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MEDLINE (1996-May 2010) and EMBASE (1996-May 2010) databases were searched using highly sensitive search strategies for clinical trials in a paediatric population (children up to age 18 years).
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An electronic database search was conducted using the key words; relevant articles were then hand searched and websites (FDA, EMA, Otsuka, Lundbeck, NIH) reviewed.
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Pharmacokinetic analyses revealed P-gp activity for aripiprazole and ziprasidone. This was indicated by 3.1- and 1.9-fold higher ratios of brain to plasma concentrations of drugs in knock-out to WT animals. Acute doses of ariprazole or ziprasidone impaired motor behaviour on the RotaRod. Effects were similar after injection of haloperidol, whereas the serotonin receptor ligands buspirone and ketanserin enhanced RotaRod performance. Genotype dependent differences of motor performance were found for aripiprazole but not for ziprasidone.
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Cases were selected if they contained any of 10 preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) that described the abnormal behaviors. We used the proportional reporting ratio (PRR) to compare the proportion of target events to all serious events for the study drugs with a similar proportion for all other drugs.
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In age-grouped YMRS item assessments of bipolar mania, anger dyscontrol was most prominent for youth, whereas disordered thought content was paramount for adults.
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Varenicline is a promising agent with demonstrated efficacy in the promotion of smoking cessation. However, from the time of initial trials, it has been associated with significant psychiatric adverse effects. We describe a case where mixed mood and psychotic disturbance developed in an individual with a history of depression and a family history of bipolar disorder. Based on this case, we hypothesize a possible mechanism of action for these adverse effects and preventive measures that could be undertaken in its effective use.
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Sexual dysfunction is a frequent side effect associated with antipsychotic treatment. It is known to be caused by the hyperprolactinemia that results from the D2 receptor blockade that is characteristic of antipsychotic drugs. The D2 partial dopaminergic agonism of aripiprazole could explain why its use does not usually cause this side effect, and may even revert it when added to another antipsychotic.
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To quantify the prevalence of pre-existing risk factors for AEs and potential drug-drug interactions (DDIs) associated with AA treatment among patients with schizophrenia (SCZ), bipolar disorder (BD), or major depressive disorder (MDD) newly-initiating AA treatment.
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Six RCTs with a total of 528 subjects (ARI treatment group: n = 253; control group: n = 275) met the inclusion criteria. These included two RCTs (n = 255) that compared ARI monotherapy with tiapride (TIA). Tic symptoms control assessed by Yale Global Tic Severity Scale (Standard Mean Difference (SMD) = -0.38 (Confidence Interval (CI) = -1.32 to 0.56); I(2) = 90%, P = 0.42) revealed no significant differences between the two groups. Extrapyramidal symptoms were significantly different when ARI (1.5%) was compared with haloperidol (HAL) (43.5%). No significant group differences were found in the rates of nausea/vomiting, dizziness, and dry mouth between ARI and TIA (RR = 0.57 to 1.00 (95%CI = 0.14-4.20); I(2) = 0% to 69%, P = 0.35 to 1.00).
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Strategies for transitioning therapy to aripiprazole from alternative antipsychotics in schizophrenia have been investigated in randomized trials, but studies have failed to establish a preferred method. Despite the lack of evidence, experts recommend an overlap strategy that includes maintaining the current antipsychotic dosage while titrating to a therapeutic dose of aripiprazole.
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Antipsychotic switching in SZA is a neglected topic that would need better profiling. Clinicians should keep in mind the receptor binding characteristics of drugs in order to optimize transitions. Evidence supports the switch to aripiprazole and lurasidone, less strongly to risperidone and ziprasidone. The switch to risperidone long-acting injectable is supported, especially in patients with limited treatment adherence to oral therapy.
Blockade of the dopamine D2 receptor is a key mechanism in the antipsychotic treatment of patients with a psychotic disorder, but may also induce emotional deficits. The partial D2 agonistic profile of aripiprazole has, therefore, been suggested to favor emotional wellbeing compared with the pure dopamine antagonistic properties of traditional antipsychotics.
The aripiprazole augmentation remission rate was 36.5%. Multiple logistic regression analysis indicated that aripiprazole augmentation was significantly more effective for bipolar depression than for major depressive disorder, and both absence of comorbid anxiety disorders and current episode duration >3 months were significantly associated with the efficacy of aripiprazole augmentation.
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In the present study, we longitudinally investigated the effects of risperidone, olanzapine, and aripiprazole on plasma levels of catecholamine metabolites and brain-derived neurotrophic factor (BDNF) in first-episode unmedicated schizophrenic patients. The subjects were 59 Japanese schizophrenic patients (35 males and 24 females; age range: 18-46 years; mean+/-SD: 25+/-16 years). The patients were treated with risperidone (n=32) in a dose range of 2-6 mg/day (mean+/-SD=3.4+/-1.9), olanzapine (n=18) in a dose range of 5-20 mg/day (mean+/-SD=12.1+/-5.8), or aripiprazole (n=9) in a dose range of 12-30 mg/day (mean+/-SD=22.8+/-10.1). All three drugs significantly decreased plasma homovanillic acid (HVA) levels within 8 weeks, although aripiprazole transiently raised this level before 8 weeks. All three drugs also significantly increased plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels within 8 weeks. On the other hand, none of them altered plasma BDNF levels. These results indicate that risperidone, olanzapine, and aripiprazole affect catecholaminergic systems in the brain, that the effects of aripiprazole on the dopaminergic systems seem to slightly different than those of risperidone and olanzapine, and that these atypical antipsychotic drugs might not alter BDNF levels, at least within 8 weeks of treatment.
