Lithium is among the most classically recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with lithium requires achieving plasma levels above 0.5 mEq/L. Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate derivatives or lamotrigine have not demonstrated conclusive therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Thyroid hormones are considered among the currently recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with thyroid hormones requires achieving plasma concentration of TSH close to the lower limits at the normal range (0.4 μUI/L) or even below it. Second-generation antipsychotics such as aripiprazole or quetiapine have consistently demonstrated significant therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Second-generation antipsychotics however require the careful monitoring of both cardiovascular and metabolic adverse effects.
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This study showed for the first time that the partial dopamine antagonist aripiprazole increases BOLD-signal during a WM task in the cognitive part of the ACC in schizophrenia patients, which may reflect its beneficial effect on cognitive deficits.
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We found 11 studies for depression treatment and 1 study for psychosis treatment that met our inclusion and exclusion criteria. Selective serotonin reuptake inhibitors (SSRIs; especially fluoxetine) and tricyclic antidepressants appear to be effective in treating depressive symptoms in patients with HIV infection without affecting immune status. Testosterone, stimulants, and dehydroepiandrosterone may also be effective in subsyndromal depression; however, studies on these agents in general were limited by small sample size. There are limited data for antipsychotics, with the only controlled study found for haloperidol and chlorpromazine used for AIDS delirium. Drug-drug interactions and potentiation of metabolic syndrome are concerns for the combined use of antidepressants and antipsychotics with antiretrovirals.
Modelling the cost-effectiveness of different treatment sequences for stable schizophrenia is appropriate given that patients rarely remain on one treatment for long periods. The treatment sequence aripiprazole followed by risperidone was the most cost-effective option for patients with stable schizophrenia in the UK.
The study of atypical antipsychotics in rapid cycling bipolar disorder is in its infancy. Although atypical antipsychotics are useful in acute mania, current data do not support their use as maintenance agents. Future double-blind, randomized studies are needed to establish their efficacy relative to traditional mood stabilizers and their utility as adjuvant agents in this subset of patients.
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To describe a case of torsades de pointes (TdP) in a patient treated with aripiprazole.
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There is a lack of studies designed to address the efficacy of medications in mixed affective symptoms. Guidelines do not fully reflect the current evidences.
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Remission of treatment-resistant late-life depression (defined as a Montgomery-Åsberg Depression Rating Scale score of ≤10 at both of the last 2 consecutive visits).
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The inhibition potencies of aripiprazole and its active metabolite, dehydroaripiprazole, on the activities of human multidrug resistance protein 1 (MDR1/ABCB1; P-glycoprotein), breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance-associated protein 4 (MRP4/ABCC4), that are drug efflux transporters expressed both in the intestine and at the blood-brain barrier (BBB), were investigated. Aripiprazole and dehydroapripiprazole showed relatively strong inhibitory effects on human MDR1 with IC(50) values of 1.2 and 1.3 µm in human MDR1-transfected Mardin-Darby canine kidney (MDCKII-MDR1) cells, respectively. The inhibition potencies of other atypical antipsychotics (risperidone, paliperidone, olanzapine and ziprasidone) for human MDR1 were also evaluated using the same in vitro experimental system and IC(50) values were more than 10-fold higher than those of the two compounds. Aripiprazole and dehydroaripiprazole also had inhibition potencies against human BCRP with IC(50) values of 3.5 and 0.52 µm, respectively. The ratios of steady-state unbound concentrations of aripiprazole and dehydroaripiprazole to their IC(50) values against human MDR1 and BCRP activities were less than 0.1, whereas the theoretically maximum gastrointestinal concentration of aripiprazole ([I](2) ) to its IC(50) values was much higher than the cut-off value of 10, proposed by the International Transporter Consortium (ITC) and the Food and Drug Administration (FDA). In contrast, aripiprazole and dehydroaripiprazole showed almost no inhibitory effect against the activity of human MRP4. These findings indicate that aripiprazole is unlikely to cause drug-drug interactions (DDIs) at the BBB when co-administered with substrate drugs of these drug transporters investigated. However, interactions at the intestinal absorption process may be of concern.
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QUALIFY was a 28-week, randomized, open-label, head-to-head trial that assessed improvements across multiple measures in stable patients with schizophrenia with aripiprazole once-monthly 400 mg vs paliperidone palmitate.
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to assess differences in the speed of onset of antimanic efficacy between haloperidol (as most studied first-generation antipsychotic) and second-generation antipsychotics.
