Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study.
OBJECTIVE
To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders.


METHODS
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.
Findling
Robert L
RL
Case Western Reserve University. robert.findling@uhhospitals.org
Johnson
Jacqueline L
JL
McClellan
Jon
J
Frazier
Jean A
JA
Vitiello
Benedetto
B
Hamer
Robert M
RM
Lieberman
Jeffrey A
JA
Ritz
Louise
L
McNamara
Nora K
NK
Lingler
Jacqui
J
Hlastala
Stefanie
S
Pierson
Leslie
L
Puglia
Madeline
M
Maloney
Ann E
AE
Kaufman
Emily Michael
EM
Noyes
Nancy
N
Sikich
Linmarie
L
D000293:Adolescent; D017109:Akathisia, Drug-Induced / Q000209:etiology; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008972:Molindone / Q000009:adverse effects / Q000627:therapeutic use*; D000077152:Olanzapine; D011388:Prolactin / Q000097:blood; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D011619:Psychotropic Drugs / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D015430:Weight Gain / Q000187:drug effects; D055815:Young Adult
D011619:Psychotropic Drugs; D001569:Benzodiazepines; D011388:Prolactin; D018967:Risperidone; D000077152:Olanzapine; D008972:Molindone