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Mirror-image studies do not include a parallel active control; as each patient serves as their own control, it cannot be determined whether other treatments may have similar effects. Treatment and trial effects may be difficult to separate. Independent factors such as admission patterns, insurance coverage, availability of hospital beds, and community support may influence rates of hospitalisation.
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The regional difference in the expression of c-fos mRNA induced by typical and atypical antipsychotics was determined in prefrontal cortex, striatum, N. accumbens and lateral septum in rats by in situ hybridization. Two typical antipsychotics, haloperidol (2 mg/kg) and fluphenazine (2 mg/kg), and three atypical antipsychotics, (-)sulpiride (100 mg/kg), clozapine (20 mg/kg) and OPC-14597 (40 mg/kg), were used. Brains were fixed with 4% paraformaldehyde 45 min after drug administration (i.p.). Brain sections of 30 microns-thickness were made in a cryostat and hybridized with 35S-labelled for c-fos oligonucleotide probe. These sections were apposed to X-ray films and the autoradiograms were semi-quantitatively analysed by computer-assisted densitometry. All antipsychotics used increased c-fos mRNA expression in N. accumbens shell, a region of the forebrain associated with limbic systems. On the other hand, two typical antipsychotics (haloperidol and fluphenazine) that cause a high incidence of acute motor side effects increased the expression of c-fos mRNA in the dorsolateral striatum, an extrapyramidal region primarily involved in motor control. Only clozapine induced c-fos mRNA in the medial prefrontal cortex and lateral septum. These results strongly suggest that the shell region of N. accumbens may be a common site of therapeutic action of antipsychotics.
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The number of patients remaining on treatment at 2 years (and included in this study) was 28/84 and 27/92 for RLAI and aripiprazole respectively. Two patients treated with RLAI and three treated with aripiprazole were lost to follow up. Therefore, 5-year outcome data were available for 50 patients. Fifteen patients from each group were continuers at 5 years. Of these, four receiving RLAI and three receiving aripiprazole were coprescribed other antipsychotics at study endpoint. Reasons for discontinuation of RLAI and aripiprazole respectively were lack of effect (n = 4; n = 4), adverse effects (n = 3; n = 1), noncompliance or patient choice (n = 2; n = 4) and patient death (n = 2; n = 0).
Psychosis (delusions and/or hallucinations) is a common nonmotor feature of Parkinson's disease (PD). Use of the older 'typical' antipsychotic drugs led to worsening of motor symptoms. The introduction of 'atypical' antipsychotics opened up a range of therapeutic options. These agents include clozapine, risperidone, olanzapine, aripiprazole and quetiapine. All have been used to treat psychosis in PD with varying success. Clozapine is the only drug with proven efficacy. We review the evidence for the efficacy of quetiapine. Eight open-label studies have assessed quetiapine use in 191 patients, with improvement in psychosis recorded in 152 (80%). In addition to the open-label studies, there have been two single-blind, randomized trials comparing quetiapine and clozapine. These studies suggest that quetiapine has similar efficacy to clozapine in controlling psychosis. Following the promising results of the open-label and clozapine comparison studies, five randomized, controlled trials (RCTs) have been performed to further establish the efficacy of quetiapine. Unfortunately, the results have been disappointing. The only positive placebo-controlled study excluded patients with delusions, which seem to be harder to treat than hallucinations. The four negative RCTs discussed seriously undermine the evidence from the open-label studies. The differences in design and interpretation of the RCTs emphasizes the need for further large, well-controlled trials, using strict inclusion criteria, appropriate psychosis rating scales, carer input and clinical significance. Currently, many physicians continue to cautiously offer a trial of low-dose quetiapine empirically. Clozapine should be considered in patients who can tolerate the required blood monitoring.
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Previous meta-analyses of atypical antipsychotics for depression were limited by few trials with direct comparisons between two treatments. We performed a network meta-analysis, which integrates direct and indirect evidence from randomized controlled trials (RCTs), to investigate the comparative efficacy and tolerability of adjunctive atypical antipsychotics for treatment-resistant depression (TRD).
