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To assess the effectiveness of substituting aripiprazole for other antipsychotic drugs taken by stable schizophrenic patients suffering from antipsychotic agent-induced symptomatic hyperprolactinemia.
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Nearly all atypical antipsychotic drugs (AAPDs) of second- generation are associated with body weight gain in adults with prolonged exposure; but reports on third-generation AAPDs like Aripiprazole (ARI) and weight gain are scanty and ambiguous. This may be attributed to some unknown mechanism of action, the study of which is essential to investigate gestational exposure of equivalent therapeutic doses of ARI on maternal and fetal weight gain and its longlasting impact on postnatal development and growth of offspring in rodent model. 30 pregnant Wistar rats were exposed to selected doses (2mg, 3mg and 5mg/kg BW) of ARI from GD3-21 orally, with control subjects. Half of the pregnant subjects of each group were sacrificed at GD22 and rest dams were allowed to deliver normally and pups were reared postnatally up to 10 weeks of age. In ARI treated groups, there was no substantial alteration of body weight gain and food intake in pregnant subjects while significant reduction was found in fetal and postnatal (pre-and post weaning) body weight gain. ARI was found neutral for substantial weight gain in pregnant rats but may induce significant weight loss in fetuses, creating long-lasting negative impact on offspring growth (in weight) till PND70. Therefore, ARI could be a good alternative of second- generation AAPDs for adult females but may not be safe for developing fetuses and offspring.
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23 patients were eligible for analysis. Patients had not achieved symptom remission despite a mean of over 3 prior SRI trials. Aripiprazole was continued to be used in seven patients (30%) at the time of last follow-up. Thirteen patients (57%) discontinued the drug due to side effects, and three patients (13%) discontinued aripiprazole citing no improvement. Six patients (26%) were noted to have ≥25% reduction on the Yale-Brown Obsessive-Compulsive Scale.
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Deficits in working memory (WM) are a core symptom of schizophrenia patients and have been linked to dysfunctional prefrontal activation, which might be caused by a mesocortical hypodopaminergic state. Aripiprazole--a partial dopamine antagonist--is a novel antipsychotic, which increases frontal dopamine concentrations in preclinical studies. However, little is known about specific medication effects on the modulation of frontal activation during WM performance.
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Three optimal sampling times were identified for each antipsychotic medicine. For aripiprazole, clozapine, olanzapine, perphenazine, risperidone, 9-OH risperidone, quetiapine and ziprasidone the CV% of the apparent clearance using optimal sampling strategies were 19.5, 8.6, 9.5, 13.5, 12.9, 10.0, 16.0 and 10.7, respectively. Using the MCS and linear regression approach to predict AUC, the recommended sampling windows were 16.5-17.5 h, 10-11 h, 23-24 h, 19-20 h, 16.5-17.5 h, 22.5-23.5 h, 5-6 h and 5.5-6.5 h, respectively.
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All six atypicals had an EB05 >/= 2 for at least one DRAE. The most common event was diabetes mellitus (2,784 cases). Adjusted reporting ratios (CIs) for diabetes mellitus were: olanzapine 9.6 (9.2-10.0; 1306 cases); risperidone 3.8 (3.5-4.1; 447 cases); quetiapine 3.5 (3.2-3.9; 283 cases); clozapine 3.1 (2.9-3.3; 464 cases); ziprasidone 2.4 (2.0-2.9; 74 cases); aripiprazole 2.4 (1.9-2.9; 71 cases); haloperidol 2.0 (1.7-2.3; 139 cases). Logistic regression odds ratios agreed with adjusted reporting ratios.
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Long-term adjunctive aripiprazole therapy was well tolerated with an acceptable long-term safety and tolerability profile in patients with major depressive disorder who had not responded to treatment with one or more antidepressant therapies. Clinically significant weight gain was observed in about one-third of patients. Overall, the adverse event profile was consistent with that reported in the short-term trials and readily managed clinically.
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This cost-effectiveness analysis is the first to use patient-level data from a randomized, double-blind study comparing olanzapine and aripiprazole in the treatment of patients with schizophrenia. Olanzapine was found to be a dominant cost-effective choice, as it was associated with greater effectiveness at lower total costs relative to aripiprazole.
Quetiapine was more effective than placebo treatment. Aripiprazole and quetiapine and partly also olanzapine and risperidone augmentation showed beneficial effects compared to placebo. Some evidence indicated beneficial effects of low-dose amisulpride for dysthymic people. Most SGAs showed worse tolerability.
