Quetiapine Group Research Articles

Anti-inflammatory effect of quetiapine on collagen-induced arthritis of mouse

Quetiapine is an atypical antipsychotic and has also been used in the treatment of depression. Since anti-inflammatory effects of antidepressants are well established, we hypothesized that quetiapine may also exert anti-inflammatory effects. Thus this study was designed to examine the anti-inflammatory effect of quetiapine in murine collagen-induced arthritis. Mice were immunized with collagen type II for the induction of arthritis and treated with quetiapine (10mg/kg) daily for 2weeks. Mice were divided into 3 groups: control, CIA, and CIA+quetiapine treatment. Arthritic index and paw thickness were used to compare severity of arthritis. In additions, radiological and histological assessments were employed. Anti-type II collagen-specific antibody, interleukin-6 (IL-6), interleukin-17 (IL-17), and prostaglandin E2 (PGE2) were evaluated at the end of the treatment period. Both arthritic index and paw thickness were markedly improved in CIA+quetiapine treatment group compared with those in CIA groups (arthritic index; P<0.01, paw thickness; P<0.05). Radiologic assessment revealed decreased cartilage damage and bone erosion in CIA+quetiapine treatment group compared with those in CIA groups. Articular cartilage destruction observed in CIA group was not found in CIA+quetiapine group. The concentrations of anti-type II collagen-specific antibody, IL-6, IL-17, and PGE2 in CIA+quetiapine group were significantly lower than those in CIA groups (P<0.05). Weight gain which is commonly observed with the treatment of antipsychotics was not observed. Taken together, these results suggest that quetiapine shows anti-inflammatory effects in murine collagen-induced arthritis.

Neurocognitive effectiveness of quetiapine, olanzapine, risperidone, and ziprasidone: A pragmatic, randomized trial

PurposeCognitive effects of second generation antipsychotics (SGAs) are indicated in efficacy studies but the generalizability of the results may be limited by rigid designs and selected samples. The aim of this naturalistic, industry-independent study is to investigate whether differential neurocognitive effectiveness can be found among olanzapine, quetiapine, risperidone, and ziprasidone in a clinically relevant sample with psychosis. Subjects and methodsAdult patients acutely admitted to an emergency ward for psychosis were randomized to risperidone, olanzapine, quetiapine or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale and a repeatable neurocognitive test battery. ResultsA total of 226 patients were included and 171 patients underwent neurocognitive assessments. The sample had a global cognitive performance score at baseline about one standard deviation below that of the general population. The ziprasidone group had the fastest increase in global functioning which was significantly superior to that of the olanzapine group for the entire follow-up period. Before 90 days, the quetiapine group had the fastest increase which was statistically superior to the olanzapine group. DiscussionZiprasidone and quetiapine demonstrated superiority to olanzapine in increasing global neurocognitive performance in this naturalistic sample.

Extent of attaining and maintaining symptom remission by antipsychotic medication in the treatment of chronic schizophrenia: Evidence from the CATIE study

BackgroundData on attaining and maintaining symptom remission associated with specific antipsychotic medications are rare and variant. AimsTo examine remission rates and their variation by antipsychotic medication in chronic schizophrenia in the National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) given it has an 18-month duration and representative antipsychotic medications. MethodsSymptom remission was examined using the Remission in Schizophrenia Working Group remission criteria of attaining and maintaining for 6months with mild ratings on 8 specific Positive and Negative Syndrome Scale (PANSS) items. Remission rates were assessed (a) up to 18months across CATIE's switching phases (n=1332); and (b) in phase 1 (that involved double-blind randomization to one of five antipsychotic medications) to compare antipsychotic medication differences in attaining and maintaining remission among patients not in remission at baseline (n=941). ResultsAt baseline 16.2% of patients were in symptomatic remission. Across the medication phases of CATIE only 11.7% attained and then maintained at least 6months of symptomatic remission, and 55.5% (n=623) experienced no symptom remission at any visit. During the first medication randomization phase, attaining and maintaining remission for 6months was highest for the olanzapine (12.4%) medication group followed by the quetiapine (8.2%), perphenazine (6.8%), ziprasidone (6.5%), and risperidone (6.3%) groups. ConclusionsAs currently defined, remission appears to be a very difficult therapeutic target to attain and maintain in chronic schizophrenia and may differ by antipsychotic medication. Pragmatically, remission gradients may be effectively studied by applying modified duration and symptom criteria.

