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2010-Repantis.Pdf Pharmacological Research 62 (2010) 187–206 Contents lists available at ScienceDirect Pharmacological Research journal homepage: www.elsevier.com/locate/yphrs Review Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review Dimitris Repantis a,∗, Peter Schlattmann b,1, Oona Laisney a, Isabella Heuser a a Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany b Department of Biometry and Medical Statistics, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10098 Berlin, Germany article info abstract Article history: The term neuroenhancement refers to improvement in the cognitive, emotional and motivational Received 11 March 2010 functions of healthy individuals through, inter alia, the use of drugs. Of known interventions, psychophar- Received in revised form 14 April 2010 macology provides readily available options, such as methylphenidate and modafinil. Both drugs are Accepted 14 April 2010 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 Keywords: their actual effects, as has been demonstrated in single- or double-blind randomised controlled trials. Only Modafinil studies with sufficient extractable data were included in the statistical analyses. For methylphenidate Methylphenidate Neuroenhancement an improvement of memory was found, but no consistent evidence for other enhancing effects was Enhancement uncovered. Modafinil on the other hand, was found to improve attention for well-rested individuals, Cognitive enhancement while maintaining wakefulness, memory and executive functions to a significantly higher degree in sleep Cognitive performance deprived individuals than did a placebo. However, repeated doses of modafinil were unable to prevent Sleep deprivation deterioration of cognitive performance over a longer period of sleep deprivation though maintaining Healthy young adults wakefulness and possibly even inducing overconfidence in a person’s own cognitive performance. Systematic review © 2010 Elsevier Ltd. All rights reserved. Neuroethics Contents 1. Introduction .......................................................................................................................................... 188 2. Objectives ............................................................................................................................................ 188 3. Methods .............................................................................................................................................. 188 3.1. Criteria for considering studies for this review .............................................................................................. 188 3.1.1. Types of studies ..................................................................................................................... 188 3.1.2. Types of participants ............................................................................................................... 188 3.1.3. Types of interventions .............................................................................................................. 189 3.1.4. Types of outcome measures ........................................................................................................ 189 3.2. Search methods for identification of studies................................................................................................. 189 3.3. Methods of the review ....................................................................................................................... 189 3.3.1. Selection of studies ................................................................................................................. 189 3.3.2. Quality assessment ................................................................................................................. 189 3.3.3. Data extraction ..................................................................................................................... 189 3.3.4. Data analysis ........................................................................................................................ 189 4. Results ................................................................................................................................................ 189 4.1. Results of the search.......................................................................................................................... 189 4.2. Description and methodological quality of included studies ................................................................................ 190 ∗ Corresponding author. Tel.: +49 30 8445 8293; fax: +49 30 8445 8726. E-mail addresses: [email protected] (D. Repantis), [email protected] (P. Schlattmann). URLs: http://www.charite-psychiatrie.de (D. Repantis), http://www.charite.de/biometrie/de/index.html (P. Schlattmann). 1 Tel.: +49 30 450 562007. 1043-6618/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.phrs.2010.04.002 188 D. Repantis et al. / Pharmacological Research 62 (2010) 187–206 4.3. Outcomes ..................................................................................................................................... 196 4.3.1. Mood ................................................................................................................................ 196 4.3.2. Motivation .......................................................................................................................... 201 4.3.3. Wakefulness ........................................................................................................................ 201 4.3.4. Attention and vigilance ............................................................................................................. 201 4.3.5. Memory and learning............................................................................................................... 202 4.3.6. Executive functions and information processing .................................................................................. 202 5. Results of the analyses ............................................................................................................................... 202 5.1. Methylphenidate ............................................................................................................................. 202 5.1.1. Single drug administration ......................................................................................................... 202 5.1.2. Repeated drug administration studies ............................................................................................. 202 5.1.3. Methylphenidate in sleep deprived individuals ................................................................................... 202 5.2. Modafinil ..................................................................................................................................... 203 5.2.1. Single drug administration studies ................................................................................................. 203 5.2.2. Repeated drug administration studies ............................................................................................. 203 5.2.3. Modafinil in sleep deprived individuals ............................................................................................ 203 5.3. Adverse effects of MPH or modafinil ......................................................................................................... 203 6. Discussion ............................................................................................................................................ 203 7. Reviewers’ conclusion ............................................................................................................................... 204 Acknowledgments ................................................................................................................................... 205 Appendix A. Supplementary data................................................................................................................. 205 References ........................................................................................................................................... 205 1. Introduction of neuroenhancement effects can be found in the existing litera- ture, then this fact should be made known to those healthy people The term neuroenhancement has been coined to denote who are ready to accept the risk of consuming MPH or modafinil interventions by which healthy people improve their cognitive, [11,12] because of their belief in such not empirically supported emotional and motivational functions [1,2]. If psychopharma- benefits. ceutical substances are used to achieve such improvements, it is called pharmaceutical neuroenhancement. Apparently, 2. Objectives psychostimulants are popular among healthy people seeking neuroenhancement [3]. In this article, we examine possible neu- The aim of this review was to assess the effect of MPH and roenhancement properties of two substances that have often modafinil on emotional, cognitive and motivational processes and been in the spotlight of both the scientific [4,5] and popular press the safety of their use by healthy individuals. Although these drugs
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