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Neurocognitive outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders study.

ABSTRACT: To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS).Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated in a four-site, randomized, double-blind clinical trial comparing molindone, olanzapine, and risperidone. The primary outcomes were overall group change from baseline in neurocognitive composite and six domain scores after 8 weeks and continued treatment up to 52 weeks. Age and sex were included as covariates in all analyses.Of 116 TEOSS participants, 77 (66%) had post-baseline neurocognitive data. No significant differences emerged in the neurocognitive outcomes of the three medication groups. Therefore, the three treatment groups were combined into one group to assess overall neurocognitive outcomes. Significant modest improvements were observed in the composite score and in three of six domain scores in the acute phase, and in four of six domain scores in the combined acute and maintenance phases. Partial correlation analyses revealed very few relationships among Positive and Negative Syndrome Scale (PANSS) baseline or change scores and neurocognition change scores.Antipsychotic intervention in youth with early-onset schizophrenia spectrum disorders (EOSS) led to modest improvement in measures of neurocognitive function. The changes in cognition were largely unrelated to baseline symptoms or symptom change. Small treatment effect sizes, easily accounted for by practice effects, highlight the critical need for the development of more efficacious interventions for the enduring neurocognitive deficits seen in EOSS. Clinical trial registry information-Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS); http://www.clinicaltrials.gov; NCT00053703.

SUBMITTER: Frazier JA

PROVIDER: S-EPMC3337647 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Neurocognitive outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders study.

Frazier Jean A JA Giuliano Anthony J AJ Johnson Jacqueline L JL Yakutis Lauren L Youngstrom Eric A EA Breiger David D Sikich Linmarie L Findling Robert L RL McClellan Jon J Hamer Robert M RM Vitiello Benedetto B Lieberman Jeffrey A JA Hooper Stephen R SR

Journal of the American Academy of Child and Adolescent Psychiatry 20120313 5

<h4>Objective</h4>To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS).<h4>Method</h4>Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated in a four-site, randomized, double-blind clinical trial comparing molindone, olanzapine, and risperidone. The primary outcomes were overa ...[more]

PMID: 22525956

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Project description:Objectives: We investigated the time course of clinical response in the Treatment of Early Onset Schizophrenia Spectrum Disorders Study (TEOSS). Methods: TEOSS randomized 119 predominantly outpatient youth ages 8-19 years with schizophrenia or schizoaffective disorder to 8 weeks of treatment with molindone, risperidone, or olanzapine. We used proportional hazards regression to determine whether these three antipsychotics differed in the time until clinical response, defined as the time from treatment initiation to the point of achieving a Clinical Global Impressions-Improvement (CGI-I) scale score of 1 ("very much improved") or 2 ("much improved") that was maintained until week 8. Results: Of the 116 youth who initiated treatment, 56 (48%) achieved clinical response. Among clinical responders, the median (±interquartile range) time until clinical response was 4.0 (±4.0) weeks for olanzapine, 4.5 (±4.0) weeks for risperidone, and 6.0 (±4.0) weeks for molindone. There were no significant differences in time course for clinical response between medications (p = 0.84). Youth without symptom improvement (CGI-I ≥ 4) after 3 weeks were more likely to be clinical nonresponders at week 8 (relative risk ratio = 1.98, 95% confidence interval 1.29-3.05), compared with youth with at-least-minimal symptom improvement after 3 weeks when looking at all antipsychotics combined. Conclusion: To our knowledge, our study is the first to investigate medication differences in treatment response timing in early onset schizophrenia spectrum disorders. Clinical response times for molindone, risperidone, and olanzapine were not significantly different. Furthermore, while lack of early improvement predicted clinical nonresponse, whether or not to continue antipsychotic treatment after 3 or more weeks without symptom improvement should be based on clinical judgment after weighing potential risks, benefits, and alternatives. ClinicalTrials.gov Identifier: NCT00053703.

