The “Seroquel” Outcomes Study (SOS): Efficacy and tolerability of quetiapine in a long-term,naturalistic study of patients with schizophrenia

Objective. The “Seroquel” Outcomes Study (SOS) aimed to assess the efficacy and tolerability of quetiapine in patients with schizophrenia in the clinical practice setting. Methods. A 6-month, non-comparative, open-label study in adults with schizophrenia in a standard care setting in Spain. Outpatients received flexibly dosed quetiapine. Efficacy was evaluated using the Brief Psychiatry Rating Scale (BPRS) and the Clinical Global Impression (CGI) scale. BPRS response was defined as≥30% decrease from baseline. Tolerability was assessed using the Simpson–Angus Scale (SAS) and a modified Udvalg for Kliniske Undersogelser (UKU) side-effects scale. Results. A total of 2029 patients enrolled. Significant changes from baseline to Month 6 were recorded for BPRS total and subscale scores (P<0.001). Compared with doses of≥600 mg/day, doses of<400 mg/day were a strong predictor of a lower response rate (OR 0.62; 95% CI: 0.48, 0.82) and higher withdrawal rate (OR 3.3; 95% CI: 2.5, 4.4). Mean change in weight was minimal (+0.4 kg). Somnolence (26.7%), asthenia (12.5%), and constipation (9.8%) were the most common adverse events. Conclusion. Quetiapine was found to improve symptoms of schizophrenia, as indicated by a significant decrease in BPRS scores, and was well tolerated by patients in clinical practice.     

A 26-week open-label study of quetiapine in children with conduct disorder

OBJECTIVE: The aim of this study was to describe the long-term safety and effectiveness of quetiapine in conduct disorder (CD). METHODS: This was an 18-week outpatient follow-up study of an acute trial that enrolled aggressive children ages 6-12 years with a primary diagnosis of CD. To be enrolled into this study, subjects had to have successfully completed participation in the initial 8-week, open-label, outpatient quetiapine trial. Psychometric measures included the Rating of Aggression Against People and/or Property Scale (RAAPP), the Nisonger Child Behavior Rating Form (NCBRF), the Conners' Parent Rating Scale (CPRS-48), the Clinical Global Impressions Scale of Severity (CGI-S), and the Children's Global Assessment Scale. RESULTS: Nine males with a mean age of 8.9 (SD = 1.2) years were treated. The median quetiapine dose at end of study was 150 mg/day (range 75-350). Mean psychometric scores did not change substantively from baseline. No patients experienced extrapyramidal side effects. Three subjects discontinued due to study nonadherence. No patients discontinued treatment due to an adverse event. CONCLUSIONS: These preliminary data suggest that quetiapine might be a generally safe and effective maintenance treatment for aggressive children with CD who initially respond to an acute therapeutic trial of quetiapine. More research is needed to confirm or refute these initial findings.     

奎硫平与锂盐治疗双相障碍急性躁狂的随机双盲对照多中心研究

目的 评价奎硫平单药治疗双相障碍急性躁狂患者的疗效及安全性.方法 采用随机、双盲双模拟、阳性药物平行对照、多中心研究.根据中国精神障碍分类与诊断标准第3版诊断为双相障碍躁狂发作,并且根据Young躁狂评定量表(YMRS)总分≥20分的住院患者被随机分配接受奎硫平(每日2次口服,最大剂量达800 mg/d)或碳酸锂(每日2次口服,最大剂量达2000 mg/d)治疗,共观察4周.主要疗效指标为从基线至治疗第28天YMRS总分的改变(末次观察值结转).安全性指标包括不良事件、实验室和心电图检查等.结果 共随机分配155例患者(奎硫平组为78例,碳酸锂组为77例).意向性治疗人群共154例(两组各77例).奎硫平和碳酸锂的平均剂量分别为642.9 mg/d和1377.7 mg/d.从基线至治疗第28天奎硫平组和碳酸锂组YMRS减分值分别为-18.2分和-15.9分.治疗第28天,奎硫平组的有效率(78%)明显高于碳酸锂组(60%),差异有统计学意义(P=0.013).奎硫平组和碳酸锂组的不良事件发生率分别为78%和69%.奎硫平在最大剂量达800 mg/d的情况下耐受性较好,其最常见的不良事件为便秘(35%)、头晕(15%)和腹泻(10%);碳酸锂组最常见的不良事件为恶心(17%)、便秘(13%)和呕吐(13%).碳酸锂组中有3例患者因不良事件而中止研究,其中有1例为严重不良事件;奎硫平组无因不良事件而中止的研究者.结论 奎硫平单药治疗双相障碍急性躁狂有效,且耐受性较好.     

