial of up to 240 mg ziprasidone. Analyses included comparisons of the very different results from two sites. Of the 36 study subjects, 12 terminated early. The 17 outpatients from Buffalo, who were older and on lower doses of antipsychotics pre-study, improved significantly. The 19 inpatients from the Bronx, overall younger and on higher pre-study doses, barely changed. Improvements in PANSS total score were significantly associated with older age, greater baseline severity, and lower doses of antipsychotics pre-study. The subjects improved on metabolic parameters. The results suggest that ziprasidone may be just as effective as previous antipsychotics taken by these severely mentally ill patients, and with fewer metabolic side effects.

Pharmacokinetics of aripiprazole and concomitant lithium and valproate.

The objective of this study was to assess the pharmacokinetics of the antipsychotic aripiprazole when coadministered with lithium or valproate. Two open-label, sequential treatment design studies were conducted in chronically institutionalized patients with schizophrenia or schizoaffective disorder requiring treatment with lithium (n = 12) or valproate (divalproex sodium) (n = 10). Patients received aripiprazole 30 mg/day on days 1 to 14 and aripiprazole with concomitant therapy on days 15 to 36. Lithium was titrated from 900 mg until serum concentrations reached 1.0 to 1.4 mEq/L for at least 5 days. Valproate was titrated to 50 to 125 mg/L. Coadministration with lithium increased mean Cmax and AUC values of aripiprazole by about 19% and 15%, respectively, whereas the apparent oral clearance decreased by 15%. There was no effect on the steady-state pharmacokinetics of the active metabolite of aripiprazole. Coadministration with valproate decreased the AUC and Cmax of aripiprazole by 24% and 26%, respectively, with minimal effects on the active metabolite. Therapeutic doses of lithium and divalproex had no clinically significant effects on the pharmacokinetics of aripiprazole in patients with schizophrenia or schizoaffective disorder.

The impact of cognitive remediation on psychiatric symptoms of schizophrenia.

OBJECTIVE: The relationship between psychopathology and cognitive functioning in schizophrenia is of interest, both for an understanding of the nature of the disease, and for comprehensive treatment planning. The aim of this study was to investigate how psychiatric symptoms affect, and are affected by, cognitive remediation. METHOD: Fifty-four psychiatric inpatients received either cognitive remediation exercises (remediation group) or no cognitive intervention (control group). The subjects' scores on tests of cognition and on the Positive and Negative Symptoms Scale (PANSS) were measured before, after the 10 session treatment, and again 4 weeks post treatment. RESULTS: Only the remediation group showed significant and persistent improvement on all three PANSS Subscales as well as on the Positive Symptoms and Depression Factors. There were no significant between-group differences on any PANSS pre/posttreatment change scores. Baseline measures of psychopathology did not correlate meaningfully with amount of change made on cognitive measures after rehabilitation. CONCLUSIONS: A brief 10-session course of cognitive remediation is sufficient to benefit cognition and has some positive effects on psychopathology as measured by the PANSS, but does not add significantly to the effects of standard psychiatric treatment on psychopathology. Furthermore, psychiatric symptom profile is not predictive of the degree to which cognitive symptoms respond to cognitive remediation. The differential impact of cognitive remediation on cognition and psychopathology may imply that psychopathology and cognitive functioning follow fairly independent treatment courses.

Did schizophrenia change the course of English history? The mental illness of Henry VI.

Henry VI, King of England, at age 19 founded Eton College and King's College, Cambridge. At 31 he had a sudden, dramatic mental illness in which he was mute and unresponsive. Before, he had been paranoid, grandiose, and indecisive. After, he was apathetic with deterioration of ability, drive, interest and self-care, and hallucinations and religious delusions. This illness, which is consistent with a diagnosis of schizophrenia, robbed Henry of his personality, his crown, his wife, his only son, and his life. It led to three decades of brutal fighting for the crown (the 'Wars of the Roses') that resulted in a new dynasty with a dramatic impact on the country: the Tudors, Henry VIII, and Elizabeth I and their descendants. Henry's story illustrates how schizophrenia can devastate individuals and families and change the course of history and yet it raises questions about how achievement and illness are related.

Prisoner mental health in the USA.

The mental health of prisoners in the USA is affected by American history: Dorothea Dix's 1830s campaign; the Civil War and slavery; presidential interventions; the Great Depression; and the introduction of Medicaid and the Affordable Care Act. In 1934, the ratio of prisoners to mental hospital patients was 0.4; now, it is 3:1, with states varying from 10:1 to 1:1. Those states with the highest ratios also have the highest rates of imprisonment and the lowest expenditures on mental health. Litigation is likely to improve mental health services in prisons and to keep people who are mentally ill out of prisons.

Effects of pioglitazone on metabolic abnormalities, psychopathology, and cognitive function in schizophrenic patients treated with antipsychotic medication: a randomized double-blind study.

