How effective are pharmaceuticals for cognitive enhancement in healthy adults? A series of meta-analyses of cognitive performance during acute administration of modafinil, methylphenidate and d-amphetamine.

Modafinil, methyphenidate (MPH) and d-amphetamine (d-amph) are putative cognitive enhancers. However, efficacy of cognitive enhancement has yet to be fully established. We examined cognitive performance in healthy non-sleep-deprived adults following modafinil, MPH, or d-amph vs placebo in 3 meta-analyses, using subgroup analysis by cognitive domain; executive functions (updating, switching, inhibitory control, access to semantic/long term memory), spatial working memory, recall, selective attention, and sustained attention. We adhered to PRISMA. We identified k=47 studies for analysis; k=14 studies (64 effect sizes) for modafinil, k=24 studies (47 effect sizes) for Methylphenidate, and k=10 (27 effect sizes) for d-amphetamine. There was an overall effect of modafinil (SMD=0.12, p=.01). Modafinil improved memory updating (SMD=0.28, p=0.03). There was an overall effect of MPH (SMD=0.21, p=.0004) driven by improvements in recall (SMD=0.43, p=0.0002), sustained attention (SMD=0.42, p=.0004), and inhibitory control (SMD=0.27, p=.03). There were no effects for d-amph. MPH and modafinil show enhancing effects in specific sub-domains of cognition. However, data with these stimulants is far from positive if we consider that effects are small, in experiments that do not accurately reflect their actual use in the wider population. There is a user perception that these drugs are effective cognitive enhancers, but this is not supported by the evidence so far