Effects of theophylline on behavior and learning in children with asthma
L. Rappaport, H. Coffman, R. Guare, T. Fenton, C. DeGraw and F. Twarog
Division of Ambulatory Pediatrics, Children's Hospital, Boston, MA 02115.
This study examined the potential side effects of theophylline on behavior,
attention, memory, and fine motor function in children with asthma.
Seventeen children of normal intelligence who were intermittent
theophylline users were recruited. Each was not taking medication at the
initiation of the study. During the study, each child took the study
medication (Theo-Dur tablets, 14 to 16 mg/kg per day or their usual dose,
whichever was higher, or placebo) divided every 12 hours for 3 1/2 days
(seven doses). A double-blind crossover design was employed such that each
subject was randomly assigned to a group receiving theophylline/placebo or
placebo/theophylline. After the first period, subjects were tested on a
neuropsychological battery designed to assess cognitive performance, while
the children, parents, and teachers filled out questionnaires concerning
behavior and attention. The same procedure was repeated two weeks later
(period 2) under the opposite drug condition. Data were analyzed by means
of an analysis of variance, with time (period 1 vs period 2 [performance])
as a repeated measure and medication group as a between-subjects factor.
Dependent variables consisted of 27 measures of performance, behavior, and
attention. Only one of the 27 analyses revealed a significant group by time
interaction. This analysis suggested a significant improvement in memory
while taking theophylline; however, a different form of the same test
showed no effect. Children and parents also completed a side-effects scale
under both drug conditions. When the children were taking theophylline,
parents and children noted that the children had more stomachaches and
children noted more "shaking hands." The following observations suggest
that the failure to find significant behavioral side effects while taking
theophylline is not due to the relatively small sample size: (1) Almost all
of the analyses fell far short of statistical significance, with findings
indicating no trends toward poor performance while taking medication. (2)
Correlations between the theophylline level and change in performance
clustered around zero, with positive and negative values occurring with
about equal frequency. (3) Neither parents nor children could accurately
guess the child's medication condition. Thus, although there have been
numerous reports on the behavioral side effects of theophylline, such
reactions were not revealed in this study.
