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)

Aripiprazole is a new atypical antipsychotic with a mode of action that is distinct from currently available antipsychotic drugs. In phase III comparative clinical studies, aripiprazole 15-30 mg/day was at least as effective as haloperidol and risperidone in short term treatment of acute exacerbation of schizophrenia but superior to haloperidol in long term maintenance therapy. Consistent with an atypical profile, aripiprazole is effective against positive, negative and cognitive symptoms of schizophrenia and has a favourable side effect profile with the incidence of extrapyramidal symptoms (EPS) comparable to placebo. It is also devoid of side effects such as clinically significant hyperprolactinaemia, hypercholesterolaemia and cardiotoxicity, and has a low propensity for weight gain. Symptom relief is achieved without significant sedation. These clinical data suggest its usefulness in psychosocial rehabilitation, as well as in long-term prevention of schizophrenic relapse. Recent results from a multicentre, open-label study in a general psychiatric setting provide the first evidence that aripiprazole is also effective under naturalistic conditions. However, only post-marketing experience will show whether the positive results of these controlled trials can be replicated in everyday practice.
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PMID:Aripiprazole: a new atypical antipsychotic with a different pharmacological mechanism. 1558 48

Aripiprazole (Abilify) is an atypical antipsychotic drug that has been recently introduced for clinical use in the treatment of schizophrenia. Aripiprazole has a unique pharmacologic profile that includes partial agonism at several G-protein coupled receptors (GPCRs) [especially dopamine (D2) and 5-HT1A] and antagonistic action at others (especially 5-HT2A). Clinical trials indicate that aripiprazole is effective in treating the positive and negative symptoms of schizophrenia. In short-term studies rapid onset of action (within one week) has been demonstrated. Preliminary data indicate that aripiprazole may also be effective in the treatment of manic symptoms of bipolar disorder. At recommended doses, aripiprazole appears to be safe and well tolerated in most adult patients with schizophrenia and schizoaffective disorder. There is only limited information available on the use of aripiprazole in children and adolescents, and pilot data suggest that a revised dosing strategy, based on weight, is indicated in this population. In the long-term studies, the use of aripiprazole was associated with continued efficacy, good compliance and increased time-to-relapse. Aripiprazole represents the first functionally selective atypical antipsychotic drug.
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PMID:Aripiprazole: a novel atypical antipsychotic drug with a uniquely robust pharmacology. 1559 81

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

Schizophrenia is a chronic disabling disease which in the majority of cases requires long-term treatment with antipsychotic medication. Before the development of atypical antipsychotics, treatment choice was restricted to conventional (or typical) antipsychotics, which are known to cause a range of side effects including extrapyramidal symptoms. Although atypical agents provide a favourable alternative (advocated by the National Institute of Clinical Excellence in the UK), they are associated with side effects. These differ between agents, but can include weight gain, sedation and hyperprolactinaemia. Aripiprazole is a newly available atypical antipsychotic for the treatment of schizophrenia. With the apparent imitations of currently available medications, aripiprazole provides clinicians with another treatment option. The purpose of these guidelines is to outline the consensus reached by the Schizophrenia Innovation Working Group on best practice in prescribing and appropriate use of aripiprazole in the UK.
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PMID:Aripiprazole in schizophrenia: consensus guidelines. 1585 69

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

Aripiprazole is the first clinically approved atypical antipsychotic agent having dopamine D2 receptor partial agonist activities. To evaluate aripiprazole's agonist and antagonist properties, we established a Chinese hamster ovary cell line expressing high and low densities of the long and short isoforms of human dopamine D2 receptors, then compared its properties with 7-{3-[4-(2,3-dimethylphenyl)piperazinyl]propoxy}-2(1H)-quinolinone (OPC-4392), S(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((-)-3-PPP), and terguride (other partial agonists) using forskolin-stimulated cAMP accumulation as an index. In cells expressing high receptor densities, all partial agonists predominantly behaved as agonists. However, in cells expressing low receptor densities, the partial agonists showed significantly lower maximal effects than dopamine. Aripiprazole showed the lowest intrinsic activities. In addition, all compounds blocked the action of dopamine with a maximum effect equal to that of each compound alone. Aripiprazole's low intrinsic activities may account for the clinical finding that, unlike the other partial agonists, it is substantially active against both positive and negative symptoms of schizophrenia.
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PMID:Aripiprazole's low intrinsic activities at human dopamine D2L and D2S receptors render it a unique antipsychotic. 1589 11

