The results of the present study confirmed a similar side effect profile to those of previous studies [12
], with the side effects of insomnia
and decreased appetite
having significantly greater prevalence in the MPH condition than the placebo condition.
The purpose of the correlation analyses was to investigate any relationships between the side effects observed while on MPH and the therapeutic response, as judged by parents through the SERS and CGI-P, respectively. The analysis yielded significant negative correlations between the response to MPH (CGI-P, emotional liability) and the side effects of irritability (also significant correlation with CGI-P, restless-impulsive), proneness to crying, and anxiousness. However, what is striking is that the most frequently reported side effects of insomnia, decreased appetite, and headaches did not show a significant correlation. Thus, it appears that the more "mood/anxiety" side effects, such as irritability, proneness to crying, and anxiousness, do affect how parents judge the behavioral improvement. This interpretation of the results is further supported by the fact that side effects such as irritability, proneness to crying, and anxiousness are far more non-specific. Furthermore, these side effects did not show a significant change in frequency or severity while on MPH, when compared to placebo, despite being the most frequently reported side effects (with the exception of decreased appetite and insomnia). This could mean that it is not MPH that is causing an increase in parent-reported irritability, anxiousness, or proneness to crying, but the fact that they were given any treatment at all, whether it is in the form of MPH or placebo.
We postulated initially that the relationships found between side effects and the parent-rated therapeutic response could be due to a shared biological mechanism, meaning that with increased therapeutic effects there will be also increased side effects. However, if this were true, we will expect that the same correlations found between side effects and the parent-rated therapeutic response should have been found with the teacher-rated therapeutic response. This correspondence was not observed in the correlational analysis. Thus, the relationships between side effects and the parent-rated therapeutic response are not likely due to common biological mechanisms, but are more an effect of the parental evaluation itself. The greater "mood/anxiety" sides effects on methylphenidate and placebo, the less the parents observe improvement of their children while treated with methylphenidate.
There are several limitations to our study that should be mentioned. The first is that while the method is experimentally appropriate, giving children 0.5 mg/kg for a 1- week period deviates from common clinical practice. Studies investigating a wider dosage range and longer period of treatment would be required to determine whether stronger significant correlations between side effects induced by and therapeutic effects of methylphenidate exist.
Another limitation is the use of only the parent report for the side effects data. The American Academy of Pediatrics practice guidelines call for a multimodal assessment battery to monitor treatment effects, such as teachers, and other caretakers in the child's environment[30
]. Although teachers are better informants regarding treatment response, parents are better informants regarding the adverse effects of medication[31
]. This could be due to children being more comfortable complaining about adverse effects to their parents than to their teachers.
There are a few other limitations which could modify or even mediate some of the correlations observed in this study. The study design does not include a measure of parents' treatment expectations and the presence of ADHD among parents. Finally, the majority of parental evaluations were done by mothers or both parents together, and we did not have data on the teachers' gender. This precluded us from using gender (parents and teachers) as a covariate in the analyses.