Randomized Comparison of Olanzapine Versus Risperidone for the Treatment of First-Episode Schizophrenia: 4-Month Outcomes

Robinson, Delbert G.; Woerner, Margaret G.; Napolitano, Barbara; Patel, Rahulkumar; Sevy, M.B.A. Serge M.; Gunduz‐Bruce, Handan; Soto-Perello, Jose M.; Mendelowitz, Alan; Khadivi, Ali; Miller, Leslie; McCormack, Lalla; Lorell, L.C.S.W. Beth S.; Lesser, Martin; Schooler, Nina R.; Kane, John M.

doi:10.1176/ajp.2006.163.12.2096

Cited by 79 publications

(77 citation statements)

References 31 publications

(29 reference statements)

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“…A high rate of akathisia was seen with ziprasidone in EUFEST (Kahn et al, 2008) and concomitant medication use suggested a slight EPS advantage for quetiapine over olanzapine (McEvoy et al, 2007) and olanzapine over risperidone (Crespo-Facorro et al, 2006Robinson et al, 2006). These tentative differences are consistent with those seen in large meta-analyses, predominantly in patients with chronic schizophrenia (e.g.…”

Section: Rates Of Epssupporting

confidence: 75%

“…Four trials were open (Crespo-Facorro et al, 2006Glenthoj et al, 2007;Kahn et al, 2008;Robinson et al, 2006) though raters were blind to treatment in one (Robinson et al, 2006). The remaining seven trials were double blind.…”

Section: Trial Design Including Durationmentioning

confidence: 99%

“…McEvoy et al (2007) defined parkinsonism as a rating > 1 on any SAS item, akathisia as > 2 on the global severity item of the BAS and dyskinesia as > 2 on the global severity item of the AIMS. Robinson et al (2006) defined parkinsonism as present if two or more items on the SAS were rated 2 or one item was rated 3 or higher. Möller et al (2008) calculated incidence rates using two different thresholds on the AIMS, BAS and SAS.…”

Section: Assessment and Reporting Of Epsmentioning

confidence: 99%

“…McEvoy et al (2007) found that more patients treated with olanzapine received medications for parkinsonism or akathisia than those treated with quetiapine (11% vs. 4%). Robinson et al (2006) reported a trend for lower prescribing of anticholinergics and propranolol with olanzapine versus risperidone. The two remaining trials (Crespo-Facorro et al, 2006Khan et al, 2008) included a haloperidol arm as well as two or more SGAs (Figure 3).…”

Section: Concomitant Medication Use and Drop-outs Due To Side Effectsmentioning

confidence: 99%

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Antipsychotic drugs and extrapyramidal side effects in first episode psychosis: a systematic review of head–head comparisons

et al. 2011

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This systematic review aimed to determine whether the risk of extrapyramidal side effects (EPS) differed between antipsychotic drugs used in first episode psychosis (FEP). We identified 11 RCTs comparing two or more antipsychotics in FEP and reporting on EPS. All trials assessed one or more second generation antipsychotics (SGAs), one assessed chlorpromazine, one zuclopenthixol and seven trials assessed haloperidol. Assessment and reporting of EPS varied. Compared with one or more SGA comparators, haloperidol was associated with significantly higher rates/severity of parkinsonism (seven trials) and akathisia (six trials) and greater use of anticholinergics (five trials) and beta-blockers (two trials). Two trials with low-dose haloperidol (≤ 4 mg) showed significantly worse EPS outcomes versus a SGA. Two of four long-term haloperidol trials (≥ 1 year) found a higher dyskinesia-risk with haloperidol versus olanzapine and risperidone respectively; the remaining two trials found no difference (various SGA comparators). There was an EPS advantage for clozapine versus chlorpromazine (one trial) and risperidone versus zuclopenthixol (one trial). There was little evidence of EPS-differences between SGAs, possibly reflecting use of low doses. We conclude that SGAs offer an EPS advantage over FGAs in FEP though the evidence largely relates to comparisons with haloperidol. Standardized assessment and reporting of EPS would assist future research. Keywords Method Search strategyWe conducted a PubMed search, with no starting date limit, up to April 2011 using terms 'first episode schizophrenia' and 'antipsychotic' with limits specified as 'Humans, Randomized Controlled Trial and English'. The abstracts of all papers were reviewed to determine whether they met inclusion/exclusion criteria and if there was doubt the full paper was examined. Additional studies, identified through the reference list of papers in the primary search or known to the authors, were reviewed to see if they met inclusion/exclusion criteria. Inclusion criteria1. RCT comparing two or more antipsychotic drugs. 2. Diagnosis of schizophrenia plus related disorders including schizophreniform disorder and schizoaffective disorder made according to standard criteria (any). 3. Patients explicitly described as 'first episode' by the authors. Although we did not define this further we recorded key criteria that the researchers employed to define this population, e.g. maximum age, maximum duration of illness and maximum cumulative antipsychotic treatment length. 4. EPS assessed using a standard rating scale. 5. Quantitative data on incidence or severity of EPS provided. 6. Paper published in English. Exclusion criteria1. Studies of a single antipsychotic. 2. Non-randomized studies. 3. Studies of early onset schizophrenia (i.e. samples largely composed of subjects < 18 years old). AnalysisKey data from the studies that met the inclusion/exclusion criteria were extracted. This included EPS ratings for parkinsonism, akathisia, dyskinesia and dystonia made us...

