Newer Antipsychotics No Better Than
Older Drug in Treating Child and Adolescent Schizophrenia
Two newer atypical antipsychotic medications were no more effective
than an older conventional antipsychotic in treating child and
adolescent schizophrenia [http://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml]
and may lead to more metabolic side effects, according to a new
study funded by the National Institutes of Health’s National Institute
of Mental Health (NIMH). The study was published online September
15, 2008, in the American Journal of Psychiatry.
"Schizophrenia and schizophrenia-related disorders are rare
in childhood. But when they do occur, those afflicted generally
have more severe symptoms and a worse prognosis than those who
develop the disorder in adulthood," said NIMH Director Thomas
R. Insel, M.D. "The newer atypical antipsychotics are often
used to treat these children, but until now, it has been unclear
how effective and safe they really are in children. The side effects
of the newer medications should be factored into making treatment
The six-year, multisite Treatment of Early Onset Schizophrenia
Study (TEOSS) included 116 youth between 8 and 19 years old, diagnosed
with early onset schizophrenia spectrum disorder (EOSS). The TEOSS
team randomly assigned the children to eight weeks of either olanzapine
(Zyprexa) or risperidone (Risperdal) — both new generation
atypical antipsychotics — or to the older conventional antipsychotic
molindone (Moban) plus benztropine, a medication often used to
reduce side effects like uncontrolled shaking or tremor that can
be associated with molindone. The children were monitored throughout
the study by an NIMH oversight board to ensure their safety.
Response rates after eight weeks of treatment were comparable
among the three medications — 50 percent of the children
taking molindone improved, 46 percent taking risperidone improved,
and 34 percent taking olanzapine improved. Children taking olanzapine
or risperidone improved within the first two weeks, while the children
on molindone improved within three weeks.
The treatment groups did differ in side effects. The children
taking olanzapine gained about 13 pounds (6 kilograms) during the
trial on average, while children taking risperidone gained about
8 pounds (3.6 kilograms), and those taking molindone did not gain
weight. The olanzapine group also showed increases in cholesterol
levels and other metabolic disruptions that may have become dangerous.
The outcome prompted the safety review board to end the olanzapine
arm of the study in 2006.
"Atypical antipsychotics are commonly used to treat kids
with EOSS, but these results question the wisdom of that approach,"said
lead author Linmarie Sikich, M.D., of the University of North Carolina
at Chapel Hill. "They also remind us that we need to develop
safer, more effective medications to treat these children, given
the limited effectiveness of both the atypical and the conventional
Study coauthor Jeffery Lieberman, M.D., of Columbia University
Medical Center, noted that TEOSS is the first documented evidence
of how newer antipsychotics compare to older ones when treating
children and adolescents with schizophrenia. "Doctors need
to educate families about the potentially serious side effects
these drugs can have so that strategies can be put into place to
address them," he reiterated. The TEOSS results are similar
to those found in the NIMH-funded Clinical Antipsychotic Trials
of Intervention Effectiveness (CATIE) [ http://www.nimh.nih.gov/health/trials/practical/catie/index.shtml],
for which Lieberman was the principal investigator. CATIE found
that the newer antipsychotics were no more effective than an older
antipsychotic in treating adults with schizophrenia.
TEOSS was conducted at the University of North Carolina at Chapel
Hill, Harvard University, Seattle Children’s Hospital, and Case
Western Reserve University.
The National Institute of Mental Health (NIMH) mission is to reduce
the burden of mental and behavioral disorders through research
on mind, brain, and behavior. More information is available at
the NIMH website, http://www.nimh.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and Centers
and is a component of the U.S. Department of Health and Human Services.
It is the primary federal agency for conducting and supporting basic,
clinical and translational medical research, and it investigates
the causes, treatments, and cures for both common and rare diseases.
For more information about NIH and its programs, visit www.nih.gov.
Reference: Sikich L, Frazier JA, McClellan J, Findling
RL, Vitiello B, Ritz L, Ambler D, Puglia M, Maloney AE, Hunt-Harrison
T, Jackson JA, De Jong S, Slifka K, Noyes N, Michael E, Hlastala
S, Pierson L, McNamara NK, Delporto-Bedoya D, Anderson R, Hamer RM,
Lieberman JA. Comparative efficacy of antipsychotics in early onset
schizophrenia. American Journal of Psychiatry. Online ahead
of print Sept 15, 2008