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PubMed2006

Improvement or worsening of psychotic symptoms after treatment with low doses of aripiprazole.

Aripiprazole, an antipsychotic recently introduced for clinical use, may worsen psychotic symptoms, even at low dose. In other cases, aripiprazole may exercise an antipsychotic action and induce extrapyramidal side-effects, even at low dose. There are no clear-cut criteria to differentiate the patients whose psychotic symptoms will or will not respond to aripiprazole favourably. Conversely, the effectiveness on negative symptoms seem consistent both in patients with or without antipsychotic response. A low dose may be indicated at the beginning of treatment to assess the kind of response.

Adult↗
PubMed2006

Aripiprazole: pharmacodynamics of a dopamine partial agonist for the treatment of schizophrenia.

Aripiprazole is the first approved atypical antipsychotic with a mechanism of action that exerts a partial agonism with high affinity at Dopamin D2- and Serotonin-5-HT1A-receptors as well as an antagonism at Serotonin-5-HT2A-receptors. Aripiprazole provides good clinical effectiveness and a favorable profile of safety and tolerability. The special pharmacodynamics of aripiprazole are described herein.

Antipsychotic Agents↗
PubMedDate not supplied

Aripiprazole augmentation in treatment-resistant depression.

BACKGROUND: Evidence is accumulating to support the use of atypical neuroleptics as adjunctive treatment for refractory mood disorders, although there are currently no published data on the efficacy of an atypical neuroleptic in treatment-resistant depression when a previous trial of drug from the same class has failed. The authors hypothesized that aripiprazole would be efficacious in augmenting antidepressant treatment in resistant patients with non-psychotic unipolar depression who had previously failed a trial of another atypical neuroleptic. METHODS: This study was a retrospective chart review of the efficacy of aripiprazole augmentation in 30 treatment-resistant unipolar depression patients who had failed multiple previous antidepressant trials and had also failed augmentation with at least one other atypical neuroleptic. Prospective Global Assessment of Functioning and Clinical Global Impressions-Improvement scores were completed on each patient throughout treatment. RESULTS: Utilizing an intent-to-treat analysis (including 9 patients who dropped out prior to completion of 6 weeks), 46.7% (14/30) patients were rated much improved or very much improved with treatment. This improvement negatively correlated with Thase-Rush staging of treatment resistance. GAF scores also showed a significant improvement. Six of the 14 patients who initially improved subsequently relapsed (yielding a long-term net response rate of 26.7%). CONCLUSION: Aripiprazole may be effective as an antidepressant augmentation agent in highly treatment resistant patients who had failed a prior trial of another atypical neuroleptic.

Adult↗
PubMed2004

Aripiprazole and neuroleptic malignant syndrome.

Aripiprazole, an atypical antipsychotic with a novel method of action, has only recently been awarded a license in the UK. We report our first patient to receive this drug, who had treatment-resistant schizophrenia and developed neuroleptic malignant syndrome (NMS) with aripiprazole. To our knowledge, this is the first published case report involving aripiprazole and NMS in a potentially fatal medical emergency. Further experience with this drug should indicate whether this is an isolated case (as described with other atypical antipsychotics) or constitutes a more serious risk than that suggested by the relatively beneficial therapeutic profile described in the literature to date.

Adult↗
PubMed2006

Aripiprazole in the management of post-traumatic stress disorder symptoms in returning Global War on Terrorism veterans.

The present study illustrates the potential use of aripiprazole as part of the management of post-traumatic stress disorder (PTSD) in returning Global War on Terrorism (GWOT) veterans. Five consecutive cases of GWOT combat-related PTSD, managed in part with the atypical antipsychotic medication aripiprazole, are presented and discussed. In four of the five cases reported, the medication was well-tolerated and was effective in the management of sleep disturbances, such as nightmares and agitated behaviours during sleep, and was also helpful in the management of hyper-arousal. In one case, the veteran experienced a paradoxical excitation response to the medication. Aripiprazole, in conjunction with other medications or psychotherapeutic interventions, should be studied further for its potential role in the management of PTSD.