Brief Rating of Aggression by Children and Adolescents (BRACHA): development of a tool for assessing risk of inpatients' aggressive behavior

This study evaluated the Brief Rating of Aggression by Children and Adolescents-Preliminary Version (BRACHA 0.8), an actuarial method of assessing the risk of aggressive behavior by hospitalized children and adolescents. Licensed psychiatric social workers used a 16-item questionnaire to assess all patients seen in the emergency department (ED) of a major urban children's hospital. Over a six-month period, 418 patients (age range, 3.5-19.0 years) underwent psychiatric hospitalization after ED evaluation. The hospital nursing staff recorded the inpatients' behavior, with the Overt Aggression Scale (OAS). Inpatients were deemed aggressive if, during the first six days of their hospital stay, they scored one or higher on any OAS subscale. We evaluated questionnaire properties, items, and demographic covariates (e.g., age, sex, and living situation) by using factor analyses, logistic regression models, and receiver operating characteristic (ROC) methods. A total of 292 aggressive acts were committed by 120 (29% of 418) patients. Fourteen of the 16 items predicted (p < .007) inpatient aggression and showed good internal consistency (Cronbach's α = 0.837). Age was inversely related to probability of aggression and was incorporated into the final assessment instrument. Predictive power was comparable with other published risk assessment instruments (ROC areas of .75 for any aggression and .82 for aggression toward others). BRACHA 0.8 shows promise in rapidly assessing risk of inpatient aggression, but further studies are needed to establish the reliability and validity of the instrument.     

Quetiapine improves psychotic symptoms and cognition in Parkinson's disease.

Twenty-nine elderly patients who failed treatment with clozapine, risperidone, or olanzapine entered this 24-week, single-center, open-label trial to assess the efficacy of quetiapine (12.5-400 mg/day) for psychosis in patients with Parkinson's disease (PD). Psychiatric, motor, and cognitive assessments were administered at baseline and at periodic intervals for 24 weeks. These included the Brief Psychiatric Rating Scale (BPRS), Neuropsychiatric Inventory (NPI), Unified Parkinson's Disease Rating Scale (UPDRS) and tests of intellectual functioning, attention, and memory. Repeated measures statistical analysis was used to assess change from baseline. The results revealed significant improvements in the 24-week BPRS total score and NPI psychosis subscale scores, with no decline in UPDRS total or motor subscale scores. There was also significant improvement in recall scores on cognitive measures. These results indicate that quetiapine may treat psychotic symptoms and improve cognition without worsening motor function in patients with PD, suggesting that quetiapine is an effective and well-tolerated antipsychotic in this population.     

An Independent Investigation Into the Psychometric Properties of the Adult Scale of Hostility and Aggression (A-SHARP)

