Efficacy of 3-year psychiatric daycare treatment in patients with schizophrenia

The present study investigated the efficacy of a 3-year psychiatric daycare (DC) program with regard to psychiatric symptoms and difficulties with daily living experienced by patients with schizophrenia. The subjects were 28 patients who met the diagnostic criteria from the 4th edition of the Diagnostic and Statistical Manual for schizophrenia and continued DC treatment for 3 years. The present study assessed participants at two points: at the start of DC and after 3 years, by evaluating socioeconomic factors and Brief Psychiatric Rating Scale (BPRS) scores. In addition, in order to measure difficulties with daily living, the Life Assessment Scale for the Mentally Ill (LASMI) and the Etoh Daycare Assessment Scale (ETODAS) developed at the Etoh Hospital, were used. Results indicated that no significant changes in socioeconomic factors or BPRS scores occurred during the 3-year period of DC treatment. However, over this period, mean scores (+/- standard deviation [SD]) for LASMI subcategories decreased from 1.6 +/- 0.8 points to 0.9 +/- 0.7 for daily living and from 1.7 +/- 0.8 to 1.2 +/- 0.7 for interpersonal relations, indicating significant improvement (P < 0.05). In addition, mean scores (+/-SD) for the ETODAS subcategories increased from 3.4 +/- 0.8 to 4.1 +/- 0.8 for expressiveness, from 3.3 +/- 0.9 to 4.0 +/- 0.8 for communication, from 3.1 +/- 0.6 to 3.6 +/- 1.0 for initiative within a group, and from 3.4 +/- 0.5 to 3.8 +/- 0.7 for cooperation in work activities, indicating significant improvement (P < 0.05). The present study suggests that DC can enable patients with schizophrenia to maintain their condition without worsening the psychiatric symptoms, and to improve their daily living skills, social skills in human relations, and work skills.     

Suicide and undetermined death by drowning

INTRODUCTION : To compare the efficacy and safety of olanzapine and haloperidol in partial-responder paranoid schizophrenic patients. METHOD : In this multi-centre, double-blind study, 28 patients with DSM-IV paranoid schizophrenia were randomized to receive 14 weeks treatment with either olanzapine or haloperidol at flexible doses. The pre- and post-treatment assessment included the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the CGI, the Simpson-Angus Rating Scale, and the Barnes Akathisia Rating Scale. RESULTS : The two treatment groups showed similar improvement on the BPRS positive symptoms subscale, while the improvement of BPRS negative symptoms subscale was significant only in the olanzapine group (ANOVA with repeated measures, group effect: F=5.89, P =0.023). Only the olanzapine-treated patients experienced a significant improvement of negative symptoms as rated by the SANS (ANOVA with repeated measures, group effect: F=6.81, P =0.016). No significant differences were found between the two groups on the Simpson and Angus Rating Scale scores, but a significant difference was found in the Barnes Akathisia Rating Scale scores: no patient in the olanzapine-treated group experienced akathisia, while a few patients in the haloperidol-treated group showed this side-effect, thus resulting in a significant group effect detected by the ANOVA (F=4.23, P =0.05). CONCLUSIONS : These preliminary results suggest that olanzapine is superior to haloperidol in the treatment of partial-responder paranoid schizophrenic patients, and also shows a better tolerability profile. Further investigations, including different diagnostic subgroups, are still needed to further clarify the clinical profile of olanzapine. (Int J Psych Clin Pract 2002; 6: 107-111)     

Validation of the Personal and Social Performance (PSP) Scale in a German sample of acutely ill patients with schizophrenia

