Antipsychotic-treated Patients Research Articles

Switching Outpatients With Bipolar or Schizoaffective Disorders and Substance Abuse From Their Current Antipsychotic to Aripiprazole

Substance abuse is extremely common in patients with bipolar disorders, although minimal data are available on the treatment of this important clinical population. Aripiprazole is an atypical antipsychotic that is approved for the treatment of mania and that has a novel mechanism of action, acting as a dopamine-2 receptor partial agonist, thereby increasing dopamine release in some parts of the brain and decreasing dopa-mine release in other brain regions. Dopamine release is implicated in substance use, and both dopaminergic agonists and antagonists have been examined for the treatment of substance abuse. To our knowledge, dopa-mine receptor partial agonists have not been investigated for treatment of substance abuse in humans. Twenty antipsychotic-treated patients with bipolar or schizoaffective disorder and current substance abuse were switched to open-label aripipra-zole using an overlap and taper method. At baseline, diagnoses were confirmed using the Mini-International Neuropsychiatric Interview based on DSM-IV criteria. Psychiatric symptoms, side effects, and substance use and craving were assessed over 12 weeks. Psychiatric symptoms were assessed with the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS). Substance craving was assessed with visual analogue scales, and side effects were monitored using the Abnormal Involuntary Movement Scale, Simpson-Angus Scale, Barnes Akathisia Scale, and patient report. Study enrollment was from April 2003 to February 2004. Significant baseline-to-exit improvement in HAM-D (p = .002), YMRS (p = .021), and BPRS (p = .000) scores were observed without a significant change in antipsychotic-induced side effect scales. In 17 participants with current alcohol dependence, significant reductions in dollars spent on alcohol (p = .042) and alcohol craving (p = .003) were found. In 9 participants with cocaine-related disorders, significant reductions in cocaine craving (p = .014), but not use, were found. A change to aripiprazole was associated with symptomatic improvement. Limitations of the study include a small sample size, high attrition, and an open-label design. Controlled trials in dual-diagnosis patients are needed to confirm these findings.

Increased Pituitary Volume in Antipsychotic-Free and Antipsychotic-Treated Patients of the Æsop First-Onset Psychosis Study

Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78 age- and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naïve), 26 were receiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls (+22%, p< 0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15% larger in antipsychotic-free patients (p=0.028), 17% larger in patients receiving atypicals (p=0.01), and 30% larger in patients receiving typicals (p<0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together (+11%, p=0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24% larger in patients with schizophrenia/schizophreniform disorder (n=40, p<0.001), 19% larger in depressed patients (n=13, p=0.022), 16% larger in bipolar patients (n=16, p=0.037), and 12% larger in those with other psychoses (n=9, p=0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effect on pituitary volume, likely to be related to activation of prolactin-secreting cells. This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis.

Impact of Schizophrenia and Chronic Antipsychotic Treatment on [ 123I]CNS-1261 Binding to N-Methyl-D-Aspartate Receptors In Vivo

Antipsychotic drugs modulate N-methyl-D-aspartate (NMDA) receptor function in animals. The novel single photon emission tomography (SPET) radiotracer [123I]CNS-1261 binds to the PCP/MK-801 intrachannel site of the NMDA receptor, allowing the noninvasive estimation of NMDA receptor activity in living humans. We used [123I]CNS-1261 to determine whether binding to the NMDA receptor intrachannel PCP/MK-801 site is affected by schizophrenia or by treatment with typical antipsychotics and clozapine in vivo. Three groups of schizophrenia patients were recruited-drug free (n = 5), typical antipsychotic treated (n = 7), and clozapine treated (n = 9)-as well as a control group of healthy normal volunteers (n = 13). All underwent [123I]CNS-1261 SPET scanning. Total volume of distribution of [123I]CNS-1261 was determined within predefined user-independent regions of interest after alignment of all images to a common template. There was no apparent difference in total volume of distribution of [123I]CNS-1261 in drug-free patients relative to healthy control subjects. A nonsignificant reduction in total volume of distribution was observed in typical antipsychotic treated patients. A significant decline in total volume of distribution of [123I]CNS-1261 was observed in all examined brain regions in the clozapine-treated patient group relative to healthy control subjects (p < .005). Clozapine treatment resulted in a global reduction in [123I]CNS-1261 binding to the NMDA receptor intrachannel PCP/MK-801 site in vivo. This supports an effect of the drug on glutamatergic systems that could be exploited for future antipsychotic drug discovery.

