Behavior Abnormalities and Poor School Performance Due to Oral Theophylline Use

Abstract

Studies evaluating adverse effects of oral theophylline on learning and behavior have been performed on children with asthma receiving long-term theophylline therapy. To further differentiate the effects of asthma itself from the drugs used, we evaluated 20 asthmatic children (6 to 12 years of age) who had not received oral bronchodilators for at least 6 months. A double blind, placebo-controlled, parallel format was used with a 4-week theophylline or placebo period preceded by a 2-week baseline. Theophylline serum levels were maintained between 10 to 20 µg/mL. During baseline and treatment periods, the child's home and school behavior/performance were monitored independently by their parents and teachers using standardized report forms. A battery of psychologic tests was administered at the end of baseline and treatment periods. Seven children receiving theophylline were noted to have a change in school behavior and/or performance during their 4 weeks on drug compared to baseline, whereas none of the children receiving placebo were noted to be different (P = .004). Thus, the short-term administration of theophylline to asymptomatic asthmatic children not receiving oral bronchodilators can adversely affect school performance and behavior. Because this population represents the majority of asthmatic children, one needs to use theophylline cautiously in this age group, monitor school performance closely, or seek other treatment modalities.

Are asthmatic children educationally handicapped?

“…In a study of 14 asthmatic children, parental reports of improved behavior in the second week of treatment led the authors to conclude that behavior changes are present only after the initial introduction of theophylline (Stein & Lerner, 1993). Three additional blinded studies found no statistically significant changes on any neurocognitive test or parent questionnaire (Rachelefsky et al, 1986; Rappaport et al, 1989; Schlieper, Alcock, Beaudry, Feldman, & Leikin, 1991). The absence of any treatment-related differences in these studies is impressive given the large number of dependent measures included to evaluate potential changes.…”

“…A methylated xanthine similar to caffeine, theophylline is also a central nervous system stimulant. The CNS effects of theophylline have been widely reported to cause significant behavior change in asthmatic children, including inhibition of attention (Springer, Goldenberg, Ben Dov, & Godfrey, 1985; Furukawa et al, 1988), memory (Rachelefsky, et al, 1986; Springer et al, 1985; Williams-McCargo, 1984), and motor skills (Williams-McCargo, 1984; Springer et al, 1985). In a controversial but widely cited study reported in a leading pediatric journal in 1986, two groups of children, one treated with theophylline and one treated with placebo, were evaluated with a battery of cognitive tests and questionnaires completed by the children’s teachers and parents.…”

Diseases of the respiratory system.

“…Because children with severe, poorly controlled asthma are likely to receive more medications at larger doses, risk factors increase to the greatest degree in this segment of the population with asthma. Although the psychological effects of theophylline are not as severe as once believed (Rachalefsky et al, 1986), the caffeine-like effects of theophylline have been documented and include a slight trend toward more anxiety and hand tremor in treated versus untreated children. These behaviors are accompanied by slightly increased attention, verbal memory, or both (Bender, Lerner, & Poland, 1991;Bender & Milgrom, 1992;Schlieper, Adcock, Beaudry, Feldman, & Leikin, 1991 ).…”

Behavioral effects of caffeine and other methylxanthines on children.

“…For example, among 42 children (8–12 years old) with mild to moderate asthma whose parents reported a history of marked behavior problems from theophylline treatment, theophylline (15 mg/kg/day) had no effect on an anxiety scale, a depression scale, and a parent rating scale (Bender & Milgrom, 1992). In another study, theophylline (serum levels 10–20 μg/ml) had no effect on parents' ratings in 20 children (mean age = 10 years), but teachers rated the children as less attentive during the theophylline condition than during the placebo condition (Rachelefsky et al, 1986). In a final study, theophylline (14 to 16 mg/kg/day) had no effect on an anxiety scale, parent and teacher rating scales, and a parent and teacher activity/attention questionnaire in 17 children (6–12 years old; Rappaport et al, 1989).…”