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Two hundred and twenty schizophrenia patients, treated with antipsychotic monotherapy and followed-up in psychiatric outpatient clinics of Universities of Milan and Utrecht were included in the study. A survival analysis (Kaplan-Meier) of the 36-month follow-up period was performed to compare the single treatment groups. End-point was considered as discontinuation of treatment for recurrence, side effects or non-compliance.
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Psychiatrists, GPs and trainees in Flanders clearly favour olanzapine and risperidone, followed by quetiapine and aripiprazole above all other agents. This behaviour is supported by the conviction that SGAs have superior efficacy and a more benign side effect profile, compared with FGA. Frequent contact with drug representatives is correlated with a preference of SGA over FGA. 41% of the respondents acknowledge to be influenced by the pharmaceutical industry, which is more than that previously reported.
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Stevens-Johnson syndrome is a severe and potentially life-threatening cutaneous reaction associated with lamotrigine. The incidence of developing Stevens-Johnson syndrome during lamotrigine therapy is low. On the basis of the glutamate and dopamine neuron dysregulation hypothesis in schizophrenia, we propose new strategies for the treatment of schizophrenic patients using a glutamate system stabilizer lamotrigine as an adjunctive treatment for the poor responders of a dopamine system stabilizer, aripiprazole. The finding of Stevens-Johnson syndrome in two cases out of three treated with lamotrigine plus aripiprazole, however, has a much higher index of suspicion and it is correct to warn of its possible raised risk. As lamotrigine is currently licensed for the prophylactic treatment of bipolar depression, many of these patients have psychotic features where it would be considered reasonable to add an antimanic atypical antipsychotic such as aripriprazole. The two case reports raised the question about the possible increased risk of Stevens-Johnson syndrome with the combination therapy.
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A 52-week follow-up of patients switched to aripiprazole or with aripiprazole added on, conducting a specific analysis of markers of bone turnover: urinary NTX (a biomarker of bone resorption) and serum BSAP (a biomarker of bone formation). Baseline and serial measurements of bone markers NTX, BSAP and of hormones prolactin, oestrogen and testosterone were done at weeks 0 and 1, 2, 6, 12, 26 and 52, respectively.
Our results suggest that ARI applied in the experiment had no antidepressant effect and failed to improve spatial memory in study rats. Potential antidepressant and procognitive properties of this drug resulting from its mechanism of action encourage attempts (design) of further research aimed at developing a dose, which will show such effects in alcohol-preferring animals.
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Elevated AP plasma levels, which were associated with some clinically significant SE and some negative symptoms, were found in most patients. In this regard, therapeutic drug monitoring is a promising method for the individualization of schizophrenia exacerbation treatment in routine clinical practice.
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A retrospective chart review of the first 32 children treated with aripiprazole at an urban clinic for children with DD was conducted.
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Atypical antipsychotics (AP) are increasingly being used in children and adolescents for the treatment of psychiatric disorders. Atypical AP may cause QT prolongation on the electrocardiogram (ECG), which predisposes patients to an increased risk of developing threatening ventricular arrhythmias. Although this phenomenon has been exhaustively reported in adults, few studies investigated the safety of these drugs in pediatric patients. We performed an open-label, prospective study to assess the arrhythmic risk of aripiprazole and risperidone in a pediatric population. A total of 60 patients (55 M/5F, mean age 10.2+2.6 years, range 4-15 years), receiving a new prescription of aripiprazole or risperidone in monotherapy underwent a standard ECG before and after two months from the beginning of antipsychotic treatment. Basal and post-treatment ECG parameters, including mean QT (QTc) and QT dispersion (QTd), were compared within treatment groups. Twenty-nine patients were treated with aripiprazole (mean dosage 7.4+3.1mg/day) and 31 with risperidone (mean dosage 1.5+1mg/day). In our series, no patient exhibited pathological values of QTc or QTd before and after treatment for both drugs. However, treatment with risperidone was associated with a slight increase of both mean QTc and QTd values (407.4+11.9 ms vs 411.2+13.0 ms, p<0.05; and 40.0+4.4 ms vs 44.7+5.5 ms, p<0.001, respectively). Treatment with aripiprazole was associated with no changes of mean QTc, even if a small increase of QTd, (40.6+6.5 ms vs 46.3+7.2 ms, p<0.01) was observed. Although our data suggest a slight effect of aripiprazole and risperidone on ventricular repolarization, it is unlikely that such a change results in clinically relevant effects. The treatment with risperidone and aripiprazole in children with psychiatric disorders is not associated with clinically relevant modifications of QT interval. Caution in prescribing these drugs, however, is necessary in patients with family history of a genetic predisposition to arrhythmias in order to warrant a reliable assessment of drug-induced QT prolongation.
