Nine RCTs were included (n=477): five cross-over and four parallel-group RCTs. Sample size ranged from 11 to 148. Six studies involved fewer than 50 patients.
Methylphenidate derivatives: Methylphenidate was associated with a statistically significant improvement in ADHD symptoms compared to placebo (ES 0.73, 95% CI 0.53 to 0.94; three RCTs). There was no significant difference in pooled effect size for tic symptoms (four RCTs). There was significant heterogeneity in the outcome of tic symptoms (I2=56.8%). Side effects were not well described in any of the studies.
Amphetamine derivatives: Dexamphetamine was associated with a statistically significant increase in tic severity (ES -0.59, 95% CI -1.06 to -0.13; one cross-over study, n=12). No changes in ADHD severity were reported.
Alpha-2 agonists: Alpha-2 agonists were associated with a statistically significant improvement in tic severity (ES 0.74, 95% CI 0.44 to 1.04; two studies) and ADHD symptoms (ES 0.61, 95% CI 0.32 to 0.90; three studies). There was increased sedation compared to placebo (41% to 48% versus 6%).
Tricyclic antidepressants: Desipramine was associated with a statistically significant improvement in ADHD symptoms compared to placebo (ES 0.80, 95% CI 0.02 to 1.57; significant heterogeneity was found, I2=86%; two studies). There was no significant difference in tic severity (one study). Adverse effects were more common in desipramine compared to placebo groups in both studies. One trial reported a significant increase in diastolic blood pressure and pulse rate in the desipramine group compared to the placebo group.
Atomoxetine: Atomoxetine was associated with a statistically significant improvement in ADHD symptoms (ES 0.51, 95% CI 0.27 to 0.74; one study, n=148) and tic severity (ES 0.32, 95% CI 0.09 to 0.56; one study, n=148). Nausea and decreased appetite were more common in atomoxetine compared to groups (16% versus 1% to 3%).
Deprenyl: There was no significant differences between deprenyl and placebo in ADHD, tic severity and adverse effects (one study).
Combination treatments: Clonidine plus methylphenidate was associated with a statistically significant improvement in ADHD symptoms (ES 1.09, 95% CI 0.72 to 1.45; one study, n=103) and tic severity (ES 0.75, 95% CI 0.38 to 1.12; one study). Sedation was more common in combination treatment groups compared to placebo (21% versus 6%).
Where possible, results of effects of different medications on inattention and hyperactivity/impulsivity symptoms were reported.