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Section: Rates Of Epssupporting

confidence: 75%

Section: Trial Design Including Durationmentioning

confidence: 99%

Section: Assessment and Reporting Of Epsmentioning

confidence: 99%

Section: Concomitant Medication Use and Drop-outs Due To Side Effectsmentioning

confidence: 99%

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Antipsychotic drugs and extrapyramidal side effects in first episode psychosis: a systematic review of head–head comparisons

et al. 2011

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“…All but two patients had participated in a clinical treatment trial comparing the efficacy of risperidone vs olanzapine. Further details regarding the ascertainment of patients and the clinical trial are available in Robinson et al (2006). In the present study we defined recent onset as having a duration of illness from the index episode or entry into the clinical trial to the MRI exam of 4.25 years or less (median ¼ 79 weeks, mode ¼ 0, range ¼ 0-4.25 years).…”

Section: Subjectsmentioning

confidence: 99%

Clinical and Neuropsychological Correlates of White Matter Abnormalities in Recent Onset Schizophrenia

Szeszko

Robinson

Ashtari

et al. 2007

Neuropsychopharmacol

Self Cite

224

184

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The objective of this study was to investigate the clinical and neuropsychological correlates of white matter abnormalities in patients with schizophrenia studied early in the course of illness. A total of 33 (21 male/12 female) patients with recent onset schizophrenia and 30 (18 male/12 female) healthy volunteers completed structural and diffusion tensor imaging exams. Patients also received clinical and neuropsychological assessments. Fractional anisotropy (FA) maps were compared between groups in the white matter using a voxelwise analysis following intersubject registration to Talairach space and correlated with functional indices. Compared to healthy volunteers, patients demonstrated significantly (po0.001, cluster size X100) lower FA within temporal lobe white matter regions corresponding approximately to the right and left uncinate fasciculus, left inferior fronto-occipital fasciculus, and left superior longitudinal fasciculus. There were no areas of significantly higher FA in patients compared to healthy volunteers. Lower FA in the bilateral uncinate fasciculus correlated significantly with greater severity of negative symptoms (alogia and affective flattening), and worse verbal learning/memory functioning. In addition, higher FA in the inferior fronto-occipital fasciculus correlated significantly with greater severity of delusions and hallucinations. White matter abnormalities are evident in patients with schizophrenia early in the course of illness, appearing most robust in left temporal regions. These abnormalities have clinical and neuropsychological correlates, which may be useful in further characterizing structure-function relations in schizophrenia and constraining neurobiological models of the disorder.

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Association Between Common Variants Near the Melanocortin 4 Receptor Gene and Severe Antipsychotic Drug–Induced Weight Gain

Malhotra

Correll

Chowdhury

et al. 2012

Arch Gen Psychiatry

164

113

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Context Second-generation antipsychotics (SGAs) are increasingly used in the treatment of many psychotic and non-psychotic disorders. Unfortunately, SGAs are often associated with substantial weight gain, with no means to predict which patients are at greatest risk. Objective To detect alleles of single nucleotide polymorphisms (SNPs) associated with antipsychotic drug-induced weight gain. Design Pharmacogenetic association study Setting Discovery cohort was collected at a U.S. general psychiatric hospital. Three additional cohorts were collected from psychiatric hospitals in the U.S. and Germany, and from a European antipsychotic drug trial. Participants The discovery cohort was comprised of 139 pediatric patients undergoing first exposure to SGA treatment. An additional three cohorts were comprised of 73, 40 and 92 subjects. Intervention Patients in the discovery cohort were treated with SGAs for twelve weeks. Additional cohorts were treated for six and twelve weeks. Main outcome measure We conducted a genome-wide association study (GWAS) assessing weight gain associated with twelve weeks of SGA treatment in patients undergoing first exposure to antipsychotic treatment. We next genotyped three independent cohorts of subjects assessed for antipsychotic drug-induced weight gain. Results GWAS yielded twenty SNPs at a single locus exceeding a statistical threshold of p < 10−5. This locus, near the melanocortin 4 receptor (MC4R) gene, overlaps a region previously identified by large-scale GWAS of obesity in the general population. Effects were recessive, with minor allele homozygotes gaining extreme amounts of weight over the 12-week trial. These results were replicated in three additional cohorts with SNP rs489693 demonstrating consistent recessive effects; meta analysis revealed a genome-wide significant effect (p=5.59×10−12). Moreover, we observed consistent effects on related metabolic indices, including triglycerides, leptin, insulin, and HOMA-IR in our discovery cohort. Conclusion These data implicate the MC4R locus in extreme SGA-induced weight gain and related metabolic disturbances. A priori identification of high-risk subjects could lead to alternative treatment strategies in this population.

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Randomized Comparison of Olanzapine Versus Risperidone for the Treatment of First-Episode Schizophrenia: 4-Month Outcomes

Abstract: Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine.

Cited by 79 publications

References 31 publications

Antipsychotic drugs and extrapyramidal side effects in first episode psychosis: a systematic review of head–head comparisons

Antipsychotic drugs and extrapyramidal side effects in first episode psychosis: a systematic review of head–head comparisons

Clinical and Neuropsychological Correlates of White Matter Abnormalities in Recent Onset Schizophrenia

Association Between Common Variants Near the Melanocortin 4 Receptor Gene and Severe Antipsychotic Drug–Induced Weight Gain

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