A Meta-Analysis of Head-to-Head Comparisons of Second-Generation Antipsychotics in the Treatment of Schizophrenia

Universidad de La Frontera, Ciudad Temuco, Araucanía, Chile
American Journal of Psychiatry (Impact Factor: 12.3). 11/2008; 166(2):152-63. DOI: 10.1176/appi.ajp.2008.08030368
Source: PubMed


Whether there are differences in efficacy among second-generation antipsychotics in the treatment of schizophrenia is a matter of heated debate. The authors conducted a systematic review and meta-analysis of blinded studies comparing second-generation antipsychotics head-to-head.
Searches of the Cochrane Schizophrenia Group's register (May 2007) and MEDLINE (September 2007) were conducted for randomized, blinded studies comparing two or more of nine second-generation antipsychotics in the treatment of schizophrenia. All data were extracted by at least three reviewers independently. The primary outcome measure was change in total score on the Positive and Negative Syndrome Scale; secondary outcome measures were positive and negative symptom subscores and rate of dropout due to inefficacy. The results were combined in a meta-analysis. Various sensitivity analyses and metaregressions were used to examine bias.
The analysis included 78 studies with 167 relevant arms and 13,558 participants. Olanzapine proved superior to aripiprazole, quetiapine, risperidone, and ziprasidone. Risperidone was more efficacious than quetiapine and ziprasidone. Clozapine proved superior to zotepine and, in doses >400 mg/day, to risperidone. These differences were due to improvement in positive symptoms rather than negative symptoms. The results were rather robust with regard to the effects of industry sponsorship, study quality, dosages, and trial duration.
The findings suggest that some second-generation antipsychotics may be somewhat more efficacious than others, but the limitations of meta-analysis must be considered. In tailoring drug treatment to the individual patient, small efficacy superiorities must be weighed against large differences in side effects and cost.

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    • "Cohen's guideline was adopted such that ESs of 0.2, 0.5, and 0.8 corresponded to small, medium, and large effects, respectively (Cohen, 1988). Since the study of Prins and colleagues (Prins et al., 2014) did not report standard deviation of %TBV/y and %HV/y, we imputed the SD from Schuff et al. (2011) as has been done before (Leucht et al., 2009). The Cochrane risk of bias criteria (Cochrane Collaboration, "
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    ABSTRACT: There has not been a conclusive evidence for prevention of brain atrophy by anti-dementia drugs (ADDs) in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Relevant studies were identified through searches of PubMed®, databases of the Cochrane Library©, and PsycINFO citations up to 5/16/2015. Only double-blind, randomized, placebo-controlled clinical trials (RCTs) of ADDs in patients with MCI or AD were included. Primary outcomes were annualized percent change of total brain volume (%TBV/year), annualized percent change of hippocampal volume (%HV/year), and annualized percent change of ventricular volume (%VV/year) measured by magnetic resonance imaging. Standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated for relevant outcomes. Seven RCTs (n=1708) were found to meet the inclusion criteria, including 4 MCI studies (n=1327) and 3 AD studies (n=381) [3 donepezil studies (2 MCI studies and 1 AD study), 1 galantaime study for MCI, 2 mementine studies for AD and 1 rivastigmine study for MCI]. Pooled ADDs showed superior protective outcomes compared to placebo regarding %TBV/year (SMD=-0.21, 95%CI=-0.37 to -0.04, p=0.01, N=4, n=624) and %VV/year (SMD=-0.79, 95%CI=-1.40 to -0.19, p=0.01, N=3, n=851). However, %HV/year failed to show difference between both groups. Among ADDs, donepezil showed significantly greater protective effects than placebo regarding %TBV/year (SMD=-0.43, 95%CI=-0.74 to -0.12, p=0.007, N=1, n=164) and %VV/year (SMD=-0.51, 95%CI=-0.73 to -0.29, p<0.00001, N=2, n=338). Rivastigmine was also superior to placebo regarding %VV/year (SMD=-1.33, 95%CI=-1.52 to -1.14, p<0.00001). The results favored the hypothesis that ADDs may prevent brain atrophy in patients with MCI and AD. © The Author 2014. Published by Oxford University Press on behalf of CINP.
    Full-text · Article · Jun 2015 · The International Journal of Neuropsychopharmacology
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    • "Furthermore, because of the esthetic consequences and social stigmatism associated with being overweight or obese, patient compliance is reduced, which increases the risk of relapse and re-hospitalization (Lieberman et al., 2005). Although several other antipsychotics on the market today are less likely to induce weight gain (especially ziprasidone and aripiprazole), none has proved to be as therapeutically effective as olanzapine (Leucht et al., 2009; Komossa et al., 2010). It is, therefore, necessary to develop novel treatment strategies that obtain an equal therapeutic response without increasing body weight. "

    Full-text · Dataset · Mar 2015
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    • "Many patients have benefited from the availability of second-generation antipsychotics (SGAs), which provide improved overall efficacy with reduced incidence of extrapyramidal symptoms compared with first-generation antipsychotics.2,4 Conversely, some SGAs are associated with a relatively greater risk of weight gain and metabolic side effects.5–7 There are significant variations in the receptor-binding profiles of SGAs that contribute to their differing efficacy across many of the symptomatic domains of schizophrenia8 as well as to differences in their tolerability.9 "
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    ABSTRACT: Introduction Prompt administration of antipsychotic treatment that is adhered to is essential for the optimal treatment of schizophrenia. Many patients have benefited from the advent of second-generation antipsychotics, which can offer good symptomatic control with reduced incidence of extrapyramidal symptoms, although with higher risk of metabolic side effects. It is unsurprising that accounts as to whether first- and second-generation antipsychotics differ in their efficacy vary, since treatment effectiveness is a broad notion and difficult to define. Objectives Numerous factors may be used to gauge treatment effectiveness and, while it has largely been defined in terms of improvements in four domains (symptoms of disease, treatment burden, disease burden, and health and wellness), the real-world clinical utility of this consensus is unclear. Therefore, this article aims to provide a framework that can aid psychiatrists in making assessments about treatment effectiveness. Methods and results A panel of 12 psychiatrists and psychopharmacologists convened to develop and propose an accessible and globally-applicable framework for assessing the effectiveness of antipsychotic treatments in patients with schizophrenia. Following presentation of a preliminary proposal to a wider group of psychiatrists from across Europe, it was refined into a framework comprising five domains: symptomatic remission and retention of treatment; affective symptoms; cognitive functioning; treatment satisfaction; and personal and social functioning – each of which is discussed in this article. Conclusions This article provides a framework that can aid psychiatrists in making assessments about treatment effectiveness. It is anticipated that the framework outlined here may contribute to improving clinical practice through the promotion of a patient-centered approach to the assessment of treatment effectiveness, using five specified domains, in patients with schizophrenia.
    Full-text · Article · Sep 2014 · Neuropsychiatric Disease and Treatment
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