Faculty Bibliography

Positive psychotic symptoms, such as threat/'control-override' delusions or command hallucinations, have been related to aggression in patients with schizophrenia. However, retrospective data collection has hampered evaluation of the direct influence of psychopathology on aggressive behavior. In this study, we monitored aggressive behavior and psychopathology prospectively and in close temporal proximity in 157 treatment-resistant inpatients diagnosed with chronic schizophrenia or schizoaffective disorder participating in a 14-week double-blind clinical trial. Aggressive behavior was rated with the overt aggression scale (OAS). Psychopathology was assessed using the positive and negative syndrome scale (PANSS). At baseline, subjects who would be aggressive during the study had higher scores on only two PANSS items: hostility and poor impulse control. During the study PANSS positive subscale scores were significantly higher in aggressive subjects. Total PANSS scores were higher within 3 days of an aggressive incident, as were positive and general psychopathology subscale scores. However, in a smaller subsample for whom PANSS ratings were available within 3 days before aggressive incidents, only scores on the PANSS positive subscale were significantly higher. These findings in chronic, treatment resistant inpatients support the view that positive symptoms may lead to aggression

Standard psychiatric treatment programs have limited success in reducing recidivistic violent and criminal behavior in patients with persistent mental illness. A specialized, cognitive behavioral treatment program was developed for such a population. The purpose of this study was to identify factors that contribute to the patients' completing the program and to improve the selection criteria for program admission, so that those who participate are more likely to complete the program and be discharged. One hundred eighty-one patients with persistent mental illness with histories of aggression, crime, or both participated in a cognitive skills inpatient treatment program adapted for use with psychiatric patients. Ninety patients were able to complete the program and were discharged into the community. In comparison with the 91 who did not complete the program, those who did were less cognitively impaired and less impulsive. We present a new, intensive treatment program and define the predictors of successful completion of the program

BACKGROUND: The safety and efficacy of the first long-acting injectable atypical antipsychotic, risperidone, were assessed in stable patients with schizophrenia switched from oral antipsychotic medications. METHOD: Data were collected between July 1, 2001, and October 25, 2002. The study population included patients from clinics, hospitals, and physicians' offices. After a 4-week run-in period, symptomatically stable patients with schizophrenia (DSM-IV) who had been taking haloperidol (N = 46), quetiapine (N = 45), or olanzapine (N = 50) received 25 mg of long-acting risperidone. The oral antipsychotics were continued for 3 weeks after the first injection of long-acting risperidone. Injections were administered every 2 weeks at 25 mg up to a maximum dose of 50 mg for 12 weeks in this multicenter, open-label study. RESULTS: Long-acting risperidone was well tolerated. Of the 141 patients who participated in the study, the most frequently reported adverse events were insomnia (16%), headache (15%), psychosis (11%), and agitation (11%). The mean increase in body weight was 0.4 kg. No other clinically relevant laboratory abnormalities or significant electrocardiogram changes were observed during the 12-week treatment. Extrapyramidal Symptom Rating Scale total scores were reduced during treatment with long-acting risperidone. Improvements in symptoms of schizophrenia were observed with long-acting risperidone at week 4 and continued through the 12-week treatment with significant reductions in total Positive and Negative Syndrome Scale (PANSS) scores at week 8 (-2.5, p <.01) and week 12 (-3.9, p <.001). At endpoint, 37% (50/135) of these stable patients were rated as clinically improved (> or = 20% decrease in PANSS total scores). CONCLUSIONS: Switching treatment from oral antipsychotics to long-acting risperidone without an intervening period of oral risperidone was safe and well tolerated. Long-acting risperidone also significantly reduced the severity of symptoms in these stable patients with schizophrenia

OBJECTIVE: Schizophrenia is characterized by high suicide risk and low awareness of disorder. Although awareness has benefits for medication compliance and clinical outcome, it is unclear how it may relate to suicide risk in this population. METHOD: This multicenter investigation assessed awareness and suicide-related behavior in 980 patients with schizophrenia or schizoaffective disorder. Patients were followed over 2 years and assessed by blinded raters for suicide-related events. RESULTS: Awareness of psychiatric condition at baseline was associated with increased risk of suicide events over the follow-up. This effect was mediated by depression and hopelessness levels. By contrast, changes in awareness associated with treatment decreased the risk of suicide. CONCLUSIONS: Although some patients may become depressed after acknowledging the clinical handicaps of their disorder, treatment-related changes in awareness are generally associated with a positive outcome relative to suicide risk. The complex interactions and mediation effects of these clinical variables require careful monitoring.