A Double‐Blind, Placebo‐Controlled Trial to Assess the Efficacy of Quetiapine Fumarate XR in Very Heavy‐Drinking Alcohol‐Dependent Patients

Despite advances in developing medications to treat alcohol dependence, few such medications have been approved by the Food and Drug Administration. Identified molecular targets are encouraging and can lead to the development and testing of new compounds. Atypical antipsychotic medications have been explored with varying results. Prior research suggests that the antipsychotic quetiapine may be beneficial in an alcohol-dependent population of very heavy drinkers. In this double-blind, placebo-controlled trial, 224 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either quetiapine or placebo and Medical Management behavioral intervention. Patients were stratified on gender, clinical site, and reduction in drinking prior to randomization. No differences between the quetiapine and placebo groups were detected in the primary outcome, percentage heavy-drinking days, or other drinking outcomes. Quetiapine significantly reduced depressive symptoms and improved sleep but had no effect on other nondrinking outcomes. Results from a subgroup analysis suggest that patients who reduced their drinking prior to randomization had significantly better drinking outcomes during the maintenance phase (p < 0.0001). No significant interactions, however, were observed between reducer status and treatment group. Finally, quetiapine was generally well tolerated. Statistically significant adverse events that were more common with quetiapine versus placebo include dizziness (14 vs. 4%), dry mouth (32 vs. 9%), dyspepsia (13 vs. 2%), increased appetite (11 vs. 1%), sedation (15 vs. 3%), and somnolence (34 vs. 9%). This multisite clinical trial showed no efficacy for quetiapine compared with placebo at reducing alcohol consumption in heavy-drinking alcohol-dependent patients.

Neurocognitive effects of first- and second-generation antipsychotic drugs in early-stage schizophrenia: A naturalistic 12-month follow-up study

The study aimed to assess the cognitive effects of first- and second-generation antipsychotics on neurocognition under naturalistic treatment conditions. In a 12-month, open-label, multicenter study, 698 patients with early-stage schizophrenia (duration of illness ≤5 years) were prescribed chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine, or aripiprazole monotherapy. A neuropsychological battery including tests of attention, processing speed, learning/memory, and executive functioning was administered at baseline, 6- and 12-months. The primary outcome was change in a cognitive composite score after 12-months of treatment. At 12 months, treatment resulted in mild to moderate neurocognitive improvements of z = 0.32 for chlorpromazine, 0.33 for sulpiride, 0.43 for clozapine, 0.51 for risperidone, 0.69 for olanzapine, 0.64 for quetiapine and 0.46 for aripiprazole. However, the olanzapine and quetiapine groups demonstrated greater improvement in the composite score and processing speed than did the chlorpromazine and sulpiride groups. Both first- and second-generation antipsychotics may improve cognitive function in patients with early-stage schizophrenia. Given that some neurocognitive improvement is attributable to a practice effect, any improvement is likely to be in the range of a small effect size.

Metabolic Effects of Olanzapine and Quetiapine: A Six-Week Randomized, Single Blind, Controlled Study

The objective of this study is to compare the course of metabolic effects of olanzapine and quetiapine, two atypical antipsychotics with similar structure and receptor binding affinities but clinically observed different metabolic ef- fects. This 6 week, single blind, randomized, controlled study was carried out during a structured treatment protocol in a female inpatient service, thus enabled to control effects of energy expenditure and other life style related factors. Subjects were randomly assigned into olanzapine (n=15) and quetiapine (n=15) groups. Weight and calorie intake (CI) were meas- ured daily. Symptom severity and serum leptin levels (SLL) were measured biweekly. Serum lipids were measured at baseline and 6th week. Olanzapine treatment was associated with more severe weight gain (F=11.2, p<0.01), increase in CI (F=8.1, p<0.01) and a more disturbed lipid profile than quetiapine. The course of SLL were similar between the groups (F=1.39, p=0.26). Weight, CI and SLL changed in a similar pattern within the groups but the patterns were different for each drug, suggesting that the two drugs have different mechanisms for weight change. The explanation probably involves different affinities for 5HT2C receptors leading to different patterns of CI which we propose as possible targets of inter- vention to manage antipsychotic induced weight gain.