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A 42-year-old white male with schizophrenia, diabetes, hypertension, and a history of stroke was admitted to the intensive care unit following 2 days of fever, diarrhea, and altered mental status. Following the resolution of his acute illness, previous therapy with quetiapine 400 mg orally at bedtime was resumed for schizophrenia and presumed delirium. Quetiapine was discontinued after 1 dose because of QTc interval prolongation. Twenty-three days later, with a baseline QTc interval of 414 milliseconds, aripiprazole 2.5 mg orally once daily was initiated. Following 5 days of aripiprazole therapy, the patient had a cardiac arrest due to TdP. Normal sinus rhythm was restored after 30 seconds of cardiopulmonary resuscitation, 1 shock of 200 Joules, and 4 g of intravenous magnesium sulfate. Serial electrocardiographs obtained after aripiprazole discontinuation revealed resolution of QTc interval prolongation.
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The utilization of olanzapine is predicted in this model to result in better clinical outcomes and lower total direct health care costs compared to generic risperidone, quetiapine, ziprasidone, and aripiprazole. Olanzapine may, therefore, be a cost-effective therapeutic option for patients with schizophrenia.
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Tardive dystonia is a side effect of dopamine receptor-blocking agents, which are mainly used as antipsychotic drugs. The treatment of tardive dystonia is difficult and often unsuccessful. An 82-year-old woman experienced mandibular deviation to the left due to spasm of the masticatory muscles with involuntary chewing movement and Parkinsonism. She had been treated with sulpiride for motility disorder for 5 years. Parkinsonism almost disappeared after the withdrawal of sulpiride, but tardive oromandibular dystonia showed no improvement. Aripiprazole treatment at 3 mg/day improved tardive oromandibular dystonia without worsening Parkinsonism. Low-dosage aripiprazole may be effective for tardive oromandibular dystonia in patients with no other psychiatric disorder.
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Within the observation period significant improvements of CGI, SF-12 and SIWM-PsySo scores over time versus baseline values were observed (p<0.001) when starting with or switching to aripiprazole. Physicians observed improvements in 80.7% of the patients at endpoint; in 62% of the patients the disease state was considered "much" or "very much" improved. Aripiprazole was overall well tolerated; 19.9% of patients discontinued treatment after 12 months. Adverse effects in general were moderate to mild and corresponded to the known tolerability profile of aripiprazole. Psychotic side effects reported were probably due to a recurrence of the underlying schizophrenic disorder.
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Treatment of bipolar depression is complicated by variable response and risk of switch to mania. Guidance is informed by the strength of evidence rather than by comparative data.
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The aim of this study was to verify whether or not an increased prevalence of excessive daytime sleepiness (EDS) or EEG abnormalities is observed in patients with schizophrenia spectrum disorders (SSD), and to compare the effects of second generation antipsychotics (SGA) on patients' daytime sleepiness level and EEG recordings.
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NMS was primarily associated with type of antipsychotic and polypharmacy rather than overall dose. Variation in risk by ethnicity requires further research.
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The combination of aripiprazole and quetiapine seemed to control supersensitivity effects at the D (2) receptor after clozapin withdrawal in this case.
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This analysis, to the best of our knowledge, is the first of its kind to assess the cost effectiveness of antipsychotics based on French observational data. Paliperidone LAI appeared to be a cost-effective option in the treatment of schizophrenia from the French health insurance perspective.