Correlation of serum ghrelin levels with body mass index and carbohydrate metabolism in patients treated with atypical antipsychotics

The prevalence of diabetes mellitus and metabolic syndrome is higher in patients with schizophrenia than in the normal population. Atypical antipsychotic drugs are used in psychiatry since the beginning of 1990. These drugs differ from the “typical” antipsychotics used previously, as they have less extrapyramidal side effects, and because of this they are tolerated better, but are associated with weight-gain and disturbances in carbohydrate metabolism. Ghrelin is an orexigen hormone partaking in body weight regulation. It is produced in the enteroendocrine P/D1 cells of the gastric mucosa and secreted to the circulation. The aim of our study was to determine ghrelin levels of atypical antipsychotic-treated patients in relationship with their body mass index (BMI) and carbohydrate metabolism. We measured the fasting serum ghrelin levels in 56 patients (male/female: 16/40, age mean ± S.D.: 50.6 ± 5.6 years) treated with atypical antipsychotics (clozapine, olanzapine, risperidon and quetiapine), and in 75 healthy control subjects, age and gender matched (RIA Linco, USA) in relationship with their BMI and their fasting and 75 g OGTT 120 min blood glucose values. The serum ghrelin levels of the patient group were notably higher (1333 ± 659 pg/ml) than in the control group (368 ± 103, p < 0.0001; Mann–Whitney). We found no difference among the four antipsychotics in weight-gain, diabetes prevalence and the serum ghrelin levels. The BMI of the patient group was significantly higher (29.3 ± 7.2 kg/m 2 versus 24.3 ± 3.7 kg/m 2, p < 0.0001; Mann–Whitney); 32% of them had blood glucose abnormality (18/56). There was no difference between the ghrelin levels in diabetic and non-diabetic patients. We found a significant negative linear correlation between the serum ghrelin and BMI ( r = −0.35, p = 0.0078; Spearman), the ghrelin and fasting blood glucose ( r = −0.32, p = 0.015) and OGTT 75 g 120 min blood glucose levels ( r = −0.27, p = 0.036). The orexigen effect of elevated serum ghrelin levels can contribute to the weight-gain and high diabetes prevalence associated with atypical antipsychotic treatment. The link between atypical antipsychotic treatment and elevated serum ghrelin levels is unknown so far, but a dysregulation of the central feedback mechanism can be hypothesised.

Safety, effectiveness, and patterns of use of olanzapine in acute schizophrenia: a multivariate analysis of a large naturalistic study in the hospital setting

This study assessed the safety and effectiveness of the atypical antipsychotic olanzapine for the treatment of inpatients with acute schizophrenia. Furthermore, we evaluated patterns of use of olanzapine and their relationship to safety and effectiveness. This was a prospective, comparative, nonrandomized, open-label, observational study of 848 patients with schizophrenia (International Classification of Diseases, 10th edition) hospitalized due to an acute psychotic episode. Data were collected during patients' entire hospital stay. Safety of antipsychotic therapy was assessed with an extrapyramidal symptoms questionnaire (based on the Udvalg for Kliniske Undersøgelser scale) and the report of spontaneous adverse events. Clinical status was assessed with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate statistical approach was employed. Patients treated with olanzapine in monotherapy had the lowest risk of developing extrapyramidal symptoms (11.2%), whereas patients treated with conventional antipsychotics had a higher risk (39.0%; p < 0.001). Patients treated with olanzapine in monotherapy (even patients with prominent positive symptoms) displayed a higher rate of response compared with conventional antipsychotics-treated patients (p = .007). Olanzapine is a safe and effective treatment for patients with acute schizophrenia in the hospital setting, even for patients with prominent positive or agitation symptoms.

