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 an agent for treating schizophrenia. The authors assume that aripiprazole as a dopamine receptor partial agonist may be useful in treating PD patients. Three cases are presented in this study. All patients were evaluated by the same clinician, a neuropsychiatrist well trained in the use of Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI). Aripiprazole was effective for reducing psychosis in each case.
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PMID:Aripiprazole in psychosis associated with Parkinson's disease. 1617 68

Aripiprazole is a new chemical entity with a unique pharmacological profile. It has strong affinities for certain dopamine receptors, and intermediate affinity for serotonin, adrenergic and histamine receptors. Partial agonism of the D2 dopamine and 5HT1A serotonin receptors, and antagonism of the 5HT2 serotonin receptor are believed to be the functional basis of its therapeutic efficacy. Its clinical effects are best documented in patients suffering from schizophrenia and bipolar disorder, in which it has been demonstrated to have antipsychotic and antimanic properties superior to placebo in dose ranges of 10-30 mg/day. Two published longer term trials document maintenance of antipsychotic effects and relapse prevention in schizophrenia patients. In general, aripiprazole seems to be a well-tolerated drug, especially with regard to metabolic side effects. The most commonly reported side effects include restlessness/akathisia, somnolence and nausea. These may be dose-dependent and usually occur early on during treatment, with many patients developing tolerance. Aripiprazole is an interesting and important addition to the currently available spectrum of antipsychotic drugs. Further studies in other indications and clinical trials that confirm results from the Phase II and III clinical development programme are eagerly awaited.
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PMID:Aripiprazole. 1619 61

(1) Neuroleptics are the standard treatment for schizophrenia. The first drugs of this class, such as haloperidol, were marketed nearly 50 years ago, and neuroleptics released over the past 15 last years have provided no major advance. (2) Aripiprazole is a new neuroleptic licensed for the treatment of schizophrenia. (3) Five double-blind placebo-controlled trials lasting 4 to 6 weeks showed that aripiprazole was a little more effective than placebo at daily doses of 10 mg to 30 mg, without a clear dose-response relationship. Based on the least demanding definition of "treatment response" (a 30% reduction in the PANSS global score), less than 50% of patients responded to aripiprazole. (4) In a double-blind trial lasting 6 months, aripiprazole 15 mg/day was more effective than placebo in preventing acute relapses of schizophrenia (34% versus 57%), but the clinical relevance of the combined endpoint used to define relapse is unclear. (5) The only double-blind comparison versus another neuroleptic (haloperidol) involved two trials that were pooled for analysis. Haloperidol was provided at a moderate dose (10 mg/day). These trials were designed to demonstrate the superiority of high-dose aripiprazole (30 mg/day), but failed to do so. The proportion of patients who "responded" during an acute episode, based on the least stringent definition, was about 70% in both groups. In both groups, response persisted in approximately three-quarters of patients. (6) Aripiprazole exhibits the adverse effects classically seen with neuroleptics. In clinical trials, daily doses of aripiprazole, ranging from 15 mg to 30 mg, provoked fewer extrapyramidal disorders than haloperidol 10 mg/day. In contrast, there was no difference in the frequency of extrapyramidal disorders with aripiprazole 20 or 30 mg/day and risperidone (6 mg). Aripiprazole has no proven advantage over haloperidol in terms of the risk of tardive dyskinesia. One trial showed no difference between aripiprazole and olanzapine in the risk of diabetes. Weight gain appears to be comparable with aripiprazole and haloperidol. Aripiprazole provoked postural hypotension and neuroleptic malignant syndrome, but the precise risk relative to other neuroleptics has not been documented. Supra-therapeutic doses of aripiprazole cause dose-dependent QT prolongation. (7) Increased mortality was seen in elderly patients treated with aripiprazole. (8) Animal studies have shown retinal degeneration in rats and biliary lithiasis in monkeys. These adverse effects have not been observed in clinical trials, but they have not been specifically assessed in humans. (9) Animal studies raised the possibility of fetal toxicity and teratogenicity. (10) The aripiprazole dose must be either halved or doubled during co-administration with inhibitors or inducers of cytochrome P450 isoenzymes CYP 3A4 and CYP 2D6. (11) In practice, there are too many unanswered questions to recommend aripiprazole for patients with schizophrenia.
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PMID:Aripiprazole: new drug. Just another neuroleptic. 1628 69

