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)

For various reasons large numbers of patients treated with Clozapine end up discontinuing the treatment. The authors present the results of switching to Aripiprazole in patients who had to discontinue Clozapine because of neutropenia below the acceptable level for treatment with Clozapine. To summarize and present three cases of individuals with treatment resistant schizophrenia based on the ICD-10 diagnosti criteria. In all cases Clozapine was discontinued and treatment changed to Aripiprazole. Favorable clinical results were noticed in all three patients. The findings from this case series suggest that there is scope for a trial of Aripiprazole for patients with treatment resistant schizophrenia and an invitation for further research of this area.
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PMID:Use of Aripiprazole in treatment resistant schizophrenia. 1830 5

An intramuscular formulation of the atypical antipsychotic aripiprazole (Abilify) has been developed and is approved in the EU for use in agitation and disturbed behaviour associated with schizophrenia. In the US, it is approved for the treatment of agitation associated with schizophrenia or bipolar I disorder (manic or mixed). In large, well designed trials, intramuscular aripiprazole was an effective and generally well tolerated treatment for agitation associated with schizophrenia, schizoaffective disorder, schizophreniform disorder or bipolar I disorder. Intramuscular aripiprazole was more effective than placebo in these patient populations and was noninferior to intramuscular haloperidol in those with agitation associated with schizophrenia and its related disorders. Aripiprazole is associated with a low risk for extrapyramidal symptoms (EPS), cardiac effects, hyperprolactinaemia, weight gain and other metabolic disturbances. Head-to-head trials comparing intramuscular aripiprazole with other intramuscular atypical antipsychotics are required before the relative position of each of these agents can be fully determined. In the meantime, intramuscular aripiprazole, with its favourable tolerability profile, is a valuable treatment option for agitation in patients with schizophrenia, schizoaffective disorder, schizophreniform disorder or bipolar I disorder.
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PMID:Intramuscular aripiprazole : a review of its use in the management of agitation in schizophrenia and bipolar I disorder. 1833 61

The activation of the inflammatory/immunological response system is suggested to be related to the pathophysiology of schizophrenia. Aripiprazole is a novel atypical antipsychotic, which is a high-affinity dopamine D(2) receptor partial agonist. Atypical antipsychotics, all of which have dopamine D(2) receptor antagonism, have recently reported to have significantly inhibitory effects on interferon (IFN)-gamma-induced microglial activation in vitro. In the present study, we investigated whether or not aripiprazole also has anti-inflammatory effect on IFN-gamma-induced microglial activation. Not quinpirole, dopamine D(2) full agonist, but aripiprazole significantly inhibited the generation of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha from IFN-gamma-activated microglia and suppressed the IFN-gamma-induced elevation of intracellular Ca(2+) concentrations ([Ca(2+)](i)) in murine microglial cells. Increased [Ca(2+)](i) has been reported to be required, but by itself not sufficient, for the release of NO and certain cytokines. As a result, we can speculate that aripiprazole may inhibit IFN-gamma-induced microglial activation through the suppression of IFN-gamma-induced elevation of [Ca(2+)](i) in microglia. Our results demonstrated that not only antipsychotics which have dopamine D(2) receptor antagonism but also aripiprazole have anti-inflammatory effects via the inhibition of microglial activation. Antipsychotics may therefore have a potentially useful therapeutic effect on patients with schizophrenia by reducing the microglial inflammatory reactions.
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PMID:Inhibitory effects of aripiprazole on interferon-gamma-induced microglial activation via intracellular Ca2+ regulation in vitro. 1842 30

Among the second generation antipsychotics, aripiprazole presents a new pharmacological profile, basically differentiated by a partial agonist effect on the D2 and D3 dopaminergic receptors. Five short-term efficacy studies, conducted on 1648 patients presenting with schizophrenia or acute relapse of schizoaffective disorders, demonstrated the greater efficacy of aripiprazole than the placebo and comparable efficacy to that of haloperidol and risperidone. The short-term tolerance profile was characterised by a lesser incidence of the extrapyramidal side effects and drowsiness than with haloperidol. Two thousand six hundred and eighty five patients were followed-up over a period of 26 to 52 weeks in five clinical trials versus a placebo and haloperidol, olanzapine, quetiapine and risperiodone: demonstrated efficacy in maintaining the response to treatment and on the delay before relapse was comparable to the other antipsychotics. The classical side effects of antipsychotics decreased in the long-term. Versus olanzapine, a glucid and lipid profile, clearly in favour of aripiprazole, was completed by a lesser incidence of hyperprolactinaemia. Aripiprazole is effective on all the dimensions of schizophrenia: the positive and negative and depressive and anxious symptomatology. It appears to be of interest, notably on the cognitive dimension, which should motivate more in-depth exploration of its place in the treatment in the early stages of schizophrenia. Its therapeutic schedule and the methods of initiation are an essential criterion to the success of treatment, notably during the substitution of other antipsychotics. The clinical and pharmacological originality of aripiprazole would justify the terminology of a "third generation antipsychotic".
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PMID:[Present data and treatment schedule of aripiprazole in the treatment of schizophrenia]. 1851 55