Background: The Adult Scale of Hostility and Aggression (A-SHARP) rating scale assesses the frequency/severity (problem scale) and the reactive-proactive motivation (provocation scale) of aggressive behaviors in adults with intellectual disabilities (ID). Items are assigned to five subscales (Verbal Aggression, Physical Aggression, Hostile Affect, Covert Aggression, and Bullying). Although psychometric properties reported by the scale’s developers were very good, we wanted to corroborate them independently. We were also interested in whether the reactive-proactive distinction of aggressive behavior is related to a behavioral/functional classification. Method: Staff at a day-treatment program for adults with ID completed ratings for 155 clients using the A-SHARP, the Behavior Problems Inventory-01 (BPI-01), and the Questions about Behavioral Function (QABF). Results: Internal consistency was found to be excellent, and the A-SHARP Physical Aggression subscale had good congruent and clinical validity. Confirmatory factor analysis showed sufficient evidence toward the factorial validity of the A-SHARP’s problem scale. The reactive-proactive classification of aggressive behavior motivation by the A-SHARP’s provocation scale was independent of the functional classification. Conclusions: The A-SHARP is a useful addition to a small number of existing instruments for assessing aggressive behavior in adults with ID, especially its problem scale. We discuss how the A-SHARP provocation scales might provide therapy-relevant information. Empirical evidence for the clinical utility of the A-SHARP provocation scale will have to be established by future research.     

Extended release quetiapine fumarate as adjunct to antidepressant therapy in patients with major depressive disorder: pooled analyses of data in patients with anxious depression versus low levels of anxiety at baseline

Objectives. To evaluate quetiapine XR in patients with anxious depression, as defined by HAM-A total and HAM-D anxiety/somatisation factor scores. Methods. Post hoc analyses of pooled data from two 6-week, double-blind, randomised, placebo-controlled studies of adjunctive quetiapine XR (150 or 300 mg/day) in patients with MDD and inadequate response to antidepressants. Patients were stratified in a primary analysis using HAM-A (HAM-A total score at baseline ≥ 20 [“high”] or < 20 [“low”]) and a secondary analysis using HAM-D (anxious depression defined as HAM-D anxiety/somatisation factor score ≥ 7). Outcomes included change in MADRS total score. Results. In patients with high anxiety levels (HAM-A total score ≥ 20), reductions in MADRS total score were –15.20 (P = 0.122) and –15.92 (P < 0.05) for quetiapine XR 150 and 300 mg/day, respectively, vs. placebo (–13.49). In patients with low levels of anxiety (HAM-A total score < 20), both quetiapine XR doses (P < 0.001) improved MADRS total scores vs. placebo. In the secondary analysis, quetiapine XR 150 (P < 0.01) and 300 mg/day (P < 0.001) improved MADRS total score vs. placebo in patients with HAM-D anxiety/somatisation factor score ≥ 7. Conclusions. Adjunct quetiapine XR demonstrates efficacy in patients with anxious and non-anxious depression, assessed using HAM-A total score, and anxious depression assessed using HAM-D anxiety/somatisation factor score.     

Long-term treatment of adjunctive quetiapine for bipolar mania

This study evaluated the overall effectiveness and tolerability of adjunctive quetiapine as a continuation therapy for the long-term treatment of bipolar mania. Twenty-three patients were enrolled in this study and received quetiapine add-on treatment in combination with their existing or new mood stabilizers. The clinical assessment was carried out using the Young Mania Rating Scale (YMRS), Clinical Global Impression-severity(CGI-s), Hamilton Depression Rating Scale scores-17 item, Simpson-Angus Rating Scale and Barnes Akathisia Rating Scale at the baseline, 1, 4, 12 and 24 weeks. The YMRS and CGI-s decreased significantly from the baseline to the endpoint by 89.7% and 78.3%, respectively (p < 0.0001; p < 0.0001). By the end of the study, 22 patients showed at least 50% improvement in the YMRS score. This study suggests that quetiapine can be used as an adjunct in the long-term treatment of bipolar mania.     

