A systematic review and economic model of the effectiveness and ...

assessed by parents and teachers. In this study, the
non-drug intervention involved a behavioural
programme incorporating parent training, teacher
consultation and a point system. They observed
significant differences in favour of the MPH plus
non-drug intervention group (p < 0.001 for both
parent and teacher ratings).
Adverse events
Of the 11 trials, six contributed data to the
analysis of adverse events. Pelham 81 examined the
tolerability of two medium doses of MPH, 0.75
and 0.90 mg/kg/day. No significant differences in
the incidence of headache, 80–82,88 stomach
ache 80–82,88 or insomnia 77,78,80–82,88 were detected
between treatment phases in any trial reporting
these outcomes. Participants in the Pelham 82 trial
displayed significantly reduced appetite in the
MPH treatment phase compared with the placebo
phase (RR = 5.67; 95% CI 1.74 to 18.48). None of
the other three trials 80,81,88 reporting this outcome
detected differences in incidence. No study
reported data on weight.
Summary
MPH plus non-drug interventions (one-to-one
reading therapy, parent training and cognitive
therapy) were found to be better than the nondrug
intervention alone. None of the studies in
this category evaluated CGI as a core outcome.
No significant differences in the incidence of
headache, stomach ache or insomnia were
reported between treatment groups, although one
study reported significantly reduced appetite in
the MPH group. Overall, these studies did not
score very well in the quality assessment, and any
results should be interpreted with caution.
MPH high dose (>30 mg/day) plus non-drug
intervention versus non-drug intervention
Seven trials (presented in eight papers) evaluated
high-dose (>30 mg/day) immediate-release MPH
plus non-drug intervention compared with a nondrug
intervention (Table 26; with additional
information in Appendix 12). All of these studies
examined MPH administered two or more times
daily.
The majority of studies in this category did not
assess hyperactivity, but examined
inattention/overactivity using a Conners’ scale as a
main outcome measure. 69,79,80,88 The results of
comparisons between treatment groups were not
clearly presented in most of these studies.
Hyperactivity
Three of the studies reported results on
hyperactivity, 51,65,86 but one of them presented
© Queen’s Printer and Controller of HMSO 2006. All rights reserved.
Health Technology Assessment 2006; Vol. 10: No. 23
data in graphs only and was not included in
Table 27. 51 The remaining two studies both
assessed hyperactivity using Conners’ scales and
also other measures. In Schachar and colleagues’
study, 86 the non-drug intervention was parent
training or support, and in the Klein and
Abikoff 65 study, the non-drug intervention
involved parent and teacher education. These
parallel studies both reported significant
differences in favour of MPH plus non-drug
intervention compared with non-drug intervention
when assessed by teachers, but not when assessed
by parents.
Quality of life
Elia and colleagues 51 assessed CGI as assessed by
physicians. They reported that children receiving
MPH plus a behaviour modification programme
and a low monoamine diet had better behaviour
than children in the non-drug intervention group
(p < 0.05). In addition, Klein and Abikoff 65
evaluated Clinical Global Improvement as assessed
by teachers, mothers and psychiatrists. After
8 weeks of treatment, the physicians rated 97% of
children in the MPH plus parent and teacher
education group to be improved compared with
50% in the non-drug intervention group.
Adverse events
Of the seven trials comparing a high dose of MPH
plus a non-drug intervention with a non-drug
intervention alone, three informed analysis of
adverse events. Smith and colleagues 88 examined
the tolerability of two high doses of MPH
combined with a non-drug intervention – 50 and
75 mg daily. No differences in the incidence of
headache 80,88 or stomach ache 80,88 were detected.
Participants in Elia and colleagues’ trial 51 suffered
from loss of appetite and insomnia to a
significantly greater extent in the MPH treatment
phase of the trial (RR = 83.00; 95% CI 5.25 to
1311.65 and RR = 2.92; 95% CI 1.80 to 4.75,
respectively). The remaining two trials did not
detect differences in the incidence of insomnia or
reduced appetite. Heterogeneity of results did not
appear to be explained by participant age,
outcome measurement or trial duration. Data on
weight were not presented in any of the trials in
this comparison group.
Summary
Two studies presented results for hyperactivity
using different scales, including those of
Conners. 65,86 In these studies, the non-drug
interventions were parent training or support, and
parent and teacher education, respectively. For
both studies, the results were generally significant
49