Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Second-generation 'atypical' antipsychotics appear to be more effective than first-generation 'typical' antipsychotics in improving negative symptoms in schizophrenia; it is unclear, however, if this greater improvement represents a direct beneficial effect or is mediated indirectly by an antidepressant effect or the absence of extrapyramidal symptoms (EPS). To address this issue with reference to quetiapine ('Seroquel'), data were evaluated from four randomized, controlled clinical studies involving 1106 patients employing a path analysis model. The total effect of quetiapine on negative symptoms was measured using the Scale for Assessment of Negative Symptoms (SANS) total score. Indirect effects on negative symptoms via positive, depressive and EPS were assessed using appropriate instruments. Effect sizes were calculated by path analysis for the difference between treatment groups in change from baseline to endpoint in SANS total score. Analysis confirmed that quetiapine produced a greater overall improvement in negative symptoms than placebo (effect size 1.96); this was explained by a significant direct effect (p = 0.001; 44.2% of total improvement), and a secondary effect of improved positive symptoms (p < 0.001; 47.5% of total improvement), but was not a consequence of changes in depressive symptoms or EPS. Within the constraints of the path analysis methodology, these results indicate that quetiapine has a substantial direct effect on improving the negative symptoms of schizophrenia.
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PMID:Quetiapine has a direct effect on the negative symptoms of schizophrenia. 1548 60

Quetiapine is a novel atypical antipsychotic drug with multi-receptorial affinity. Using in vivo microdialysis, we investigated if quetiapine modulates extracellular noradrenaline and dopamine in brain areas generally believed to be involved in the pathophysiology of schizophrenia and in the action of antipsychotic drugs. Quetiapine (5, 10 and 20 mg/kg, i.p.) increased levels of noradrenaline in both the prefrontal cortex and the caudate nucleus, while it increased dopamine levels mainly in the prefrontal cortex. It is argued that the marked increase of dopaminergic transmission in the prefrontal cortex induced by quetiapine might be relevant to its therapeutical action.
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PMID:The atypical antipsychotic quetiapine increases both noradrenaline and dopamine release in the rat prefrontal cortex. 1550 22

Quetiapine is an atypical antipsychotic agent for the treatment of schizophrenia. After an oral dose it is absorbed rapidly and extensively metabolized in the liver, resulting in low plasma concentrations of the parent drug. A sensitive analytical method is needed. A liquid chromatographic-electrospray-tandem mass spectrometric (LC-ESI-MS-MS) method combined with a simple liquid-liquid extraction has been developed for the measurement of quetiapine in human plasma and in human liver microsomes (HLM). Clozapine is used as internal standard. Plasma samples or microsomes quenched with methanol (100 microL) were made basic and extracted with 3 mL n-butyl chloride. The reconstituted extracts were analyzed by LC-ESI-MS-MS. Selective reaction monitoring of MH(+) at m/z 384 and 327 resulted in strong fragment ions at m/z 253 and 192 for quetiapine and clozapine, respectively. Recovery of quetiapine and clozapine ranged from 62 to 73%. Intrarun accuracy and precision determined at 1.0 (lower limit of quantitation), 2.5, 200, and 400 ng/mL did not exceed 7% deviation from target and the %CV did not exceed 5.5%. The % target +/- %CV for interrun accuracy and precision were at least 95% +/- 7.4% at concentrations of 2.5, 200, and 400 ng/mL. Plasma samples (2.5 and 400 ng/mL) stored at room temperature for 24 h or after 3 cycles of freeze/thaw were all stable (maximum % deviation < or = 11.0%). Processed extracts (2.5 and 400 ng/mL) stored for 7 days at -20 degrees C or 6 days on the autosampler were all stable (maximum % deviation < or = 11.5%). The method has been used to study quetiapine utilization during incubation with HLM or with cDNA-expressed human cytochrom P450s (CYP). Quetiapine is extensively metabolized by CYP 3A4 and CYP 2D6 and to a lesser extent by CYP 3A7, CYP 3A5, and CYP 2C19.
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PMID:A liquid chromatographic-electrospray-tandem mass spectrometric method for quantitation of quetiapine in human plasma and liver microsomes: application to study in vitro metabolism. 1551 94