The emergence of partial dopamine agonists reinforces the argument for the dopamine hypothesis of schizophrenia. Aripiprazole (Abilify) is the first of these compounds for the treatment of schizophrenia to be launched in the UK. Aripiprazole has a promising efficacy and favourable tolerability profile that suggests it has a significant role to play in the management of schizophrenia.
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PMID:Partial dopamine agonists in schizophrenia. 1592 Aug 62

Aripiprazole is a recently released antipsychotic medication which differs from other atypical antipsychotic agents by its partial agonist activity at postsynaptic D2 receptors. It is administered orally and is distinguished by a long elimination phase half-life relative to other antipsychotic medications. Randomized studies have demonstrated the efficacy of aripiprazole relative to placebo in the treatment of acute relapse of schizophrenia and schizoaffective disorder, maintenance treatment of schizophrenia, and treatment of acute bipolar mania. Aripiprazole is generally well tolerated relative to other antipsychotic medications, although commonly reported side effects include worsening extrapyramidal symptoms and motoric activation similar to akathisia. Further studies and postmarketing data will be helpful in providing additional information about the comparative safety, efficacy and tolerability of aripiprazole.
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PMID:Aripiprazole: pharmacology, efficacy, safety and tolerability. 1593 62

Drugs used to treat psychiatric disorders, although effective, are often restricted by adverse events. The use of partial agonists for treating hypertension was found to limit some of the side-effects in some patients. This led to the investigation of partial agonists as a treatment modality in psychiatric disorders. Partial agonists have a lower intrinsic efficacy than full agonists leading to reduced maximum response. They can act as antagonists by competing for receptor binding with full agonists. The level of activity depends on the level of endogenous receptor activity. Buprenorphine, a partial agonist at the mu-opioid receptor, is used to treat patients with addiction and decreases the symptoms of withdrawal and risks of overdose and intoxication. The anxiolytic buspirone shows partial agonism at 5-HT(1A) receptors, and this seems to provide anxioselective effects, without inducing extrapyramidal side-effects, convulsions, tolerance or withdrawal reactions. In schizophrenia, partial dopamine agonism results in antagonistic effects at sites activated by high concentrations of dopamine and agonistic effects at sites activated by low concentrations of dopamine. This stabilizes the dopamine system to effect antipsychotic action without inducing adverse motor or hormonal events. Aripiprazole is the first 'dopamine system stabilizer', and the data are promising, with efficacy at least equivalent to that with current atypical antipsychotics but fewer of the troublesome side-effects. Partial agonists seem to provide a way to fine-tune the treatment of psychiatric disorders by maximizing the treatment effect while minimizing undesirable adverse events.
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PMID:The place of partial agonism in psychiatry: recent developments. 1598 97

The success of long-term therapy in schizophrenia is contingent upon real-world effectiveness or improvements in several domains, including efficacy, safety and tolerability. This report describes the Investigator's Assessment Questionnaire (IAQ), a new 10-item instrument designed to assess relative effectiveness (efficacy, safety and tolerability) of antipsychotic medications in patients with schizophrenia or schizoaffective disorder. To measure content validity, 300 psychiatrists rated the importance of the IAQ items. Efficacy (i.e., positive and negative symptoms) was considered most important, but importance scores relative to the mean ranged only from 0.87 to 1.18, suggesting similar importance of the items. Cronbach's coefficient alpha values showed that the items were internally consistent. Factor analyses indicated that all IAQ items belong to a single domain. Data from the US Broad Effectiveness Trial of Aripiprazole were used for construct validation. Total IAQ score correlated significantly with time to treatment discontinuation (r=-0.50), Clinical Global Impressions-Improvement (CGI-I) score (r=0.76) and medication preference of patients (r=0.71) or caregivers (r=0.70). A one-unit decrease in IAQ score corresponded to an additional 1.35 days in the study and a decrease in CGI-I of 0.21 units. These results provide initial validation of the IAQ as a tool for evaluating antipsychotic response in patients with schizophrenia or schizoaffective disorder.
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PMID:Validation of the Investigator's Assessment Questionnaire, a new clinical tool for relative assessment of response to antipsychotics in patients with schizophrenia and schizoaffective disorder. 1611 90


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