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

Abstract

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.

Waist Circumference is a Sensitive Screening Tool for Assessment of Metabolic Syndrome Risk in Children Treated with Second-Generation Antipsychotics

“…In fact, the younger age of the SGA-treated group, along with lower smoking rates, are clinical features that would have tended to bias against our finding an increased risk of metabolic complications. Given the challenges in obtaining long-term, randomized, prospective safety data on SGA treatment, as noted in the Treatment of Early-Onset Schizophrenia Spectrum follow-up study, 59 where only 12% of children continued on their originally randomized treatment at 52 weeks, our naturalistic cross-sectional prospective data, in which 40% of subjects had been receiving SGA treatment for 1 year or more, makes an important contribution to the literature. Nonetheless, prospective observational studies on the longterm metabolic effects of SGA therapy, along with CVD risk over the long term, need to be conducted in a controlled manner.…”

Management of Adverse Effects of Second-generation Antipsychotics in Youth

“…These two compounds increased total cholesterol rate, and quetiapine also increased HDL cholesterol [14]. With regard to weight change, as mentioned above, no significant differences emerged among the compounds in most of these parameters during maintenance treatment of the TEOSS study [26]. Of note, data are insufficient to conclude any metabolic effect of clozapine.…”

“…In the first part of the study, weight gain was significantly higher in patients treated with olanzapine, but in the extension trial, no significant differences in weight gain emerged among the various compounds during maintenance treatment [26,32].…”

“…Of note, in our review of the Treatment of Early-Onset Schizophrenia Study (TEOSS) assessing long-term safety and effectiveness of olanzapine, risperidone, or molindone among 54 children and adolescents with early-onset schizophrenia, we considered only the olanzapine and risperidone arms, as molindone is not an SGA. [26,32]. We did not find sufficient data on asenapine and will not discuss any results with this compound.…”

“…First, we will discuss the major AEs found in both short-and long-term studies on the use of SGAs in youth. This is based on an in-depth literature review of a Bayesian meta-analysis based on short-term studies [12•]; a review of long-term studies in SGAs [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]; and our own clinical experience in managing such treatment in youth. Second, we will present the major AEs by compound.…”