March 1996

Behavioral and Cognitive Effects of MethylxanthinesA Meta-analysis of Theophylline and Caffeine

Author Affiliations

From the Section of Child and Adolescent Psychiatry, Departments of Psychiatry and Pediatrics, The University of Chicago (Ill) (Drs Stein and Leventhal and Messrs Krasowski and Phillips), and the National Jewish Center for Immunology and Respiratory Medicine and Department of Psychiatry, University of Colorado, Boulder (Dr Bender).

Arch Pediatr Adolesc Med. 1996;150(3):284-288. doi:10.1001/archpedi.1996.02170280054010

Background:  Theophylline has been extensively studied as a treatment of asthma. However, some studies have suggested that theophylline may precipitate adverse behavioral and cognitive effects on children. Other reports have evaluated the effects of caffeine, another commonly used methylxanthine, as a treatment of attentiondeficit hyperactivity disorder.

Objective:  To present a meta-analysis of research on the behavioral and cognitive effects of methylxanthines in children.

Methods:  The meta-analyses were conducted on 12 studies of theophylline and nine studies of caffeine that met inclusion criteria.

Results:  In contrast to popular beliefs and earlier scientific reports, meta-analyses of controlled studies did not indicate that either theophylline or caffeine resulted in significant deleterious effects on cognition or behavior. In fact, there was a small, positive effect on parental report of externalizing behavior for both methylxanthines.

Conclusions:  There is little evidence to suggest that methylxanthines have adverse cognitive or behavioral effects on children. Questions remain with regard to the identification and determinants of either responsive or sensitive subgroups, dose-response relationships, and the effects of parent-teacher expectancies on behavioral ratings.(Arch Pediatr Adolesc Med. 1996;150:284-288)