Dyskinesia and soft neurological signs in schizophrenia: a comparative study

Objective. Several neurological abnormalities can be found at a greater frequency in patients with schizophrenia, including neurological soft signs (NSS) and signs of the “pyramidal” and “extrapyramidal” systems. We aimed to explore the frequency of movement disorders in patients with antipsychotic naïve schizophrenia and to compare and contrast with antipsychotic-treated patients and healthy controls. Methods. Twenty-two antipsychotic naive schizophrenic patients, 22 antipsychotic treated patients and 22 healthy control subjects were assessed by Neurological Evaluation (NES), Abnormal Involuntary Movements (AIMS), and Positive and Negative Syndrome (PANSS) Scales. Results. The NES scores of the never-medicated schizophrenic group were significantly higher than those of normal controls but did not differ significantly from the medicated group. Dyskinesia rates in the both schizophrenic groups were higher than in healthy controls. Medicated and non-medicated schizophrenic patient scores did not differ in AIMS with regard to facial and oral movements, but medicated patients scored higher than non-medicated subjects with respect to extremity movements. Conclusion. Our data suggest that: soft neurological signs and abnormal involuntary movements in the facial region are more prevalent in patients with schizophrenia, whether they are medicated or antipsychotic naïve. On the contrary, abnormal involuntary movements in the trunk and the extremities seem to be associated with medication.

Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele.

Hyperprolactinaemia induced by D(2) dopamine receptor antagonist antipsychotic medication can result in significant health problems. To examine the role of DRD2 polymorphism on prolactin levels in patients treated with antipsychotic medication. Antipsychotic drugs with different degrees of D(2) receptor binding were given to 144 patients with schizophrenia. Serum prolactin levels were obtained and Taq1A DRD2 alleles were determined. Prolactin levels increased across medication groups reflecting increasingly tight D(2) receptor binding (clozapine, olanzapine, typical antipsychotics and risperidone). In the combined medication group, patients with the DRD2(*)A1allele had 40% higher prolactin levels than patients without this allele. In patients treated with clozapine (the loosest D(2) receptor binding agent), patients with the DRD2(*)A1allele had prolactin levels twice those of patients without this allele. Patients with the DRD2A1 allele receiving antipsychotic medications had higher prolactin levels and were overrepresented among those with hyperprolactinaemia, suggesting greater functional D(2) receptor binding in this group.

Cu, Zn- and Mn-superoxide dismutase levels in brains of patients with schizophrenic psychosis

Impaired oxidative stress defense has been reported in blood of both drug-naïve and antipsychotic-treated patients suffering from schizophrenic psychosis, indicating the involvement of free radical metabolism in the pathogenetic processes of schizophrenia. In this study, the concentrations of two isoenzymes of superoxide dismutase (SOD), Cu, Zn- and MnSOD, were determined with ELISA in various cortical (frontal, parietal, temporal and occipital cortex) and subcortical areas (putamen, caudate nucleus, thalamus, and substantia innominata) of post-mortem brain tissue from patients diagnosed with a schizophrenia spectrum disorder and compared with those of controls. Post-mortem brain tissue from individuals without neuropsychiatric disorders served for control. Cu, Zn- and MnSOD levels were significantly increased in frontal cortex and substantia innominata of the index group, respectively. In all other areas both types of SOD remained virtually unchanged. Detection of SOD changes in the brain supports previous reports of alterations of antioxidant indices in blood cells of patients with schizophrenia and suggests a specific neuroanatomical distribution pattern of oxidative stress processes possibly related to the pathophysiology of schizophrenia.

Prolactinemia is uncoupled from central D2/D3 dopamine receptor occupancy in amisulpride treated patients.

