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When [35S]GTPgammaS binding assays were performed in buffers containing Na+, some agonists (aripiprazole, AJ-76, UH-232) exhibited very low efficacy whereas other agonists exhibited measurable efficacy. When Na+ was substituted by N-methyl D-glucamine, the efficacy of all agonists increased (relative to that of dopamine) but particularly for aripiprazole, aplindore, AJ-76, (-)-3-PPP and UH-232. In ligand binding assays, substitution of Na+ by N-methyl D-glucamine increased receptor/G protein coupling for some agonists -. aplindore, dopamine and (-)-3-PPP - but for aripiprazole, AJ-76 and UH-232 there was little effect on receptor/G protein coupling.
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Considering just the clinical profile of iloperidone, it represents a promising drug for treating schizophrenia, particularly in patients who are intolerant to previous antipsychotics, as well as being suitable as first-line therapy. Cost-effectiveness comparisons are needed to justify its use in clinical practice.
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In this 4-week double-blind study, 404 patients were randomized to 20 mg/d (n = 101) or 30 mg/d (n = 101) of aripiprazole, placebo (n = 103), or 6 mg/d of risperidone (n = 99). Efficacy assessments included Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression scores. Safety and tolerability evaluations included extrapyramidal symptoms and effects on weight, prolactin, and corrected QT (QTc) interval.
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Changes in moods are one of the comorbid psychiatric manifestations that frequently occur in patients with Tourette's syndrome. The assessment of a manic episode in children with Tourette's syndrome is challenging. Furthermore, the treatment of children with comorbid mania and Tourette's syndrome has not been extensively studied. We present a 10-year-old boy who suffered from both Tourette's syndrome and mania, whose symptoms improved after using lithium and risperidone. The child was diagnosed with Tourette's syndrome at 7 years of age when he suffered from tics and experienced his first manic episode. He received monotherapy, including haloperidol, risperidone and aripiprazole, and the response was poor. When the combination of lithium and risperidone was used, the tics and mania subsided. It is important to assess individuals with Tourette's syndrome for associated bipolar disorder. The treatment of children with both disorders is a major clinical issue, and our case may serve as an example for successful treatment strategies.
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Since it is a well-known fact that among the newly discovered active pharmaceutical ingredients the number of poorly water soluble candidates is continually increasing, dissolution enhancement of poorly water soluble drugs has become one of the central challenges of pharmaceutical studies. So far the preclinical studies have been mainly focused on formulation methods to enhance the dissolution of active compounds, in many cases disregarding the fact that the formulation matrix not only affects dissolution but also has an effect on the transport through biological membranes, changing permeation of the drug molecules. The aim of this study was to test an electrospun cyclodextrin-based formulation of aripiprazole with the novel μFlux apparatus, which monitors permeation together with dissolution, and by this means better in vitro-in vivo correlation is achieved. It was evinced that a cyclodextrin-based electrospun formulation of aripiprazole has the potential to ensure fast drug delivery through the oral mucosa owing to the ultrafast dissolution of the drug from the formulation and the enhanced flux across membranes as shown by the result of the novel in vitro dissolution and permeation test.
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Aripiprazole was superior to placebo in reducing PANSS Hostility factor scores in adolescents with schizophrenia. After 6 weeks, aripiprazole 10 mg/day and aripiprazole 30 mg/day showed a statistically significant improvement versus placebo (-3.0, -3.7, versus -2.1; p < 0.05; last observation carried forward [LOCF]) in the PANSS Hostility factor. For aripiprazole 30 mg/day, statistically significant separation from placebo was evident from week 3 through week 6 and at week 6 for aripiprazole 10 mg/day. Individual PANSS Hostility, Uncooperativeness, and Poor Impulse Control Items showed statistically significant improvement with aripiprazole 30 mg/day over placebo at end point.
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La depresión en la edad avanzada (DEA) es una preocupación creciente de salud general y pública, con diversas manifestaciones clínicas y etiologías. Este artículo revisa de manera resumida los hallazgos de las neuroimágenes asociados con la depresión en adultos mayores y la variabilidad de la respuesta terapéutica. La DEA se ha asociado con atrofia cerebral, disminución de la integridad de la mielina y lesiones cerebrales en las regiones límbicas-frontoestriatales. Estas asociaciones ayudan a explicar el síndrome de disfunción ejecutiva de la depresión observado en la DEA y apoyan la carga cerebrovascular como un mecanismo patogénico. Este artículo sugiere además que los hallazgos esenciales de las neuroimágenes de la resistencia al tratamiento también reflejan la carga cerebrovascular. Entre las teorías etiológicas de la DEA, la carga cerebrovascular puede mediar la resistencia al tratamiento. Esta revisión propone que las neuroimágenes tienen un potencial en la traslación clínica. Los ensayos controlados pueden identificar biomarcadores de neuroimágenes que orienten el tratamiento al identificar adultos con depresión que probablemente remitirán con farmacoterapia, identificar dosis terapéuticas individualizadas y facilitar las mediciones de respuesta terapéutica precoz. Las neuroimágenes también tienen el potencial de orientar de manera similar la variabilidad de la respuesta terapéutica del tratamiento con aripiprazol (modulador dopaminérgico) y con buprenorfina (modulador opiáceo).
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Our findings suggest that many older people with Alzheimer's dementia and NPS can be withdrawn from chronic antipsychotic medication without detrimental effects on their behaviour. It remains uncertain whether withdrawal is beneficial for cognition or psychomotor status, but the results of this review suggest that discontinuation programmes could be incorporated into routine practice. However, two studies of people whose agitation or psychosis had previously responded well to antipsychotic treatment found an increased risk of relapse or shorter time to relapse after discontinuation. Two other studies suggest that people with more severe NPS at baseline could benefit from continuing their antipsychotic medication. In these people, withdrawal might not be recommended.