Adult↗
PubMed2005

Aripiprazole in schizophrenia: consensus guidelines.

Schizophrenia is a chronic disabling disease which in the majority of cases requires long-term treatment with antipsychotic medication. Before the development of atypical antipsychotics, treatment choice was restricted to conventional (or typical) antipsychotics, which are known to cause a range of side effects including extrapyramidal symptoms. Although atypical agents provide a favourable alternative (advocated by the National Institute of Clinical Excellence in the UK), they are associated with side effects. These differ between agents, but can include weight gain, sedation and hyperprolactinaemia. Aripiprazole is a newly available atypical antipsychotic for the treatment of schizophrenia. With the apparent imitations of currently available medications, aripiprazole provides clinicians with another treatment option. The purpose of these guidelines is to outline the consensus reached by the Schizophrenia Innovation Working Group on best practice in prescribing and appropriate use of aripiprazole in the UK.

Antipsychotic Agents↗
PubMed2006

Aripiprazole use in a pregnant schizoaffective woman.

BACKGROUND: There are few or no clinical data on the safety of aripiprazole during pregnancy and lactation. CASE REPORT: A 27-year-old schizoaffective woman conceived while receiving aripiprazole 15 mg/day. The drug was withdrawn during the eighth week of gestation. She relapsed at week 20, and resumed treatment with the drug at a dose of 10 mg/day. She responded well, and the drug was continued through the rest of the pregnancy. The pregnancy was uneventful, but unexplained fetal tachycardia necessitated a cesarean section at full term. The newborn infant was normal in all regards and developed normally during a 6-month follow up. The infant required to be bottle-fed because of a failure of lactation. CONCLUSION: In this case, exposure to aripiprazole during different trimesters of pregnancy was not associated with intrauterine death, morphological teratogenicity, impaired fetal growth, neonatal toxicity, or neurobehavioral teratogenicity. Maternal health was not adversely affected during pregnancy. However, lactation failure occurred after delivery.

Adult↗
PubMed2006

Patients with schizophrenia treated with aripiprazole, a multicentre naturalistic study.

OBJECTIVE: The purpose was to carry out a naturalistic study on efficacy, safety and tolerability of aripiprazole during treatment of schizophrenia. Fifty-one patients with an ICD-10 diagnosis of schizophrenia and partial responders to prior antipsychotic medication were offered treatment with aripiprazole as monotherapy or in combination their prior medication. Inclusion criteria were lack of therapeutic effect or adverse events on former antipsychotic treatment. METHOD: Six-month open multicentre naturalistic study with prospective assessments including Body Mass Index (BMI), Clinical Global Impression-Severity (CGI-S), Clinical Global Impression-Improvement, Global Assessment of Functioning Scale (GAF) and adverse events. RESULTS: A statistically significant improvement in the different measures of psychopathology and global functioning (CGI-S reduction 34.7%; GAF improvement 14%) was shown in combination with a statistically significant reduction in BMI of 2.9%. Nine patients (17.6%) did not complete the 6-month treatment. CONCLUSION: In an open multicentre naturalistic study, aripiprazole showed to improve the severity of psychotic symptoms and the global level of functioning. However, many of the patients (47%) were also given another antipsychotic drug at the same time. Also, high compliance and few side effects were reported. However, because of the study design, the results must be interpreted conservatively.

Activities of Daily Living↗
PubMedDate not supplied

Aripiprazole in the treatment of delirium.

Antipsychotic drugs are the primary treatment for symptoms of delirium, but their side effects can be problematic. Treatment of delirium with aripiprazole has yet to be evaluated. The authors report on 14 patients with delirium treated with aripiprazole. Twelve patients had a >or=50% reduction in Delirium Rating Scale, Revised-98 scores, and 13 showed improvement on Clinical Global Impression scale scores. There was a low rate of adverse side effects. Aripiprazole may be an appropriate first-line agent for the treatment of delirium because of its minimal effect on QTc interval, weight, lipids, and glucose levels. Controlled comparison studies should be performed to confirm this impression.

Aged↗
PubMed2005

Aripiprazole in psychosis associated with Parkinson's disease.