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We included 28 trials with 8487 participants on five SGAs: amisulpride, aripiprazole, olanzapine, quetiapine and risperidone.Three studies (1092 participants) provided data on aripiprazole augmentation in MDD. All efficacy data (response n = 1092, three RCTs, OR 0.48; 95% CI 0.37 to 0.63), (MADRS n = 1077, three RCTs, MD -3.04; 95% CI -4.09 to -2) indicated a benefit for aripiprazole but more side effects (weight gain, EPS) .Seven trials (1754 participants) reported data on olanzapine. Compared to placebo fewer people discontinued treatment due to inefficacy; compared to antidepressants there were no efficacy differences, olanzapine augmentation showed symptom reduction (MADRS n = 808, five RCTs, MD -2.84; 95% CI -5.48 to -0.20), but also more weight or prolactin increase.Quetiapine data are based on seven trials (3414 participants). Compared to placebo, quetiapine monotherapy (response n = 1342, three RCTs, OR 0.52; 95% CI 0.41 to 0.66) and quetiapine augmentation (response n = 937, two RCTs, OR 0.68; 95% CI 0.52 to 0.90) showed symptom reduction, but quetiapine induced more sedation.Four trials (637 participants) presented data on risperidone augmentation, response data were better for risperidone (n = 371, two RCTs, OR 0.57; 95% CI 0.36 to 0.89) but augmentation showed more prolactin increase and weight gain.Five studies (1313 participants) presented data on amisulpride treatment for dysthymia. There were some beneficial effects compared to placebo or antidepressants but tolerability was worse.
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Ninety-six children (62 males; mean age of 6.9 (SD = 1.7), received APZ for an average length of treatment of 12.5 (SD = 3.9) weeks. Significant improvements in YMRS, CDRS-R, CGAS, and Clinical Global Impressions Scale-Severity scores (p < 0.001) were noted at the end of study participation. Sixty of the subjects (62.5%) met a priori response criteria at study's end. The most common side effects noted were stomachache, increased appetite, and headache. Two subjects were removed from the study due to side effects [epistaxis (n = 1); akathisia (n = 1)]. Subjects experienced an average weight gain of 2.4 (SD = 1.9) kg.
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There is a long history of using antipsychotic medications in the treatment of depressive disorders. Atypical antipsychotics, which have fewer side effects than traditional antipsychotics, have been used as monotherapy or adjunctively with antidepressants to treat depressive disorders with or without psychotic symptoms. The antidepressant effect of atypical antipsychotics involves regulation of monoamine, glutamate, gamma-aminobutyric acid (GABA), cortisol, and neurotrophic factors. To date, the United States Food and Drug Administration (USFDA) has approved aripiprazole and quetiapine slow-release tablets as adjunctive treatment for depressive disorders, and the combination of olanzapine and fluoxetine for the treatment of treatment-resistant depression. When using atypical antipsychotics in the treatment of depressed patients, clinicians need to monitor patients for the emergence of adverse effects including extrapyramidal symptoms (EPS), weight gain, and hyperglycemia.
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The study provides support that aripiprazole, olanzapine, quetiapine, and risperidone augmentation therapy could be effective in reducing psychiatric service utilization among MDD patients.
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Previous studies have documented increased risk of pneumonia with antipsychotic use in the elderly; however, differential risk across individual atypical antipsychotics remains unaddressed. This study examines the effect of individual atypical antipsychotics on risk of pneumonia in elderly patients.
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Well-tolerated and effective therapies for bipolar mania are required.
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AOM LAI is an efficacious and well-tolerated antipsychotic treatment for schizophrenia.
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Treatment-resistant depression (TRD) presents major challenges for both patients and clinicians. There is no universally accepted definition of TRD, but results from the US National Institute of Mental Health's (NIMH) STAR*D (Sequenced Treatment Alternatives to Relieve Depression) programme indicate that after the failure of two treatment trials, the chances of remission decrease significantly. Several pharmacological and nonpharmacological treatments for TRD may be considered when optimized (adequate dose and duration) therapy has not produced a successful outcome and a patient is classified as resistant to treatment. Nonpharmacological strategies include psychotherapy (often in conjunction with pharmacotherapy), electroconvulsive therapy and vagus nerve stimulation. The US FDA recently approved vagus nerve stimulation as adjunctive therapy (after four prior treatment failures); however, its benefits are seen only after prolonged (up to 1 year) use. Other nonpharmacological options, such as repetitive transcranial stimulation, deep brain stimulation or psychosurgery, remain experimental and are not widely available. Pharmacological treatments of TRD can be grouped in two main categories: 'switching' or 'combining'. In the first, treatment is switched within and between classes of compounds. The benefits of switching include avoidance of polypharmacy, a narrower range of treatment-emergent adverse events and lower costs. An inherent disadvantage of any switching strategy is that partial treatment responses resulting from the initial treatment might be lost by its discontinuation in favour of another medication trial. Monotherapy switches have also been shown to have limited effectiveness in achieving remission. The advantage of combination strategies is the potential to build upon achieved improvements; they are generally recommended if partial response was achieved with the current treatment trial. Various non-antidepressant augmenting agents, such as lithium and thyroid hormones, are well studied, although not commonly used. There is also evidence of efficacy and increasing use of atypical antipsychotics in combination with antidepressants, for example, olanzapine in combination with fluoxetine (OFC) or augmentation with aripiprazole. The disadvantages of a combination strategy include multiple medications, a broader range of treatment-emergent adverse events and higher costs. Several experimental pharmaceutical treatment alternatives for TRD are also being explored in combination with antidepressants or as monotherapy. These less studied alternative compounds include pindolol, inositol, CNS stimulants, hormones, herbal supplements, omega-3 fatty acids, S-adenosyl-L-methionine, folic acid, lamotrigine, modafinil, riluzole and topiramate. In summary, despite an increasing variety of choices for the treatment of TRD, this condition remains universally undefined and represents an area of unmet medical need. There are few known approved pharmacological agents for TRD (aripiprazole and OFC) and overall outcomes remain poor. This might be an indication that depression itself is a heterogeneous condition with a great diversity of pathologies, highlighting the need for careful evaluation of individuals with depressive symptoms who are unresponsive to treatment. Clearly, more research is needed to provide clinicians with better guidance in making those treatment decisions--especially in light of accumulating evidence that the longer patients are unsuccessfully treated, the worse their long-term prognosis tends to be.