In trying to more broadly define outcome in the efficient long-term treatment of patients with schizophrenia it is necessary to consider not only a reduction in psychopathological symptoms but also a successful psychosocial reintegration. Thus, a more exact assessment of psychosocial functioning is needed. Since the GAF (Global Assessment of Functioning) scale and the SOFAS (Social and Occupational Functioning Assessment Scale) are less operationalized and confuse psychosocial facts with psychopathological symptoms, the Personal and Social Performance (PSP) scale was developed [Morosini, P.L., Magliano, L., Brambilla, L., Ugolini, S., Pioli, R. (2000). Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to assess routine social functioning. Acta Psychiatrica Scandinavica, 1001, 323-329.] containing the four main areas "socially useful activities, personal and social relationships, self-care, as well as disturbing and aggressive behaviour". Validation of the PSP scale was conducted in a sample of 62 patients with acute schizophrenia. Rating instruments were PSP, GAF, SOFAS, PANSS, CGI, and Mini-ICF-P (Mini-ICF-Rating for Mental Disorders). The results showed good reliability with alpha=.64-.84, high test-retest reliability as well as good inter-rater reliability for the PSP scale. Furthermore, PSP proved good validity with high correlations to GAF (r=.91), SOFAS (r=.91), and Mini-ICF-P (r=-.69). The hypothesis that more critically ill patients would show lower scores on PSP than lesser ill patients was only confirmed for PANSS negative symptoms. Thus, the findings prove the PSP scale to be a reliable and valid instrument for assessing social functioning of patients with schizophrenia during the course of treatment as well as in the acute state.     

万拉法新与氯丙咪嗪治疗精神分裂症后抑郁对照研究

目的 验证万拉法新治疗精神分裂症后抑郁的疗效及安全性。方法 对65例精神分裂症后抑郁患者随机入组,分别以万拉法新与氯丙咪嗪治疗6周。采用汉密尔顿抑郁量表(HAMD)、简明精神病量表(BPRS)、阴性症状量表(SANS)评定临床疗效,采用副反应量表(TESS)评定副反应。结果 万拉法新组与氯丙咪嗪组治疗前后HAMD、BRPS、SANS评分及减分率比较均无显著性差异(P>0.05)。万拉法新组的副反应较氯丙咪嗪组少而轻,但各有1例精神病症状恶化。结论 万拉法新治疗精神分裂症后抑郁的疗效确切,但极个别病例精神病症状恶化。     

Clozapine, but not typical antipsychotics, correct P50 suppression deficit in patients with schizophrenia.

OBJECTIVE: To find out if there is a difference in P50 suppression between patients using typical antipsychotic drugs and those using clozapine, as well as to confirm the findings of abnormal P50 suppression in patients with schizophrenia, when compared to healthy volunteers. METHODS: Fifty patients with schizophrenia and 25 healthy volunteers were divided into 3 groups: group 1 - patients using typical antipsychotics; group 2 - patients using clozapine; group 3 - controls. Before the examination, all patients were interviewed by a psychiatrist using the Brief Psychiatry Rating Scale (BPRS). RESULTS: The average S2/S1 ratio was 0.82+/-0.45 in group 1, 0.57+/-0.41 in group 2, and 0.44+/-0.27 in group 3 (P=0.003). Statistical analysis showed a significant difference when the results of group 1 were compared to those of groups 2 (P=0.045) and 3 (P=0.001). There was no significant difference between groups 2 and 3 (P=0.182). There was a significant difference in the S1-S2 difference only between groups 1 and 3 (P=0.007), but a non-significant trend towards a similar difference was found between groups 1 and 2 (P=0.067). There was no correlation between the BPRS values and any P50 parameter. CONCLUSIONS: The suppression of P50 among patients using clozapine was significantly greater than that obtained in patients using typical antipsychotics. SIGNIFICANCE: This study confirms, in a more evident way, the improvement of the suppression of P50 potential in schizophrenics using clozapine. Additionally, it discusses the physiopathological mechanism involved.     

Association between the polymorphic GRM3 gene and negative symptom improvement during olanzapine treatment