Aripiprazole is an agent for treating schizophrenia. The authors assume that aripiprazole as a dopamine receptor partial agonist may be useful in treating PD patients. Three cases are presented in this study. All patients were evaluated by the same clinician, a neuropsychiatrist well trained in the use of Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI). Aripiprazole was effective for reducing psychosis in each case.

Aged↗
PubMed2005

Aripiprazole in children and adolescents: clinical experience.

Despite few supportive data, aripiprazole was being administered to children and adolescents for management of mood instability, aggression, and psychosis. Using a retrospective review (n = 11) and prospective recruitment (n = 6), 17 children and adolescents received aripiprazole 5 to 20 mg/day. Only 4 of 16 bipolar and autistic subjects (25%) demonstrated reduced aggression without adverse events, and the symptoms of 2 of 4 psychotic subjects improved. Coadministration of sedative medications (particularly guanfacine or clonidine) and weight < 58 kg increased the risk of adverse events, such as increased lability and aggression. All three children < 8.6 years old, all four children < 34 kg, and all five children receiving alpha2-agonists developed adverse events prior to clinical efficacy. Age > 11 years, weight > 58 kg, and absence of sedative medications were associated with a 56% (five of nine) success rate. Until larger, prospective studies are completed, caution is advised when considering aripiprazole for smaller children and children receiving sedative medications.

Adolescent↗
PubMed2005

Aripiprazole.

Aripiprazole is a new chemical entity with a unique pharmacological profile. It has strong affinities for certain dopamine receptors, and intermediate affinity for serotonin, adrenergic and histamine receptors. Partial agonism of the D2 dopamine and 5HT1A serotonin receptors, and antagonism of the 5HT2 serotonin receptor are believed to be the functional basis of its therapeutic efficacy. Its clinical effects are best documented in patients suffering from schizophrenia and bipolar disorder, in which it has been demonstrated to have antipsychotic and antimanic properties superior to placebo in dose ranges of 10-30 mg/day. Two published longer term trials document maintenance of antipsychotic effects and relapse prevention in schizophrenia patients. In general, aripiprazole seems to be a well-tolerated drug, especially with regard to metabolic side effects. The most commonly reported side effects include restlessness/akathisia, somnolence and nausea. These may be dose-dependent and usually occur early on during treatment, with many patients developing tolerance. Aripiprazole is an interesting and important addition to the currently available spectrum of antipsychotic drugs. Further studies in other indications and clinical trials that confirm results from the Phase II and III clinical development programme are eagerly awaited.

Antipsychotic Agents↗
PubMed2005

Aripiprazole, a novel antipsychotic agent: dopamine D2 receptor partial agonist.

It is obvious that DA is an important neurotransmitter in vivo. It is involved in a variety of physiological processes such as mental processes, motor function and hormone regulation. In this context, it is quite understandable that a DA D2 receptor antagonist that inhibits the DA D2 receptor regardless of the state of activity of dopaminergic neurotransmission and inhibit the physiological function of DA can have a variety of adverse effects. In contrast to DA D2 antagonists, aripiprazole acts as an antagonist at the DA D2 receptor in the state of excessive dopaminergic neurotransmission, while it acts as an agonist at the DA D2 receptor in the state of low dopaminergic neurotransmission, and thus attempts to bring the state of dopaminergic neurotransmission to normal. This activity of aripiprazole to regulate dopaminergic neurotransmission is physiologically reasonable, and can be regarded as a stabilizing effect, for which aripiprazole is called a dopamine system stabilizer.

Animals↗
PubMed2005

Atypical experience: a case series of pediatric aripiprazole exposures.