Quetiapine is an atypical antipsychotic agent that has been approved for the treatment of schizophrenia in over 75 countries; it has been used to treat more than 4 million individuals since its launch in 1997. After quetiapine was found to improve mood and reduce aggression in patients with schizophrenia, researchers began investigating the drug in other indications. Quetiapine, as monotherapy or combined with mood stabilizers, significantly reduces measures of disease severity and acute mania in a variety of bipolar disorder patients, and displays excellent tolerability for a drug in its class. Of particular note is the incidence of extrapyramidal symptoms at levels similar to those seen with placebo. A phase III trial program in bipolar disorder is presently ongoing and includes five randomized, double-blind, controlled trials already reported and several other studies which are ongoing or planned.
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PMID:Quetiapine in bipolar disorder: Increasing evidence of efficacy and tolerability. 1560 18

This study evaluated the effect of switching outpatients with schizophrenia and antipsychotic-induced sexual dysfunction to open-label quetiapine treatment. Secondary objectives were to compare the antipsychotic and prolactin-related effects of quetiapine versus prestudy antipsychotic treatment. Eight patients with at least moderately severe antipsychotic-induced sexual dysfunction (N = 7 taking risperidone, 4-6 mg/d; N = 1 taking haloperidol, 10 mg/d) were evaluated prospectively after they switched to 6 weeks of quetiapine treatment. The assessments that we used included evaluations of sexual functioning (Arizona Sexual Experience Scale [ASEX]; McGahuey et al., 2000), psychopathology (Positive and Negative Syndrome Scale [PANSS]; Kay, Fiszbeinm, & Opler, 1997), adverse events, and plasma prolactin levels. Quetiapine was associated with clinically and statistically significant improvement in ASEX total scores (p = 0.008) and significantly decreased PANSS total scores (p = 0.03). Plasma prolactin levels tended to decrease after the transition to quetiapine (p = 0.09). Quetiapine appears to offer an option to reduce antipsychotic-induced sexual dysfunction for outpatients with schizophrenia.
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PMID:An open-label trial of quetiapine for antipsychotic-induced sexual dysfunction. 1567

A post hoc analysis of data from three placebo-controlled, double-blind, randomized trials was carried out to determine the efficacy of quetiapine in aggression and hostility in patients with schizophrenia. Quetiapine treatment induced statistically significantly greater improvements in BPRS positive symptom cluster scores and three measures of hostility derived from the BPRS, compared with placebo, in patients symptomatic at baseline. A path analysis showed that the improvements in hostility were highly correlated with improvements in positive symptoms and there was no consistent relationship between sedation and hostility. Aggressive behaviour appears to be related to positive symptoms of schizophrenia. Quetiapine may be a suitable option for patients with schizophrenia and aggressive behaviour.
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PMID:The effect of quetiapine on aggression and hostility in patients with schizophrenia. 1583 Apr 2

Quetiapine is a new atypical antipsychotic that was approved in 1997 by the U.S. Food and Drug Administration for the treatment of schizophrenia. It possesses a high affinity for 5-HT2 receptors and a low affinity for D1 and D2 dopamine receptors. Because quetiapine has only been released recently to the U.S. market, little information exists regarding therapeutic, toxic, and lethal concentrations. This study reports the detection of quetiapine in 13 postmortem cases. Following a basic liquid-liquid extraction, quetiapine was identified and quantitated by capillary gas chromatography with nitrogen phosphorus detection. Confirmation was accomplished by full scan electron impact gas chromatography/mass spectrometry. Heart blood quetiapine concentrations ranged from 0.07 to 18.37 mg/L (N = 12, mean +/- SD = 3.42 +/- 5.67, median 0.62) and femoral blood concentrations ranged from 0.06 to 19.25 mg/L (N = 10. mean +/- SD = 3.89 +/- 6.12, median 0.81). The average heart blood/femoral blood ratio was 1.31 (range 0.55 to 2.57, N = 10). Urine, bile, and gastric contents were assayed in all cases in which they were submitted. In three cases, the cause of death was determined to be quetiapine toxicity. In these cases heart blood concentrations ranged from 0.72 to 18.37 mg/L (N = 3). These data may provide a basis for establishing levels associated with quetiapine toxicity as well as therapeutic concentrations in postmortem specimens.
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PMID:Disposition of quetiapine in biological specimens from postmortem cases. 1583 Oct 21