PURPOSE: The excitatory neurotransmitter glutamate has become an important area of focus for schizophrenia researchers. Polymorphisms in the type-three metabotropic glutamate receptor gene (GRM3) have been associated with the pathogenesis of schizophrenia. The purpose of this study was to determine whether a pharmacogenetic relationship exists between six polymorphisms of GRM3 and clinical improvement during olanzapine treatment in persons with schizophrenia. METHOD: Forty-two subjects meeting DSM-IV criteria for schizophrenia started olanzapine and were titrated to a fixed dose of 7.5-20 mg/day for 6 weeks. The Brief Psychiatric Rating Scale (BPRS) total score and the Scale for Assessment of Negative Symptoms (SANS) were completed at baseline and then weekly to assess psychopathology. RESULTS: The principle finding of this study is that GRM3 polymorphisms were collectively significant predictors of negative symptom improvement in persons with schizophrenia treated with the atypical antipsychotic olanzapine. After controlling for baseline SANS scores, the genotypes as a whole were significant predictors of negative symptom improvement, accounting for approximately 28% of the variance in scores (F = 16.30, df = 29, p < 0.001). The single nucleotide polymorphism SNP1 (rs274622), located in a potential promoter region, had the most significant influence on SANS scores, but the effects of this locus could not be fully separated from the other polymorphisms. The mean decrease in SANS scores was 21% vs. 51% for SNP1 T/T + T/C and SNP1C/C subjects, respectively. CONCLUSION: These data suggest that polymorphisms in the GRM3 gene may be useful as predictors of negative symptom improvement in persons with schizophrenia treated with olanzapine.     

One-year outcome after response to ECT in middle-aged and elderly patients with intractable catatonic schizophrenia

BACKGROUND AND OBJECTIVE: ECT is one of the most efficacious treatments for catatonic schizophrenia. However, there has been no study on the efficacy of ECT in elderly patients with catatonic schizophrenia. Thus, we conducted prospective studies on the short-term (phase 1 study) and long-term (phase 2 study) effects of acute ECT on intractable catatonic schizophrenia in middle-aged and elderly patients. SUBJECTS AND METHODS: The phase 1 study included 11 consecutive patients over 45 years of age who fulfilled the DSM-IV criteria for catatonic schizophrenia and were referred to Tohoku University Hospital for the first time for acute ECT between January 1, 1998, and August 31, 2003, after other treatments had failed. We evaluated the clinical response of these patients to acute ECT by means of the Brief Psychiatric Rating Scale (BPRS). We also evaluated adverse effects of acute ECT. The patient or guardian provided written informed consent. Exclusion criterion was a history of dementia or substance abuse. Patients were considered clinical responders if they had a BPRS score ;ek 25 for 1 week after the final ECT session. The phase 2 study included 11 consecutive patients who responded to acute ECT in the phase 1 study. Patients provided written informed consent. Patients' BPRS scores were evaluated weekly (18 items, rated 0-6) for 48 weeks or until relapse/recurrence, during which time they received pharmacotherapy. Patients were considered clinical "relapsers" if they had a BPRS score of at least 37 for 3 consecutive days. Differences in clinical characteristics between patients with and without recurrence were analyzed statistically by the Mann-Whitney U test. RESULTS: All 11 patients completed the phase 1 study, and the acute ECT response rate was 100%. No patient experienced a severe adverse cognitive or physical effect during the course of acute ECT. All 11 patients also completed the phase 2 study. The mean dose of continuation neuroleptics in all 11 cases was 296.8 +/- 277.6 mg (range, 0-982 mg) (chlorpromazine [CPZ] equivalent). Relapse occurred in 7 cases, and all occurred within 6 months. The 1-year recurrence rate was 63.6%. The mean (+/-SD) relapse prevention time in the 7 cases was 76.0 +/- 64.7 days (range, 11-163 days). A significant difference in daily neuroleptic dose before acute ECT was found between the patients suffering recurrence and those not suffering recurrence (766.7 +/- 521.8 CPZ-equivalent mg with recurrence versus 101.9 +/- 75.2 CPZ-equivalent mg without recurrence, U = 2.0, P = 0.923). There was a trend toward a lower Global Assessment of Functioning (GAF) score just before ECT (7.3 +/- 4.0 with recurrence versus 16.8 +/- 11.2 without recurrence, U = 4.5, P = 0.073). CONCLUSIONS: The short-term efficacy of acute ECT for middle-aged and elderly patients with intractable catatonic schizophrenia is excellent. However, the 1-year recurrence rate, especially the 6-month relapse rate, after response to acute ECT is high, despite continuation pharmacotherapy. The need for more effective relapse-prevention strategies, such as continuation ECT, is urgent.     