Augmentative quetiapine in partial/nonresponders with generalized anxiety disorder

Generalized anxiety disorder (GAD) is a chronic and disabling condition. The aim of this study was to evaluate the effectiveness of low-dose augmentative quetiapine (mean dose=50 mg/day) in patients with GAD and partial/no response to selective serotonin reuptake inhibitors (SSRIs). Twenty patients with GAD and partial/no response to SSRIs were randomized to quetiapine (n=10) or placebo (n=10) for 8 weeks, continuing their treatment with SSRIs. Analyses of variance with repeated measures on Hamilton Anxiety Rating Scale (HAM-A) and Clinical Global Impression (CGIs; severity of illness) were carried out at baseline and after 8 weeks and the number of responders/remitters was computed and compared between the groups. HAM-A scores at baseline were 15.60 (± 4.48) in the placebo group and 18.50 (± 6.59) in the quetiapine group, and at the end-point, HAM-A scores in the placebo group were 10.40 (± 4.88) and 9.20 (± 5.86) in the quetiapine group. A significant time-by-treatment effect was found on the HAM-A (F=5.19, P=0.035) and CGIs scores (F=19.60, P<0.001) in favor of the quetiapine group. The number of responders was numerically superior in the quetiapine group (60 vs. 30%) without reaching statistical significance (χ=1.82, degree of freedom=1, P=0.37, φ=0.30). Remitters were 40% for the quetiapine group versus 20% for the placebo group (χ=0.95, degree of freedom=1, P=0.63, φ=0.22). Low-dose augmentative quetiapine may be an useful treatment option for patients with GAD and partial/no response to SSRIs. The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results. Larger randomized controlled trials are warranted to confirm these data.

P01-113 - Quetiapine for the treatment of cocaine dependence

BackgroundCocaine abuse continues to be epidemic, and yet there are no FDA approved medications for the treatment of cocaine use disorders. A previous pilot study conducted by this author suggested that quetiapine may help reduce the cravings for cocaine in 22 individuals with cocaine dependence.MethodsThis 12-week, prospective, intent-to-treat, double-blind, randomized, placebo-controlled study examined the effectiveness of quetiapine (Seroquel SR™) versus matched placebo for the treatment of cocaine dependence in non-psychotic individuals. Sixty individuals with a diagnosis of cocaine dependence were randomized in this study, 29 into the quetiapine arm, and 31 into the placebo arm. Those who were randomized to quetiapine were titrated up to a target dose of 400 mg/day of quetiapine, while those on the placebo arm were given a matched placebo. All subjects had weekly clinic visits for a cognitive-behavioral therapy group session. Outcome measures included questionnaires of cocaine use, cravings for cocaine, and urine drug screen.ResultsInitial analyses indicate that the intensity, frequency, and length of cocaine cravings were reduced over 6 weeks in both the quetiapine and placebo groups. All hazard analyses indicated that the total money spent on cocaine also decreased in both groups, with a trend toward greater decrements in cocaine use the longer they remained in the study. Data analyses are ongoing to determine the potential effect of quetiapine on treatment of cocaine addiction.ConclusionsConclusions regarding the use of quetiapine as a treatment for cocaine dependence will be discussed.

