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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interplay between dopamine and glutamate appears to be relevant in the etiopathology of schizophrenia. Although currently used antipsychotics do not interact with glutamatergic receptors, previous results have demonstrated that the expression profile of ionotropic glutamate receptors can be regulated by drugs such as haloperidol or clozapine. In the present investigation, the mRNA levels for NMDA and AMPA receptor subunits were measured after chronic treatment with the novel antipsychotic agent Seroquel (quetiapine fumarate, quetiapine) as compared to haloperidol and clozapine. Similarly to the prototype atypical clozapine, quetiapine reduced the mRNA expression for NR-1 and NR-2C, two NMDA forming subunits, in the nucleus accumbens. Furthermore, quetiapine, but not haloperidol or clozapine, increased the hippocampal expression for the AMPA subunits GluR-B and GluR-C. The differences between classical and atypical antipsychotics, as well as among the novel agents, might be relevant for specific aspects of their therapeutic activity and could provide valuable information for the role of glutamate in specific symptoms of schizophrenia.
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PMID:Regulation of ionotropic glutamate receptors in the rat brain in response to the atypical antipsychotic seroquel (quetiapine fumarate). 1043 69

Quetiapine (Seroquel) is a member of a new class of antipsychotic agents used in the treatment of schizophrenia. Its pharmacologic effect is primarily mediated via antagonistic binding to serotonergic (5HT2) and dopaminergic (D2) receptors. Presented is a case of acute quetiapine overdose in a patient with associated tachycardia, hypotension, prolonged QTc, and rapid progression to coma. Management included activated charcoal, i.v. saline, and intubation for airway protection. The patient's mental status rapidly improved within several hours of the ingestion, and the prolonged QTc and tachycardia resolved by the second and third days of hospitalization, respectively, without further intervention. This case illustrates the potential for hemodynamic instability and sudden deterioration in level of consciousness, warranting close monitoring and early intubation for airway protection. All patients with acute quetiapine overdose requiring hospitalization should be admitted to an intensive care unit setting.
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PMID:Acute quetiapine poisoning. 1059 86

Quetiapine fumarate is a novel dibenzothiazepine antipsychotic developed by Zeneca. It is marketed under the trade name 'Seroquel'. Quetiapine is well tolerated and clinically effective in the treatment of schizophrenia. The initial hope of investigators was that quetiapine would have antipsychotic potential and that it might share some of the properties of clozapine without its toxicity to white blood cells. The effective dosage range is usually 300-450 mg/day split into two doses. The dose is titrated upwards from 25 mg twice daily from day 1 to 300 mg/day on day 4. Elderly patients or patients with liver problems should be started on lower doses. It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 mg/day to 750 mg/day, and is an effective treatment for negative symptoms. Somnolence is the most common adverse event. Abnormalities of the QT interval on ECG appear very infrequently and there is no need for a baseline ECG or blood pressure monitoring, as used to be the case with sertindole. There is no need for haematological monitoring as with clozapine. Quetiapine, across the full dosage range, is associated with no greater extrapyramidal symptoms than placebo. Quetiapine's general efficacy and side-effect profile suggest that, unless there are unforeseen post-marketing complications, it deserves a major place in the initial and long-term management of schizophreniform disorders.
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PMID:Focus on quetiapine. 1062 20

The recent introduction of several antipsychotic medications has raised expectations for better pharmacological management of schizophrenia. Although conventional and new neuroleptics (Risperidone, Olanzapine, Seroquel and soon to be released Ziprasidone) are generally comparable in terms of efficacy; the new antipsychotic medications possess a better side-effects profile and are overall, much better tolerated. The reintroduction of Clozapine as an effective antipsychotic for treatment refractoriness has also improved management for a segment of the schizophrenic population who failed to respond adequately to other antipsychotic medications. Such increased benefits from new antipsychotic medications come with a higher acquisition cost that has somewhat strained the historically low psychiatric budgets. The question then was whether the expected benefits of the new antipsychotics can offset the high cost of these medications in the long-term. In that context, quality of life assessment has provided a tool for the comparative analysis of new and conventional antipsychotic medications, particularly regarding their impact on functional status and satisfaction. In a recently concluded study, we demonstrated that the new antipsychotic medications are subjectively much better tolerated and have a more favourable impact on quality of life compared with conventional neuroleptics. The ultimate question is whether such favourable benefits can translate in the future into better compliance with medications and improved long-term outcomes.
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PMID:Quality of life and new antipsychotics in schizophrenia. Are patients better off? 1068 10