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This study investigated the dosing patterns for aripiprazole augmentation for major depressive disorder (MDD) in a naturalistic treatment setting. Between 1 January 2009 and 31 March 2012, patients with a diagnosis of MDD who were receiving aripiprazole augmentation in conjunction with an ongoing antidepressant were recruited for this study. The electronic medical records and clinical data for a total of 276 patients were reviewed up to a year. The mean duration of aripiprazole augmentation was ∼5 months; the mean time to the first increase of aripiprazole was about 3 weeks; and the mean initial, first up-titrated, maximal, and maintenance doses were 3.4, 4.2, 4.7, and 4.4 mg/day, respectively. The most frequent adverse events were insomnia, followed by anxiety and sedation. The current results indicate that the actual doses of aripiprazole augmentation with ongoing antidepressant for MDD should be lower than the doses used in placebo-controlled clinical trials and those recommended by the US Food and Drug Administration. Adequately powered and well-controlled prospective studies are needed to better understand the exact role of low doses of aripiprazole augmentation in the treatment of MDD, particularly in routine practice.
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Compulsive behaviors such as gambling, hypersexuality and new sexual orientation are common in patients with Parkinson's disease treated with dopaminergic agonists. These behaviors involve the reward system, with an enhanced dopaminergic activity in the mesolimbic pathways and occur more frequently in young subjects, males with previous gambling habits and tobacco use. A few cases of aripiprazole-induced pathological gambling as well as aripiprazole-induced hypersexuality have been reported. To our knowledge, we are the first to report a case of gambling disorder associated with hypersexuality and change of sexuality orientation. Aripiprazole is the only antipsychotic with agonist properties for the D2 dopamine receptor. It may also act as an enhancer in the mesolimbic dopaminergic pathways. Aripiprazole also has 5-HT1A partial agonist and 5-HT2A antagonist properties that may promote sexual activity.
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A total of 361 patients with schizophrenia, ranging from 18 to 65 years, entered the study.
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To review the literature on weight gain associated with atypical antipsychotic treatment in schizophrenia.
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Open-label treatment was completed by 323 patients (32.2%). At endpoint (n = 987), the mean dose of aripiprazole was 10.1 mg/day. Common (>15% of patients) spontaneously reported adverse events were akathisia (26.2%), fatigue (18.0%), and weight gain (17.1%). The incidence of serious adverse events was 4.0%. Four spontaneous reports of possible tardive dyskinesia were submitted (0.4%); all resolved within 45 days of drug discontinuation. Mean weight change was 4.4 kg; 36.6% experienced ≥7% increase in weight from baseline (observed case analysis, n = 303). No clinically relevant changes in other metabolic parameters were seen. At the end of open-label treatment, 221 patients (69.7%) had a Clinical Global Impression-Severity of Illness score of 1 (not at all ill) or 2 (borderline ill).
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This very small study of aripiprazole, given to children with OCD resistant to at least 12 weeks treatment with at least two SSRIs and CBT, demonstrated striking improvement in CGI scores (all subsets, p≤0.002) for 13 of 16 children, and halved all CY-BOCS subscores after ∼12 weeks of treatment.
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Of the 26 patients at the initial visit, 22 (84.6%) completed the study. The mean dose of aripiprazole at the endpoint was 8.0 ± 4.0 mg/day. During the 8-week aripiprazole treatment period, motor tics, phonic tics, and impairment on the YGTSS all showed significant improvement. Home behaviors on the SAICA and child domain on the PSI also showed significant improvement. Patients' phonic tics, but not motor tics, showed a positive correlation with their school function and peer relationships. The child domain on the PSI was positively correlated with motor tics, phonic tics, and impairment, as measured by the YGTSS.
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Physically healthy adults aged 18 to 65 years with DSM-IV schizophrenia and a minimum score of 16 on the Yale-Brown Obsessive Compulsive Scale (YBOCS) were eligible to participate in this 6-week, open-label, flexible-dose trial of aripiprazole monotherapy. Patients currently taking another antipsychotic medication were concurrently down-titrated from their current antipsychotic and up-titrated with aripiprazole, starting with 15 mg/day. Coadministration of the 2 medications lasted from 7 to 14 days, until a stable therapeutic dose of 10 to 30 mg/day was reached. Subjects were recruited into the study, which was conducted at the Schizophrenia Clinic of Stanford University School of Medicine, between January 2005 and December 2006.
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