Second-generation antipsychotics for anxiety disorders

Anxiety disorders are common and disabling conditions, with a lifetime prevalence of 17% in the general population. Due to high rates of treatment resistance, there is interest in new pharmacological treatment options such as second-generation antipsychotics. To evaluate the efficacy and tolerability of second-generation antipsychotics as monotherapy or adjunctive treatment for people with anxiety disorders. The Cochrane Depression, Anxiety and Neurosis Group's controlled trial registers (CCDANCTR-Studies and CCDANCTR-References) were searched up to 21 July 2010. The author team ran complementary searches on ClinicalTrials.gov. We included all randomised trials (RCTs) comparing second-generation antipsychotic drugs with placebo, benzodiazepines, pregabalin or antidepressants. Participants were people with generalised anxiety disorder, panic disorder and specific phobias including social phobia. Two authors extracted data independently. For dichotomous data we calculated odds ratios (OR) and their 95% confidence intervals (CI). For continuous data we calculated mean differences (MD) based on a random-effects model. The review currently includes eleven RCTs with 4144 participants on three second-generation antipsychotics (olanzapine, quetiapine, risperidone). Nine studies investigated the effects of second-generation antipsychotics in generalised anxiety disorder, only two studies investigated the effects in social phobia. There were no studies on panic disorder or any other primary anxiety disorder.Seven studies investigated the effects of quetiapine. Participants with generalised anxiety disorder responded significantly better to quetiapine than to placebo (4 RCTs, N = 2265, OR = 2.21, 95% CI 1.10 to 4.45). However, they were more likely to drop out due to adverse events, to gain weight, to suffer from sedation or to suffer from extrapyramidal side effects. When quetiapine was compared with antidepressants, there was no significant difference in efficacy-related outcomes, but more participants in the quetiapine groups dropped out due to adverse events, gained weight and feeling sedated. Only two very small studies with a total of 36 participants examined olanzapine and found no difference in response to treatment. Two trials compared adjunctive treatment with risperidone with placebo and found no difference in response to treatment. We identified eligible trials on quetiapine, risperidone and olanzapine. The available data on olanzapine and risperidone are too limited to draw any conclusions. Monotherapy with quetiapine seems to be efficacious in reducing symptoms of generalised anxiety disorder and this effect may be similar to that of antidepressants. However, quetiapine's efficacy must be weighed against its lower tolerability.

Comparative study of aripiprazole and quetiapine on treatment of schizophrenia

Objective To compare efficacy and safety of aripiprazole and quetiapine on the treatment of schizophrenia. Methods 142 patients with first episode schizophrenia were randomly divided into aripiprazole groupor quetiapine group. Positive and negative symptom scale (PANSS) and treatment emergent symptom cale (TESS) were used to evaluate the efficacy and adverse events of drugs before and after 2,4,8 weeks of treatments. Results The therapeutic efficacy in aripiprazole group was similar to that in quetiapine, the curative effectiveness of aripiprazole was 81.69%, and the curative effectiveness of quetiapine was 78.87%, there was no significant different between the two groups(P ＞ 0. 05 ). The side effects of aripiprazole is less than that of quetiapine, there was significant different between the two groups (P ＜ 0. 05 ). Conclusion Aripiprazole is one of effective and safe drugs in the treatment of schizophrenia. Key words: Schizophrenia; Aripizole; Quetiapine

A Double‐Blind, Placebo‐Controlled Study With Quetiapine as Adjunct Therapy With Lithium or Divalproex in Bipolar I Patients With Coexisting Alcohol Dependence

This study evaluated the efficacy of quetiapine versus placebo as an adjunct to lithium or divalproex in reducing alcohol consumption in patients with bipolar I disorder and coexisting alcohol dependence. Male and female outpatients (21 to 60 years) with a history of bipolar I disorder and alcohol dependence were included in this 12-week, placebo-controlled study. Patients treated with lithium or divalproex (ongoing or assigned at screening) were randomized to receive quetiapine (dosed up to 400 mg/d over 7 days, followed by 300 to 800 mg/d flexible dosing until study end) or placebo. The primary outcome measure was the change in the proportion of heavy drinking days from baseline to Week 12 (as derived from the Timeline Followback method). Secondary outcome measures included time to the first consecutive 2 weeks of abstinence, changes from baseline to Week 12 in the proportion of nondrinking days, mean number of standardized drinks per day, and Clinical Global Impressions-Severity of Illness score. Of 362 enrolled patients (mean 38.6 years), 176 were randomized to receive quetiapine and 186 to placebo. The mean proportion of heavy drinking days at baseline was 0.66 in the quetiapine group and 0.67 in the placebo group. At Week 12, the mean change in the proportion of heavy drinking days was -0.36 with quetiapine and -0.36 with placebo (p = 0.93). No statistically significant differences in any of the secondary outcome measures were noted between the quetiapine and placebo groups. The incidence of adverse events was consistent with the previously known tolerability profile of quetiapine. The efficacy of quetiapine in the treatment of bipolar disorder is already well established. In this study, however, quetiapine added to lithium or divalproex did not result in significantly greater improvement compared with placebo in measures of alcohol use and dependence in patients with bipolar I disorder and alcohol dependence.