In clinical practice, a proportion of patients with psychotic or mood disorders are treated with electroconvulsive therapy (ECT) while receiving concomitantly antipsychotic and/or other psychotropic agents. Aripiprazole is a second-generation antipsychotic that seems to have a favorable side-effect profile. However, to the best of our knowledge, there are, as yet, no available reports on the safety of ECT-aripiprazole combination. We report the cases of 4 female inpatients--3 suffering from major depression and 1 from schizophrenia--who underwent ECT--1 of them twice--while receiving aripiprazole (10-15 mg/d), as part of their regimen. In all cases, the combination was well tolerated and only minimal side effects were reported.
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PMID:The safety of the electroconvulsive therapy-aripiprazole combination: four case reports. 1856 46

Aripiprazole is indicated for the treatment of schizophrenia in Europe and the United States, and for bipolar disorders in the latter. Nevertheless, a review of recent literature has shown that aripiprazole has been studied in many other disorders, notably resistant depression, anxiety, obsessive-compulsive disorder, borderline personality, Tourette syndrome, addiction, psychotic symptoms in children and adolescents, and neurological and psychiatric disorders in the elderly (late onset delusional disorders, Alzheimer, Parkinson, and delirium). The study of aripiprazole in these numerous indications is motivated by its excellent tolerance and original pharmacological effect (partial agonistic effect on the D2 and 5-HT1A receptors, and antagonistic effect on the 5-HT2A receptors). This paper reviews the recent literature, with particular attention paid to the level of proof provided by these various studies.
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PMID:[Clinical potentialities and perspectives for the use of aripiprazole in other disorders than its classical indications. A critical analysis of the recent literature]. 1859 28

This multicenter, open-label, sequential-cohort, dose-escalation study explored the tolerability and pharmacokinetics (PK) of aripiprazole up to the maximum approved adult dose (30 mg/d) in children and adolescents (aged 10-17 years) preferentially with primary psychiatric diagnoses of a bipolar or schizophrenia spectrum disorder. During a dose-escalation phase, patients received aripiprazole for up to 12 days using forced titration to achieve doses of 20, 25, or 30 mg/d. In the subsequent fixed-dose phase, patients received the maximum dose for that cohort for an additional 14 days. Tolerability in each fixed-dose cohort was assessed by measures including evaluation of spontaneously reported adverse events (AEs) and vital signs. If 4 of 6 patients tolerated the maximum dose for the cohort, the dose was considered tolerated, and enrollment in the next dose level began. Of 21 enrolled patients, 17 completed the fixed-dose phase. Aripiprazole treatment was generally well tolerated, with criteria for tolerability met for all doses tested. All patients experienced at least 1 AE, none of which met the regulatory criteria for a serious AE. There were no deaths or clinically relevant changes in vital signs or weight. Aripiprazole PK seemed to be linear across the tested dose range and was comparable with previous PK observations in adults. This study provides information regarding the tolerability and PK of aripiprazole up to the maximum adult dose in children and adolescents. These data provided support for exploration of a 30-mg/d dose in child/adolescent schizophrenia and bipolar disorder.
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PMID:Tolerability and pharmacokinetics of aripiprazole in children and adolescents with psychiatric disorders: an open-label, dose-escalation study. 1862 72

Cognitive impairment is a key feature of schizophrenia and may be the most important determinant of outcome in schizophrenia. This impairment is diffuse and may reflect abnormalities in frontal cortex, hippocampus and other brain regions. While deficits in glutamatergic, GABAergic, dopaminergic and cholinergic impairment have received the most attention as the basis of this impairment, there are many reasons for considering the role of serotonin (5-HT) in contributing to these deficits. This may be via its influence on dopaminergic, cholinergic, glutamatergic and GABAergic function, as well as various growth factors that have been implicated in schizophrenia. Of the 14 known serotonin receptors, the 5-HT(1A) receptor is a key candidate for mediating at least some of the influence 5-HT has on cognition. 5-HT(1A) receptors are upregulated in postmortem specimens from patients with schizophrenia, suggesting a deficit in 5-HT(1A) function in this disorder. Atypical but not typical antipsychotic drugs stimulate the efflux of dopamine from cortex by a 5-HT(1A)-dependent mechanism. A series of studies from this laboratory involving the 5-HT(1A) partial agonists tandospirone and buspirone have reported a modest ability of these agents to improve some domains of cognition in patients receiving typical or atypical antipsychotic drugs. Preclinical studies have been mixed in regard to the ability of 5-HT(1A) partial agonists to improve cognition in various paradigms; some studies report that 5-HT(1A) antagonists are effective to improve cognition. Aripiprazole, clozapine, olanzapine, perospirone, quetiapine risperidone, and ziprasidone are examples of atypical antipsychotic drugs which are either direct or indirect 5-HT(1A) agonists which have been shown to improve cognitive function in patients with schizophrenia. Further study is needed to determine the role of the 5-HT(1A) receptor to improve cognitive function in schizophrenia.
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PMID:Does stimulation of 5-HT(1A) receptors improve cognition in schizophrenia? 1870 69

