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Although risperidone and aripiprazole have the strongest evidence in reducing ABC-I in youth with ASD, a few other compounds also showed significant efficacy with fewer potential side effects and adverse reactions in single studies.
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We examined the 2005 Medicare Current Beneficiary Survey Cost and Use file for 11,236 survey participants. Antipsychotic utilization was characterized in terms of class: FGA (ie, chlorpromazine, fluphenazine, haloperidol, loxapine, perphenazine, thiothixene, thioridazine, or trifluoperazine) or SGA (ie, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, or ziprasidone). Hospitalization was defined in terms of whether a Medicare beneficiary was admitted to the hospital for any reason in 2005, and was measured in terms of the number of hospital visits. In our final model, we included the following confounding variables: disability status (> or =1 limitation in activities of daily living), Rosow-Breslau impairment score (difficulty with walking, stooping, crouching, kneeling, or doing heavy housework), cognitive impairment (diagnosis of Alzheimer's disease or memory loss that interfered with daily activity), and health behavior variables (body mass index and smoking status).
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To comparatively assess the incidence of tardive dyskinesia in patients with schizophrenia receiving either aripiprazole or haloperidol.
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Six cocaine-dependent human subjects were maintained on aripiprazole (15 mg) and placebo for 10 days in counterbalanced order prior to assessing the physiological and subject-rated effects of intranasal cocaine.
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Aripiprazole was superior to placebo and not significantly different from haloperidol in reducing hostility.
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Currently, there is not an effective pharmacotherapy for the core symptoms of the autism spectrum disorders (ASD), which include aberrant social behavior, delayed communication and repetitive behavior and/or restricted interests. There are several drugs that treat the symptoms associated with autism including irritability, aggressiveness and hyperactivity. Current drug research is based on the ongoing genetic, animal model and neuropathologic research. Two areas in particular, the glutamate and oxytocin systems, provide exciting new avenues for drug discovery.
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We conclude that the orthostatic hypotensive effect in rats of the antipsychotic drugs investigated is mediated through alpha1A-ARs.
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Seven patients responded to treatment, two did not respond, and one had a partial response. The mean Clinical Global Impression Scale scores improved from 6 (severely ill) at baseline to 2.3 (much improved) at discharge. Treatment was discontinued in the two patients who did not respond. Of the seven patients who responded, four presented with positive symptoms and showed significant improvement while three presented with positive and negative symptoms and both symptoms improved significantly. Four patients had preexisting extrapyramidal symptoms (EPS) and these symptoms decreased in three patients. In addition, two patients were able to discontinue antiparkinson medications. One patient who had severe tardive dyskinesia showed significant improvement in the dyskinetic symptoms. Four patients showed postural hypotension (without clinical symptoms) which resolved over time without treatment. Six patients showed a mean weight loss of 5.2 lbs. No adverse consequences occurred when divalproex sodium, carbamazepine, clonazepam or citalopram were given concurrently.
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We searched the MEDLINE and Embase databases (2003-10 April 2016) for clinical trials in pediatric patients (aged 0-18 years) using the keywords 'aripiprazole' (regardless of the formulation) and 'extrapyramidal symptoms'. We evaluated the abstracts of papers using the following exclusion criteria: (1) study design: case report, letter to the editor, editorial, or poster presentation data; (2) unrelated PICOS (population, intervention, comparators, outcomes, study) structure. We performed a meta-analysis, in which we used effect sizes with 95 % confidence intervals (CIs). To examine the homogeneity of the effect size distribution, we used a Q-statistic. When we observed heterogeneity in effect sizes, we assessed the possible influence of moderator variables (age and sex, mean dose, study duration, and method of measuring EPS incidence) and evaluated the suitability of either a fixed or a random model. Finally, we assessed the incidence of EPS in children and adolescents treated with aripiprazole compared with placebo.
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After initial positive, short case reports and clinical trials, larger studies failed to show the effectiveness of AAPs combined with antidepressants for TRD. More recently, larger scale clinical trials have supported the effectiveness of at least some of these medications. While AAPs have gained in popularity for TRD, there are nagging concerns regarding risks such as metabolic syndrome and tardive dyskinesia.
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A critical issue in the treatment with atypical APs is represented by their metabolic side effect profile (e.g. weight gain, lipid and glycaemic imbalance, risk of diabetes mellitus and diabetic ketoacidosis) which may limit their use in particular clinical samples. Electrolyte imbalance, ECG abnormalities and cardiovascular adverse effects may recommend a careful baseline and periodic assessments.
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Although second-generation antipsychotics (SGAs) are characterized by fewer prolactin (PRL)-related side effects compared with first-generation antipsychotics, the detailed effects of SGAs on the plasma PRL levels still remain unclear. We examined the differences in plasma PRL levels among 268 patients treated for schizophrenia with olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), quetiapine (QTP), or perospirone (PER). The participants had received antipsychotic monotherapy with stable doses of OLZ, RIS, ARP, QTP, or PER for ≥ 3 weeks, and fasting blood samples were drawn to examine plasma PRL levels. The differences in median plasma PRL levels in all (P<0.001), male (P<0.001) and female patients (P<0.001) among the five SGA groups were statistically significant. A stepwise multiple regression analysis showed that ARP treatment was found to contribute to lower plasma PRL level, while female sex, RIS, OLZ and chlorpromazine equivalent dose were found to contribute to a higher plasma PRL level. The median value of plasma PRL level in the RIS group was twice as much compared with that in the OLZ group, although this was not statistically significant. In this study, OLZ had a considerable effect on plasma PRL level, similar to RIS, while PER did not affect plasma PRL levels, similar to QTP. Further studies are needed to clarify the differences in plasma PRL levels among SGAs.