Add-on of aripiprazole improves outcome in clozapine-resistant schizophrenia

Although clozapine proved effective in treating 30-50% of the cases of resistant schizophrenia, its clinical use is hampered by significant side effects. To overcome this problem, augmentation with other atypical antipsychotics has been attempted, with conflicting results. A clozapine-aripiprazole combination showed interesting properties, due to the favourable complementary pharmacodynamic receptor profile and to the negligible metabolic interactions. In this retrospective case series, we investigated the change in BPRS scores and metabolic features like BMI, fasting glucose, total and LDL cholesterol, triglycerides, functional outcome HoNOS Rome and PSP scores after aripiprazole augmentation in 16 persons with treatment-resistant schizophrenia who were already treated with clozapine. The results demonstrated a statistically significant improvement in metabolic indices, psychopathology and functional outcome measures from baseline to endpoint (6 weeks) after augmentation with aripiprazole. Statistically significant correlations were observed between psychopathological and behavioural measures at baseline and at endpoint. Linear regression analysis defined a tripartite model, in which item HoNOS Rome 11, measuring autonomy in everyday life, explained nearly half of functional outcome PSP score predictive variance, together with BPRS total psychopathology score and HoNOS Rome total social functioning score. Adequately conducted randomised double-blind studies should provide further specific data highlighting the role of a clozapine-aripiprazole combination in improving functional outcome of persons with treatment-resistant schizophrenia.     

The relationship of the Brief Assessment of Cognition in Schizophrenia (BACS) to functional capacity and real-world functional outcome

The Brief Assessment of Cognition in Schizophrenia (BACS) assesses five different domains of cognitive function with six tests, and takes about 30-35 minutes to complete in patients with schizophrenia. Previous work has demonstrated the reliability of this measure, and its sensitivity to the deficits of schizophrenia. However, the relationship of this brief cognitive measure to functional outcome has not been determined. Further, future registration trials for potentially cognitive enhancing compounds may not only assess efficacy with cognitive performance measures, but with assessments of real-world functional outcome and functional capacity. The purpose of this study was to determine the relationship between the BACS and a potential co-primary measure for treatment studies of cognition in schizophrenia, and to determine if such a measure accounts for significant variance in functioning beyond that provided by cognitive function. The current study assessed 60 patients with schizophrenia over the course of six months. Cognitive functions were measured with the BACS. Functional capacity was measured with the UCSD Performance-based Skills Assessment (UPSA). Real-world functional outcome was measured with the Independent Living Skills Inventory (ILSI). BACS composite scores were significantly correlated with functional capacity as measured by the UPSA (r = .65, df = 55, p < .001), and real-world functional outcome as assessed by the ILSI (r = .37, df = 56, p = .005). In multiple regression analyses, UPSA scores did not account for additional variance in real-world functioning beyond that accounted for by the BACS. These data suggest that brief cognitive assessments such as the BACS are able to assess aspects of cognition that are related to important functional measures in clinical trials of cognitive enhancement. They also suggest that the measures being considered as potential co-primary indicators of cognitive function for registration trials are significantly correlated with cognition as assessed by brief cognitive assessments.     

Clozapine in treatment-resistant patients with schizophrenia,schizoaffective disorder,or psychotic bipolar disorder: a naturalistic 48-month follow-up study

BACKGROUND: The aim of this study was to evaluate the long-term efficacy and safety of clozapine in patients with treatment-resistant schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features. METHOD: 101 patients with a DSM-III-R diagnosis of schizophrenia (N = 34); schizoaffective disorder, bipolar type (N = 30); or bipolar disorder with psychotic features (N = 37) were naturalistically treated with clozapine at flexible doses over a 48-month period. Data were collected from 1994 to 2000. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impressions-Severity of Illness scale total predicted scores over time were estimated with random-effects regression models. Time to response to clozapine, defined as 50% reduction of BPRS score, was analyzed in the 3 diagnostic groups using the Kaplan-Meier method. Survival curves were compared using the log-rank test. RESULTS: The BPRS total predicted score halved its baseline value in 3 months for bipolar disorder patients, in 6 months for schizoaffective disorder patients, and in 24 months for schizophrenia patients. The proportion of subjects who satisfied the criterion for response to clozapine after 48 months of follow-up was significantly (p <.01) higher in the schizoaffective and bipolar disorder groups (90.0% and 83.8%, respectively) than in the schizophrenia group (64.7%). Baseline scores on the Global Assessment of Functioning (GAF) showed low levels of psychosocial and occupational functioning in all 3 groups. After 48 months of treatment, GAF scores showed a functional improvement in all 3 groups, with significantly (p <.01) greater improvement in the bipolar disorder group compared with the other groups. CONCLUSION: The findings of this study confirm the efficacy and safety of clozapine for treatment-resistant patients with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features. Patients with schizoaffective disorder and those with bipolar disorder show greater clinical improvement than those with schizophrenia. Patients with bipolar disorder have the shortest time to response and the highest psychosocial and occupational functioning levels. Patients with schizoaffective disorder have the lowest treatment discontinuation rate.     

