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

Quality of life
Only one of the 12 studies examined physicianrated
GGI (used as a proxy for QoL in this
SR). This study, conducted by Werry and
colleagues, 96 reported no significant difference
between the MPH and placebo groups for this
outcome.
Two other studies reported outcomes that
could also be used to indicate QoL: Fitzpatrick
and colleagues, 55 presented parent and
teacher comments ratings and Manos and
colleagues 72 reported composite ratings as
measured by a clinician (see Appendix 12
for results).
Adverse events
Of the 12 studies comparing low-dose MPH with
placebo, only two presented usable data on adverse
events. 55,60 The occurrence of headache was not
significantly different between treatment arms in
either trial [relative risk (RR) = 1.00; 95% CI 0.16
to 6.38; and RR = 3.00; 95% CI 0.14 to 66.53,
respectively]. With regard to loss of appetite,
neither study detected differences between the
treatment arms (RR = 3.00; 95% CI to 0.34 to
26.33; and RR = 5.00; 95% CI 0.69 to 36.13,
respectively). Similarly, incidence of stomach ache
did not appear to differ between participants
assigned to low doses of MPH and those receiving
placebo (RR = 3.00; 95% CI 0.13 to 69.31; and
RR = 3.00; 95% CI: 0.14 to 66.53). One trial 55
reported the occurrence of insomnia which was
not significantly different between treatment arms
(RR = 2.67; 95% CI 0.83 to 8.55). Weight data
were not adequately reported in any trial.
Summary
In summary, there seems to be variation in the
results for low-dose MPH compared with placebo.
There were no differences in adverse events for
both groups. These studies did not score very well
in the quality assessment, and the results should
be interpreted with caution.
MPH medium dose (15–30 mg/day) versus
placebo
Twenty-one studies examined medium-dose
(15–30 mg/day) immediate-release MPH
compared with placebo (Table 5; with additional
information presented in Appendix 12). Two
studies examined medium-dose MPH
administered once daily and 19 examined MPH
administered two or more times daily.
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Health Technology Assessment 2006; Vol. 10: No. 23
MPH administered once daily
Both Rapport and colleagues 85 and DuPaul and
Rapport 49 evaluated the effectiveness of mediumdose
MPH administered once daily using the
Abbreviated CTRS total score as a main outcome
measure. Both studies reported a significant
improvement in the treatment group compared
with placebo (p < 0.01).
MPH administered two or more times daily
Of the 19 studies that examined MPH administered
more than once daily, nine measured hyperactivity
and will be discussed below. In addition, four
studies 35,39,44,52 reported data only for adverse
events. These are also discussed separately below.
The first of the six remaining studies is that by
Manos and colleagues. 72 In this study, two
medium doses of MPH were evaluated: 20 and
30 mg/day. However, as reported above, Manos
and colleagues did not report data separately for
low-dose MPH and the medium doses (see
Appendix 12), hence any results comparing
medium-dose MPH versus placebo cannot be
extracted from this study. In their results, they
stated that ‘best dose’ was better than placebo.
Kolko and colleagues 69 presented results for
inattention/overactivity using the
Inattention/Overactivity with Aggression (IOWA)
CTRS. They reported that medium-dose MPH
was better than placebo (p < 0.0001). This scale
was also used by Pliszka and colleagues, 83 where
medium-dose MPH was also observed to improve
behaviour compared with placebo (p < 0.05), and
by Pelham and colleagues, 79 where results showed
improvement with treatment (see Appendix 12).
In the study by Barkley and colleagues, 40 five
treatment arms were examined, including
medium-dose MPH and a placebo group. The
main core outcome examined was ADHD total
ratings as evaluated by parents and teachers
(mathematics and English teachers). Overall
statistical analyses resulted in no significant
differences between the treatment arms.
Tervo and colleagues 2002 93 also compared a
medium-dose MPH group and a placebo group.
A main outcome examined was CBCL as rated by
parents. Direct statistical comparisons with placebo
were not reported, although the authors found a
significant linear response to medication
(p = 0.001).
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