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

Schizophrenia is generally a chronic and disabling mental illness. Pharmacological therapy, which is used for relief of acute psychotic episodes and prevention of subsequent relapse, is essential for the effective management of schizophrenia. In order to alleviate the positive symptoms of schizophrenia, all antipsychotic agents act on the dopaminergic system. However, strong, high-affinity dopamine D(2)-receptor blockade may also be responsible for debilitating extrapyramidal symptoms (EPS) and hyperprolactinaemia. Unlike conventional antipsychotic agents, atypical antipsychotics also exert activity at other receptors, and it is generally acknowledged that, compared with conventional antipsychotics, atypical agents are associated with a broader spectrum of clinical efficacy and are better tolerated. However, other adverse effects such as weight gain and metabolic changes are cause for concern with some atypical antipsychotics. The novel atypical antipsychotic agent aripiprazole is a partial agonist at D(2) receptors that has been shown in clinical trials to be effective in treating both the positive and the negative symptoms of schizophrenia, and to be well tolerated, with a low propensity for EPS and no clinically significant weight gain, hyperprolactinaemia or corrected QT-interval prolongation. Aripiprazole thus provides clinicians with another treatment option, and in October 2005, schizophrenia experts participated in an expert consensus meeting that aimed to agree on a set of guidelines for best-practice use of aripiprazole in the acute and long-term management of schizophrenia in Italy. This report describes the outcome of the meeting. Our recommendations for dosage and administration of aripiprazole are in agreement with the manufacturer's prescribing information. Ideally, optimal dosing should be evaluated on an individual basis, taking into account patients' characteristics such as the presence or absence of agitation. Overall, in our experience, aripiprazole is generally a well accepted, well tolerated, safe and broadly effective first-line antipsychotic agent. Switching to aripiprazole from maintenance therapy with another antipsychotic also works well, provided the change is made gradually, involving tapering of the original medication.
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PMID:Aripiprazole in the treatment of schizophrenia: a consensus report produced by schizophrenia experts in Italy. 1717 76

Atypical antipsychotics have been used to treat patients with schizophrenia for many years, but now there is increasing evidence of their utility in the treatment of mood disorders. In the past few years, several atypical agents have received regulatory approval for use in mania. The evidence shows that atypical antipsychotics are effective in the treatment of manic symptoms, either alone or in combination with traditional mood stabilizers, such as lithium and divalproex. Although emerging data indicate that atypical antipsychotics will be a promising addition to those therapies that are currently available for managing patients during the maintenance phase of bipolar illness, their potential in the long-term management of bipolar disorder remains to be fully explored. Aripiprazole is a recently released antipsychotic medication that differs from other atypical antipsychotic agents by its mode of action as a dopamine D2 partial agonist. It is administered orally and has a long half-life. Randomized studies have demonstrated the efficacy of aripiprazole compared with placebo in the treatment of acute relapse of schizophrenia and schizoaffective disorder, maintenance treatment of schizophrenia, treatment of acute mania, and prevention of manic relapse in patients who responded to the drug during a manic episode. Further studies are ongoing in bipolar and unipolar depression. Aripiprazole is generally well tolerated compared with other antipsychotic medications, although commonly reported side effects include extrapyramidal symptoms and motoric activation similar to akathisia. Further studies and postmarketing data will be helpful in providing additional information regarding the comparative safety, efficacy and tolerability of aripiprazole in the treatment of affective disorders.
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PMID:Role of aripiprazole in treating mood disorders. 1718 24

Compared with the general population, persons with schizophrenia have up to a 20% shorter lifespan, with cardiovascular disease as the leading cause of death. In addition, persons with schizophrenia have increased prevalence of the metabolic syndrome (obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, and hypertension), increased prevalence of risk factors such as smoking, poverty, and poor nutrition, and reduced access to medical care. Results from the recent Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) provide further evidence of the metabolic risk associated with different atypical antipsychotics. Based on this study and a growing number of other randomized clinical trials, clozapine and olanzapine treatment can produce substantial mean changes in weight and an increased risk of associated metabolic disturbances. Risperidone and quetiapine treatment can produce intermediate changes in mean weight in comparison to treatment with other atypical antipsychotics, with discrepant results with respect to metabolic risk. Aripiprazole and ziprasidone treatment induced the lowest mean changes in weight gain and had no effect on risk for adverse metabolic changes, among currently available atypical agents. Considerable evidence indicates that mentally ill patients often do not receive adequate recognition of, monitoring of, or care for their medical illnesses. There is a critical need for psychiatrists and primary care professionals to increase awareness of and attention to the physical health problems of persons with mental illness, including appropriate management of metabolic adverse events associated with psychiatric medications.
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PMID:Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. 1728 24