BACKGROUND: Aripiprazole is a new psychotropic agent that possesses a unique pharmacologic profile. The drug demonstrates mixed dopamine and serotonin agonist-antagonist activity and has been labeled a third-generation antipsychotic and dopamine-serotonin system stabilizer. Overdose experience is limited, especially in pediatrics. CASE SERIES: Of five pediatric cases identified, toxicity was mainly evident in younger patients. A 2-year-old who ingested 40 mg experienced vomiting and significant lethargy lasting approximately 30 h. A 6-year-old who received two doses of aripiprazole therapeutically experienced lethargy, drooling, and flaccid facial muscles which improved with diphenhydramine. Two adolescents remained asymptomatic despite doses of 120 mg and 300 mg while a third adolescent with an unknown dose experienced transient lethargy. CONCLUSION: Aripiprazole is capable of producing marked lethargy and gastrointestinal upset in pediatric patients. Adolescents in this series experienced only minor, if any, clinical effects. Major clinical effects, i.e., seizures, dysrhythmias, were not reported in this series.

Adolescent↗
PubMed2003

Treatment for mood and anxiety disorders: quetiapine and aripiprazole.

Atypical antipsychotic agents have a broad range of therapeutic efficacy, a relatively low incidence of causing extrapyramidal adverse effects, and a low tardive dyskinesia profile. This has led to very rapid growth in the use of these compounds as broad-spectrum psychotropic agents, and it has been reported that more than 70% of prescriptions for atypical antipsychotic medications are being used for conditions other than schizophrenia. In the area of bipolar disorder, in particular, atypical antipsychotic agents appear to positively affect illness outcome, and are considered potential first-line treatment agents. Quetiapine was approved by the US Food and Drug Administration in 1997, and is currently marketed in the US to treat schizophrenia. Aripiprazole was recently approved for the treatment of schizophrenia by the US Food and Drug Administration in late 2002, and is being used increasingly in clinical settings. Recent reports suggest that quetiapine and aripiprazole are valuable additions to the psychotropic armamentarium for the treatment of mood and anxiety disorders. Data from clinical trials and clinical reports are discussed herewith.

Antipsychotic Agents↗
PubMed2005

High performance liquid chromatographic methods for the determination of aripiprazole with ultraviolet detection in rat plasma and brain: application to the pharmacokinetic study.

High performance liquid chromatographic (HPLC) methods were validated for the determination of aripiprazole (OPC-14597, Abilify) in rat plasma and brain. Separation was by Nova-pak phenyl column; flow rate, 1.0 ml/min; mobile phase, acetonitrile-methanol-20 mM sodium sulfate-acetic acid (27:25:48:1, v/v/v/v); UV detection at 254 nm. Reproducibility in plasma and brain showed excellent precision (within 7.8 and 10.6%) and accuracy (96.0-102.4% and 99.0-108.7%) with calibration curve ranges 10.0-2000 ng/ml and 30.0-6000 ng/g, respectively. Validated HPLC methods were successfully applied to pharmacokinetic study of aripiprazole in rats, demonstrating brain concentrations after oral administration five times higher than plasma concentrations.

Animals↗
PubMed2005

Development and validation of an LC-MS/MS method for the quantitative determination of aripiprazole and its main metabolite, OPC-14857, in human plasma.

An accurate, sensitive, reproducible, and selective liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for determination of aripiprazole and its main metabolite, OPC-14857, in human plasma was developed and validated. Chromatographic separation was achieved isocratically on a C18 reversed-phase column within 7.5 min. The calibration curve, ranging from 0.1 to 100 ng/ml, was fitted to a 1/y2-weighted linear regression model. The assay showed no significant interference. Lower limit of quantitation (LLOQ) for both analytes was 0.1 ng/ml using 0.4 ml of plasma. Intra- and inter-assay precision and accuracy values for aripiprazole and OPC-14857 were within regulatory limits.

Aripiprazole↗
PubMed2006

Benefits of combining aripiprazole to clozapine: three case reports.

OBJECTIVE: A substantial number of patients treated with clozapine shows insufficient response. The author presents the results of adding aripiprazole in patients resistant to clozapine. METHOD: Three cases of individuals with psychotic symptoms despite clozapine use and with significant side effects that were treated via this combination are presented. Response was evaluated by clinical assessment. RESULTS: Good clinical results were obtained in all three patients, with improvement of psychotic symptoms and of some of the side effects of clozapine. CONCLUSION: The findings from this case series suggest that adjunctive therapy with aripiprazole can be of benefit for treating clozapine resistant schizophrenic patients.

Adult↗