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Innovation in atypical antipsychotic agents continues with new preparations of available drugs as well as novel agents. In this article, we provide an update on these novel products by reviewing information from a computerised literature search, recent abstracts and discussions with industry representatives. A generic formulation of clozapine is now available. It may be less well absorbed and/or less effective than Clozaril, although evidence is conflicting. A fatty acid amide derivative of clozapine is in early development. A liquid formulation of risperidone is currently available, which may be a useful treatment for psychotic agitation as well as a preferable alternative to tablets for some patients. A depot formulation is in development for the long-term management of psychosis. An orally disintegrating tablet formulation of olanzepine is a useful alternative to standard tablets. A short-acting injectable formulation of the drug is in development for psychotic agitation. Sachets and slow-release formulations of quetiapine are in development. Ziprasidone, a recently launched agent, is available in tablet form for schizophrenia/schizoaffective disorder, psychotic depression and mania. A short-acting injectable formulation is in development for psychotic agitation. Aripiprazole (tablets) and iloperidone (tablets and depot injection) are two antipsychotics in development for schizophrenia/schizoaffective disorder (available information regarding iloperidone is very limited). These new formulations and agents should broaden options for the treatment of psychosis.
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The aim of this systematic review was to examine the efficacy and safety of second-generation antipsychotics (SGAs) in nonpsychotic major depressive disorder (MDD).
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The total number of queries on psychotropic drugs performs in CZTIS more than 30% of all calls, constantly. We enrolled a total of 43 women exposed to SSRI and 37 women (1x twins) exposed to new psychotropic drugs (APD) in the study. Exposure to SSRI was often associated with poly-therapy. The most frequent SSRI used were citalopram and/or escitalopram (56%), and setraline (26%). Other SSRI were used sporadically. We observed significantly higher frequency of elective terminations in group of SSRI and higher frequency of abortions a prematurity in APD group. Frequency of malformations does not varied, being in all groups in expected range.
Aripiprazole is the first of a new generation of antipsychotics that possesses a unique mechanism of action as a partial dopamine agonist. After the release of aripiprazole, case reports appeared conveying an acute psychosis/agitation reaction occurring after the initiation of treatment, most specifically after patients were switched from a previous antipsychotic to aripiprazole. The primary objective of this study was to compare relapse rates among patients with schizophrenia who were switched to aripiprazole with those who switched to a second-generation antipsychotic (SGA) from another antipsychotic.
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A 73-year-old Caucasian woman with a recent diagnosis of Parkinson disease and a history of chronic obstructive pulmonary disease, hyperlipidemia, chronic osteoarthritis, and hypothyroidism was hospitalized for altered mental status, weakness, and ambulatory dysfunction. The diagnosis of Parkinson disease was made approximately four months prior. Despite initiation of carbidopa-levodopa, the patient's symptoms did not improve, and her mental and physical status declined. The patient was taking olanzapine 30 mg daily for bipolar disorder and had a 40-pack-year history of smoking, but she quit smoking approximately four months before this hospitalization. The results of a neurologic evaluation suggested that the patient did not have Parkinson disease but was possibly experiencing olanzapine toxicity secondary to smoking cessation. Carbidopa-levodopa was discontinued. Psychiatry was consulted, and a monthlong cross-taper to discontinue olanzapine and initiate aripiprazole with a target dosage of 20 mg daily was recommended. During the course of therapy, the patient's level of alertness and bradykinesia improved. Overall, it was noted that her extrapyramidal symptoms were gradually improving; two days before hospital discharge, she was noted to have no definite remaining evidence of parkinsonism. In this case, use of the Naranjo et al. adverse-drug-reaction probability scale and the drug interaction probability scale indicated that the adverse effects were probably related to the interaction between smoking and olanzapine.
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The initial enthusiasm for atypical antipsychotics, with a lower incidence of extra pyramidal symptoms, was tempered by the association with metabolic disorders. The presence of metabolic alterations significantly influences morbidity and patients' quality life. We performed this open-study to determine the relationship between antipsychotic efficacy and side effects, especially the impact of various antipsychotics on metabolic parameters after 20-year treatment with atypical (SGA) and typical antipsychotics (FGA).
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Data regarding allocation of typical and atypical antipsychotics, over the period 2004 to 2013, were extracted from the electronic records of SAREL, Israel's largest private supplier of drugs to healthcare and medical facilities. The data were converted to defined daily doses (DDD) per 1000 inpatients per day.