Thirteen studies (239 patients) were identified. Sample sizes ranged from one to 92 (mean 18). Study designs included double-blind randomised controlled trials (six RCTs), open label trials (three) and case series/reports (four).
Eight studies (three RCTs, two open label trials and three case series/reports) that measured apathy showed improvement with psychostimulants, but the magnitude of improvement was variable. One RCT showed a statistically significant improvement in apathy with methylphenidate compared with placebo, but the effect was small.
Two studies (one open label trial, one case report) reported on excessive daytime sedation. A single case report found a beneficial effect of methylphenidate in a single patient. Five of eight patients responded to modafinil in an open label trial.
Six studies (four RCTs, two open label trials) of cognition were identified. Two open label non-controlled trials of methylphenidate reported an improvement in cognition, although four RCTs found no significant differences between the psychostimulant and placebo groups.
A range of adverse effects were reported (details in paper).