A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression

OBJECTIVE: There is a major unmet need for effective options in the treatment of bipolar depression. METHOD: Five hundred forty-two outpatients with bipolar I (N=360) or II (N=182) disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 8 weeks of quetiapine (600 or 300 mg/day) or placebo. The primary efficacy measure was mean change from baseline to week 8 in the Montgomery-Asberg Depression Rating Scale total score. Additional efficacy assessments included the Hamilton Depression Rating Scale, Clinical Global Impression of severity and improvement, Hamilton Anxiety Rating Scale, Pittsburgh Sleep Quality Index, and Quality of Life Enjoyment and Satisfaction Questionnaire. RESULTS: Quetiapine at either dose demonstrated statistically significant improvement in Montgomery-Asberg Depression Rating Scale total scores compared with placebo from week 1 onward. The proportions of patients meeting response criteria (> or =50% Montgomery-Asberg Depression Rating Scale score improvement) at the final assessment in the groups taking 600 and 300 mg/day of quetiapine were 58.2% and 57.6%, respectively, versus 36.1% for placebo. The proportions of patients meeting remission criteria (Montgomery-Asberg Depression Rating Scale < or =12) were 52.9% in the groups taking 600 and 300 mg/day of quetiapine versus 28.4% for placebo. Quetiapine at 600 and 300 mg/day significantly improved 9 of 10 and 8 of 10 Montgomery-Asberg Depression Rating Scale items, respectively, compared to placebo, including the core symptoms of depression. Treatment-emergent mania rates were low and similar for the quetiapine and placebo groups (3.2% and 3.9%, respectively). CONCLUSIONS: Quetiapine monotherapy is efficacious and well tolerated for the treatment of bipolar depression.     

An open multicentre pilot study examining the safety,efficacy and tolerability of fast titrated (800 mg/day by day 4) quetiapine in the treatment of schizophrenia/schizoaffective disorder

Objective. Rapid dose escalation of quetiapine could offer prompt and effective therapy to patients requiring hospitalization for schizophrenia or schizoaffective disorder. This study evaluated the safety, tolerability, and efficacy of a rapid dose escalation of quetiapine to 800 mg/day over 4 days in patients with severe psychotic symptoms diagnosed as schizophrenia or schizoaffective disorder. Methods. In this open-label, multicenter, pilot study, 14 patients aged 18 years or older, requiring hospitalization for schizophrenia or schizoaffective disorder, received quetiapine orally twice daily for 14 days. Quetiapine was administered according to the schedule: 200, 400, 600, and 800 mg/day on the first four treatment days, followed by flexible dosing within the range 400–800 mg/day during the next 10 days. The primary endpoint was to evaluate the safety and tolerability of a fast titration of quetiapine (200, 400, 600, 800 mg/day on the first four treatment days). Effectiveness of a fast titration of quetiapine was the secondary objective of this investigation. Efficacy assessments in the intent-to-treat (ITT) population included changes in the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Severity of Illness (CGI-S) scores from Day 1 (baseline) to Day 14. Results. In 4 days 14 patients were titrated up to a dose of 800 mg/day. Ten patients were diagnosed with schizophrenia, one subject was suffering from schizoaffective disorder of the depressive type and three patients were diagnosed with schizoaffective disorder of the bipolar type. Eleven patients (79%) completed the study. Two patients discontinued the trial because of non-compliance and one patient because of a prolonged QTcB interval. Overall, 29 AEs were reported during this trial, all were considered mild or moderate in severity. During the first 7 days of the trial, 25 AEs were reported in 11 patients. The majority of AEs were considered as possibly related to the study medication. No deaths or serious adverse events were reported. Physical examination at the last trial visit revealed no clinically relevant changes versus baseline and there were no consistent changes over time in vital signs. The BARS and SAS scores indicated an improvement of EPS during the study. After 4 days of fast titration, the mean total PANSS score decreased from 92.8 at baseline to a value of 87.4, there was a further decrease to 78.2 at endpoint. This corresponds to a statistically significant decrease by 14.6 versus baseline (P<0.01). After 4 days of fast titration, the mean CGI-S score was improved from 4.7 at baseline to a value of 4.3 and improved further to 3.8 at endpoint, corresponding to a statistically significant decrease of 0.9 points versus baseline (P<0.01). Conclusion. In this study, fast titration of quetiapine to 800 mg/day over 4 days was generally well tolerated and effective in reducing psychotic symptoms in patients requiring hospitalization for schizophrenia/schizoaffective disorder.     