Atypical antipsychotic drugs are classically associated with lower propensity to extrapyramidal symptoms (EPS) and hyperprolactinemia than typical antipsychotic drugs. It has not been clarified why some atypical antipsychotic drugs, such as amisulpride, induce prolactin plasma concentration (PRL) elevation, but little EPS. Previous studies have found an association between striatal D2/D3 receptor occupancy and PRL in typical antipsychotic treated patients suggesting that PRL is a marker of central D2/D3 receptors blockade. We have evaluated the relationship between PRL and central (striatum, temporal cortex and thalamus) D2/D3 receptor occupancy in amisulpride treated schizophrenic patients. Single photon emission tomography (SPET) and [123I]-epidepride were used to determine D2/D3 receptor occupancy in eight amisulpride treated patients. PRL was measured concurrently with the scans. The mean PRL was 1166 (range 499-1892 mIU/l) for a mean amisulpride dose of 406 mg/day (range 150-600 mg/day). Amisulpride plasma concentration and central D2/D3 receptor occupancy were positively correlated (r=0.83-0.89, df=4, P<0.05). No significant correlations were observed between PRL and amisulpride (daily dose or plasma concentration, P>0.05), or between PRL and central D2/D3 receptor occupancy (P>0.05). Our findings show that amisulpride-induced hyperprolactinemia is uncoupled from central D2/D3 receptor occupancy. Amisulpride has poor blood-brain barrier penetration and reaches much higher concentration at the pituitary, which is outside the blood-brain barrier. Higher D2/D3 receptor occupancy at the pituitary gland than at central regions is a possible explanation for amisulpride PRL elevation with low EPS. Further studies evaluating pituitary D2/D3 receptor occupancy in vivo are necessary to confirm this hypothesis.

Ziprasidone-Induced Pisa Syndrome after Clozapine Treatment

Ziprasidone-Induced Pisa Syndrome after Clozapine Treatment

Grey and white matter changes in the aesop first-onset psychosis study: A voxel-based analysis of brain structure

Neuregulin-1 (Nrg-1)1 gene has been considered as a schizophrenia susceptibility gene. In order to observe the association of Nrg-1 gene with schizophrenia, the study was designed to investigate the effect of anti-psychotic treatment on the Nrg-1 mRNA expression in peripheral blood lymphocytes of the patients with a diagnosis of schizophrenia. The Nrg-1 mRNA expression in peripheral blood lymphocytes (PBLs) was measured by using semi-quantitative RT-PCR in 31 first-onset schizophrenia patients, 16 sibling controls and 31 no-sibship controls. Results showed that Nrg-1 mRNA expression in PBLs of patients was lower than that in other two control groups (F = 6.722, P = 0.002). However, as follow-up time extended, from the second week, Nrg-1 mRNA expression of PBLs in antipsychotic treated patients gradually increased and has obvious statistical significance compared the efficacy of taking anti-psychotic before and after therapy. These results demonstrated that Nrg-1 gene has association with schizophrenia. It is possible to select Nrg-1 mRNA expression of PBLs in schizophrenia patients as a potential therapeutic marker.

Clinical and psychophysiology correlates of a large cavum septum pellucidum in schizophrenia

Neuregulin-1 (Nrg-1)1 gene has been considered as a schizophrenia susceptibility gene. In order to observe the association of Nrg-1 gene with schizophrenia, the study was designed to investigate the effect of anti-psychotic treatment on the Nrg-1 mRNA expression in peripheral blood lymphocytes of the patients with a diagnosis of schizophrenia. The Nrg-1 mRNA expression in peripheral blood lymphocytes (PBLs) was measured by using semi-quantitative RT-PCR in 31 first-onset schizophrenia patients, 16 sibling controls and 31 no-sibship controls. Results showed that Nrg-1 mRNA expression in PBLs of patients was lower than that in other two control groups (F = 6.722, P = 0.002). However, as follow-up time extended, from the second week, Nrg-1 mRNA expression of PBLs in antipsychotic treated patients gradually increased and has obvious statistical significance compared the efficacy of taking anti-psychotic before and after therapy. These results demonstrated that Nrg-1 gene has association with schizophrenia. It is possible to select Nrg-1 mRNA expression of PBLs in schizophrenia patients as a potential therapeutic marker.

