Efficacy and safety of anti-manic agents in children and adults.
OBJECTIVE
Pediatric trials in depression have led to major concerns about potential suicide inducing properties of antidepressants and doubts about their efficacy. Several trials of anti-manic agents in children were recently conducted and regulatory reviews of the data have become available.


METHODS
We acquired pediatric and adult anti-mania agent Medical and Statistical Reports from the U.S. FDA. We used these to evaluate efficacy, mortality, severe adverse events and suicidality.


RESULTS
The six pediatric studies enrolled 1,228 patients (828 drug/460 placebo). The seven adult drug approval programs enrolled 4,228 patients (2,356 drug/1,932 placebo). Mean mania rating scale baseline (pediatric=30.3/adult=30.3) scores were identical, and drug-placebo difference scores (pediatric=5.8/ adult=5.2) were not significantly different. There were no reported deaths during the pediatric trials. During the 23 adult trials there were 8 deaths (3 in drug group/5 in placebo group), a mortality rate of 3,290/100,000 patient exposure years. The proportion of patients that reported severe adverse events was slightly lower for the pediatric (4.2%) as compared to adult (4.7%) trials. A higher proportion of children (5/460, 1.1%) than adult (7/2,012, 0.3%) patients assigned to placebo reported suicidality, χ2(df=1)=4.2, p=0.04. We did not find evidence of increased suicidality for children assigned to drug (7/828, 0.8%) as compared to the children assigned to placebo (5/460, 1.1%).


CONCLUSIONS
These data suggest remarkable similarity between the outcomes of pediatric and adult trials for bipolar mania. The therapeutic profile of these anti-manic agents in children is notably better than that for some other psychotropic drugs, for example, antidepressants.
Northwest Clinical Research Center, Bellevue, Washington, U.S.A. Department of Psychiatry and Behavioral Health, Duke University, Durham, North Carolina, U.S.A.
Arif
A
Khan
James
J
Faucett
Graham J
GJ
Emslie
Walter A
WA
Brown
D000328:Adult; D018692:Antimanic Agents / Q000009:adverse effects* / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D006801:Humans; D015990:Placebo Effect; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration / Q000706:statistics & numerical data
D018692:Antimanic Agents