Efficacy of olanzapine versus quetiapine on cognitive dysfunctions in patients with an acute episode of schizophrenia

Neurocognitive impairment is a core feature in the pathology of schizophrenia and considered to be relatively persistent towards psychopharmacological interventions. There are hints that atypical antipsychotics can influence neurocognitive dysfunctions more favorable than conventional compounds. But little is known about differences in efficacy on neurocognitive dysfunctions linked to the variety of receptor profiles of different atypical antipsychotics. This study compared the effects of the atypical antipsychotics quetiapine and olanzapine on cognitive function in patients with an acute episode of schizophrenia. Patients were randomized to receive quetiapine or olanzapine for 8 weeks. Cognitive function was assessed at baseline, week 4 and week 8. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Improvement Scale (CGI). Tolerability was assessed each week using the Extrapyramidal Symptom Rating Scale (ESRS), the Barnes Akathisia Scale (BAS) and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU). In total, 52 patients were enrolled in the study. Data from the 33 patients who completed cognitive assessments at two or more time points out of three (baseline, Week 4 and Week 8) are analyzed here. Both quetiapine and olanzapine improved global cognitive index z-scores, however, this was more marked with quetiapine. Between-group comparisons showed significantly greater improvements in reaction quality/attention with quetiapine than olanzapine. Quetiapine and olanzapine produced significant improvements from baseline to week 8 in PANSS total and subscale scores. Both treatments were well tolerated, especially no EPS occurred during 8 weeks of treatment. Both quetiapine and olanzapine improved cognition; however, the improvement in cognitive index scores was more marked in patients receiving quetiapine. Furthermore, quetiapine produced a significantly greater improvement in reaction quality/attention than olanzapine.     

Association of aggressive behavior in Korean male schizophrenic patients with polymorphisms in the serotonin transporter promoter and catecholamine-O-methyltransferase genes

The incidence of aggressive behavior in patients with schizophrenia is higher than in the general population. Among particular gene polymorphisms posited to be involved in psychiatric disorders, the catecholamine-O-methyltransferase (COMT) and serotonin transporter (5-HTTPR) genes have been the focus of recent research on aggression. In this study, we hypothesized that both the COMT and the 5-HTTPR genotypes may be dependent on and related to aggression in Korean patients with schizophrenia. The subjects were 168 unrelated male schizophrenic patients diagnosed according to DSM-IV. Among two psychiatric hospital staff and medical university students, 158 unrelated male subjects with no lifetime history of psychiatric disorders were recruited to establish the COMT and 5-HTTPR genotype distribution in the general population. All episodes of aggression from the last discharge to readmission were rated. The Total Overt Aggression Scale (OAS) score (sum of the scores of all episodes of aggression), highest OAS score (highest individual episode score, 0-16), OAS category, and OAS category score (mean score within each category) were recorded. There were statistically significant effects of COMT genotype on the mean OAS 4 (physical aggression against other people) score and the highest OAS score. The most predictive was the OAS 4 score. There was a statistically significant effect of 5-HTTPR genotype on mean total score. Thus, the COMT gene is associated with the severity of aggression and with physical aggression against other people, whereas the 5-HTTPR gene is associated with the summary score of all episodes of aggression.     

A Naturalistic, Single-blind Comparison of Rapid Dose Administration of Divalproex ER Versus Quetiapine in Patients with Acute Bipolar Mania

Objective: When treating acute bipolar mania, the speed of onset of anti-manic effects is crucial. Quetiapine and divalproex ER are widely used agents to treat acute mania. Rapid dose administration regimens for divalproex ER and for quetiapine have been described. We conducted a naturalistic, head-to-head, pilot study comparing the efficacy and safety of rapidly titrated divalproex ER and quetiapine in acutely manic inpatients, with the primary outcome being improvement within the first seven days.Method: Thirty consenting bipolar patients with acute mania (Young Mania Rating Scale >17 ) needing hospitalization due to acute mania were randomized to receive rapidly loaded divalproex ER (30mg/kg/day) or rapidly titrated quetiapine (200mg Day 1, raised by 200mg/day up to 800mg as tolerated). Assessments were made on Day 1 (baseline), Day 3, Day 7, Day 14, and Day 21 and included Young Mania Rating Scale, Clinical Global Impressions-Severity, Clinical Global Impressions-Improvement, and Montgomery-Asberg Depression Rating Scale. Raters but not patients or treating physicians were blinded (single-blinded study).Results: Subjects in both treatment groups exhibited significant and rapid improvement in their mania starting at Day 3 with few significant adverse effects; however, there were no significant differences in the degree or rate of improvement between the two treatment groups in any of the efficacy or adverse effects scales.Conclusion: Results of this small study indicate that rapid-dose administration of both quetiapine and divalproex ER produce rapid improvement in acute mania within the first seven days and both seem to be well tolerated.     