Aripiprazole is a novel atypical antipsychotic drug with neuroprotective properties. As excessive glutamate release is now considered to be part of the pathophysiology of schizophrenia, the objective of this study was to use an in vitro assay system to investigate the effect of aripiprazole and its human metabolite OPC14857 on the release of endogenous glutamate from isolated nerve terminals (synaptosomes), freshly prepared from rat prefrontal cortex. Both aripiprazole and OPC13857 potently inhibited 4-aminopyridine (4-AP)-evoked glutamate release in a concentration-dependent manner. Inhibition of glutamate release by aripiprazole and OPC13857 was associated with a reduction of 4AP-evoked Na+ influx and depolarization, as well as downstream elevation of cytoplasmic free calcium concentration mediated via N- and P/Q-type voltage-dependent Ca2+ channels (VDCCs). Release induced by direct Ca2+ entry with Ca2+ ionophore (ionomycin) was unaffected by aripiprazole or OPC13857, indicating that the inhibitory effect of aripiprazole or OPC13857 is not due to directly interfering with the release process at some point subsequent to Ca2+ influx. In addition, the dopamine D2 receptor antagonist haloperidol and the 5-HT 1A receptor antagonist WAY100635 all effectively blocked the aripiprazole or OPC13857-mediated inhibition of 4-AP-evoked glutamate release. Moreover, aripiprazole or OPC13857 modulation of 4-AP-evoked glutamate release appears to involve a protein kinase A (PKA) signaling cascade, insofar as pretreatment of synaptosomes with the PKA inhibitor H89 suppressed the inhibitory effect of aripiprazole or OPC13857. Together, these results suggest that aripiprazole and its human metabolite OPC14857 inhibit glutamate release from rat prefrontocortical nerve terminals, likely by the activation of dopamine D2 and 5-HT 1A receptors, which subsequently results in the reduction of nerve terminal excitability and downstream VDCC activation through a signaling cascade involving PKA. These actions of aripiprazole may contribute to its neuroprotective effect in excitotoxic injury.
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PMID:Aripiprazole and its human metabolite OPC14857 reduce, through a presynaptic mechanism, glutamate release in rat prefrontal cortex: possible relevance to neuroprotective interventions in schizophrenia. 1872 Apr 21

Although recent treatment guidelines for schizophrenia recommend that the prior antipsychotic agent should remain stable for at least 2 weeks when aripiprazole is introduced, there is no trial-based evidence to support this strategy. This study was designed to compare this strategy with another conventional one in patients with schizophrenia. We conducted a randomized, 14-week, open-label trial to compare the following 2 switching strategies: (1) add-on of aripiprazole on a current regimen, wait for 4 weeks, and the tapering of prior antipsychotics and (2) add-on of aripiprazole and the simultaneous tapering of prior antipsychotics in patients with schizophrenia. Aripiprazole was initiated at 12 mg/d and then titrated between 12 and 30 mg. The previous antipsychotic medication was reduced biweekly by 25%. Assessments included the Clinical Global Impression Scale Schizophrenia version, the Drug-Induced Extrapyramidal Symptoms Scale, and the Subjective Well-being Under Neuroleptics, Short Version, Japanese Edition. Impressions toward their assigned strategy were also subjectively evaluated at baseline and end point. Fifty-three patients were enrolled, and 48 patients completed this trial. No significant differences were found in changes from the baseline in the total Clinical Global Impression Scale Schizophrenia version severity, Drug-Induced Extrapyramidal Symptoms Scale, and Subjective Well-being Under Neuroleptics, Short Version, Japanese Edition scores throughout the study period between the 2 strategies. Both strategies were judged by subjects to be tolerable and favorable without between-group differences. In conclusion, both strategies were found to be objectively safe and well tolerated. Taken together with similar results from subjective assessments, it would be reasonable to choose either of these 2 strategies in clinical practice based on a patients' preference.
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PMID:A randomized, open-label comparison of 2 switching strategies to aripiprazole treatment in patients with schizophrenia: add-on, wait, and tapering of previous antipsychotics versus add-on and simultaneous tapering. 1879 50


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