Antipsychotics and Parkinson's disease: association with disease and drug choice during the first 5 years of antiparkinsonian drug treatment

Psychosis is a common complication of the drug treatment of Parkinson's disease (PD). Treatment of this complication is difficult as most antipsychotic drugs worsen motor symptoms of PD. Only the atypical antipsychotic clozapine improves psychosis without worsening of parkinsonism. The aim of the present study was to assess the rate of initiation of antipsychotic treatment in patients with PD compared with controls. The quality of pharmacotherapy was determined by assessing which antipsychotic drugs were initiated. Data came from the PHARMO database, which includes drug-dispensing information for all residents of six Dutch cities. Selected were all persons aged 55 years and older who used levodopa for at least 180 days and who started antiparkinsonian drugs at least 180 days after entry into PHARMO. These patients were matched to at most three controls for age, gender, pharmacy and time of use. The association between rate of initiation of antipsychotic drug treatment and PD was determined using the Cox proportional hazards model. The study included 271 patients with PD and 748 controls. During follow-up, 38 patients and 25 controls started taking an antipsychotic drug; relative risk was 3.9 (95% confidence interval 2.3, 6.4). Six patients with PD received an atypical agent (16%). Clozapine was given to five patients with PD. No control used clozapine. Haloperidol was most frequently prescribed to the patients (29%) and the controls (36%). Patients with PD began taking antipsychotic drugs almost four times more frequently than controls. The quality of pharmacotherapy can be improved by prescribing atypical antipsychotic drugs to patients with PD.

Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia.

Hyperglycemia and type 2 diabetes mellitus are more common in schizophrenia than in the general population. Glucoregulatory abnormalities have also been associated with the use of antipsychotic medications themselves. While antipsychotics may increase adiposity, which can decrease insulin sensitivity, disease- and medication-related differences in glucose regulation might also occur independent of differences in adiposity. Modified oral glucose tolerance tests were performed in schizophrenic patients (n = 48) receiving clozapine, olanzapine, risperidone, or typical antipsychotics, and untreated healthy control subjects (n = 31), excluding subjects with diabetes and matching groups for adiposity and age. Plasma was sampled at 0 (fasting), 15, 45, and 75 minutes after glucose load. Significant time x treatment group interactions were detected for plasma glucose (F(12,222) = 4.89, P<.001) and insulin (F(12,171) = 2.10, P =.02) levels, with significant effects of treatment group on plasma glucose level at all time points. Olanzapine-treated patients had significant (1.0-1.5 SDs) glucose elevations at all time points, in comparison with patients receiving typical antipsychotics as well as untreated healthy control subjects. Clozapine-treated patients had significant (1.0-1.5 SDs) glucose elevations at fasting and 75 minutes after load, again in comparison with patients receiving typical antipsychotics and untreated control subjects. Risperidone-treated patients had elevations in fasting and postload glucose levels, but only in comparison with untreated healthy control subjects. No differences in mean plasma glucose level were detected when comparing risperidone-treated vs typical antipsychotic-treated patients and when comparing typical antipsychotic-treated patients vs untreated control subjects. Antipsychotic treatment of nondiabetic patients with schizophrenia can be associated with adverse effects on glucose regulation, which can vary in severity independent of adiposity and potentially increase long-term cardiovascular risk.

Drug-induced Pisa syndrome (pleurothotonus): epidemiology and management.