Duration of untreated psychosis may predict acute treatment response in first-episode schizophrenia

There is growing evidence for a relationship between the duration of untreated psychosis (DUP) and the prognosis in schizophrenia. The objective of this study is to evaluate whether DUP and premorbid level of social functioning are related to treatment response in acute treatment of first-episode schizophrenia. Seventy-nine first-episode schizophrenia patients were assessed with BPRS, SAPS, and SANS on admission and discharge during their first hospitalisation. Percentage of the difference between admission and discharge in total scores of all scales were taken as measures of absolute symptom reduction. The median DUP was 6 months (mean=8.6). DUP was correlated with reduction in BPRS and SAPS scores but not SANS scores. Patients with a short DUP (n=41) also showed a higher reduction in BPRS, and SAPS scores than those with a long DUP. Premorbid Adjustment Scale (PAS) scores were inversely correlated with age at onset and positively correlated with BPRS scores at admission. We did not find any relationship between PAS scores and response to treatment. Our findings suggest that DUP may be an important predictor of response in acute treatment of first-episode schizophrenia and thus, attempts for early diagnosis may also have a positive effect on acute treatment response.     

The illness and everyday living: close interplay of psychopathological syndromes and psychosocial functioning in chronic schizophrenia

The interaction of psychopathological states and psychosocial functioning determine the long-term course of schizophrenia and its treatment. To be able to achieve this interplay better, exact assessment of psychosocial functioning is needed besides measurement of psychopathology. Using the Personal and Social Performance (PSP) Scale, examination of the association between psychosocial functioning and psychopathology was conducted in a sample of 103 patients with chronic schizophrenia. Rating instruments were in addition Global Assessment of Functioning Scale and Social and Occupational Functioning Assessment Scale, as well as Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, and Mini-ICF-APP-Rating for Mental Disorders (Mini-ICF-APP). Besides good psychometric properties for the PSP scale in this chronic sample, we found, as expected, significant associations between the two relevant outcome domains: results showed significant negative correlations between PSP and PANSS. Findings prove the close interplay between social functioning and psychopathology in the chronic course of schizophrenia.     

Clozapine utilization and outcomes by race in a public mental health system: 1994-2000

OBJECTIVE: This study aimed to assess racial differences in clozapine prescribing, dosing, symptom presentation and response, and hospitalization status. This study extends previous studies of clozapine by examining patient- and treatment-related factors that may help explain or eliminate reasons for differential prescribing. METHOD: Clozapine records for 373 white and African American patients with schizophrenia or schizoaffective disorder treated between March 1, 1994, and December 31, 2000, in inpatient mental health facilities in the state of Maryland were examined. Records for this study were derived from 3 state of Maryland databases: the Clozapine Authorization and Monitoring Program, the State of Maryland Antipsychotic Database, and the Health Maintenance Information System Database. RESULTS: A total of 10.3% of African Americans (150/1458) with schizophrenia received clozapine treatment compared with 15.3% of whites (223/1453) (chi2 = 16.74, df = 1, p < .001) during inpatient treatment in the public mental health system in Maryland. Clozapine doses were lower in African Americans relative to whites (385.3 +/- 200.6 vs. 447.3 +/- 230.3 mg/day) (t = -2.66, df = 366, p = .008). At the time of clozapine initiation, whites had more activating symptoms as measured by the Brief Psychiatric Rating Scale (BPRS) (t = -3.98, df = 301, p < .0001); however, African Americans had significantly greater improvements in BPRS total symptoms (F = 4.80, df = 301, p = .03) and in anxiety/ depressive symptoms during 1 year of treatment with clozapine (F = 10.04, df = 303, p = .002). The estimated rate of hospital discharge was not significantly different for African Americans compared to whites prescribed clozapine (log-rank chi2 = 0.523, df = 1, p = .470); however, African Americans were more likely than whites to discontinue clozapine during hospitalization (log-rank chi2 = 4.19, df = 1, p = .041). CONCLUSION: Our data suggest underutilization of clozapine in African American populations. This racial disparity in clozapine treatment is of special concern because of the favorable outcomes associated with clozapine in treatment-resistant schizophrenia and in the specific benefits observed in African American patients. More research is needed to determine why disparities with clozapine treatment occur and why African Americans may be discontinued from clozapine at a higher rate, despite potential indicators of equal or greater effectiveness among African Americans compared with whites.     

