Analysis of behavior-related adverse experiences in clinical trials of montelukast.
BACKGROUND
Frequencies of behavior-related adverse experiences (BRAEs) in controlled clinical studies of leukotriene modifier drugs have not been summarized.


OBJECTIVE
We sought to compare the frequency of BRAEs in patients receiving montelukast or placebo in a retrospective analysis of Merck clinical trial data.


METHODS
An adverse experience database was constructed to include all double-blind, placebo-controlled trials of montelukast meeting prespecified criteria. BRAEs (described using the Medical Dictionary for Regulatory Activities controlled vocabulary dictionary) were prespecified to include any term in the Psychiatric Disorders System Organ Class, selected terms related to general disorders, and terms related to akathisia. Frequencies of BRAEs (overall, leading to study discontinuation, and/or serious) were summarized. Analyses estimated the odds ratios (ORs) for montelukast versus placebo based on the frequency of patients with BRAEs in each study.


RESULTS
In total 35 adult and 11 pediatric placebo-controlled trials were included; 11,673 patients received montelukast, 8,827 received placebo, and 4,724 received active control. The frequency of patients with 1 or more BRAEs was 2.73% and 2.27% in the montelukast and placebo groups, respectively; the OR for montelukast versus placebo was 1.12 (95% CI, 0.93-1.36). The frequency of patients with a BRAE leading to study discontinuation was 0.07% and 0.11% in the montelukast and placebo groups, respectively (OR, 0.52; 95% CI, 0.17-1.51). The frequency of patients with a BRAE considered serious was 0.03% in both treatment groups.


CONCLUSIONS
Reports of BRAEs were infrequent in clinical trials of montelukast. Those leading to study discontinuation or considered serious were rare. Frequencies were similar regardless of treatment group.
Philip
George
G
Merck & Co, Inc, North Wales, Pa. 19454, USA. george_philip@merck.com
Hustad
Carolyn M
CM
Malice
Marie-Pierre
MP
Noonan
Gertrude
G
Ezekowitz
Alan
A
Reiss
Theodore F
TF
Knorr
Barbara
B
D000085:Acetates / Q000009:adverse effects* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000523:psychology*; D001526:Behavioral Symptoms / Q000139:chemically induced* / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003521:Cyclopropanes; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000139:chemically induced* / Q000453:epidemiology; D008875:Middle Aged; D011804:Quinolines / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D013440:Sulfides; D055815:Young Adult
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; C093875:montelukast