Project description:Abstract Background We sought to characterize the trajectory of symptom change in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study (TEOSS), the largest randomized control trial in early-onset schizophrenia. Methods TEOSS randomized 119 youths ages 8–19 years old to 8 weeks of treatment with molindone, risperidone, or olanzapine (First Randomization). TEOSS defined treatment response as: completion of 8 weeks of treatment with the randomized antipsychotic, a Clinical Global Impression-Improvement (CGI-I) Scale score of 1(“very much improved”) or 2 (“much improved”), and a 20% reduction in symptoms on the Positive and Negative Syndrome Scale (PANSS). If participants did not respond to the initial randomized antipsychotic, participants were re-randomized to one of the two remaining antipsychotics (Second Randomization, n=50). If participants did not respond to the second antipsychotic, participants received the remaining antipsychotic (Third Randomization, n=23). Prior work found there was no statistically significant difference in response rates in the First Randomization when comparing molindone (50%), risperidone (46%), and olanzapine (34%) [Sikich et al. 2008]. Our study extends prior work by reporting the response rates for the Second and Third Randomizations, and also by reporting how long it took for youths to improve clinically with each antipsychotic. Results When combining all three Randomizations, response rates were: molindone 36.8% (25/68), risperidone 48.4% (31/64), and olanzapine 33.3% (20/60) (p=0.19). Response rates for the Second and Third Randomizations were: molindone 14.8% (4/27), risperidone 40.9% (9/22), and olanzapine 33.3% (8/24) (p=0.28). For youths who responded in the First Randomization (n=55), those randomized to molindone took 5.4 weeks (SD=2.4), risperidone 4.4 weeks (SD=2.3), and olanzapine 4.1 weeks (SD=2.4) to achieve and sustain a CGI-I of 1 (“very much improved”) or 2 (“much improved”) (p=0.24). When we combined the Second and Third Randomizations, it took youths randomized to molindone (n=4) 5.3 weeks (SD=2.8), risperidone (n=13) 4.8 weeks (SD=2.4), and olanzapine (n=4) 6.0 weeks (SD=2.2) to achieve and sustain a CGI-I of 1 or 2 (p=0.71).When we combined all three Randomizations, it took youths randomized to molindone (n=25) 5.4 weeks (SD=2.4), risperidone (n=33) 4.6 weeks (SD=2.3), and olanzapine (n=18) 4.6 weeks (SD=2.4) to achieve and sustain a CGI-I of 1 or 2 (p=0.39). Discussion This is the largest study in early-onset schizophrenia to look at response rates after failing randomized antipsychotic treatment. Furthermore, our study reports the average time it takes to achieve clinically-significant improvement in early-onset schizophrenia. ClinicalTrials.Gov Identifier: NCT00053703.

Project description:BackgroundAntipsychotic-related weight gain is a common clinically relevant side effect when treating psychotic disorders in pediatric populations, yet few predictors and no moderators of antipsychotic-related weight gain are known.MethodsThe Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) study randomized 119 youths (age 8-19 years) with schizophrenia or schizoaffective disorder to 8 weeks of antipsychotic treatment with molindone, risperidone, or olanzapine and assessed treatment response and side effects. In this secondary analysis, we used multivariable linear regression and receiver operating characteristic analysis to investigate predictors and moderators of weight change and percent weight change from baseline to week 8.ResultsTreatment assignment was the most discriminant predictor of weight change [F(2, 66) = 17.00, p < 0.001] and percent weight change [F(2, 66) = 16.85, p < 0.001]. Mean weight gain was 0.74 (standard deviation ±3.51) kg for molindone, 4.13 ± 3.79 kg for risperidone, and 7.29 ± 3.44 kg for olanzapine. After adjusting for treatment assignment, lower pretreatment hemoglobin A1C (HgbA1C) predicted more weight gain [F(1, 55) = 4.71, p = 0.03]. Diagnosis (schizoaffective vs. schizophrenia) moderated weight change [F(2, 63) = 6.02, p = 0.004] and percent weight change [F(2, 63) = 5.26, p = 0.008] such that schizoaffective diagnosis predicted larger weight gain for youths in the risperidone treatment arm. Age, sex, family income, baseline weight, and symptoms neither predicted nor moderated weight change or percent weight change.ConclusionWe identified prognostic subgroups and novel risk factors for antipsychotic-related weight gain. We confirmed that antipsychotic choice is extremely important for predicting future weight gain. We also found that younger age did not predict greater weight gain, in contrast to prior studies. Our findings require replication in an independent sample because we did not adjust for multiple comparisons to minimize false negatives. ClinicalTrials.gov Identifier: NCT00053703.

Dataset Information

Neurocognitive outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders study.

Publications

Neurocognitive outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders study.

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