Faculty Bibliography

OBJECTIVE: The second-generation antipsychotic agents clozapine and olanzapine have been associated with weight gain and increased lipid and glucose blood levels. Since some of the neurotransmitters that are impaired in aggressive patients are involved in lipid/glucose metabolism, aggressive patients may represent a subgroup with a differential profile of adverse metabolic reactions to these medications. The goal of this study was to assess the effects of clozapine and olanzapine in comparison to the first-generation agent haloperidol on these metabolic parameters in aggressive patients with schizophrenia. METHOD: 110 inpatients with schizophrenia and a history of physical assaults were included in a randomized double-blind 12-week study. Fasting glucose, cholesterol and triglycerides were collected at baseline and at the end of the study. Ninety-three patients provided blood samples at baseline and at least at one point after randomization to clozapine (N=34), olanzapine (N=31) or haloperidol (N=28). RESULTS: There were significant differences among the three medication groups in weight gain and in increases in blood lipids and glucose. Patients on haloperidol showed no increase on any of these parameters. Patients on olanzapine gained the most weight, but patients on clozapine had the greatest increases in cholesterol, triglyceride, and glucose. An effect of ethnicity was observed, as African-American patients were more likely to develop metabolic abnormalities than other ethnic groups, especially on clozapine. CONCLUSIONS: In this prospective randomized trial, clozapine and olanzapine were associated with weight gain. Clozapine was associated with increases in both lipids and glucose. This effect was most prominent in the African-American patients

The purpose of this study was to compare the effects of olanzapine, clozapine, and haloperidol on neurocognitive function in schizophrenic patients who present with documented episodes of physical aggression and to determine whether change in cognitive function is related to aggression. One hundred physically aggressive schizophrenic inpatients were assigned to a randomized, double-blind, parallel-group, 12-week treatment, and received cognitive evaluations at baseline. There were 33, 34, and 33 subjects in the clozapine, olanzapine, and haloperidol groups, respectively. They were administered a battery of tests assessing psychomotor function, general executive function, visual and verbal memory, and visuospatial ability. A general cognitive index was derived from the above battery. The overall score on the Modified Overt Aggression Scale was used to measure the number and severity of the aggressive events. Psychiatric symptoms and side effects were also assessed. The improvement in the general cognitive index differed significantly among the 3 treatment groups, with olanzapine being superior to both haloperidol and clozapine. Further analyses revealed significantly greater improvement with olanzapine in several cognitive domains. Furthermore, improvement in the general cognitive index was significantly associated with a decrease in aggression in the olanzapine group but not in the other 2 medication groups. In violent schizophrenic patients, olanzapine treatment is associated with better cognitive functioning relative to haloperidol and clozapine. This improvement in neurocognitive function is associated with a decrease in aggressive behavior. As clozapine markedly reduced aggression, there may be different pathways for the antiaggressive effect of olanzapine and that of clozapine

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

OBJECTIVES: To better understand the relationship between suicidal behavior and violence directed toward others among patients with major psychiatric disorders, this study examined how suicide attempts and violent behaviors were associated with various psychosocial problems. METHODS: Participants were inpatients in two psychiatric state hospitals. They included 216 inpatients who had physically assaulted another patient or a staff member and a comparison group of 81 inpatients who had not assaulted anyone. History of suicide attempts and historical information about various risk factors for violence and suicide were obtained through chart review and patient interviews. RESULTS: Patients in the violent group did not differ from those in the nonviolent group in whether they had attempted suicide. Suicide attempts and violence were associated with different historical variables. Suicide attempts were associated with a history of head trauma, harsh parental discipline, and parental psychopathology. Violence against others was associated with having a history of school truancy and foster home placement. CONCLUSIONS: Among inpatients with major psychiatric disorders, violence and suicide attempts were not related to each other and were associated with dissimilar psychosocial risk factors

The relationship between violence directed at the self and violence directed at others has intrigued psychiatrists for several decades. The goal of this study was to examine the relationship between suicide and violence against others in patients with major psychiatric disorders and to compare psychiatric symptoms associated with suicide in violent and non-violent patients. Subjects included physically assaultive psychiatric inpatients and a nonviolent comparison group. Physical and verbal assaults were recorded prospectively for 4 weeks. History of suicide attempts was obtained through chart review and patient interviews. The Brief Psychiatric Rating Scale was administered at the end of the 4 weeks by raters who were blind to both suicidal and violent behavior. The suicide attempters did not differ from the non-attempters on any measure of violent behavior or hostility. Suicide attempts were not accompanied by different symptoms in violent and non-violent patients; however, violence and suicide attempts were accompanied by dissimilar psychiatric symptoms. The physically assaultive patients presented with more severe positive psychotic symptoms than the non-assaultive patients. The suicide attempters, on the other hand, did not differ from non-attempters on psychotic symptoms, but presented with more severe depression and anxiety. The relationship between these symptoms and suicide attempts was noteworthy in its temporal stability, as most of the patients had attempted suicide many years prior to this study

OBJECTIVE: Men are more violent than women in the general population, but this has not been found to be the case among psychiatric inpatients. The reason for this exception is poorly understood. The present study investigated gender differences in violent behaviors among patients with major psychiatric disorders. It examined various clinical symptoms and psychosocial factors to determine their differential impact on violence in men and women. METHOD: Physical assaults and verbal assaults committed by psychiatric inpatients were recorded prospectively. Patients whose violent incident occurred during their first 2 months of hospitalization were eligible for the study. Patient history of community violence was also obtained. Psychiatric symptoms and ward behaviors were assessed upon entry into the study and after 4 weeks. RESULTS: A similar percentage of women and men had an incident of physical assault in the hospital. Among the patients entered into the study, the women had a much higher level of verbal assaults throughout the evaluation period and a higher level of early physical assaults (i.e., within the first 10 days of the 4-week study period). Positive psychotic symptoms were more likely to result in assaults in women than in men. Physical assaults in the community, on the other hand, were more common in men and were associated with substance abuse, property crime, and a history of school truancy. CONCLUSIONS: There are gender differences in the patterns of violent behavior among patients with major psychiatric disorders. Furthermore, psychiatric symptoms and psychosocial risk factors have a different impact on this behavior in men and women. This has important implications for the prediction and differential treatment of violent behavior

There has been much interest in the role of serotonin in aggressive behavior during the past two decades, but no simple one-to-one causal relationship has been found between this biological variable and aggression. The influence of serotonin is best analyzed within a broader framework that includes consideration of its role in the inhibition of impulses, the regulation of emotions and social functioning, domains that are closely linked to aggression. Impulsivity and strong emotional states often accompany violent acts. Aggressive individuals are likely to experience general difficulties with impulse control and emotional regulation, and they show impaired social cognition and affiliation. Serotonergic dysfunction will influence aggression differently, depending on the individual's impulse control, emotional regulation, and social abilities. Yet, aggressive acts occur in a broader social context. As such, serotonergic function has an effect not only on the individual but also on the group dynamics, and it is in turn influenced by these dynamics. Whether aggression will occur when serotonin dysfunction is present will depend on individual differences as well as the overall social context