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There appeared to be significant risk of QT prolongation with amisulpride and thioridazine overdoses. Although there were abnormal QT intervals for quetiapine, olanzapine, and risperidone overdoses, they were associated with tachycardia and not dose dependent, and so were unlikely to be associated with increased torsade de pointes risk.
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A high prevalence of constipation, often severe and needing medical interventions, was confirmed during the study period. Early detection, monitoring over treatment and early intervention of constipation could prevent serious consequences such as ileus.
12 adults (67% female, mean age = 45±12) with recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens (stimulants, dopamine agonists, bupropion [≥300mg/day], aripiprazole [≤2.5mg/day], or sertraline [≥150mg/day]) were randomized to naltrexone 1mg b.i.d. (n=6) or placebo (n=6) augmentation for 3 weeks.
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To evaluate the effects of aripiprazole for people with schizophrenia and schizophrenia-like psychoses.
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French clinical recommendations suggest prescribing long-acting injectable (LAI) antipsychotics to patients with a maintenance treatment indication in schizophrenia. Despite this, and due to their relatively high acquisition and administration costs, LAIs are still underused in clinical practice in France, thus highlighting the need for pharmacoeconomic evaluations.
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Studies were required to have ≥24 weeks of follow-up. Patients had to be stable at randomization. Studies were not eligible for inclusion if efficacy of acute and maintenance phase treatment was not reported separately. Six trials were identified (0.5% of initially identified studies), allowing comparisons of aripiprazole once-monthly, risperidone LAI, paliperidone palmitate, olanzapine pamoate, haloperidol depot, and placebo.
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The case report describes a 39-year-old woman with restless legs syndrome (RLS) and trichotillomania (TTM). She was treated with venlafaxine and clonazepam with partial remission of RLS and no response for TTM. When aripiprazole was added to the clonazepam both RLS and TTM fully remitted. We suggest that aripiprazole might be worth investigating for treatment of these disorders.
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BETA was designed to evaluate the overall effectiveness of aripiprazole in patients with schizophrenia or schizoaffective disorder treated in a general psychiatry outpatient practice setting.
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Aripiprazole is a new anti psychotic with a unique receptor binding profile that combines partial agonistic activity at D2 receptor and 5-HT 1A receptor and potent antagonism at 5-HT 2A receptor. This receptor profile makes it possible for it to act as a dopamine system stabilizer. Based on various short term and long term studies, aripiprazole has been found to be effective in schizophrenia and has no significant adverse effect on QTc prolongation, prolactin, serum lipids, and has a low potential for weight gain. Present study aims to evaluate the efficacy and tolerability of aripiprazole (10-15mg/day) in the treatment of Indian patients of schizophrenia and to see its effect on QTc interval, prolactin levels, serum lipids, plasma sugar and weight gain in these patients. Outpatients with an ongoing/newly diagnosed ICD-10 Schizophrenia (n=136) were randomly assigned to 10 or 15 mg dose of Aripiprazole for a period of six weeks. Clinical response was evaluated by the Positive And Negative Symptoms Scale (PANSS), Clinical Global Impression (CGI) scale and safety was evaluated by observing spontaneously reported adverse events and changes in various laboratory parameters. Switching schizophrenic patients to aripiprazole (10/15 mg) from both conventional and atypical anti-psychotics was safe and well tolerated. Six weeks after switching to aripiprazole, patients showed improvements in PANSS scores (P< 0.001), EPS, prolactin levels and weight over the baseline levels. No difference was seen in the 10 or 15mg dose groups. One hospitalization was reported (due to hepatitis E). Common side effects reported were insomnia, somnolence, nausea, vomiting and diarrhea. Aripiprazole is a safe and effective anti psychotic in Indian patients - both in newly diagnosed, as well as, in patients not responding to or intolerant to other available typical and atypical antipsychotics.