Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizoaffective disorder: Findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study

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

Research output: Contribution to journalArticle

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 ≥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.

Original languageEnglish (US)
Pages (from-to)1420-1431
Number of pages12
JournalAmerican Journal of Psychiatry
Volume165
Issue number11
DOIs
StatePublished - Nov 2008
Externally publishedYes

Fingerprint

olanzapine
Molindone
Psychotic Disorders
Antipsychotic Agents
Schizophrenia
Risperidone
Weight Gain
Therapeutics
Benztropine
Safety
Psychomotor Agitation
Transaminases
Double-Blind Method
LDL Cholesterol
Self Report
Fasting
Public Health
Insulin
Pediatrics

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizoaffective 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; De Jong, Sandra; Slifka, Karen; Noyes, Nancy; Hlastala, Stefanie; Pierson, Leslie; McNamara, Nora K.; Delporto-Bedoya, Denise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.

In: American Journal of Psychiatry, Vol. 165, No. 11, 11.2008, p. 1420-1431.

Research output: Contribution to journalArticle

Sikich, L, Frazier, JA, McClellan, J, Findling, RL, Vitiello, B, Ritz, L, Ambler, D, Puglia, M, Maloney, AE, Michael, E, De Jong, S, Slifka, K, Noyes, N, Hlastala, S, Pierson, L, McNamara, NK, Delporto-Bedoya, D, Anderson, R, Hamer, RM & Lieberman, JA 2008, 'Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizoaffective disorder: Findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study', American Journal of Psychiatry, vol. 165, no. 11, pp. 1420-1431. https://doi.org/10.1176/appi.ajp.2008.08050756
Sikich, Linmarie ; Frazier, Jean A. ; McClellan, Jon ; Findling, Robert L ; Vitiello, Benedetto ; Ritz, Louise ; Ambler, Denisse ; Puglia, Madeline ; Maloney, Ann E. ; Michael, Emily ; De Jong, Sandra ; Slifka, Karen ; Noyes, Nancy ; Hlastala, Stefanie ; Pierson, Leslie ; McNamara, Nora K. ; Delporto-Bedoya, Denise ; Anderson, Robert ; Hamer, Robert M. ; Lieberman, Jeffrey A. / Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizoaffective disorder : Findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study. In: American Journal of Psychiatry. 2008 ; Vol. 165, No. 11. pp. 1420-1431.
@article{e9b5390159094f848f5b7afe4faff6f0,
title = "Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizoaffective disorder: Findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study",
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 ≥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.",
author = "Linmarie Sikich and Frazier, {Jean A.} and Jon McClellan and Findling, {Robert L} and Benedetto Vitiello and Louise Ritz and Denisse Ambler and Madeline Puglia and Maloney, {Ann E.} and Emily Michael and {De Jong}, Sandra and Karen Slifka and Nancy Noyes and Stefanie Hlastala and Leslie Pierson and McNamara, {Nora K.} and Denise Delporto-Bedoya and Robert Anderson and Hamer, {Robert M.} and Lieberman, {Jeffrey A.}",
year = "2008",
month = "11",
doi = "10.1176/appi.ajp.2008.08050756",
language = "English (US)",
volume = "165",
pages = "1420--1431",
journal = "American Journal of Psychiatry",
issn = "0002-953X",
publisher = "American Psychiatric Association",
number = "11",

}

TY - JOUR

T1 - Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizoaffective disorder

T2 - 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.

PY - 2008/11

Y1 - 2008/11

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 ≥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.

AB - 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 ≥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.

UR - http://www.scopus.com/inward/record.url?scp=55749083565&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55749083565&partnerID=8YFLogxK

U2 - 10.1176/appi.ajp.2008.08050756

DO - 10.1176/appi.ajp.2008.08050756

M3 - Article

C2 - 18794207

AN - SCOPUS:55749083565

VL - 165

SP - 1420

EP - 1431

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

SN - 0002-953X

IS - 11

ER -