Acute and maintenance ECT with flupenthixol in refractory schizophrenia: sustained improvements in psychopathology,quality of life,and social outcomes

OBJECTIVE: To determine the effects of ECT combined with antipsychotic medication therapy on psychopathology, quality of life, and social functioning in patients with refractory schizophrenia. METHOD: An open acute (Phase I) and maintenance (Phase II) study of the combination of ECT and flupenthixol in the treatment of 46 schizophrenic patients who were nonresponsive to antipsychotic medication from at least two different classes. Scales used: the Brief Psychiatric Rating Scale (BPRS), the Quality of Life Scale (QLS), Social and Occupational Functioning Assessment Scale (SOFAS), Global Assessment of Functioning (GAF), and Mini-Mental State Exam (MMSE). The duration of Phase II was 1 year. RESULTS: In Phase I, there were marked reductions in the BPRS scores, and substantial increases in the QLS, SOFAS, GAF, and MMSE scores. During Phase II, the BPRS negative symptoms worsened but remained improved from baseline. Changes in other outcome measures were negligible. CONCLUSION: ECT and MECT combined with flupenthixol were effective in improving psychopathology in patients refractory to antipsychotic medication alone. Ratings of psychopathology, quality of life, and social functioning all improved in Phase I and were generally sustained during Phase II in patients who had remitted.     

Reliability, validity and ability to detect change of the Personal and Social Performance scale in patients with stable schizophrenia

This report describes the measurement properties of the Personal and Social Performance scale (PSP), a clinician-reported measure of severity of personal and social dysfunction, in an outpatient population with stabilized schizophrenia. Pooled data from two similar antipsychotic clinical studies were analyzed (n=411). The PSP showed good test-retest reliability (intraclass correlation coefficient=0.79). The PSP was more highly correlated with the Strauss-Carpenter Level of Function, an instrument measuring a similar construct, than the Positive and Negative Syndrome Scale, an instrument measuring a different construct. There was a statistically significant difference between mean PSP scores in subjects grouped by their severity rating on the Clinical Global Impression-Severity (CGI-S) (mild or less versus at least moderate), indicating the ability to discriminate between known groups. Effect sizes for mean change in the PSP based on 1-category improvement (0.72) or worsening (-0.88) versus no change in the CGI-S were moderate to large, demonstrating the ability to detect change. Estimates of between-group minimum important difference suggest that a 7-point improvement in the PSP may be clinically meaningful in a clinical trial setting. Initial reliability and validity assessments suggest the PSP may be a useful measure of social functioning in patients with stable schizophrenia.     