Aripiprazole exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors, moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors. The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydroaripiprazole, respectively. Steady-state concentrations are attained within 14 days of dosing for both active moieties. At least 1 to 2 weeks, and sometimes up to 4 weeks, may pass before aripiprazole reaches its full effect. The efficacy of aripiprazole was investigated in the treatment of schizophrenia, in the treatment of acute manic episode associated with Bipolar I Disorder, and in the treatment of psychosis associated with Alzheimer's dementia. Aripiprazole has demonstrated superiority to placebo in clinical studies of the treatment of both schizophrenia and acute bipolar mania. Aripiprazole has been evaluated for safety in 5592 patients who participated in multiple dose, premarketing trials in schizophrenia, bipolar mania, and dementia of the Alzheimer's type. The recommended starting and target dose for aripiprazole is 10 or 15 mg/day administered on a once-a-day schedule without regard to meals. Aripiprazole has been systematically evaluated and shown to be effective in a dose range of 10 to 30 mg/day. Dosage increases should not be made before 2 weeks of continuous therapy, the time needed to achieve steady state. At least 1 to 2 weeks, and sometimes up to 4 weeks, may pass before aripiprazole reaches its full effect. In this presentation was given an overview of novel antipsychotic aripiprazole.
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PMID:Aripiprazole: an overview of a novel antipsychotic. 1639 46

This is a case report of a 56-year-old lady who was admitted to a psychiatric ward because she was showing a plethora of positive and negative symptoms of schizophrenia. She has a positive history of mental illness; her mother had a diagnosis of schizophrenia. The patient did not have any medical history of relevance and was not taking any medication. She was commenced on Aripiprazole and after 5 weeks developed disabling extra-pyramidal side effects. On discontinuation of Aripiprazole, the side effects subsided and disappeared quickly. According to the authors' knowledge, this is the first case of a patient developing extra-pyramidal side effects following treatment with Aripiprazole, not previously exposed to other antipsychotic, and with no co-morbid medical conditions. The authors suggest titrating Aripiprazole slowly.
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PMID:A case of Aripiprazole and extra pyramidal side effects. 1640 61

Aripiprazole is a newer atypical antipsychotic agent used for effective treatment of schizophrenia. It significantly reduces unwanted side effects of older typical antipsychotics by targeting, with high affinity, dopamine D2/D3 and serotonin 5-HT1A/5-HT-2A receptors. Its documented mechanism of action makes it an unlikely agent to cause syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present the first reported case of SIADH caused by aripiprazole in a patient with history of schizophrenia without other precipitating factors to explain hyponatremia or SIADH.
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PMID:Aripiprazole-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH). 1685 73

Aripiprazole is an oral atypical antipsychotic drug used in the treatment of schizophrenia and potentially other behavior disorders. The purpose of this study was to describe the epidemiology of aripiprazole exposures reported to Texas poison control centers. Human aripiprazole exposures reported to six Texas poison control centers were identified and comparisons were made between isolated and nonisolated cases with respect to various demographic and clinical factors. Of 280 human exposures involving aripiprazole, 35% were isolated and 65% were nonisolated. The patients were female in 52% of isolated and 60% of nonisolated cases. Isolated cases were significantly more likely to involve children < 6 yr of age. Fifty-eight percent of isolated cases were unintentional while 68% of nonisolated cases were intentional. Nonisolated cases were much more likely to already be at or en route to a health care facility when the poison control center was contacted. Of those cases with a known medical outcome, no adverse clinical effect was reported in 52% of isolated cases and 35% of nonisolated cases. The adverse clinical effects associated with isolated aripiprazole exposures were mainly neurological, cardiovascular, and gastrointestinal, with the most frequently reported adverse clinical effect being drowsiness or lethargy. The most commonly reported treatments for isolated aripiprazole exposures were single dose of activated charcoal, cathartic, intravenous fluids, dilution, lavage, and antihistamines. In conclusion, isolated and nonisolated aripiprazole exposures varied with respect to patient age, exposure reason, management site, and clinical outcome.
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PMID:Aripiprazole exposures reported to Texas poison control centers during 2002-2004. 1686 22

