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At least 19 recordsLinked to original sources
PubMed1997

Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group.

BACKGROUND: Quetiapine fumarate (Seroquel [ICI 204,636]) is an atypical dibenzothiazepine antipsychotic with a greater affinity for 5-hydroxytryptamine2 (5-HT2) receptors than for D2 dopamine receptors; its efficacy in patients with schizophrenia was shown in early phase 2 trials (maximum dose, 750 mg/d). METHODS: In this multicenter, double-blind, placebo-controlled trial, 286 patients hospitalized with chronic or subchronic schizophrenia (DSM-III-R) were randomized to 6 weeks of treatment with high-dose quetiapine fumarate (< or = 750 mg/d), n = 96; low-dose quetiapine fumarate (< or = 250 mg/d), n = 94; or placebo, n = 96. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Severity of Illness item scores were the primary efficacy variables. Secondary efficacy variables included the BPRS positive-symptom cluster score, the Modified Scale for the Assessment of Negative Symptoms summary score (United States only), and the total score from the negative scale of the Positive and Negative Syndrome Scale (Europe only). Scores were analyzed using an analysis of covariance for change from baseline at end point with last observations carried forward. The model included baseline score (covariate), center, and treatment. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale and the Barnes Akathisia Scale; abnormal involuntary movements were assessed using the Abnormal Involuntary Movement Scale. Frequency distributions of grouped change-from-baseline scores were analyzed using chi 2 tests. RESULTS: Of 280 patients in whom the efficacy of quetiapine was evaluated, 159 (42% of those receiving high-dose treatment; 57%, low-dose treatment; and 59%, placebo) withdrew before trial completion, primarily because of treatment failure. Significant (P < .001, BPRS; P = .003, Clinical Global Impression Severity of Illness item; and P = .003, BPRS positive-symptom cluster) differences were identified between patients receiving high-dose quetiapine and placebo for both primary efficacy variables, with end point differences in the BPRS positive-symptom cluster score showing quetiapine's consistency in reducing positive symptoms. The reduction of negative symptoms was less consistent; high-dose quetiapine was superior on the Modified Scale for the Assessment of Negative Symptoms but not on the negative scale of the Positive and Negative Syndrome Scale. Quetiapine was well tolerated and did not induce extrapyramidal symptoms, sustained elevations of prolactin, or clinically significant changes in hematologic parameters. CONCLUSIONS: Quetiapine is an effective antipsychotic with a favorable safety profile. The optimum dose is probably greater than 250 mg/d.

Adult↗
PubMed2001

Clotiapine for acute psychotic illnesses.

BACKGROUND: Acute psychotic illness, especially when associated with agitated or violent behaviour, requires urgent pharmacological tranquillisation or sedation. Clotiapine, a dibenzothiazepine neuroleptic, is being used for this purpose in several countries. OBJECTIVES: To estimate the effects of clotiapine when compared to other 'standard' or 'non-standard' treatments of acute psychotic illness in controlling disturbed behaviour and reducing psychotic symptoms. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Issue 2, 2000), The Cochrane Schizophrenia Group's Register (May 2000), EMBASE (1980-2000), MEDLINE (1966-2000), PASCAL (1973-2000) and PsycLIT (1970-2000) were methodically searched. This was supplemented by hand searching reference lists, contacting industry and relevant authors. SELECTION CRITERIA: Randomised clinical trials comparing clotiapine to any treatment, for people with acute psychotic illnesses such as in schizophrenia, schizoaffective disorder, mixed affective disorders, manic phase of bipolar disorder, brief psychotic episode or organic psychosis following substance abuse. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants in any group were lost to follow up. For binary outcomes a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI) was calculated. Where possible, the weighted number needed to treat statistic (NNT), and its 95% confidence interval (CI), was also calculated. If heterogeneity was found, a random effects model was used. For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD). Again, if heterogeneity was found a random effects model was used. A Mantel-Haenszel chi-square test was used to investigate the possibility of heterogeneity. MAIN RESULTS: Five trials were included. None compared clotiapine with placebo, but control drugs were either antipsychotics (chlorpromazine, perphenazine, trifluoperazine and zuclopenthixol acetate) or benzodiazepines (lorazepam). Versus antipsychotics: results for global clinical outcome were heterogeneous (p=0.09) but did not suggest clotiapine to be superior, or inferior, to chlorpromazine, perphenazine, or trifluoperazine (total randomised = 83). Use of clotiapine did change the proportion of people ready for hospital discharge by the end of the study in one small trial (n=49, RR 1.04 95%CI 0.96 to 2.12). Overall, attrition rates were low. No significant difference was found for those allocated to clotiapine compared with people randomised to other antipsychotics (n=121, RR 2.26 95%CI 0.40 to 13). Weak data suggests that clotiapine may result in less need for antiparkinsonian treatment compared with zuclopenthixol acetate (n=38, RR 0.43 95%CI 0.02 to 0.98). Versus lorazepam: when used to control aggressive/violent outbursts for people already treated with haloperidol, clotiapine did not significantly improve mental state compared to lorazepam (WMD -3.36 95%CI -8.09 to 1.37). Much data could not be pooled due to skew or inadequate presentation of results. Economic outcomes and satisfaction with care were not addressed. REVIEWER'S CONCLUSIONS: We found no significant evidence to support the use of clotiapine rather than other 'standard' or 'non-standard' treatments for the management of acute psychotic illness. The trials included in this review all present important methodological flaws. We do not wish to discourage clinicians from using clotiapine in the psychiatric emergency, we would just like to point out the fact that good quality controlled trials are needed on this subject.