氟哌啶醇治疗精神分裂症的增效作用

目的:评价奎硫平合并氟哌啶醇治疗精神分裂症的疗效与不良反应。方法:对110例单纯口服奎硫平的精神分裂症患者疗效不佳者合并氟哌啶醇治疗12周。用阳性症状和阴性症状量表(PANSS)评定疗效,用UKU不良反应评定量表评定不良反应。结果:治疗12周末PANSS量表总分及各分量表评分较治疗前均有显著下降(P<0.05或P<0.01);有效率达71.82%;不良反应无明显增加(P>0.05)。结论:奎硫平合并氟哌啶醇治疗精神分裂症疗效肯定,不良反应较轻。     

A randomized controlled trial of quetiapine versus placebo in the treatment of delirium

Background

Delirium is a commonly occurring complex neuropsychiatric disorder. Evidence for its treatment based on randomized controlled trials (RCTs) is poor.

Aims

To determine the efficacy and acceptability of quetiapine in the treatment of delirium.

Method

A double-blind, RCT was conducted. A total of 42 patients were randomized to quetiapine or a placebo group. The primary outcome measure was the Delirium Rating Scale Revised 98. Other scales used were the Brief Psychiatric Rating Scale, Mini-Mental State Examination and Clinical Global Improvement. In order to account for missing data, a nonlinear mixed-effects model was used to estimate the difference between the two groups.

Results

The quetiapine group improved more rapidly than the placebo group. Specifically, the quetiapine group recovered 82.7% faster (S.E. 37.1%, P=.026) than the placebo group in terms of DRS-R-98 severity score. In terms of the DRS-R-98 noncognitive subscale, the quetiapine group improved 57.7% faster (S.E. 29.2%, P=.048) than the placebo group.

Conclusions

Quetiapine has the potential to more quickly reduce the severity of noncognitive aspects of delirium. This study was underpowered for treatment comparisons at specific points in time but nonetheless detected significant differences when analyzing the whole study period. While it is not possible to draw definitive conclusions, further larger studies exploring the use of quetiapine in other delirium populations seem justified. Larger increments in the dose of quetiapine may yield even stronger results.     

Responses to antipsychotic therapy among patients with schizophrenia or schizoaffective disorder and either predominant or prominent negative symptoms

Patients with schizophrenia who have predominant negative symptoms are often considered less responsive to treatment. This analysis of patients with schizophrenia or schizoaffective disorder compares changes in symptom severity between those with predominant versus merely prominent negative symptoms. Prominent negative symptoms were defined by a baseline score of ≥4 on at least 3, or ≥5 on at least 2, of the 7 Positive and Negative Syndrome Scale (PANSS) negative subscale items. Predominant negative symptoms were defined by the foregoing plus a PANSS positive score of <19, a Barnes Akathisia score of <2, a Simpson-Angus score of <4, and a Calgary Depressive Scale score of <9. Adult patients with schizophrenia (n=227) or schizoaffective disorder (n=116) received either olanzapine (10-20mg/day, n=169) or quetiapine (300-700mg/day, n=174) for up to 24weeks. Data for both medications were pooled. Of the 343 patients enrolled in the study, 34.7% met the criteria for predominant negative symptoms, the remaining 65.3% being characterized only by their prominent negative symptoms. Changes in the severity of negative symptoms in both patient types largely followed similar trajectories during treatment, as reflected both in Marder PANSS negative subscale scores and in the Scale for Assessment of Negative Symptoms total and domain scores. Patients with either predominant or prominent negative symptoms therefore appear to respond similarly to atypical antipsychotic treatment. This distinction, incorporating an evaluation of the presence of positive, affective, and extrapyramidal symptoms, may therefore not have prognostic implications for the responsiveness of patients' negative symptoms to treatment.     

