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.

Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind 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 according to defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks.

Results: Of the 116 youths 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 nonadherence (n = 8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom decrease 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 youths with early-onset schizophrenia spectrum disorders 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 early-onset schizophrenia spectrum disorders. Clinical trial registry information-Treatment of Schizophrenia and Related Disorders in Children and Adolescents; URL: http://www.clinicaltrials.gov, unique identifier: NCT00053703.

Conflict of interest statement

Disclosure: Dr. Findling receives or has received research support, served as a consultant for and/or served on the speakers’ bureau for Abbott, Addrenex, AstraZeneca, Biovail, Bristol-Myers Squibb, Forest, GlaxoSmithKline, Johnson and Johnson, KemPharm, Eli Lilly and Company, Lundbeck, Neuropharm, Novartis, Organon, Otsuka, Pfizer, Sanofi-Aventis, Sepracore, Shire, Solvay, Supernus Pharmaceuticals, Validus, and Wyeth. Dr. Frazier receives research funding from or participates in clinical trials with Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Johnson and Johnson, Neuropharm, Otsuka America Pharmaceutical, and Pfizer. Dr. Hamer, in the past three years, received or has receives research support, served as a consultant for and served on a data safety monitoring board (DSMB) / internal displacement monitoring centre (IDMC) for Acadia, Allergan, Alpharma, AstraZeneca, Cenerx, Corcept, EnabledMD, Epix, Johnson and Johnson, Novartis, Pepper-Hamilton, Pfizer, SAS Institute, Schwartz, Solvay, Sanofi-Aventis, Takeda, Winston-Strawn (a lawsuit involving Forest, Lundbeck, Sun, Caraco), and Wyeth. He and/or his wife own stock in Bristol-Myers Squibb, Amgen, Eli Lilly and Company, Genentech, Proctor and Gamble, and Sepracor. His wife is retired from Bristol-Myers Squibb. Dr. Liberman serves on the advisory board of Bioline, GlaxoSmithKline, Intracellular Therapies, Eli Lilly and Company, Psychogenics, and Wyeth. He does not receive financial compensation or salary support for his participating as an advisor, except for Intracellular Therapies. He receives grant support from Allon, Forest Labs, Merck, and Pfizer. He holds a patent from Repligen.

Dr. Sikick receives research funding or participates in clinical trials with Janssen, Pfizer, Bristol-Myers Squibb, Neuropharm, Curemark, and Seaside Pharmaceuticals. She has receives software for a computer intervention in schizophrenia from Posit Science. In the past, Dr. Sikich received research funding from Eli Lilly and Company, Janssen, Pfizer, Otsuka, and AstraZeneca. She has served as a consultant for Sanofi Aventis and ABT Associates. Drs. Johnson, McClellan, Vitiello, McNamara, Hlastala, and Maloney, and Ms. Ritz, Ms. Lingler, Ms. Pierson, Ms. Puglia, Ms. Michael Kaufman, and Ms. Noyes report no biomedical financial interests or potential conflicts of interest.

2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Participant Disposition

Figure 2

Treatment discontinuation over time in the 52-week combined acute and maintenance studies