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Risperidone was started to treat psychotic symptoms. Psychotic symptoms disappeared but because of galactorrhoea risperidone needed to be discontinued. Subsequently, an antipsychotic treatment regimen with aripiprazole and haloperidol was prescribed. After initiating aripiprazole and haloperidol the patient's psychotic symptoms increased drastically. Therefore aripiprazole and haloperidol were discontinued. Olanzapine was prescribed and psychotic symptoms declined again.
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Musical obsessions consist of intrusive recollections of music fragments that are experienced as unwanted. Otosclerosis is caused by an abnormal bone homeostasis of the otic capsule and represents a frequent cause of hearing impairment. Many conditions causing hearing loss have been associated with musical hallucinations, but the association between musical obsessions and hearing loss is frequently overlooked.
The effects of aripiprazole on cognitive function are obscure, possibly due to the difficulty in disentangling the specific effects on cognitive function from effects secondary to the improvement of other schizophrenic symptoms. This prompts the necessity of using an intermediate biomarker relating the drug effect on the brain to change in cognitive function.
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CYP2D6 (cytochrome P450 2D6) is one of the most important enzymes involved in drug metabolism, and CYP2D6 gene variants may cause toxic effects of therapeutic drugs or treatment failure. In this research, a rapid and simple method for genotyping the most common mutant alleles in the Asian population (CYP2D6*1/*1, CYP2D6*1/*10, CYP2D6*10/*10, CYP2D6*1/*5, CYP2D6*5/*10, and CYP2D6*5/*5) was developed by allele-specific polymerase chain reaction (AS-PCR) combined with capillary electrophoresis (CE). We designed a second mismatch nucleotide next to the single nucleotide polymorphism (SNP) site in allele-specific primers to increase the difference in PCR amplification. Besides, we established simulation equations to predict the CYP2D6 genotypes by analyzing the DNA patterns in the CE chromatograms. The multiplex PCR combined with CE method was applied to test 50 patients, and all of the test results were compared with the DNA sequencing method, long-PCR method and real-time PCR method. The correlation of the analytical results between the proposed method and other methods were higher than 90%, and the proposed method is superior to other methods for being able to simultaneous detection of SNPs and copy number variations (CNV). Furthermore, we compared the plasma concentration of aripiprazole (a CYP2D6 substrate) and its major metabolites with the genotype of 25 patients. The results demonstrate the proposed genotyping method is effective for estimating the activity of the CYP2D6 enzyme and shows potential for application in personalized medicine. Similar approach can be applied to simultaneous detection of SNPs and CNVs of other genes.
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Second-generation antipsychotics (SGAs) are thought to have a lower likelihood of inducing extrapyramidal symptoms (EPS) than are first-generation antipsychotics (FGAs). Clinical observations suggest that younger patients may be more sensitive to SGA-associated EPS than are adults and require therapy with anticholinergic agents.
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Sociodemographic and treatment data were collected from medical records of 1,103 inpatients and outpatients treated for schizophrenia at Seoul National Hospital in Seoul, Korea. Anthropometric measurement and blood testing were conducted for collection of physical and biochemical data and diagnosis of metabolic syndrome. Data for metabolic syndrome prevalence were compared by sex, age, metabolic syndrome markers present, treatment of markers, and types of antipsychotics and individual drug agents used.
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In total, 316 patients were randomly assigned to receive treatment with aripiprazole (fixed-dose study, 166; flexible-dose study, 47) or placebo (fixed-dose study, 52; flexible-dose study, 51). Aripiprazole was associated with significantly greater improvement than placebo in PedsQL combined-scales total score (difference, 7.8; 95% CI, 3.8-11.8; P < 0.001) and in 3 PedsQL scale scores (differences [95% CI]: Emotional Functioning, 7.8 [3.4-12.2]; Social Functioning, 6.2 [0.7-11.8]; Cognitive Functioning, 9.3 [3.8-14.9]; all, P < 0.05). Patients who received aripiprazole were significantly more likely than those who received placebo to have a clinically meaningful improvement on the combined-scales total score (odds ratio [OR] = 1.9; 95% CI, 1.0-3.3; P < 0.05), Emotional Functioning scale (OR = 2.2; 95% CI, 1.2-4.0; P < 0.05) and Social Functioning scale (OR = 2.2; 95% CI, 1.2-4.1; P < 0.05), and were significantly less likely to experience deterioration (OR: 0.3, 95% CI: 0.1-0.8; P < 0.05) when "Stable" was used as the reference group.
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We included all randomised trials comparing oral zotepine with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole or ziprasidone in people with schizophrenia or schizophrenia-like psychoses.
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Dopamine D(2) receptor partial agonist antipsychotic drugs can modulate dopaminergic neurotransmission as functional agonists or functional antagonists. The effects of antipsychotics on presynaptic dopaminergic functions, such as dopamine synthesis capacity, might also be related to their therapeutic efficacy. Positron emission tomography (PET) was used to examine the effects of the partial agonist antipsychotic drug aripiprazole on presynaptic dopamine synthesis in relation to dopamine D(2) receptor occupancy and the resulting changes in dopamine synthesis capacity in healthy men. On separate days, PET studies with [(11)C]raclopride and L-[β-(11)C]DOPA were performed under resting condition and with single doses of aripiprazole given orally. Occupancy of dopamine D(2) receptors corresponded to the doses of aripiprazole, but the changes in dopamine synthesis capacity were not significant, nor was the relation between dopamine D(2) receptor occupancy and these changes. A significant negative correlation was observed between baseline dopamine synthesis capacity and changes in dopamine synthesis capacity by aripiprazole, indicating that this antipsychotic appears to stabilize dopamine synthesis capacity. The therapeutic effects of aripiprazole in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.