Nine studies (389 participants, range one to 103) were included in the review: two double-blind randomised controlled trials (RCTs), one case-control study, three uncontrolled open-label trials, one retrospective observational study, one case series study and one case report study. Two studies were rated for quality as level one evidence, one as level two and six as level three.
Levetiracetam (four studies): Two open-label trials (39 participants) measured behavioural disturbances using various tools and both reported significant improvements from baseline to discharge/follow-up (four weeks). All three studies (one case-control and two open-label trials; 139 participants) that reported the effects of levetiracetam on cognition reported MMSE scores. The case-control study found that MMSE scores at 52 weeks follow-up were significantly better with levetiracetam than with phenobarbital or lamotrigine (p<0.05) but all three drugs were significantly inferior to placebo (p<0.05). One open-label trial reported significant improvements in MMSE scores with levetiracetam (p<0.01) at 12 weeks follow-up but a second found a significant deterioration (p<0.05). Adverse events occurred in 6% to 26% of participants across these studies. These studies reported mixed findings for other cognition assessment tools.
Oxcarbazepine: One RCT (103 participants) compared oxcarbazepine with placebo and found similar improvements in behavioural disturbances for both groups with no significant difference between them. Adverse events were significantly more frequent in the oxcarbazepine group (p<0.01).
Topiramate: One RCT and one retrospective observational study (56 participants) evaluated topiramate alone versus antipsychotics (with or without topiramate). Improvements in behavioural disturbances were reported with all of the drugs with no significant differences observed between them. In the RCT, drop-out rates for adverse events were four out of 21 in the topiramate group and three out of 20 in the antipsychotic group.
One case report study and one case series study evaluated zonisamide and reported behavioural improvements from baseline to follow-up in three of the four participants.