Efficacy and tolerability of extended release quetiapine fumarate monotherapy as maintenance treatment of major depressive disorder: a randomized,placebo‐controlled trial

Background: Primary objective: evaluate the efficacy (time to recurrence of depressive symptoms) of once daily extended release quetiapine fumarate (quetiapine XR) as maintenance monotherapy treatment to prevent relapse for major depressive disorder (MDD). Methods: Time‐to‐event (maximum 52 weeks), double‐blind, multicenter, randomized withdrawal, placebo‐controlled study of quetiapine XR (50–300 mg/day) comprising four treatment phases: enrollment (up to 28 days), open‐label run‐in (4–8 weeks), open‐label stabilization (12–18 weeks), and randomization (up to 52 weeks). Seven hundred and seventy‐six patients stabilized on quetiapine XR were eligible for randomization (Montgomery–Åsberg Depression Rating Scale [MADRS] score ≤12 and Clinical Global Impression‐Severity of Illness [CGI‐S] score ≤3); 391 received quetiapine XR and 385 received placebo (same dose as last open‐label visit). Primary endpoint: time to recurrence of depressive event from randomization. Secondary outcomes included changes from randomization in MADRS total, CGI‐S, Pittsburgh Sleep Quality Index (PSQI) global, and Hamilton Anxiety Rating Scale (HAM‐A) total scores. Adverse events were recorded throughout. Results: Risk of recurrence of depressive event was significantly (P<.001) reduced by 66% (HR=.34; 95% CI: .25, .46) in patients randomized to continue with quetiapine XR versus patients randomized to switch to placebo. During the randomized phase, quetiapine XR maintained improvements in secondary outcomes (P<.001 for all): MADRS (0.15 versus 2.03), CGI‐S (−0.03 versus 0.23); PSQI global (0.06 versus 1.35), and HAM‐A total score (0.20 versus 1.58), respectively. The most common AEs (>10% any group) during the randomized period were headache and insomnia. Conclusions: Quetiapine XR maintenance therapy significantly reduced the risk of a depressive event in patients with MDD stabilized on quetiapine XR, with a safety and tolerability profile consistent with the known profile of quetiapine. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

Reliability and validity of the Norwegian version of the Brief Agitation Rating Scale (BARS) in dementia

Objective: To examine the test–retest reliability and validity of the Norwegian Brief Agitation Rating Scale (BARS), a short form of the Cohen-Mansfield Agitation Inventory (CMAI) assessing the frequency of agitation in dementia.

Methods: We investigated the internal consistency, test–retest reliability and the validity of BARS. In the validity study, we compared the BARS scores with the Neuropsychiatric Inventory – Nursing Home Version subscale Agitation/Aggression (NPI-NH/AA) and the Cornell Scale for Depression in Dementia subscale Agitation (CSDD/A).

Results: In the reliability study, Cronbach's alpha was 0.76; the test–retest reliability of the BARS showed a Spearman's rho of 0.64, but this increased to 0.86 when we deleted the item ‘complaining’. In the validation study, the BARS score correlated with the NPI-NH/AA and the CSDD/A scores, Spearman's rho 0.55 and 0.52, respectively. These correlations changed when controlling for the Clinical Dementia Rating (CDR) Scale stages. The highest correlations between the BARS and the NPI-NH/AA and the BARS and the CSDD/A were found among patients with CDR score 2.

Conclusions: The study indicates that the Norwegian version of BARS is a reliable and valid instrument to test agitation in dementia, but a version without the item ‘complaining’ would be better.