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.

Prazosin Versus Quetiapine for Nighttime Posttraumatic Stress Disorder Symptoms in Veterans

Posttraumatic stress disorder (PTSD) is an anxiety disorder experienced by combat veterans. Nighttime symptoms are often unrelieved by selective serotonin reuptake inhibitor therapy, and increased use of prazosin or quetiapine for treatment is seen. The purpose of this study was to determine the short- and long-term effectiveness and safety of prazosin versus quetiapine for treating nighttime symptoms in veteran PTSD patients. This is a historical prospective cohort study using retrospective chart review. Three hundred twenty-four patients with a diagnosis of PTSD, based on International Classification of Diseases, Ninth Revision coding, who were initially prescribed prazosin or quetiapine for nighttime symptoms were screened for inclusion. Short-term effectiveness was determined by documentation of symptomatic improvement within 6 months, and long-term effectiveness if patients continued therapy to study end date. Safety was assessed by comparing incidence of adverse drug effects causing discontinuation of either study drug. This study included 237 patients: 62 received prazosin, and 175 received quetiapine. Short-term effectiveness was similar for prazosin (61.3%) and quetiapine (61.7%; P = 0.54). However, patients prescribed prazosin were significantly more likely to continue their therapy to study end date compared with quetiapine (48.4% vs 24%; P < 0.001; odds ratio, 3.0; 95% confidence interval, 1.62-5.45), thus achieving long-term effectiveness. Alternatively, patients in the quetiapine group were more likely to discontinue therapy because of adverse effects compared with the prazosin group (34.9% vs 17.7%; P = 0.008). Because of similar rate of short-term effectiveness, superior long-term effectiveness, and lower incidence of events leading to discontinuation, compared with quetiapine, prazosin should be used first-line for treating nighttime PTSD symptoms in a veteran population.

Olanzapine versus other atypical antipsychotics for schizophrenia.

In many countries of the industrialised world second generation ("atypical") antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO.2. Reference searching We inspected the reference of all identified studies for more trials.3. Personal contact We contacted the first author of each included study for missing information.4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole, clozapine, quetiapine, risperidone or ziprasidone). The overall attrition from the included studies was considerable (49.2%) leaving the interpretation of results problematic.Olanzapine improved the general mental state (PANSS total score) more than aripiprazole (2 RCTs, n=794, WMD -4.96 CI -8.06 to -1.85), quetiapine (10 RCTs, n=1449, WMD -3.66 CI -5.39 to -1.93), risperidone (15 RCTs, n=2390, WMD -1.94 CI -3.31 to -0.58) and ziprasidone (4 RCTs, n=1291, WMD -8.32 CI -10.99 to -5.64), but not more than amisulpride or clozapine. This somewhat better efficacy was confirmed by fewer participants in the olanzapine groups leaving the studies early due to inefficacy of treatment compared to quetiapine (8 RCTs, n=1563, RR 0.56 CI 0.44 to 0.70, NNT 11 CI 6 to 50), risperidone (14 RCTs, n=2744, RR 0.78 CI 0.62 to 0.98, NNT 50 CI 17 to 100) and ziprasidone (5 RCTs, n=1937, RR 0.64 CI 0.51 to 0.79, NNT 17, CI 11 to 33).Fewer participants in the olanzapine group than in the quetiapine (2 RCTs, n=876, RR 0.56 CI 0.41 to 0.77, NNT 11 CI 7 to 25) and ziprasidone (2 RCTs, n=766, RR 0.65 CI 0.45 to 0.93, NNT 17 CI 9 to 100) treatment groups, but not in the clozapine group (1 RCT, n=980, RR 1.28 CI 1.02 to 1.61, NNH not estimable), had to be re-hospitalised in the trials.Except for clozapine, all comparators induced less weight gain than olanzapine (olanzapine compared to amisulpride: 3 RCTs, n=671, WMD 2.11kg CI 1.29kg to 2.94kg; aripiprazole: 1 RCT, n=90, WMD 5.60kg CI 2.15kg to 9.05kg; quetiapine: 7 RCTs, n=1173, WMD 2.68kg CI 1.10kg to 4.26kg; risperidone: 13 RCTs, n=2116, WMD 2.61kg CI 1.48kg to 3.74kg; ziprasidone: 5 RCTs, n=1659, WMD 3.82kg CI 2.96kg to 4.69kg). Associated problems such as glucose and cholesterol increase were usually also more frequent in the olanzapine group.Other differences in adverse effects were less well documented. Nevertheless, olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine (use of antiparkinson medication (6 RCTs, n=1090, RR 2.05 CI 1.26 to 3.32, NNH 25 CI 14 to 100), but less than risperidone (use of antiparkinson medication 13 RCTs, n=2599, RR 0.78 CI 0.65 to 0.95, NNH 17 CI 9 to 100) and ziprasidone (use of antiparkinson medication 4 RCTs, n=1732, RR 0.70 CI 0.50 to 0.97, NNH not estimable). It may also increase prolactin somewhat more than aripiprazole, clozapine and quetiapine, but clearly less so than risperidone (6 RCTs, n=1291, WMD -22.84 CI -27.98 to -17.69). Olanzapine may be a somewhat more efficacious drug than some other second generation antipsychotic drugs. This small superiority in efficacy needs to be weighed against a larger weight gain and associated metabolic problems than most other second generation antipsychotic drugs, except clozapine. These conclusions are tentative due to the large number of people leaving the studies early which possibly limits the validity of the findings. Further large, well-designed trials are necessary to establish the relative effects of different second generation antipsychotic drugs.

