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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.
Am J Psychiatry. 2008 Nov; 165(11):1420-31.AJ

Abstract

OBJECTIVE

Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder.

METHOD

This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5-20 mg/day), risperidone (0.5-6 mg/day), or molindone (10-140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and >or=20% reduction in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of treatment.

RESULTS

In total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia.

CONCLUSIONS

Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder. Adverse effects were frequent but differed among medications. The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia and schizoaffective disorder. The safety findings related to weight gain and metabolic problems raise important public health concerns, given the widespread use of second-generation antipsychotics in youth for nonpsychotic disorders.

Authors+Show Affiliations

University of North Carolina at Chapel Hill, NC 27514, USA. Lsikich@med.unc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18794207

Citation

Sikich, Linmarie, et al. "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." The American Journal of Psychiatry, vol. 165, no. 11, 2008, pp. 1420-31.
Sikich L, Frazier JA, McClellan J, et al. 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. Am J Psychiatry. 2008;165(11):1420-31.
Sikich, L., Frazier, J. A., McClellan, J., Findling, R. L., Vitiello, B., Ritz, L., Ambler, D., Puglia, M., Maloney, A. E., Michael, E., De Jong, S., Slifka, K., Noyes, N., Hlastala, S., Pierson, L., McNamara, N. K., Delporto-Bedoya, D., Anderson, R., Hamer, R. M., & Lieberman, J. A. (2008). 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. The American Journal of Psychiatry, 165(11), 1420-31. https://doi.org/10.1176/appi.ajp.2008.08050756
Sikich L, et al. 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. Am J Psychiatry. 2008;165(11):1420-31. PubMed PMID: 18794207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Sikich,Linmarie, AU - Frazier,Jean A, AU - McClellan,Jon, AU - Findling,Robert L, AU - Vitiello,Benedetto, AU - Ritz,Louise, AU - Ambler,Denisse, AU - Puglia,Madeline, AU - Maloney,Ann E, AU - Michael,Emily, AU - De Jong,Sandra, AU - Slifka,Karen, AU - Noyes,Nancy, AU - Hlastala,Stefanie, AU - Pierson,Leslie, AU - McNamara,Nora K, AU - Delporto-Bedoya,Denise, AU - Anderson,Robert, AU - Hamer,Robert M, AU - Lieberman,Jeffrey A, Y1 - 2008/09/15/ PY - 2008/9/17/pubmed PY - 2008/11/19/medline PY - 2008/9/17/entrez SP - 1420 EP - 31 JF - The American journal of psychiatry JO - Am J Psychiatry VL - 165 IS - 11 N2 - OBJECTIVE: Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. METHOD: This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5-20 mg/day), risperidone (0.5-6 mg/day), or molindone (10-140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and >or=20% reduction in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of treatment. RESULTS: In total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. CONCLUSIONS: Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder. Adverse effects were frequent but differed among medications. The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia and schizoaffective disorder. The safety findings related to weight gain and metabolic problems raise important public health concerns, given the widespread use of second-generation antipsychotics in youth for nonpsychotic disorders. SN - 1535-7228 UR - https://www.unboundmedicine.com/medline/citation/18794207/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_ L2 - https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2008.08050756?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -