How can we improve the assessment of safety in child and adolescent psychopharmacology?
OBJECTIVE
To identify approaches to improving methods for assessing tolerability and safety of psychotropic medications in children and adolescents.


METHODS
Strengths and limitations of current methodology were reviewed and possible alternatives examined.


RESULTS
Research on the validity of safety evaluation has been extremely limited. No evidence-based "gold standard" exists. Clinical trials remain the best design to establish causality, but sample size limitations prevent the detection of infrequent, though serious, adverse events. Other designs, such as cohort and case-control studies, and approaches, such as mining of large databases, must be considered.


CONCLUSIONS
The current lack of methodological standardization across studies prevents generalizations and meta-analyses. Because the issues relevant to drug safety are diverse, a variety of methodological approaches and instruments are needed. It is, however, possible to adopt standard basic definitions of adverse events, degree of severity, ascertainment methods, and recording procedures, as a common "core," to which more specific assessment instruments can be added. Systematic empirical testing and validation of safety methodology is needed.
Vitiello
Benedetto
B
Division of Services and Intervention Research, NIMH, Bethesda, MD 20982-9633, USA. bvitiell@nih.gov
Riddle
Mark A
MA
Greenhill
Laurence L
LL
March
John S
JS
Levine
Jerome
J
Schachar
Russell J
RJ
Abikoff
Howard
H
Zito
Julie M
JM
McCracken
James T
JT
Walkup
John T
JT
Findling
Robert L
RL
Robinson
James
J
Cooper
Thomas B
TB
Davies
Mark
M
Varipatis
Elena
E
Labellarte
Michael J
MJ
Scahill
Lawrence
L
Capasso
Lisa
L
D000293:Adolescent; D016907:Adverse Drug Reaction Reporting Systems / Q000592:standards*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D011600:Psychopharmacology; D011619:Psychotropic Drugs / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic / Q000009:adverse effects
D011619:Psychotropic Drugs