BACKGROUND: Schizophrenic patients treated with antipsychotic drugs (AP) have an increased frequency of glucose-lipid metabolic abnormalities and diabetes. Pioglitazone has been shown to be effective in the treatment of glucose and lipid abnormalities in diabetes and decreasing longer-term conversion of impaired glucose tolerance to frank diabetes. Some studies also suggest possible pro-cognitive and antidepressant effects of pioglitazone. We studied the effects of pioglitazone on potential metabolic, symptomatic and cognitive benefits in schizophrenic patients treated with AP. METHODS: 54 schizophrenic patients with at least both a)impaired glucose and b) triglycerides≥120mg/dL and/or low HDL levels, participated in a double-blind placebo controlled study of 3month treatment with Pioglitazone (30-45mg/day) or matched placebo, at 5 sites (4 U.S., 1 China). Fasting glucose and lipid parameters, and psychopathology (PANSS scale) were assessed monthly, and patients had a glucose tolerance test and cognitive testing (RBANS and CPT) at baseline and at the end of study. Statistical analysis used mixed model repeated measures analysis, supplemented by completer and LOCF analysis. RESULTS: In the total sample there was an overall effect (P's<.05 to <.01) of pioglitazone on preventing deterioration in fasting glucose and improving HDL and PANSS depression scores; in the pioglitazone group comparison of baseline vs 3month values also showed significant (P<.05) decreases in fasting insulin, 2h glucose in GTT and insulin resistance (HOMA-IR). However there were marked differences between the responses of patients in the U.S. sites vs the China site. In the U.S. sample, patients treated with pioglitazone, when compared to placebo treated patents, had significantly lower fasting glucose (F=3.99, P=0.02), improved insulin sensitivity (lower H0MA-IR, F=6.24, P=.002), lower triglycerides (F=2.68, P=.06) and increased HDL (F=6.50, P=.001). By the end of the study 52% of the pioglitazone treated patients compared to 15% of the placebo patients had fasting glucose in the normal range (Fisher's exact test P=.02). Pioglitazone also significantly improved PANSS depression factor scores (F=2.82, P=0.05). It did not improve cognitive performance on the RBANS or CPT tasks. Pioglitazone did not increase weight or produce any other significant side-effects. In the small mainland China site sample, pioglitazone treatment, as compared to placebo, did not show greater improvement in metabolic parameters or psychopathology ratings. CONCLUSIONS: In the sample of patients from the U.S., pioglitazone was an efficacious and safe treatment for glucose and lipid metabolic abnormalities in schizophrenic patients treated with AP, and it may also have beneficial effects on depressive symptoms. It may be particularly useful in patients whose weight gain effects from antipsychotics have plateaued and where weight loss is not the primary goal. The risk vs. benefits of longer term treatment with pioglitazone has to be carefully evaluated for individual patients.

Evaluation of the routine clinical use of the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS).

OBJECTIVE: To evaluate the routine clinical use of the Brief Psychiatric Rating Scale (BPRS) (in psychiatrists' monthly notes) and the Abnormal Involuntary Movement Scale (AIMS) (done at admission and annually) in a state hospital. METHODS: Two residents and a medical student were trained in the use of the BPRS and the AIMS. These "key raters" then rated 21 patients before and 28 patients after the ward psychiatrists had one retraining session on the BPRS. These raters' results were compared with the ward psychiatrists' results before and after the BPRS retraining as well as with the ward psychiatrists' annual AIMS ratings. RESULTS: The key raters had high correlations among themselves (0.85 for total BPRS and a mean of 0.83 for individual BPRS items), but the correlations with the ward psychiatrists' ratings were very low (0.17 for total BPRS and a mean of 0.37 for individual BPRS items), and those correlations improved only slightly after the retraining of the ward psychiatrists (0.33 for total BPRS and a mean of 0.41 for individual BPRS items). Ward psychiatrists both missed tardive dyskinesia and labelled parkinsonism as tardive dyskinesia. CONCLUSIONS: The BPRS and AIMS are useful, practical rating scales, but if they are to be used routinely in clinical care, users must be regularly trained and retrained and rating performance evaluated. (Journal of Psychiatric Practice 2011;17:300-303).

Clozapine, risperidone, olanzapine, and conventional antipsychotic drug effects on glucose, lipids, and leptin in schizophrenic patients.

Some reports have indicated increased rates of diabetes and increased prevalence of glucose and lipid abnormalities during treatment with second-generation antipsychotics, with most concern raised about clozapine and olanzapine. Most of the findings have come from case reports, retrospective examination of laboratory values, and analysis of health-care claims databases. This study investigated fasting levels of glucose, lipids, and leptin in a non-randomized, cross- sectional study of 210 patients, with schizophrenic or schizoaffective disorder, treated with a single antipsychotic medication - clozapine, risperidone, olanzapine, or a conventional antipsychotic. Glucose tolerance tests (GTT), with a 75-g glucose load, were preformed in a subset of patients. In this sample most mean fasting glucose and lipid levels were within the normal range and were not significantly different across the four drug treatment groups. Patients treated with clozapine and olanzapine had higher triglyceride levels than risperidone patients. In patients receiving a GTT, risperidone-treated patients had higher glucose levels at 1 h than patients treated with olanzapine, and there were more patients on risperidone who met American Diabetes Association glucose metabolic criteria for diagnosis of diabetes. Although there were no significant differences in age or body mass index among the four drug groups, we cannot rule out some potential biasing factors we did not assess which could potentially influence our results. These include unknown physician preference in drug selection based on their beliefs about the weight-inducing or diabetes potential of different antipsychotics, differences in visceral fat, and differences in patients' antipsychotic drug history.