Factors associated with achieving minimally symptomatic status by patients with schizophrenia: results from the 3-year intercontinental schizophrenia outpatients health outcomes study

The aim of this study was to describe factors associated with achieving a minimally symptomatic status outcome in outpatients with schizophrenia. Data were analysed from a 3-year, prospective observational study that examined outcomes in 7658 patients with schizophrenia. Minimally symptomatic status was defined as a postbaseline score of 1 or 2 on the Clinical Global Impressions Severity Scale-Schizophrenia version (CGI-SCH). Baseline CGI-SCH score had the strongest association with minimally symptomatic status followed by age, geographical region and hospitalisation status. The probability of becoming minimally symptomatic was consistently higher in the olanzapine and risperidone monotherapy groups compared with the clozapine, quetiapine or haloperidol groups [corrected]. The olanzapine group achieved the minimally symptomatic status in a shorter period of time than the other treatment groups (p < or = 0.016). The likelihood of patients achieving a minimally symptomatic status was greater in younger patients with lower baseline clinical severity and in patients whose treatment included olanzapine.

Assuring That Double-Blind Is Blind

Assuring That Double-Blind Is Blind

A Pilot Study of Quetiapine in Patients With Bipolar Disorder and Cocaine Dependence

Bipolar disorder is associated with high rates of substance use disorders. However, few treatment trials are reported in this population. The goal of this pilot study was to obtain randomized, placebo-controlled data on quetiapine in bipolar disorder and cocaine dependence. Twelve outpatients with bipolar disorder and cocaine dependence were randomized to 12 weeks of quetiapine or placebo as add-on therapy. Participants were titrated within one week to 400 mg/day with flexible titration to a maximum of 800 mg/day. Cocaine and other substance use, craving, mood symptoms, and safety/tolerability were assessed. No significant between-group differences were observed in cocaine use or craving. The quetiapine group had significantly fewer heavy drinking days than the placebo group and showed a trend toward longer treatment retention. Significant between-group differences in mood measures were not observed, although differences in depression scores, favoring quetiapine, showed a large effect size. Other than constipation, which was more common with quetiapine, side effects did not show significant between-group differences. Quetiapine was not associated with reduction in cocaine use, but was associated with reduction in alcohol use and longer time in treatment and was generally well-tolerated. Larger trials of quetiapine in dual diagnosis patients seem warranted.