The pharmacological choices for the treatment of schizophrenia have been greatly expanded with the availability of the atypical compounds clozapine (Clozaril, Novartis), risperidone (Risperdal, Janssen-Cilag), olanzapine (Zyprexa, Eli Lilly & Co.), quetiapine (Seroquel, AstraZeneca), ziprasidone (Geodon, Pfizer Inc.) and aripiprazole (Abilify, Otsuka Pharmaceutical Co. Ltd). In this article, the effects of the newer antipsychotics and their side effects are reviewed. Key issues in acute and maintenance treatment, often lifelong, will be reviewed. Side-effect management to ensure adherence to an optimal treatment regimen will be discussed. Coexisting syndromes must be treated in concordance with the patient's clinical presentation. For treatment-resistant patients, atypical compounds are generally more effective than their typical counterparts but medication augmentation strategies are frequently recommended. Finally, the results of recent meta-analyses comparing the effects of atypical versus typical compounds will be critically reviewed and remaining gaps in the current pharmacotherapy of schizophrenia will be explored.
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PMID:Pharmacological treatment strategies for schizophrenia. 1585 89

Ziprasidone (Geodon), risperidone (Risperdal), and aripiprazole (Abilify) appear to be associated with a relatively low risk for hyperlipidemia, whereas quetiapine (Seroquel), olanzapine (Zyprexa), and clozapine (Clozaril) are associated with a relatively high risk for hyperlipidemia. Possible underlying causes of lipid dysregulation include weight gain, dietary changes, and glucose intolerance. Given the multiple cardiovascular risk factors reported for patients with schizophrenia, great care must be exercised to minimize the additional risk for hyperlipidemia when choosing antipsychotic therapy. It is recommended that a lipid panel be obtained at baseline for all patients with schizophrenia and annually thereafter for patients taking relatively low-risk agents or quarterly thereafter for patients taking relatively high-risk agents. Patients with persistent dyslipidemia should be referred for lipid-lowering therapy or switched to a less lipid-enhancing antipsychotic agent.
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PMID:Atypical antipsychotic therapy and hyperlipidemia: a review. 1586 22

Blood-oxygenation-level-dependent (BOLD) brain changes underlying response to quetiapine were examined using passive viewing of emotionally negative stimuli. Twelve DSM-IV schizophrenia patients with blunted affect (BA+) were scanned before and after 22 weeks of quetiapine treatment. Whole-brain, voxel-based methods were used to assess the differential hemodynamic response to quetiapine. In addition, a post hoc comparison to an independent group of 11 schizophrenia patients without blunted affect (BA-) was performed to compare them with BA+ (postquetiapine) in response to emotion processing. A 22-week treatment with quetiapine resulted in significant clinical improvement in the 12 study completers (mean +/- SD posttreatment PANSS blunted affect score of 5.50 +/- 0.76 at baseline to 2.08 +/- 1.00 at end point; t = 7.78, df = 11, P < 0.0001). Treatment response was associated with significant BOLD changes: increases in prefrontal cortex activation particularly in the right dorsolateral prefrontal cortex (DLPFC, BA 46) and the right anterior cingulate cortex (ACC, BA 32); and in the left putamen, right anterior temporal pole (ATP), and right amygdala. Conversely, before treatment with quetiapine, the same subjects activated the midbrain bilaterally and the right pons. The post hoc conjunctional analyses demonstrated that BA- subjects activated the left ACC, left insula, left ATP (BA 21), left ATP (BA 38), left amygdala, and right medial prefrontal cortex. Quetiapine seems to affect clinical recovery by modulating the functioning of specific brain regions. Unique BOLD changes in the putamen and DLPFC with quetiapine, in the BA+ postquetiapine, may reflect modality-specific effects. Controlled studies are needed to further assess these preliminary findings.
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PMID:Differential hemodynamic brain activity in schizophrenia patients with blunted affect during quetiapine treatment. 1601 81


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