Antipsychotic Agents↗
PubMed2004

Clotiapine for acute psychotic illnesses.

BACKGROUND: Acute psychotic illnesses, especially when associated with agitated or violent behaviour, require urgent pharmacological tranquillisation or sedation. Clotiapine, a dibenzothiazepine neuroleptic, is being used for this purpose in several countries. OBJECTIVES: To estimate the effects of clotiapine when compared to other 'standard' or 'non-standard' treatments for acute psychotic illnesses in controlling disturbed behaviour and reducing psychotic symptoms. SEARCH STRATEGY: We updated previous searches by searching the Cochrane Schizophrenia Group Register (April 2004) SELECTION CRITERIA: The review included randomised clinical trials comparing clotiapine with any other treatment for people with acute psychotic illnesses. DATA COLLECTION AND ANALYSIS: Relevant studies were selected for inclusion, their quality was assessed and data extracted. Data were excluded where more than 50% of participants in any group were lost to follow up. For binary outcomes we calculated a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI). For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD). MAIN RESULTS: We identified five relevant trials. None compared clotiapine with placebo, but control drugs were either antipsychotics (chlorpromazine, perphenazine, trifluoperazine and zuclopenthixol acetate) or benzodiazepines (lorazepam). Versus the antipsychotics, the results for 'no important global improvement' did not suggest clotiapine to be superior, or inferior, to chlorpromazine, perphenazine, or trifluoperazine (n = 83, 3 RCTs, RR 0.82 CI 0.22 to 3.05, I-squared 58%). Use of clotiapine when compared with chlorpromazine did change the proportion of people ready for hospital discharge by the end of the study (n = 49, 1 RCT, RR 1.04 95%CI 0.96 to 2.12). Overall, attrition rates were low. No significant difference was found for those allocated to clotiapine compared with people randomised to other antipsychotics (n = 121, RR 2.26 95%CI 0.40 to 13). Weak data suggests that clotiapine may result in less need for antiparkinsonian treatment compared with zuclopenthixol acetate (n = 38, RR 0.43 95%CI 0.02 to 0.98). Compared with lorazepam, clotiapine, when used to control aggressive/violent outbursts for people already treated with haloperidol, did not significantly improve mental state (WMD -3.36 95%CI -8.09 to 1.37). We could not pool much data due to skew or inadequate presentation of results. Economic outcomes and satisfaction with care were not addressed. REVIEWERS' CONCLUSIONS: We found no evidence to support the use of clotiapine in preference to other 'standard' or 'non-standard' treatments for management of people with acute psychotic illness. All trials in this review have important methodological problems. We do not wish to discourage clinicians from using clotiapine in the psychiatric emergency, but well-designed, conducted and reported trials are needed to properly determine the efficacy of this drug.

Acute Disease↗
PubMed1991

Selective antidopaminergic effects of S(+)N-n-propylnoraporphines in limbic versus extrapyramidal sites in rat brain: comparisons with typical and atypical antipsychotic agents.

Dopamine (DA), injected unilaterally into rat forebrain after pretreatment with a monoamine oxidase inhibitor, equipotently induced locomotor arousal when placed in the nucleus accumbens septi (a limbic site) and contralateral deviation of the head when placed in the corpus striatum (an extrapyramidal target); testing was done with an ED50 dose of DA (16 micrograms). Systemic injections (IP) of the representative typical neuroleptic haloperidol showed high potency and minor striatal selectivity against the behavioral effects of intracerebral DA [accumbens ID50 = 0.090, striatum = 0.027 mg/kg (0.24 and 0.072 mumol/kg); ID50 ratio = 3.3, favoring striatum]. The atypical antipsychotic agent clozapine was less potent against DA in both brain regions but, paradoxically, showed ever greater striatal selectivity [ID50 = 12 and 1.4 mg/kg (37 and 4.2 mumol/kg); ratio = 8.8, favoring striatum], while its analog, the piperazinyl-dibenzothiazepine ICI-204,636 showed intermediate potency and the lowest striatal selectivity of these three neuroleptic agents [ID50 = 1.8 and 0.88 mg/kg (4.1 and 2.0 mumol/kg); ratio = 2.1]. In striking contrast, the S(+) isomers of N-n-propylnorapomorphine, its orally active 10,11-methylenedioxy prodrug derivative, and its 11-monohydroxy analog all induced potent antagonism of limbic DA but had little effect on extrapyramidal injections of DA except at high systemic doses [ID50, accumbens = 0.18-0.52, striatal = 10-15 mg/kg (0.50-1.6 and 29-42 mumol/kg); regional ID50 ratios = 18-69, favoring accumbens]. The S(+)aporphines showed limbic potency similar to that of haloperidol and 25-73 times greater than that of clozapine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Seroquel (ICI 204 636), a putative "atypical" antipsychotic, in schizophrenia with positive symptomatology: results of an open clinical trial and changes of neuroendocrinological and EEG parameters.