Efficacy and safety of quetiapine in critically ill patients with delirium: A prospective, multicenter, randomized, double-blind, placebo-controlled pilot study*

To compare the efficacy and safety of scheduled quetiapine to placebo for the treatment of delirium in critically ill patients requiring as-needed haloperidol. Prospective, randomized, double-blind, placebo-controlled study. Three academic medical centers. Thirty-six adult intensive care unit patients with delirium (Intensive Care Delirium Screening Checklist score > or = 4), tolerating enteral nutrition, and without a complicating neurologic condition. Patients were randomized to receive quetiapine 50 mg every 12 hrs or placebo. Quetiapine was increased every 24 hrs (50 to 100 to 150 to 200 mg every 12 hrs) if more than one dose of haloperidol was given in the previous 24 hrs. Study drug was continued until the intensive care unit team discontinued it because of delirium resolution, therapy > or = 10 days, or intensive care unit discharge. Baseline characteristics were similar between the quetiapine (n = 18) and placebo (n = 18) groups. Quetiapine was associated with a shorter time to first resolution of delirium [1.0 (interquartile range [IQR], 0.5-3.0) vs. 4.5 days (IQR, 2.0-7.0; p =.001)], a reduced duration of delirium [36 (IQR, 12-87) vs. 120 hrs (IQR, 60-195; p =.006)], and less agitation (Sedation-Agitation Scale score > or = 5) [6 (IQR, 0-38) vs. 36 hrs (IQR, 11-66; p =.02)]. Whereas mortality (11% quetiapine vs. 17%) and intensive care unit length of stay (16 quetiapine vs. 16 days) were similar, subjects treated with quetiapine were more likely to be discharged home or to rehabilitation (89% quetiapine vs. 56%; p =.06). Subjects treated with quetiapine required fewer days of as-needed haloperidol [3 [(IQR, 2-4)] vs. 4 days (IQR, 3-8; p = .05)]. Whereas the incidence of QTc prolongation and extrapyramidal symptoms was similar between groups, more somnolence was observed with quetiapine (22% vs. 11%; p = .66). Quetiapine added to as-needed haloperidol results in faster delirium resolution, less agitation, and a greater rate of transfer to home or rehabilitation. Future studies should evaluate the effect of quetiapine on mortality, resource utilization, post-intensive care unit cognition, and dependency after discharge in a broader group of patients.

The effects of quetiapine and aripiprazole on platelet 5-HT concentrations in patients with schizophrenia

Objective To study the effects caused by novel antipsychotics quetiapine and aripiprazole on concentrations of platelet 5-HT in patients with schizophrenia,and to explore the relationships among the change of platelet 5-HT concentrations, psychiatric symptoms and the sensitivity of therapy. Methods Sixty-eight patients with schizophrenia meeting International Classification of Diseases-10 (ICD-10) were enrolled in the study. They were divided into quetiapine group(n=34) and aripiprazole group(n=34) according to the sequence of admis-sion. The platelet 5-HT concentrations were measured with high performance liquid chromatography method(HPLC-ECD). The positive and negative syndrome scale (PANSS) was used to evaluate the psychopathology. Treatment emergent symptom scale (TESS) was used to evaluate the side effects. PANSS,TESS were used at pre-treatment,the end of 4th and 8th week of treatment. Results The platelet 5-HT concentrations in two groups were higher af-ter 8 weeks treatment,but had no statistically significant difference (P>0.05). In quetiapine group, the platelet 5-HT concentration was (458.89±233.36) ng/10~9 at the pre-treatment, and (554.31±313.22) ng/10~9 at the end of treatment (t=1.709, P=0.099). In aripiprazole group, the platelet 5-HT concentration was (409.83±149.32)ng/10~9 at the pretreatment, and (421.27±245.96)ng/10~9 at the end of treatment (t=0.321, P=0.819). There was no difference between two groups(P>0.05). Stepwise regression analysis showed the changing rate of platelet 5-HT concentrations was positively correlated with the dosage of quetiapine (r=0.385, P=0.039).It was positively correlated with the decreasing rate of PANSS in aripiprazole group(r=0.391, P=0.040). Con-dusion The changes of psychiatric symptoms and the dosages of antipsychotics maybe have intimate relationships with platelet 5-HT concentrations in the course of medication. Key words: Schizophrenia ; Quetiapine ; Aripiprazole ;

Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial

Objective To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment.Design 12 month...