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ClinicalTrials.gov identifier NCT01655706 . Registered July 27, 2012.
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Aripiprazole was generally safe and well tolerated in the long-term treatment of irritability associated with autistic disorder in pediatric subjects. Weight should be proactively monitored during long-term treatment.
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Aripiprazole plasma concentrations and demographic data were collected retrospectively from previous bioequivalence studies that were conducted in Chonbuk National University Hospital. Informed consent was obtained from subjects for cytochrome P450 (CYP) genotyping. The population pharmacokinetic parameters of aripiprazole were estimated using nonlinear mixed-effect modeling with first-order conditional estimation with interaction method. The effects of age, sex, weight, height, and CYP genotype were assessed as covariates.
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Seventeen outpatients with schizophrenia (9 taking aripiprazole and 8 taking risperidone) and 18 healthy controls underwent (18)F-fluoroflumazenil PET, and GABAA receptor binding potential was compared between the three groups.
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To determine the cost effectiveness of maintenance treatment with quetiapine fumarate extended-release (XR) tablets in combination with mood stabilizers (lithium or divalproex) in comparison with the following treatments: placebo in combination with lithium or divalproex; no maintenance treatment; lithium monotherapy; lamotrigine monotherapy; olanzapine monotherapy; and aripiprazole monotherapy.
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Fifteen trials (9 unpublished), generally 10 to 12 weeks in duration, including 16 contrasts of atypical antipsychotic drugs with placebo met criteria (aripiprazole [n = 3], olanzapine [n = 5], quetiapine [n = 3], risperidone [n = 5]). A total of 3353 patients were randomized to study drug and 1757 were randomized to placebo. Outcomes were assessed using standard methods (with random- or fixed-effects models) to calculate odds ratios (ORs) and risk differences based on patients randomized and relative risks based on total exposure to treatment. There were no differences in dropouts. Death occurred more often among patients randomized to drugs (118 [3.5%] vs 40 [2.3%]. The OR by meta-analysis was 1.54; 95% confidence interval [CI], 1.06-2.23; P = .02; and risk difference was 0.01; 95% CI, 0.004-0.02; P = .01). Sensitivity analyses did not show evidence for differential risks for individual drugs, severity, sample selection, or diagnosis.
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On average, patients were rated improved or very much improved compared with baseline. Sixteen of 211 patients worsened or experienced no change. Forty-four patients (21%) discontinued due to adverse effects. The group of patients who underwent off-on-off-on trials experienced statistically significant improvement when they started and restarted aripiprazole, and statistically significant worsening when they discontinued it.
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Accurate monitoring and evaluation of the hyperprolactinemia induced by xenobiotics is strongly recommended. The typical antipsychotics and some of the atypical agents (amisulpride, risperidone, paliperidone), as well as some antidepressants, antihypertensives and prokinetics, are the most important groups inducing hyperprolactinemia. The hyperprolactinemic effects are correlated with their affinity for dopamine D2 receptors, their blood-brain barrier penetration and, implicitly, the requested dose for adequate occupancy of cerebral D2 receptors. Consequently, integration of available pharmacokinetic and pharmacodynamic data supports the idea of therapeutic switch to non-hyperprolactinemic agents (especially aripiprazole) or their association, for an optimal management of antipsychotic-induced hyperprolactinemia. Possible alternative strategies for counteracting the xenobiotics-induced hyperprolactinemia are also mentioned.
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Hyperprolactinemia and associated side effects often occur with antipsychotics. The authors investigated the effect of adjunctive treatment with aripiprazole on hyperprolactinemia and psychopathology in patients with schizophrenia maintained with haloperidol.
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The mean age of the participants was 30.8 years. Prolactin levels normalized in 23 (77%) participants during the study, and menstrual disturbances normalized in 25 (83.3%). Prolactin levels normalized in most patients between days 50 and 110. The median time to recovery based on normalization of prolactin was 84 days. Psychotic symptoms were present in 26 subjects at baseline, but in only two by the end of the study.
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The child, a female patient, was seen within the first week of life. The initial complaints were abnormal eye movements, and subsequently recurrent hemiplegic episodes, that started at age two and lasted hours to days. Attacks occurred at a frequency of about three per month and lasted from several hours to three days. An established trigger was bathing with cold water. Sleep relieved symptoms. The child had evidence of global developmental delay and neurological abnormalities including ataxia. EEG and MRI were both reported as abnormal. She experienced recurrent seizures. Topiramate and several anti-convulsants were not helpful but aripiprazole reduced the frequency of attacks.
This article aims to update the GP about the initial management of the acutely psychotic patient.
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Only three studies met the required quality criteria and were included. This literature suggests that ECT is an effective, safe, and probably underutilized treatment of mixed states. Recent technical developments have made ECT more friendly, tolerable, and safe. Potential alternatives, such as vagus nerve stimulation, deep brain stimulation, or transcranial stimulation, are still far to be proved as effective as ECT.
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Antipsychotics are currently the only available pharmacologic treatments for psychotic disorders. However, information about head-to-head differences in efficacy and tolerability of antipsychotics are scarce in children and adolescents. The TEA trial aims at expanding the evidence base for the use of antipsychotics in early onset psychosis in order to inform more rational treatment decisions in this vulnerable population. Here, we account for the trial design, address methodological challenges, and discuss the estimation of sample size.
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Second generation antipsychotics (SGAs) have emerged as new treatment options for bipolar disorders (BDs). Aripiprazole (ARI) is already an SGA approved therapy for the treatment of BD type-I, both as a monotherapy as well as an add-on therapy in acute mania and in long-term maintenance therapy.