Fourteen studies (n=229 participants, range=2 to 63) were included in the review. Length of follow-up ranged from 16 days to 12 months.
Ten trials assessed folic acid (n=82 participants; comprising eight crossover, one parallel group and one unreported design), six of which were randomised, only one reported adequate sequence generation and blinding, and none reported adequate concealment. Two trials (n=83 participants) assessed L-acetylcarnitine. Both trials used parallel randomised study designs, although neither reported adequate sequence generation, concealment or blinding. One trial assessed ampakine compound CX516 (n=49 participants). This trial reported adequate sequence generation, concealment and blinding. One trial assessed dextroamphetamine and methylphenidate (n=15 participants) and reported adequate blinding, but not concealment or sequence generation.
Folic acid: Ten studies assessed efficacy and safety of folic acid. Only one trial (n=25 participants; the highest quality trial of the 10) reported a statistically significant difference in outcomes between treatment and placebo groups (a statistically significant improvement in IQ scores favoured the treatment group). Most trials did not report any statistical testing. Only one trial reported side effects (transient problems with diarrhoea, sleep delays and mood swings).
L-acetylcarnitine: One trial reported a statistically significant reduction in hyperactive behaviour in the L-acetylcarnitine group using the Conners' abbreviated parent questionnaire. One trial reported statistically significant differences between groups, which favoured L-acetylcarnitine using Conners' global index-parents (CGI-P) and Vineland adaptive behaviour (VAB) scale. No side effects were reported.
Ampakine compound CX516: One trial (n=49 participants) reported no statistically significant difference in outcomes between treatment and placebo groups. Minimal side effects, which included allergic rashes, were reported in the treatment group.
Dextroamphetamine and methylphenidate: One trial found both dextroamphetamine and methylphenidate to be associated with a statistically significant improvement in the attention deficit and hyperactivity disorder comprehensive teacher's rating scale (ACTeRS). Side effects reported included mood lability and irritability.