Twenty-six studies were included for review (n=497): 16 RCTs (n=361); one ABA design (n=10); three prospective studies (n=47); three case series studies (n=10); and three retrospective studies (n=69). Five studies were graded level I, 12 studies were graded level II and nine were graded level III.
Noradrenaline agonists (11 studies): Methylphenidate significantly improved speed of information processing, mental processing speed and attentiveness in two level I studies. A third level I study found no significant differences between groups for measures of attention. Results for level II studies of methylphenidate were mixed. One level III study showed significant benefits of d-amphetamine on functional outcome.
Dopamine agonists (10 studies): Results for the effect of amantadine in patients with acquired brain injury were mixed. One level II RCT found significant benefits of amantadine on cognitive and functional outcome; however, another level II RCT found no significant differences between groups. One level III study reported significant benefit of Levodopa on neglect. Bromocriptine did not significantly improve attention compared to control in one level II study, although a level III study found significant benefits on neglect and inattention.
Acetylcholine agonists (five studies): Donepezil significantly improved information processing and sustained attention compared to controls in one level I study. Physostigmine and CDP-choline did not significantly improve memory or attention in patients with acquired brain injury compared to controls.
None of the studies was adequately powered to detect adverse events.