Aripiprazole is a dopamine (DA) D(2) receptor partial agonist, approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia. DA receptor partial agonists have been previously assessed as potential therapeutic agents for cocaine dependence. The present experiment examined the effect of aripiprazole on methamphetamine self-administration in a rodent model of an increasing drug self-administration with prolonged session duration. Wistar rats were allowed to self-administer methamphetamine (0.05 mg/kg/injection, intravenously) in either 1-h (short access: ShA rats) or 6-h sessions (long access: LgA rats). After 15 sessions, the dose-response function of methamphetamine was determined under either a progressive- or a fixed-ratio schedule. Next, the effect of aripiprazole (0.3-10 mg/kg, subcutaneuously (s.c.)) on the dose-response function was examined. LgA rats exhibited an increasing rate of methamphetamine self-administration. Responding for methamphetamine by LgA rats was higher than that of ShA rats under both schedules. Pretreatment with aripiprazole shifted the dose-response function of methamphetamine to the right in both LgA and ShA rats. However, the effect of aripiprazole was greater in LgA than ShA rats. In in vitro receptor binding assay, no change in the level of D(2) DA receptors in the nucleus accumbens and the striatum was found in any group. The present data suggest increased sensitivity of the dopaminergic system to aripiprazole in LgA rats compared with ShA rats. However, mechanisms other than downregulation of D(2) DA receptors in the nucleus accumbens and the striatum may be responsible for the increased sensitivity of the dopaminergic function in LgA rats.
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PMID:Effect of aripiprazole, a partial dopamine D2 receptor agonist, on increased rate of methamphetamine self-administration in rats with prolonged session duration. 1732 86

Long-term treatment of stable schizophrenia focuses on treatment effectiveness, addressing direct efficacy plus treatment adherence, treatment burden, and impact on factors such as weight gain. With the introduction of atypical antipsychotics such as aripiprazole, reduced side effects may lead to improved long-term treatment. The Clinical Trials of Intervention Effectiveness (CATIE) study where 1500 patients were randomised to atypical antipsychotics (olanzapine, quetiapine, risperidone, ziprasidone), or the typical antipsychotic drug perphenazine showed high discontinuation rates of 74% after 18 months, but extrapyramidal side effects were lower after atypical antipsychotic treatment compared with perphenazine. Twenty-six weeks of aripiprazole treatment, assessed in 284 patients in the Schizophrenia Trial of Aripiprazole (STAR) showed that aripiprazole had similar discontinuation rates to the atypical antipsychotics standard of care. In the CATIE study, weight gain was common during treatment. In contrast, STAR demonstrated a favourable weight profile for aripiprazole, with a mean weight loss of 0.41 kg. Results from these naturalistic trials help define the effectiveness of atypical antipsychotics for long-term treatment.
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PMID:The stable patient with schizophrenia--from antipsychotic effectiveness to adherence. 1733 66

Patients with schizophrenia show low employment rates and low Quality of Life (QoL), and rehabilitation aims to maximise daily functioning, improve social interactions, and develop employment prospects. Evaluation of long-term treatment effectiveness should address these issues. Choice of medication can influence patient compliance and adverse experience of side effects may act as a barrier to rehabilitation. The Schizophrenia Trial of Aripiprazole (STAR), in which patients were randomised to receive 26 weeks of the atypical antipsychotic, aripiprazole (n=284) or standard of care medication (n=271) showed that aripiprazole demonstrated significantly better effectiveness in terms of Investigator Assessment Questionnaire (IAQ) total score. Like other atypical antipsychotic agents, aripiprazole shows a low rate of extrapyramidal adverse events. In addition, unlike the majority of other agents, aripiprazole treatment has a low risk of weight gain, translating into health-related QoL benefits. In summary, newer, atypical agents may improve efficacy, patient satisfaction, and aid long-term rehabilitation.
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PMID:The long term--maximising potential for rehabilitation in patients with schizophrenia. 1733 67

Aripiprazole has made a significant contribution to the treatment of schizophrenia and related disorders with an improved safety and tolerability profile, which has been attributed to its unique pharmacological profile. It has been claimed that partial agonism of the dopamine D(2) and 5-HT(1A) receptors and antagonism of the 5-HT(2) receptor contribute to the clinical profile of aripiprazole, a so-called dopamine- and 5-HT stabiliser. However, recent studies have questioned the role of the 5-HT-mediated systems in the mechanism of action of aripiprazole. This report reviews published and unpublished data that suggest that aripiprazole acts as a selective partial agonist at the dopamine D(2) receptor and does not affect 5-HT receptors at therapeutic doses.
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PMID:Aripiprazole acts as a selective dopamine D2 receptor partial agonist. 1750 90

