Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review

Abstract

The term neuroenhancement refers to improvement in the cognitive, emotional and motivational functions of healthy individuals through, inter alia, the use of drugs. Of known interventions, psychopharmacology provides readily available options, such as methylphenidate and modafinil. Both drugs are presumed to be in widespread use as cognitive enhancers for non-medical reasons. Based on a systematic review and meta-analysis we show that expectations regarding the effectiveness of these drugs exceed their actual effects, as has been demonstrated in single- or double-blind randomised controlled trials. Only studies with sufficient extractable data were included in the statistical analyses. For methylphenidate an improvement of memory was found, but no consistent evidence for other enhancing effects was uncovered. Modafinil on the other hand, was found to improve attention for well-rested individuals, while maintaining wakefulness, memory and executive functions to a significantly higher degree in sleep deprived individuals than did a placebo. However, repeated doses of modafinil were unable to prevent deterioration of cognitive performance over a longer period of sleep deprivation though maintaining wakefulness and possibly even inducing overconfidence in a person's own cognitive performance.

Introduction

The term neuroenhancement has been coined to denote interventions by which healthy people improve their cognitive, emotional and motivational functions [1], [2]. If psychopharmaceutical substances are used to achieve such improvements, it is called pharmaceutical neuroenhancement. Apparently, psychostimulants are popular among healthy people seeking neuroenhancement [3]. In this article, we examine possible neuroenhancement properties of two substances that have often been in the spotlight of both the scientific [4], [5] and popular press [3], [6], namely methylphenidate (MPH) and modafinil. The first, a stimulant used to treat attention-deficit hyperactivity disorder (ADHD), is known to have been extensively misused, especially by college students as a “study aid” [7]. The second, a wakefulness promoting agent licensed for the treatment of excessive daytime sleepiness associated with narcolepsy, sleep apnoea and shift-work sleep disorder, is already used by military personnel, as depicted for instance in the Memorandum of the United States Air Force “Modafinil and management of aircrew fatigue” (2nd December 2003), which approves the use of modafinil for missions of great duration, and in the Internet site of the United States Air Force Laboratory, who conducted the relevant research (http://www.hep.afrl.af.mil/HEPF/Research/index.html, accessed 12th April 2010). It also seems to become increasingly popular, both in business and in academia. In an online poll conducted by Nature magazine [8], 20% of the 1400 responding readers reported use of MPH, modafinil or beta-blockers (drugs prescribed for cardiac arrhythmia, that can also have an anti-anxiety effect) for non-medical reasons: 62% of users reported taking MPH and 44% modafinil. Their main reasons for doing so were to improve concentration, focus for a specific task or counteract sleep deficit or jetlag Indirect evidence for the non-medical use of MPH and modafinil can also be gained by comparing their disproportionately high prescription and sales numbers to the numbers of patients suffering from the disorders for which these substances are approved or used off-label [9], [10].

This systematic review, which has been conducted according to a pre-defined protocol, aims to collect and analyse the available evidence about the effects of MPH and modafinil in healthy individuals. If these drugs can be shown to have positive effects in healthy individuals, then this adds urgency to the question how to regulate their potential use for neuroenhancement purposes. If no evidence of neuroenhancement effects can be found in the existing literature, then this fact should be made known to those healthy people who are ready to accept the risk of consuming MPH or modafinil [11], [12] because of their belief in such not empirically supported benefits.