Quetiapine fumarate is a recently marketed atypical antipsychotic medication proved to be effective in the treatment of schizophrenia and schizoaffective disorder in the younger population. There is a paucity of studies of this drug in the elderly and more data are needed on the effects of quetiapine in this population, especially those with comorbid medical illnesses. Quetiapine was used to treat seven elderly hospitalized patients between 61 and 72 years of age who manifested signs of psychosis related to schizophrenia, schizoaffective disorder, or bipolar disorder. All patients had been treated previously with conventional antipsychotics or other atypical antipsychotics. Response was assessed by observation of patient's behavior. Four patients responded to treatment; three did not respond. Positive symptoms decreased markedly in all four responders. Negative symptoms showed marked decrease in two patients and moderate decrease in one patient. Preexisting extrapyramidal symptoms (EPS) diminished in three patients. Transient hypotension, dizziness, and somnolence occurred in two patients. No other side effects were noted. No adverse consequences occurred when lithium, carbamazepine, valproic acid, or venlafaxine was given concurrently. The reduction of positive and negative symptoms of schizophrenia and lack of significant EPS and minimal sedative, hypotensive, and anticholinergic side effects indicate that quetiapine may be a safe and effective medication for the elderly.
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PMID:Clinical experience with quetiapine in elderly patients with psychotic disorders. 1075 4

Quetiapine ('Seroquel') is a well-tolerated, novel, atypical antipsychotic with consistent efficacy in the treatment of schizophrenia. To date, no clinical studies have evaluated the effect of quetiapine in patients who only partially respond to conventional antipsychotics, yet this type of patient is most frequently seen by psychiatrists. Therefore, this international, multicentre, double-blind study was conducted to compare the efficacy and tolerability of 8 weeks' treatment of quetiapine 600 mg/day with haloperidol 20 mg/day in 288 patients who had a history of partial response to conventional antipsychotics and displayed a partial or no response to 1 month of fluphenazine (20 mg/day) treatment. Patients on quetiapine tended to have greater improvement than those on haloperidol in the primary efficacy measure, mean Positive and Negative Symptom Scale (PANSS) score, after 4 weeks' treatment (-9.05, -5.82, respectively, P = 0.061) and at study end (-11.50, -8.87, respectively, P = 0.234). Similarly, there was a trend towards patients on quetiapine demonstrating greater improvements in the secondary efficacy measures (Clinical Global Impression, PANSS subscale and Brief Psychiatric Rating Scale scores) [week 4 (baseline) to week 12 (end)], but the difference between treatments did not reach significance. Significantly more patients on quetiapine than on haloperidol showed a clinical response-patient response rates, defined as > 20% reduction in PANSS total score between weeks 4 and 12, were 52.2% for quetiapine and 38.0% for haloperidol (P = 0.043). Patients receiving quetiapine required less anticholinergic medication (P < 0.011), had greater reduction in extrapyramidal symptoms (EPS) (P = 0.005) and fewer treatment-emergent EPS-related adverse events compared to those on haloperidol (P < 0.001). Serum prolactin concentrations were elevated at the end of fluphenazine treatment in 73% of patients. Between weeks 4 and 12, elevated serum prolactin concentrations significantly decreased in quetiapine-treated patients compared to those receiving haloperidol (P < 0.001). At the end of quetiapine treatment, 83% of patients had normal prolactin levels while only 21% of patients receiving haloperidol were within the normal range. These results suggest that quetiapine may make a valuable contribution to the management of patients with a history of partial response to conventional antipsychotics.
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PMID:A comparison of the effects of quetiapine ('seroquel') and haloperidol in schizophrenic patients with a history of and a demonstrated, partial response to conventional antipsychotic treatment. PRIZE Study Group. 1087 Aug 70

1. The atypical antipsychotic quetiapine ('Seroquel') provides equivalent efficacy to the typical antipsychotics chlorpromazine and haloperidol in the short-term treatment of schizophrenia. Moreover, the incidence of extrapyramidal symptoms associated with quetiapine treatment is equivalent to that observed with placebo treatment, which may lead to increased patient compliance with quetiapine compared with typical antipsychotics. 2. This report presents the results from two small studies aimed at determining the pharmacokinetics of quetiapine in nonpsychotic subjects with renal or hepatic impairment. Equal numbers of impaired subjects and healthy control subjects were administered a single, 25 mg dose of quetiapine, and plasma concentrations were determined up to 48 hr after dosing. 3. No clinically significant differences were found when the pharmacokinetic parameters for subjects with renal or hepatic impairment were compared with those for healthy control subjects. The results indicate that dosage adjustment of quetiapine may be unnecessary in psychotic patients with decreased renal function. 4. In subjects with hepatic impairment related to alcoholic cirrhosis, the results suggest that no change is needed in the recommended quetiapine starting dose (25 mg). However, because of a noted inter-subject variability in the clearance of quetiapine in the cirrhotic group, it is recommended that dose escalation be performed with caution in patients with hepatic impairment. 5. The single dose of quetiapine 25 mg generally was well tolerated in nonpsychotic subjects in good health or with either renal or hepatic impairments. Quetiapine also had no effect on the endogenous creatinine clearance of renally impaired or healthy control subjects.
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PMID:Single-dose pharmacokinetics of quetiapine in subjects with renal or hepatic impairment. 1095 48