Multidimensionally impaired: the good news

INTRODUCTION: Long-term outcomes in children with atypical psychosis have been poorly studied. Four to 6 weeks of inpatient observation and up to 11 years (mean, 4.0 +/- 1.3 years) of follow- up have afforded us some experience with this probably heterogeneous group of transiently psychotic patients commonly mislabeled as schizophrenic. Despite severe preadmission morbidity, some patients have successfully remained neuroleptic-free since discharge. Predictors of good versus poor outcome were sought. METHODS: Of roughly 150 patients admitted with the presumptive diagnosis of schizophrenia, 32 patients were discharged meeting criteria for psychosis not otherwise specified (NOS), otherwise labeled by the NIMH team as "multidimensionally impaired" (MDI). Admission and biannual follow-up data included a semistructured clinical interview with the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS), IQ testing, clinical rating scales (e.g., Clinical Global Impression Scale (CGI), Children's Global Assessment Scale (C-GAS), Brief Psychiatric Rating Scale (BPRS), Scales for the Assessment Negative and Positive Symptoms (SANS and SAPS), and Bunney-Hamburg (B-H)). At follow-up (as of February 2005) 38% of patients (12 of 32) met criteria for bipolar 1 disorder, 12% (4 of 23) for major depressive disorder (MDD), and 3% (1 of 32) for schizoaffective disorder. The remaining 47% of patients (15 of 32) were divided into two groups on the basis of whether they were in remission and neuroleptic-free ("good outcome," n = 5) or still severely impaired and/or psychotic regardless of pharmacotherapy ("poor outcome," n = 10) at follow-up. RESULTS: Good-outcome patients had a significantly higher baseline level of functioning (on admission and on medications). This was demonstrated by better scores on CGI (3.5 +/- 0.6 versus 4.8 +/- 0.8; p = 0.03) and C-GAS (66.3 +/- 6.3 versus 38.6 +/- 11.5; p = 0.01). Groups were otherwise comparable in demographic data (gender, race, socioeconomic status, age at onset), months of neuroleptic exposure, severity of psychotic symptoms, and level of premorbid functioning. CONCLUSION: C-GAS (which correctly classified 85.7% of good-outcome subjects) and CGI at baseline appear to predict outcome. On other variables, MDI subgroups were remarkably similar.     

Relationship Between Metabolic Syndrome and Clinical Features,and Its Personal-Social Performance in Patients with Schizophrenia

The aim of this study was to evaluate the metabolic syndrome (MS) criteria and also to investigate the effects of MS on medical treatment, clinical course and personal and social performance in patients with schizophrenia. One hundred-sixteen patients with schizophrenia were included in the study. Measurements of MS were calculated in all patients. Brief Psychiatric Rating Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia, Personal and Social Performance Scale (PSP) were applied. The frequency of MS according to IDF criteria was 42.2 % among the patients. There was no significant difference between patients with and without MS in terms of age. The ratios of MS were 62.5 % for the group taking typical and atypical antipsychotics together and 35.7 % for the group taking two or more atypical antipsychotics together. The duration of disorder in patients with MS was higher than those without MS. Furthermore there was no significant difference between the schizophrenic patients with and without MS, in terms of PSP scores. Our findings showed that the duration of illness, high scores of BMI, use of clozapine or concurrent use of typical and atypical antipsychotics, depressive and negative symptoms of schizophrenia were significant risk factors for the development of MS.     

Risperidone added to clozapine: impact on serum prolactin levels

BACKGROUND: Several years ago, we reported that the addition of risperidone to clozapine improved response in some patients with schizophrenia. Risperidone, in general, is well tolerated when administered as monotherapy, but has been linked to a persistent elevation of serum prolactin and associated symptoms. The goal of this study was to determine whether the addition of risperidone to clozapine results in an elevation of serum prolactin levels in patients with chronic schizophrenia or schizoaffective disorder. METHOD: Twenty patients on clozapine-risperidone combination therapy were matched for age and gender with 20 patients treated with clozapine monotherapy. Demographic information was gathered along with clozapine and risperidone dose and the length of time on risperidone. Serum prolactin levels were measured from a single blood sample. RESULTS: The 2 groups did not differ in age, race, gender, diagnosis, age at clozapine initiation, age at onset, Abnormal Involuntary Movement Scale scores, or clozapine dose. The mean +/- SD serum prolactin level was 8.42+/-4.17 ng/mL for clozapine monotherapy patients and 35.76+/-17.43 ng/mL for combination therapy patients. The 2 medication categories showed a significant difference in log prolactin values (t = -7.97, df = 38, p < or = .0001). Sixteen combination therapy patients (80%) exhibited elevated prolactin levels (range for entire group, 9.7-69.8 ng/mL) while only 2 clozapine monotherapy patients (10%) exhibited prolactin elevation levels (range for entire group, 2.4-20.2 ng/mL; df = 1, p < .0001). CONCLUSION: The combination of risperidone and clozapine appears to result in a moderate elevation of serum prolactin levels. Additionally, controlled prospective studies are needed to clarify the risks of long-term elevations of serum prolactin level.     