The pharmacological choices for the treatment of schizophrenia have been greatly expanded with the availability of the atypical compounds clozapine (Clozaril, Novartis), risperidone (Risperdal, Janssen-Cilag), olanzapine (Zyprexa, Eli Lilly & Co.), quetiapine (Seroquel, AstraZeneca), ziprasidone (Geodon, Pfizer Inc.) and aripiprazole (Abilify, Otsuka Pharmaceutical Co. Ltd). In this article, the effects of the newer antipsychotics and their side effects are reviewed. Key issues in acute and maintenance treatment, often lifelong, will be reviewed. Side-effect management to ensure adherence to an optimal treatment regimen will be discussed. Coexisting syndromes must be treated in concordance with the patient's clinical presentation. For treatment-resistant patients, atypical compounds are generally more effective than their typical counterparts but medication augmentation strategies are frequently recommended. Finally, the results of recent meta-analyses comparing the effects of atypical versus typical compounds will be critically reviewed and remaining gaps in the current pharmacotherapy of schizophrenia will be explored

BACKGROUND: We sought to develop and validate an excitement subscale from the Positive and Negative Syndrome Scale (PANSS) to allow the investigation of mania-like excitement symptoms in clinical trials of patients with schizophrenia using the PANSS and to provide clinicians with a short assessment tool for these states. METHODS: Baseline PANSS data from six double-blind, randomized registration trials of olanzapine, three in schizophrenia and three in acute bipolar mania, were used in these post-hoc analyses. Schizophrenia study data were pooled and randomly split in half. Exploratory principal component factor analysis was performed on half of the data. Factors were extracted based on minimum eigenvalue criteria (eigenvalue> or =1); loadings were determined using an equamax rotation. Confirmatory principal component factor analysis was performed on the other half of the data, retaining the original number of factors. Principal component factor analysis was also done for the pooled bipolar studies. Change in the new mania-like factor scores was then correlated with Young Mania Rating Scale (Y-MRS) scores in each bipolar study. RESULTS: Exploratory principal components analysis on the pooled schizophrenia data extracted five factors: negative, positive, excitement, cognitive, and depressive factors. The mania-like excitement factor was represented by four items (uncooperativeness, poor impulse control, excitement, and hostility), with only moderate loadings by tension and suspiciousness/persecution. Results were similar in the confirmatory analysis and the pooled bipolar studies. Change from baseline to endpoint for the mania-like factor correlated reasonably well (0.64-0.78) with change in Y-MRS scores in the bipolar studies. At baseline, bipolar patients scored higher than patients with schizophrenia on three of four PANSS mania-like factor items: poor impulse control, excitement, and hostility; the converse was true for most other PANSS items. CONCLUSION: Factor analyses of the PANSS consistently uncovered an excitement factor including uncooperativeness, poor impulse control, excitement, and hostility items. This factor may be useful in examining manic symptoms in studies where the addition of a scale specific to mania would be burdensome and where symptoms of excitement are part of the clinical presentation

OBJECTIVE: Patients exhibiting aggressive or criminal behavior present a challenge to treaters and caregivers. After discharge from an inpatient facility, such patients are at high risk of rehospitalization and rearrest. A long-term behaviorally based cognitive skills program was developed and administered to a group of such high-risk inpatients. The authors report the results of a postdischarge follow-up of this group. METHODS: After patients entered the inpatient treatment program, their psychiatric and criminal histories were recorded, and a battery of psychological measures were administered, including IQ tests and the Hare Psychopathy Checklist. After discharge, multiple sources were used to obtain information about patients' outcomes. RESULTS: Eighty-five patients were followed for between six months and two years after discharge. Thirty-three of these patients (39 percent) remained stable in the community, 35 (42 percent) were rehospitalized, and 17 (20 percent) were arrested. Several variables that were ascertained before discharge predicted rehospitalization or arrest rates: comorbid antisocial personality disorder, higher score on the Psychopathy Checklist, history of arrests for violent crimes, and history of a learning disability. In addition, patients who developed substance use problems or did not adhere to medication treatment after discharge were more likely to be rehospitalized or arrested. CONCLUSIONS: Arrest rates were low compared with those observed in studies with similar populations. Although this outcome may be attributable to the treatment program, this naturalistic study could not prove that. The predictors of poor outcome may be used to develop a follow-up treatment program that focuses more resources on patients who are at the highest risk

The main study was designed primarily to compare the clinical effects of four antipsychotics in 157 patients with schizophrenia or schizoaffective disorder. The secondary genetic study, reported here, is based on a subset of 60 patients who consented to genotyping assays. Based on previous work with the catechol-O-methyltransferase (COMT) 158 polymorphism, we hypothesized that the Met-Met homozygotes would be more hostile than the heterozygotes and the Val-Val homozygotes. Hostility ratings at baseline were used to test this hypothesis. The Met-Met homozygotes (N = 7) were found to have significantly higher levels of hostility than the other patients (N = 53). The hypothesis was thus supported. The finding should be replicated in a larger sample