A completed phase 3 trial result was simulated 100 times on the basis of a simulation model of quetiapine fumarate (Seroquel), an antischizophrenic agent. The simulation was executed by analysts who were completely blinded from results of the actual trial until after the simulations were submitted to the holder of the trial results. Data from two clinical investigations of quetiapine in patients with schizophrenia were analyzed by use of nonlinear mixed effects modeling to derive a population pharmacokinetic- and pharmacodynamic-based simulation model. The time course of quetiapine concentrations was described by use of a one-compartment open linear pharmacokinetic model with first-order absorption and elimination. The combination of an inhibitory maximum effect pharmacodynamic model for the active treatment effect and a linear function of time for the placebo effect characterized the observed time course of change in the Brief Psychiatric Rating Scale. Simulation results were compared with those in the actual trial to evaluate how well the simulations predicted the outcome. The actual trial results for all doses except the placebo group fell within the predicted Brief Psychiatric Rating Scale scores +/- 1 SE. Unlike the phase 2 trial, from which the pharmacokinetic/pharmacodynamic model was developed, the placebo group in the actual phase 3 trial showed deterioration of Brief Psychiatric Rating Scale scores with time. We conclude that variable placebo responses observed in short-term studies of schizophrenia provide an inadequate basis for the modeling and simulation of placebo subjects in clinical trials. Knowledge of the range of placebo response observed in other studies may have provided an improved basis for the placebo effect model. The model for active drug produced adequate predictions of the actual trial outcomes.
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PMID:Prediction of the outcome of a phase 3 clinical trial of an antischizophrenic agent (quetiapine fumarate) by simulation with a population pharmacokinetic and pharmacodynamic model. 1110 59

Quetiapine fumarate ('Seroquel') is a newly introduced atypical antipsychotic with demonstrated efficacy in the treatment of positive and negative symptoms of schizophrenia. It is extensively metabolized, predominantly by cytochrome P450 3A4. Therefore, concurrent administration of drugs that induce or inhibit this enzyme may affect quetiapine pharmacokinetics. This study demonstrated that the potent cytochrome P450 enzyme-inducer phenytoin did indeed have a marked effect on the metabolism of quetiapine, resulting in a 5-fold increase in clearance when administered concomitantly to patients with DSM-IV-diagnosed schizophrenia, schizoaffective disorder, or bipolar disorder. These results indicate that dosage adjustment of quetiapine may be necessary when the two drugs are given concurrently and that caution may be required when administering other drugs that inhibit or induce cytochromes, particularly P450 3A4.
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PMID:The effects of concomitant phenytoin administration on the steady-state pharmacokinetics of quetiapine. 1119 55

Preclinical studies have shown that quetiapine (Seroquel, AstraZeneca) is an atypical antipsychotic with many similarities to clozapine. Both placebo-controlled and comparative studies in patients with schizophrenia have demonstrated that quetiapine has long-term efficacy in both positive and negative domains, as well as beneficial effects on affective and cognitive symptoms. Comparative clinical studies confirm that quetiapine is at least as effective as the standard antipsychotics, chlorpromazine and haloperidol and response rates with quetiapine are similar to those reported with other atypical antipychotics. Quetiapine has also demonstrated superior efficacy to haloperidol in partially responsive patients, who can be particularly difficult to treat. Quetiapine has a wide clinical dosing range (150-750 mg/day), although doses of 400 mg or above should be used in patients who do not fully respond to lower doses of the drug. Quetiapine is generally well tolerated with no requirement for routine ECG or blood monitoring and it has minimal effects on weight. Uniquely among other first-line atypical antipsychotics, quetiapine is associated with a placebo-level incidence of EPS and an indistinguishable effect from placebo on plasma prolactin at all doses. Thus, clinicians can confidently increase the dose of quetiapine, without increasing the risk of EPS or hyperprolactinaemia. A number of studies have also shown that quetiapine is well-tolerated and effective in patients who are particularly susceptible to EPS, including elderly and adolescent patients and those with pre-existing dopaminergic pathology, such as Alzheimer's disease and Parkinson's disease. The consistent efficacy in treating all schizophrenic domains and good tolerability, particularly placebo-level EPS, make quetiapine acceptable to patients, as demonstrated in a survey of patient satisfaction. Thus quetiapine is a suitable first-line therapy for the treatment of schizophrenia and psychosis.
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PMID:Review of quetiapine and its clinical applications in schizophrenia. 1124 16


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