Long-term administration of antipsychotics occasionally produces persistent dystonia of the trunk, a disorder known as Pisa syndrome (or pleurothotonus). The development of Pisa syndrome is most commonly associated with prolonged treatment with antipsychotics; however, it has also been reported, although less frequently, in patients who are receiving other medications (such as cholinesterase inhibitors and antiemetics), in those not receiving medication (idiopathic Pisa syndrome) and in those with neurodegenerative disorders. Drug-induced Pisa syndrome predominantly develops in females and in older patients with organic brain changes. It sometimes occurs after the addition of another antipsychotic to an established regimen of antipsychotics or insidiously arises in antipsychotic-treated patients for no apparent reason. The condition generally disappears after antipsychotic drugs are discontinued. Although a pharmacological therapy for drug-induced Pisa syndrome has not been established, we have reported that anticholinergic drugs are effective in about 40% of patients who have episodes of Pisa syndrome with the remaining patients responding to the withdrawal or reduction of daily doses of antipsychotic drugs. The characteristics of its development and prognosis indicate that drug-induced Pisa syndrome consists of two types of dystonia. Some patients develop clinical features of acute dystonia, whereas others develop symptoms similar to tardive dystonia. Like that of tardive dystonia, Pisa syndrome responds better than tardive dyskinesia to a relatively high daily dose of an anticholinergic. However, the significant improvement caused by the withdrawal of antipsychotic drugs in Pisa syndrome differentiates it from tardive dystonia. Thus, Pisa syndrome including these features is considered to be an atypical type of tardive dystonia. These clinical characteristics suggest that the underlying pathophysiology of drug-induced Pisa syndrome is complex. A dopaminergic-cholinergic imbalance, or serotonergic or noradrenergic dysfunction, may be implicated. Asymmetric brain functions or neural transmission may also be considered as underlying mechanisms of the development of Pisa syndrome that is resistant to anticholinergic drugs. Idiopathic Pisa syndrome is characterised by an adult-onset, segmental truncal dystonia in patients with no previous exposure to antipsychotics. It occurs rarely but shows a complete resolution with high doses of anticholinergic drugs.

Do We Need a Meta-Analysis Update on Antipsychotic Treatment of Behavioral and Psychological Symptoms of Dementia?

Whether we need another meta-analysis of clinical trials of antipsychotic treatment of patients with behavioral and psychological symptoms of dementia (BPSD) depends on how we define meta analysis and our expectations for the results of such an analysis.

Antipsychotic-induced weight gain: a comprehensive research synthesis.

The purpose of this study was to estimate and compare the effects of antipsychotics-both the newer ones and the conventional ones-on body weight. A comprehensive literature search identified 81 English- and non-English-language articles that included data on weight change in antipsychotic-treated patients. For each agent, a meta-analysis and random effects metaregression estimated the weight change after 10 weeks of treatment at a standard dose. A comprehensive narrative review was also conducted on all articles that did not yield quantitative information but did yield important qualitative information. Placebo was associated with a mean weight reduction of 0.74 kg. Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine. Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg. Insufficient data were available to evaluate quetiapine at 10 weeks. Both conventional and newer antipsychotics are associated with weight gain. Among the newer agents, clozapine appears to have the greatest potential to induce weight gain, and ziprasidone the least. The differences among newer agents may affect compliance with medication and health risk.

Health resource utilization and clinical outcomes with risperidone therapy in patients with serious mental illness

This report is an analysis of our experience with risperidone therapy in a veteran population with severe, suboptimally responsive psychosis from a perspective of clinical response and health resource utilization. We conducted a computer search for all patients who received risperidone therapy at our facility from February 1994 until July 1, 1996. Risperidone at our facility is prescribed when psychiatric symptoms appear to be refractory or suboptimally responsive to conventional antipsychotic therapy. A control group of patients on conventional antipsychotic therapy were also selected via the electronic data base. One hundred twenty-nine patients received risperidone therapy at a mean dosage of 5.05 ± 2.4 mg/d, for a mean duration of 247.4 ± 223.5 days. The largest proportion of patients (48.1%) had marked improvement on risperidone therapy. There were 35 patients who received at least 1 year of risperidone therapy. These patients had a significant decrease in hospital length of stay (LOS) from 80.7 to 28.7 days ( P= .003) on risperidone with no compensatory increase in outpatient visits. The group of patients who received conventional antipsychotic therapy during the study time period had a more modest mean reduction in LOS over a 2-year time period from 78.9 days during the initial identified year of conventional antipsychotic therapy to 56.4 days during the second identified year of conventional antipsychotic therapy ( P= .2). However, when change in LOS for the entire group was compared, the difference in change in LOS between risperidone and conventional antipsychotic treated patients did not reach statistical significance ( P = .2). This preliminary study concurs with other reports that risperidone therapy may be effective in severely mentally ill patients and may be associated with significant reductions in health resource utilization. Comparison of resource utilization between patients receiving risperidone and conventional antipsychotic therapy is still unclear and should be explored in larger and prospective studies.