Suicidality in middle aged and older patients with schizophrenia and depressive symptoms: relationship to functioning and Quality of Life

BACKGROUND: Suicidality is a health concern in patients with schizophrenia. We examined the hypotheses: (1) Middle aged and older patients with schizophrenia, depressive symptoms and suicidality would exhibit worse quality of life and worse everyday functioning, social skills and medication management relative to those without suicidality; (2) higher levels of suicidality would be significantly associated with worse functioning, worse quality of life and older age. METHODS: We examined 146 outpatients with schizophrenia and depression. Patients were at least 40 years old and were diagnosed with schizophrenia or schizoaffective disorder and had two or more depressive symptoms based on DSM-IV criteria for major depression. We assessed suicidality with the Intersept Suicide Scale (ISS) and functioning with the UCSD Performance-based Skills Assessment (UPSA), Social Skills Performance Assessment (SSPA), and Medication Management Ability Assessment (MMAA). Quality of life was assessed with the Heinrichs Quality of Life Scale (QLS). RESULTS: The mean age of patients was 52.4+ 6.9 years. Subjects with suicidality (ISS scores > 0) had lower QLS scores compared to those without suicidality. However, there were no differences in UPSA, SSPA nor MMAA scores between the two groups. In addition, based on Spearman's rho correlational analysis, there were significant associations of QLS scores with ISS scores (r = - 0.236) and with MMAA "total errors" scores (r = 0.174). Logistic regression demonstrated that only QLS scores predicted suicidality. CONCLUSION: Thirty-six percent of our sample had at least mild degrees of suicidality. Lower quality of life appears to be an important predictor of suicidality.     

Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses.

OBJECTIVE: To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia (AD). METHODS: In this double-blind, multicenter study, 487 institutionalized patients with psychosis associated with AD were randomized to placebo or aripiprazole, 2, 5 or 10 mg/day. Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory-Nursing Home (NPI-NH) version Psychosis Subscale score. Secondary measures included NPI-NH Total, Clinical Global Impression-Severity of Illness (CGI-S), Brief Psychiatric Rating Scale (BPRS) Core and Total, and the Cohen-Mansfield Agitation Inventory (CMAI) scores. RESULTS: Aripiprazole 10 mg/day showed significantly greater improvements (mean change [2 x SD]) than placebo on the NPI-NH Psychosis Subscale (-6.87 [8.6] versus -5.13 [10.0]; F = 6.29, df = 1, 422, p = 0.013 by analysis of covariance [ANCOVA]); CGI-S (-0.72 [1.8] versus -0.46 [1.6]; F = 4.68, df = 1, 419, p = 0.031 [ANCOVA]); BPRS Total (-7.12 [18.4] versus -4.17 [21.6]; F = 4.72, df = 1, 399, p = 0.030 [ANCOVA]); BPRS Core (-3.07 [6.9] versus -1.74 [7.8]; F = 7.30, df = 1, 407, p = 0.007 [ANCOVA]); CMAI (-10.96 [22.6] versus -6.64 [28.6]; F = 5.23, df = 1, 410, p = 0.023 [ANCOVA]), and NPI-NH Psychosis response rate (65 versus 50%; chi(2) = 5.52, df = 1, p = 0.019 [CMH]). Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores. Aripiprazole 2 mg/day was not efficacious. Cerebrovascular adverse events were reported: aripiprazole 2 mg/day, N = 1; 5 mg/day, N = 2; 10 mg/day, N = 4; placebo, N = 0. No deaths in any group (aripiprazole 2 mg/day, 3%; 5 mg/day, 2%; 10 mg/day, 7%; placebo, 3%) were considered to be treatment-related. CONCLUSION: Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD, significantly improving psychotic symptoms, agitation, and clinical global impression. However, clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population.