Patients with schizophrenia and their physicians face a number of challenges, such as long-term control of symptoms, maintaining cognitive function and subjective well-being, and preventing relapse. While randomised, placebo-controlled trials and open-label extensions can provide valuable information about the long-term efficacy and tolerability of newer antipsychotic agents, they cannot address all the variables that may affect treatment outcome. Factors such as cognitive function, antipsychotic side effects, patients' attitudes to medication and subjective well being can all affect the results of treatment in real-life clinical practice. Moreover, the patient cohorts enrolled in clinical trials are often not reflective of the wider population with schizophrenia. For example, patients with conditions such as anxiety and panic disorders or comorbid substance abuse, as well as those with severe illness and patients from certain ethnic or age groups, may often be excluded from clinical trials. In addition, patients themselves may refuse to participate in placebo-controlled studies because of a fear of being under-treated. Naturalistic studies are, therefore, an important means of providing additional data on the safety and effectiveness of antipsychotic agents in 'real-world' settings. Studies such as the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, the Schizophrenia Outpatient Health Outcomes (SOHO) study and the Broad Effectiveness Trial with Aripiprazole (BETA) studies, together with large-scale database analyses, are now producing results supplementary to those observed in long-term, open-label extension studies. Such naturalistic studies will continue to provide important data on the real-world effectiveness of atypical antipsychotics with respect to key outcomes such as treatment continuation and prolonged recovery.
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PMID:Meeting everyday challenges: antipsychotic therapy in the real world. 1687 7

People with intellectual disabilities may be at greater risk of developing movement disorders as a consequence of their underlying neurological damage, especially when they are treated with typical antipsychotic agents. Aripiprazole is a novel antipsychotic quinolone derivative that has been approved for the treatment of schizophrenia in adults. However, there are few reports on the use of aripiprazole in people with intellectual disabilities. Herein, we report on the use of aripiprazole in five individuals with intellectual disabilities and psychotic illness (four cases) or challenging behaviour (one case). Four of the five patients had an additional diagnosis of schizophrenia and one had autism spectrum disorder and challenging behaviour. Issues related to the usefulness of aripiprazole in the management of schizophrenia and challenging behaviour in people with intellectual disabilities are also discussed. Aripiprazole was well tolerated and effective in each of the cases and appears to be a safe and efficacious alternative in the management of patients with both intellectual disabilities and schizophrenia. It can also be a useful treatment option in the management of challenging behaviour, especially when it is used as a part of a biopsychosocial approach.
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PMID:Aripiprazole use in individuals with intellectual disability and psychotic or behavioural disorders: a case series. 1689 39

Aripiprazole, (+)terguride, OPC-4392 and (-)3-PPP have been classified as dopamine D(2) receptor partial agonists based largely on their activity in second messenger-based assays of dopamine D(2) receptor signalling. Nevertheless, signal transduction amplification might result in these compounds behaving as dopamine D(2) receptor full agonists at a more downstream level of signalling. We compared the intrinsic activity (E(max), expressed as a percentage of the maximal effect of dopamine) of aripiprazole, (+)terguride, OPC-4392 and (-)3-PPP using second (calcium (Ca(2+)) mobilization) and third (extracellular signal-regulated kinase 2 (ERK2) phosphoprotein expression) messenger readouts of cloned human dopamine D(2long) (hD(2L)) receptor signalling in CHO cells. These compounds were all less potent and displayed lower intrinsic activity in the Ca(2+) assay (aripiprazole = 24.3%, (+)terguride = 56.9%, OPC-4392 = 58.6% and (-)3-PPP = 75.1%), and aripiprazole (E(max) = 54.5%) displayed a substantially lower intrinsic activity than (+)terguride (E(max) = 92.3%), OPC-4392 (E(max) = 93.1%) and (-)3-PPP (E(max) = 101.1%) in the more downstream-based ERK2 phosphoprotein expression assay. These drug effects on Ca(2+) mobilization and ERK2 phosphoprotein expression were mediated through dopamine hD(2L) receptors, as they all were blocked by (-)raclopride, whereas (-)raclopride and other dopamine D(2) receptor antagonists (haloperidol, risperidone, ziprasidone, olanzapine, clozapine and quetiapine) were inactive on their own in both assays. These data are consistent with clinical evidence that only dopamine D(2) receptor partial agonists with a sufficiently low enough intrinsic activity will prove effective against the positive symptoms of schizophrenia, and also highlight the importance of using downstream-based assays in the discovery of novel D(2) receptor partial agonist therapeutics.
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PMID:In vitro functional characteristics of dopamine D2 receptor partial agonists in second and third messenger-based assays of cloned human dopamine D2Long receptor signalling. 1709 71


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