Preclinical data indicated that seroquel (ICI 204 636), a dibenzothiazepine with 5-HT2 and D2-like receptor antagonistic properties, might be an effective antipsychotic agent, causing fewer extrapyramidal side effects than typical neuroleptics. In the present study, 12 patients suffering from schizophrenia or schizophreniform disorder with predominantly positive symptomatology were treated in an open clinical trial for 4 weeks with seroquel at a maximum dosage of 750 mg/day. The drug was generally well tolerated, and virtually no adverse extrapyramidal side effects such as acute dystonia, parkinsonism or akathisia were observed. Total scores for BPRS (item score 0-6; baseline: 42.0 +/- 2.3; mean +/- SEM), SAPS (64.5 +/- 4.8) and SANS (55.0 +/- 4.3) showed a moderate decrease at the end of treatment (BPRS: 30.0 +/- 3.5; SAPS: 36.1 +/- 6.7; SANS: 42.5 +/- 5.9), when intention-to-treat analysis was applied. There were considerable interindividual differences in treatment response, with some subjects showing almost full remission of positive symptoms, in contrast to about half of the patients who showed no satisfactory clinical improvement. Interestingly, patients showing good antipsychotic response reported slight initial side effects like mild sedation. Prolactin and TSH levels were not altered during seroquel administration. As to pharmaco-EEG investigations, seroquel caused a moderate increase of the absolute power in the alpha, theta, and beta frequency bands, paralleled by a decrease of delta activity. There were no signs of paroxysmal EEG activity under seroquel.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Medical-claims databases in the design of a health-outcomes comparison of quetiapine ('Seroquel') and usual-care antipsychotic medication.

Treating schizophrenia is expensive. Preventing rehospitalization of patients with schizophrenia provides an attractive opportunity for cost savings, especially for patients with 'revolving-door' or multiple-episode schizophrenia. Reducing the occurrence of extrapyramidal symptoms and other adverse events associated with standard antipsychotic agents may increase compliance and reduce the rate of rehospitalization of patients with schizophrenia. Quetiapine ('Seroquel', ICI 204,636, Zeneca Pharmaceuticals) is a new dibenzothiazepine antipsychotic agent with a low propensity for extrapyramidal symptoms. We describe here a unique methodology to compare quetiapine with usual-care medications in real-world treatment settings. The trial objective is to determine if therapy with this new atypical antipsychotic agent can reduce the rate of rehospitalization and, therefore, treatment costs. Using two secondary medical-claims databases, we defined the minimal threshold for revolving-door status as 1.0 admission per year; this definition allows our trial to focus on the subpopulation of schizophrenic patients with the greatest potential for cost savings by either the new atypical antipsychotic quetiapine or usual-care therapy. We describe here the approach used in our trial.

Adolescent↗
PubMedDate not supplied

Quetiapine (Seroquel) concentrations in seven postmortem cases.

Quetiapine is a new antipsychotic drug that has been available in the United States since September 1997. It belongs to a new chemical class of drugs called the dibenzothiazepine derivatives and is easily detected with a basic drug screen. The Los Angeles County Department of Coroner Toxicology Laboratory has encountered quetiapine in seven postmortem cases. Tissue distributions were determined in each of the seven cases. The analysis of quetiapine from postmortem specimens consisted of an n-butylchloride basic extraction with presumptive identification and quantitation on a gas chromatograph-nitrogen-phosphorus detector. Linearity was achieved from 0.10 to 3.0 mg/L with a limit of quantitation of 0.10 mg/L. Confirmation of quetiapine was performed on a gas chromatograph-mass spectrometer by comparison with a pure analytical standard. The tissue distribution of quetiapine was as follows: heart blood present, but less than (+<) 0.10-49 mg/L (seven cases); femoral blood +< 0.10-1.4 mg/L (five cases); liver +< 0.10-112 mg/kg (five cases); spleen 4.0 mg/kg (one case); urine 0-3.0 mg/L (two cases); bile 0.60-7.5 mg/L (three cases); and gastric contents +< 0.01-18 mg total (five cases). To our knowledge, this is the first report of the presence of quetiapine in postmortem specimens.

Adult↗