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There is limited evidence for the management of sexual dysfunction and/or hyperprolactinemia resulting from use of antipsychotics in patients with schizophrenia and spectrum. The aim of this study was to review and describe the strategies for the treatment of antipsychotic-induced sexual dysfunctions and/or hyperprolactinemia. The research was carried out through Medline/PubMed, Cochrane, Lilacs, Embase, and PsycINFO, and it included open labels or randomized clinical trials. The authors found 31 studies: 25 open-label noncontrolled studies and 6 randomized controlled clinical trials. The randomized, double-blind controlled studies that were conducted with adjunctive treatment that showed improvement of sexual dysfunction and/or decrease of prolactin levels were sildenafil and aripiprazole. The medication selegiline and cyproheptadine did not improve sexual function. The switch to quetiapine was demonstrated in 2 randomized controlled studies: 1 showed improvement in the primary outcome and the other did not. This reviewed data have suggested that further well-designed randomized controlled trials are needed to provide evidence for the effects of different strategies to manage sexual dysfunction and/or hyperprolactinaemia resulting from antipsychotics. These trials are necessary in order to have a better compliance and reduce the distress among patients with schizophrenia.
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A simple, fast, and sensitive UFLC-tandem mass spectrometry method for the simultaneous measurement of commonly used antipsychotics (aripiprazole, chlorpromazine, paliperidone, quetiapine, risperidone, ziprasidone, clozapine, and olanzapine), antidepressants (citalopram, escitalopram, mirtazapine, fluoxetine, paroxetine, sertraline, venlafaxine plus O-desmethylvenlafaxine, and fluvoxamine) and an antidementia drug (donepezil) has been developed. The total run time of the chromatographic separation was 6.0 minutes. The precision and accuracy varied from 0.90% to 14% and from 88.5% to 118%, respectively. A 6-point standard curve covering the clinically relevant ranges with a power function fit was applied for calibration. Ion suppression due to matrix effects and the internal standards were investigated. Their recoveries varied from 89% to 110%.
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Mean change in Young Mania Rating Scale Total score (primary end-point) at week 3 was significantly greater with aripiprazole (-12.0; P<0.05) and haloperidol (-12.8; P<0.01) than with placebo (-9.7). Improvements were maintained to week 12 for aripiprazole (-17.2) and haloperidol (-17.8). Aripiprazole was well tolerated. Extrapyramidal adverse events were more frequent with haloperidol than aripiprazole (53.3% v. 23.5%).
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There has been an increase in the European and North American schizophrenia literature discussing the high prevalence of metabolic syndrome induced by atypical antipsychotic agents. The aim of this article was to review available data on metabolic syndrome induced by atypical antipsychotic agents in patients with schizophrenia or schizoaffective disorders selected from societies different from European and North American ones (termed non-Euro-American societies [NEAS]).
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To examine the efficacy and tolerability of aripiprazole treatment for acute bipolar depression.
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In 1993, the Food and Drug Administration (FDA) published a guideline for the study and evaluation of gender-related differences in clinical trials. However, the extent of the implementation of these recommendations has not been systematically reviewed.
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Dopaminergic stabilizers may be conceptualized as drugs with normalizing effects on dopamine-mediated behaviours and neurochemical events. (S)-(-)-OSU6162 (OSU6162) and ACR16 are two structurally related compounds ascribed such properties, principally because of their stabilizing effects on motor activity in rodents. Reports in the literature indicate possible partial D2 receptor agonist effects using various in vitro systems. This study aimed to measure D2 receptor antagonist and agonist effects of OSU6162 and ACR16 in vivo. To address this, we have studied the effects of both compounds on prolactin secretion in drug-naive and dopamine-depleted rats; dopamine depletion was induced by pretreatment with reserpine plus α-methyl-DL: -p-tyrosine. We find that OSU6162 and ACR16 both stimulate prolactin secretion in drug-naive rats with OSU6162 being considerably more potent and efficacious. Both compounds show a non-significant trend towards reversal of the increased secretion caused by dopamine depletion, whereas the D2 receptor antagonist haloperidol further increased prolactin secretion. Thus, this study suggests that OSU6162 and ACR16 act as D2 receptor antagonists under normal conditions in vivo, possibly with minor agonist effects in a state of dopamine depletion.
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Studies with a cumulative sample of ≥ 100 patients were included.
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Intramuscular aripiprazole is effective in patients with acute agitation associated with schizophrenia, comparable to IM haloperidol, and enables convenient transfer to oral aripiprazole therapy.