The objective of this study was to assess the pharmacokinetics of aripiprazole when coadministered with carbamazepine using an open-label sequential treatment design in patients with schizophrenia or schizoaffective disorder. Nine male patients were enrolled and received aripiprazole monotherapy (30 mg once daily) for 14 days, after which aripiprazole steady-state pharmacokinetics were assessed. Subjects were then administered carbamazepine together with aripiprazole for 4 to 6 weeks. The dose of carbamazepine was titrated to produce a trough serum concentration within the range of 8 to 12 mg/L. Aripiprazole pharmacokinetics were then assessed in the presence of carbamazepine. Six patients completed the study as designed. Coadministration with carbamazepine decreased the values of mean peak plasma concentration and area under the plasma concentration-time curve of aripiprazole by 66% and 71%, respectively (P = 0.001 and 0.002, respectively). Similarly, coadministration with carbamazepine decreased the values of mean peak plasma concentration and area under the plasma concentration-time curve over the 24-hour dosing interval of the major active metabolite of aripiprazole, dehydroaripiprazole, by 68% and 69%, respectively (P < 0.001). Both aripiprazole and dehydroaripiprazole are substrates for the cytochrome P-450 3A4 enzyme which is known to be induced by carbamazepine dosed to steady state. Thus, therapeutic doses of carbamazepine had significant effects on the pharmacokinetics of aripiprazole in patients with schizophrenia or schizoaffective disorder. When carbamazepine is added to aripiprazole therapy, aripiprazole dose should be doubled (to 20-30 mg/d). Additional dose increases should be based on clinical evaluation. When carbamazepine is withdrawn from combination therapy, aripiprazole dose should then be reduced.
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PMID:Pharmacokinetics of aripiprazole and concomitant carbamazepine. 1750 75

Aripiprazole is a novel antipsychotic drug for the treatment of schizophrenia and schizoaffective disorders. In this study, a new method using gas chromatography-mass spectrometry (GC-MS) was developed and validated for the detection of aripiprazole and its main metabolite, dehydroaripiprazole, in plasma. Blood samples from seven psychiatric patients treated with aripiprazole (10-20 mg/day) underwent a solid-phase extraction (SPE) and N-methyl-N-trimethylsilytrifluoroacetamide (MSTFA) derivatization. The characteristic ions of mass spectra for aripiprazole and dehydroaripiprazole were m/z 306, 292, 218 and 304, 290, 218, respectively. Extraction recoveries from this method were 75.4% (n=5) for aripiprazole and 102.3% (n=5) for dehydroaripiprazole. The calibration curves of aripiprazole and dehydroaripiprazole were linear from 16 to 500 ng/ml (r(2)=0.999) and 8 to 250 ng/ml (r(2)=0.999), respectively. The respective limits of quantification (LOQs) for aripiprazole and dehydroaripiprazole evaluated in 0.5 ml of serum were 14.4 ng/ml and 6.9 ng/ml. Intra-assay and interassay precision and accuracy were within acceptable ranges. In this study, we also found that the mean trough concentrations in plasma at steady-state were 128.9 microg/l for aripiprazole and 30.1 microg/l for dehydroaripiprazole.
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PMID:Detection and quantification of aripiprazole and its metabolite, dehydroaripiprazole, by gas chromatography-mass spectrometry in blood samples of psychiatric patients. 1760 1

This double-blind, multicenter study aimed to investigate the efficacy and safety of aripiprazole 10, 15 or 20 mg/day versus placebo. Patients requiring inpatient hospitalization for acute exacerbation of schizophrenia were randomized to once-daily aripiprazole 10, 15 or 20 mg/day or placebo for 6 weeks. The primary efficacy outcome was the mean change from baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total score (last observation carried forward). Patients with no improvement by Week 3 (Clinical Global Impression-Global Improvement score > or =4) could transfer to open-label aripiprazole 20mg/day. In total, 420 patients were randomized to placebo (n = 108); aripiprazole 10 mg/day (n = 106); 15 mg/day (n = 106); or 20 mg/day (n = 100). Of these, 142 patients (34%) completed 6 weeks of treatment, 131 (31%) discontinued to receive open-label aripiprazole, and 147 (35%) for other reasons. Aripiprazole 10, 15 and 20 mg/day each showed significantly greater improvements from baseline than placebo for all efficacy measures, including PANSS Total, Positive and Negative scores, and the CGI-Severity of Illness score. Significantly greater improvements in PANSS Total score versus placebo were achieved by Week 1 with 10 or 20 mg/day and Week 3 with 15 mg/day. All three doses were well tolerated. Overall, aripiprazole was not associated with clinically meaningful differences in extrapyramidal symptoms, prolactin or weight changes versus placebo. Aripiprazole 10 mg/day is effective and well tolerated for patients experiencing an acute exacerbation of schizophrenia.
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PMID:A randomized, double-blind, placebo-controlled, study of the efficacy and safety of aripiprazole 10, 15 or 20 mg/day for the treatment of patients with acute exacerbations of schizophrenia. 1763 14


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