Double-Blind Comparison of First- and Second-Generation Antipsychotics in Early-Onset Schizophrenia and Schizo-affective Disorder: Findings From the Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) Study

Sikich, Linmarie; Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Ritz, Louise; Ambler, Denisse; Puglia, Madeline; Maloney, Ann E.; Michael, Emily; Jong, S. de; Slifka, Karen; Noyes, Nancy; Hlastala, Stefanie A.; Pierson, Leslie; McNamara, Nora; DelPorto-Bedoya, Denise; Anderson, Robert S.; Hamer, Robert M.; Lieberman, Jeffrey A.

doi:10.1176/appi.ajp.2008.08050756

Cited by 407 publications

(290 citation statements)

References 41 publications

(46 reference statements)

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“…Acute TEOSS data found that olanzapine and risperidone were associated with significant weight gain, and olanzapine was associated with lipid and liver function changes. 3 However, those analyses included subjects that discontinued after participation in the acute study due to metabolic side effects, whereas these maintenance data include only those that tolerated acute treatment and continued in this trial. Therefore, there is a selection bias towards patients that did not develop clinically significant adverse events during acute therapy.…”

Section: Discussionmentioning

confidence: 99%

“…3,5 In this report we focus on the 44-week, double-blind extension phase that followed the 8-week, double-blind acute trial. The primary results of the acute study have been described previously.…”

Section: Methods Study Designmentioning

confidence: 99%

“…The primary results of the acute study have been described previously. 3 During maintenance, youths continued to receive the same antipsychotic drug that they were administered during the acute phase. Treatment response and side effects were assessed every 4 weeks.…”

Section: Methods Study Designmentioning

confidence: 99%

“…Overall, approximately 50 % of subjects responded to the initially randomized treatment. 3 Two "second generation" antipsychotics, risperidone and olanzapine, were not superior to a "first generation" antipsychotic, molindone, in symptom diminution or proportion of treatment responders. Both risperidone and olanzapine were associated with greater degrees of weight gain than molindone.…”

Section: Introductionmentioning

confidence: 98%

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Double-Blind Maintenance Safety and Effectiveness Findings From the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

Findling

Johnson

McClellan

et al. 2010

Journal of the American Academy of Child & Adolescent Psych

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OBJECTIVE-To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders (EOSS). (age 8-19 years) who had improved during an 8-week, randomized doubleblind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed following defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. METHOD-PatientsRESULTS-Of the 116 youth randomized in the acute trial, 54 entered maintenance treatment (molindone, N=20; olanzapine, N=13; risperidone, N=21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (N=15), inadequate efficacy (N=14), or study non-adherence (N=8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom reduction or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment.CONCLUSIONS-Only 12 % of youth with EOSS continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for EOSS.

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Section: Discussionmentioning

confidence: 99%

Section: Methods Study Designmentioning

confidence: 99%

Section: Methods Study Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Double-Blind Maintenance Safety and Effectiveness Findings From the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

Findling

Johnson

McClellan

et al. 2010

Journal of the American Academy of Child & Adolescent Psych

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“…Low-density lipoprotein and triglyceride levels were reported to increase in both groups [35]. In contrast to these findings, another study involving a different patient group observed a small increase in HDL levels in patients receiving olanzapine after 8 weeks' treatment, while a decrease was observed in HDL levels in patients treated with risperidone [36].…”

Section: Discussionmentioning

confidence: 82%

A comparison of depot and oral atypical antipsychotics in terms of metabolic syndrome markers

Aykut

Karagüzel

2017

Psychiatry and Clinical Psychopharmacology

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OBJECTIVES: The duration of life of patients with schizophrenia is shorter than that of the general population for various reasons. Especially cardiovascular diseases are one of the most important causes of death in patients with schizophrenia. Our aim in this study is comparison of second-generation depot antipsychotics and second-generation oral antipsychotics used in the treatment of patients with schizophrenia in terms of metabolic syndrome criteria. METHODS: We included 39 patients treated with second-generation depot antipsychotics and 124 patients treated with second-generation oral antipsychotics, who were diagnosed with schizophrenia. Positive and Negative Syndrome Scale was applied to all the patients and blood pressure, weight, height, body mass index, waist circumference, fasting blood glucose, triglyceride level, and high-density lipoprotein (HDL) levels were recorded. RESULTS: In terms of metabolic syndrome criteria, the waist circumference and triglyceride levels of the patients treated with the second-generation depot antipsychotics were lower than those of the patients treated with second-generation oral antipsychotics, and the HDL levels were statistically significantly higher. CONCLUSION: In this study, second-generation depot antipsychotics used in the treatment of schizophrenia patients were found to be associated with more positive results in terms of metabolic syndrome criteria than oral antipsychotic drug forms. ARTICLE HISTORY

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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

163

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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Double-Blind Comparison of First- and Second-Generation Antipsychotics in Early-Onset Schizophrenia and Schizo-affective Disorder: Findings From the Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) Study

Cited by 407 publications

References 41 publications

Double-Blind Maintenance Safety and Effectiveness Findings From the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

Double-Blind Maintenance Safety and Effectiveness Findings From the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

A comparison of depot and oral atypical antipsychotics in terms of metabolic syndrome markers

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

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