Advances in the treatment of mania: Aripiprazole
Programa de Trastornos Bipolares, Instituto Clínico de Neurociencias, Hospital Clínic, Universitat de Barcelona, IDIBAPS, CIBER-SAM, Barcelona.Actas espanolas de psiquiatria (Impact Factor: 1.2). 05/2008; 36(3):158-64.
Aripiprazole is a dopamine partial agonist antipsychotic drug that has just been approved in Europe for its use in the treatment of acute mania and for the prevention of manic episodes in bipolar disorder. Its efficacy in mania is superior to that of placebo, both as monotherapy and as adjunctive therapy, and comparable to that of haloperidol and lithium. From the safety perspective it is remarkable that it is not highly sedative and does not impair the metabolic parameters. The advantages of a non-sedative and metabolically neutral antimanic drug are particularly relevant in the long-term, due to their impact on cognition and quality of life. The experience on its use in routine clinical practice indicates that in order to avoid phenomena such as activation, abrupt worsening or akathisia, it is recommendable to start treatment with low doses and to increase them progressively, especially in those patients who are already receiving other drugs; moreover, it is advisable not to stop abruptly any ongoing treatment, unless there is an emergency, to transiently prescribe a concomitant benzodiazepine, and to maintain the dose that proved efficacious during the short term treatment during maintenance therapy.
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- "The mechanism of sinus tachycardia remains unknown, as aripiprazole possess no affinity for noradrenergic or cholinergic receptors (Otsuka 2014). Possible etiologies include the effect of other drugs, such as clozapine combined with aripiprazole (Nielsen et al. 2013), or akathisia/activation seen at times during the initial phase of aripiprazole treatment (Vieta and Franco 2008). "
ABSTRACT: Certain antipsychotics increase the risk of heart rate-corrected QT (QTc) prolongation and consequently Torsades de Pointes (TdP) and sudden cardiac death (SCD). Drug-induced Brugada syndrome (BrS) is also associated with SCD. Most SCDs occur in patients with additional cardiac risk factors. Aripiprazole's cardiac safety has not been assessed in patients at high risk for torsade, where QTc prolongation risk is highly increased. MEDLINE, Embase, and The Cochrane Library were searched for preclinical, clinical, and epidemiological studies. Eligible studies were reviewed and cardiac safety data were extracted. Continuous and dichotomous QTc data were used in the meta-analysis. Preclinical studies suggested that aripiprazole has limited affinity for the delayed rectifier potassium current. TdP was reported in two case reports and SCD was reported in one case report and one case series. No clinical studies assessing aripiprazole's cardiac safety in patients at high risk for torsade were found. No thorough QT (TQT) study with aripiprazole was found. The meta-analysis revealed that the mean ΔQTc interval was decreased with aripiprazole and QTc prolongation risk was lower compared with placebo and active controls. Epidemiological studies linked aripiprazole to weak/moderate torsadogenicity. No studies were found associating aripiprazole with BrS suggesting low affinity for the fast sodium current. Aripiprazole is a low-risk antipsychotic regarding cardiac safety in healthy patients. However, baseline and steady state electrocardiogram is recommended in patients at high risk for torsade due to marked QTc prolongation, absence of a TQT study, and lack of data in this group.
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ABSTRACT: The last decade has witnessed a growing interest to evaluate the aetiology of schizophrenia and bipolar disorders through a genetic. molecular and cellular analysis, as well as to assess the influence of epigenetic factors in the phenotypic presentation of these severe disorders. We have used the following methods: We analysed six lilies of, research: The Valencia Follow-Up study of Schizophrenia and Bipolar I Disorders, The Neurocognitive Endophenotype (Endophenocognitype) study. The Negative Comorbidity Study, Experimental Embryology, Neurogenetics. and Clinical Genetics. we have described a translational and integrated multi-disciplinary approach to set a framework aimed to identify molecular mechanisms and valid endophenotypes for schizophrenia and bipolar disorders. Conclusions:The University of Valencia and the Alicante Neuroscience Institute (UVANI) - CIBERSAM node is a specialized resource providing basic topics. clinical care, education and research in the area of severe mental disorders.
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ABSTRACT: Practitioners often combine 2 or more second-generation antipsychotics (SGAs) in patients with bipolar disorder, despite an absence of data to support their safety, tolerability, or efficacy. This study sought to evaluate the safety and tolerability of SGA polytherapy compared to SGA monotherapy in bipolar disorder patients receiving open naturalistic treatment in the 22-site Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). A longitudinal cohort of 1,958 patients who were prescribed at least 1 SGA was drawn from 4,035 bipolar patients in STEP-BD recruited between November 1999 and July 2005 and assessed at least quarterly for a mean duration of 21 months. Main outcome measures were the mean quarterly prevalence of adverse events, medical and psychiatric service usage, Global Assessment of Functioning ratings, and percentage of days spent well. Almost 10% of patients taking SGAs were prescribed SGA polytherapy. After controlling for illness onset, age, baseline illness severity, and medication load, patients prescribed SGA polytherapy, compared to monotherapy, exhibited more dry mouth (number needed to harm [NNH] = 4), tremor (NNH = 6), sedation (NNH = 8), sexual dysfunction (NNH = 8), and constipation (NNH = 11) and were almost 3 times as likely to incur more psychiatric and medical care; there was no association with greater global functioning scores or percentage of days spent well. Although SGA polytherapy was fairly common in bipolar disorder, it was associated with increased side effects and health service use but not with improved clinical status or function. Thus, SGA polytherapy in bipolar disorder may incur important disadvantages without clear benefit, warranting careful consideration before undertaking such interventions.