Lessons to take home from CATIE
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA.Psychiatric Services (Impact Factor: 2.41). 06/2008; 59(5):523-5. DOI: 10.1176/appi.ps.59.5.523
The publicly funded Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) did not support superiority hypotheses for second-generation antipsychotic drugs in schizophrenia. Instead, the study supported the view that first- and second-generation antipsychotics have similar therapeutic properties and diverse adverse effect profiles. This emphasizes the importance of designing pharmacotherapy for the individual in order to optimize the benefit-to-risk profile. First- and second-generation antipsychotic drugs are extensively similar in mechanism of action, efficacy for psychosis, and lack of efficacy for avolition and impaired cognition. However, adverse effect profiles vary between drugs. The authors review the clinical implications of these data, with an emphasis on individualizing pharmacotherapy in an effort to reduce risk. Rather than selecting drugs on the basis of unfounded expectations of superior efficacy, clinicians can focus on selecting drugs and optimizing dosages to minimize adverse effects without sacrificing efficacy. Tardive dyskinesia may be a good reason to avoid a high dosage of first-generation antipsychotics, although the evidence for differential risk is less compelling for a modest dosage of low-affinity first-generation antipsychotics. Similarly, the metabolic effects of some second-generation antipsychotics can be decisive in considering risks. In either case, the clinician should detect earliest signs and take action while dyskinetic or metabolic effects are most reversible. Bottom line: the dichotomy between first- and second-generation antipsychotics was not supported by efficacy data (and now, is not supported effectiveness data). Only clozapine has documented superiority in treatment-resistant cases.
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- "SGAs are not generally more effective than firstgeneration antipsychotics (Carpenter and Buchanan, 2008), but they have a distinct profile of adverse effects. Fewer extrapyramidal adverse effects are traded for more metabolic adverse effects including weight gain, hyperglycemia , and dyslipidemia (De Hert et al., 2012a, 2012b). "
ABSTRACT: We carried out an observational study that analyzed population characteristics, metabolic profiles, potentially interacting pharmacotherapy, and related adverse events in second-generation antipsychotics (SGAs) users of a tertiary care hospital. Within our pharmacoepidemiological database derived from electronic medical records of 82 358 hospitalizations, we identified 1136 hospitalizations contributing 9165 patient-days with exposure to SGA. Blood pressure, blood glucose, lipids, and BMI had been documented in 97.7, 75.7, 24.6, and 77.4% of hospitalizations, respectively. Among these, the prevalence of hypertension, hyperglycemia, dyslipidemia, and BMI 30 kg/m or more was 36.9, 22.6, 61.1, and 23.1%, respectively. A total of 63.4, 70.8, and 37.1% of SGA users with hyperglycemia, dyslipidemia, and hypertension, respectively, received no pharmacotherapy for these conditions. We identified 614 patient-days with SGA plus formally contraindicated comedication and another 1066 patient-days with other high-risk combinations for QTc prolongation. Among those there was one case with associated neutropenia and four cases with abnormal QTc interval. However, specific monitoring for such adverse events was not documented in 45.5% of hospitalizations with contraindicated and 89.8% with high-risk QTc-prolonging combinations. Our study identified targets for improved monitoring and management in SGA users. These may be implemented as automated alerts into electronic prescribing systems and thereby efficiently support safer pharmacotherapy in clinical practice.
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- "Moreover, we lack efficient tools for its treatment or prevention. For example, the multicenter, NIMH-funded Clinical Antipsychotic Trials in Intervention Effectiveness project recently found that newer atypical antipsychotics are not significantly more effective for treating psychosis than older typical antipsychotic medications and showed little benefit for improving cognitive symptoms  . These findings highlight the need to develop novel therapeutic interventions for schizophrenia  . "
ABSTRACT: Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.
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- "Compliance seems better in the long term despite patients' poor insight about their disorder. The crucial issue is that having either a lack of efficacy for a particular drug or getting EPS/TD will cause patients to discontinue their medications (Carpenter & Buchanan, 2008). Other considerations are the following : patient selection should avoid using patients with a long history of the disorder (i.e. "
ABSTRACT: Over the last 5 years, some studies have questioned the efficacy of second-generation antipsychotics over first-generation neuroleptics in the treatment of schizophrenia. At the same time, these study results have led to re-examination of their design--particularly CATIE and CUtLASS--which essentially measured relatively short-/mid-term outcome and did not always take into account real-world clinical practice and outcome measures (e.g. prevalence of positive acute symptoms, exclusion of comorbidity with substance abuse, predominance of chronic patients, lack of quality of life/wellbeing measures, etc.). In fact, one of the greatest challenges to treatment of schizophrenia is its life-long, multifaceted, functional disability associated with progressive cognitive deterioration after each acute episode. As such, the most important goal of the treatment is not just to deal with acute episodes, but rather to improve long-term outcome. Specifically, we aim for modest improvement and then stabilization of the different clinical dimensions involved in the overall symptomatology (i.e. negative/anergic, impulsive, positive, mood and cognitive impairments), and to achieve 'clinical stabilization' after obtaining a partial or full remission of acute symptoms, thus reducing the risk of a progressive cognitive deterioration. All these aspects need to be properly evaluated in a long-run perspective.