Cognitive Enhancement – a critical review of fifteen years of research.

The idea of improving the mental performance of healthy people with psychotropic drugs continues to receive a lot of attention. The main focus is on psychostimulants, in particular amphetamine, methylphenidate and modafinil. However, the use of cognitive enhancers is much less widespread than is generally assumed. Psychostimulants also appear to mainly compensate for fatigue effects in healthy individuals, but hardly increase cognitive performance above the original baseline level. The ethical and media debate is mainly characterized by exaggerations regarding the distribution and pharmacological possibilities.

US psychiatrist and depression expert Peter Kramer coined the term “cosmetic psychopharmacology” in his 1993 bookListening to Prozac [1]. To illustrate this idea, he described patients who did not have a psychiatric disorder but appeared to benefit from the prescription of selective serotonin reuptake inhibitors (SSRIs). He concluded people could thereby overcome inhibitions, shyness or insecurity, realize their “true self” and thus become more successful in their professional and private lives. Despite cautious criticism from experts, the book remained on bestseller lists for months and was translated into several languages. In addition, its author had the pleasure of numerous TV appearances.

The debate about “cosmetic” psychopharmacology continues to this day. What is striking, however, is that the substance class changed in the early 2000s: instead of antidepressants, the focus is now on psychostimulants such as amphetamine, methylphenidate, or modafinil, and instead of social-emotional functioning, the focus is now on improving thinking and performance skills. For the past 15 years, the recent scientific and media discussion has revolved around the concept of neuroenhancement or cognitive enhancement. We leave it to the interested reader to answer the more sociological question of whether this change in attitude reflects a spread of performance and competitive thinking in society. In this short article, we will focus on the two key questions from a psychiatric perspective regarding the demand for the relevant substances and their efficacy, in order to ultimately arrive at an informed judgment on cognitive enhancement .

Demand for neuroenhancement substances

The relevance of the discussion depends in large part on the extent to which the use of psychotropic drugs for cognitive performance enhancement is a new, widespread, and/or growing phenomenon. As the authors noted earlier [2,3], the tone-setting publications in leading scientific media were conspicuous for suggestive representations and misquotations [4–6]. Thus, nonrepresentative outlier values from epidemiological studies of nonmedical use of psychostimulants were highlighted, or selective surveys of lifestyle use of drugs were simply reinterpreted as evidence of cognitive enhancement. As a result, the opinion spread in the ethical and scientific discussion that up to 25% of students – who were identified as the most popular target group – were already turning to prescription drugs to improve their academic performance. Even though some colleagues criticized the exaggerations in the media, it is no wonder that journalists picked up on these seemingly alarmingly high circulation figures. Thus, as evidenced by an extensive examination of English-language sources, media reports portrayed the phenomenon of cognitive enhancement as widespread and/or increasing – citing scientific sources [7].

In contrast, systematic studies provided convincing evidence that nonmedical use of psychostimulants is in the single digits even among U.S. college students [8,9]. Recent representative surveys of major health insurers in Germany (DAK) and Switzerland (SUVA) also confirmed that the lifetime prevalence for the use of prescription stimulants for cognitive performance enhancement in the general population is below 1% [10,11]. Remarkably, the lifetime prevalence also includes persons who have stopped using the substances after a single or infrequent use. Among students, the proportion of individuals with an affinity for stimulants does indeed appear to be somewhat higher – lifetime prevalences of 1.3% for German and 4.1% for Swiss students have been reported [12,13] – but even in this population, the picture of an epidemic prevalence of stimulant use for performance enhancement can hardly be sustained.

Our own literature searches revealed that the phenomenon is also far from new: for example, amphetamine drugs were advertised in the 1950s and 1960s for better functioning in the workplace or directly to improve attention performance (mental alertness) [14]. As early as the 1960s, 1970s, and 1980s, there were surveys of psychotropic drug use involving nonmedical targets [15]. Some studies report comparable or even higher values for instrumental use, i.e. the substances were used to stay awake longer and/or to study [16].

In summary, therefore, the demand for cognitive enhancement does exist, but not at the high level that has been colocated in many scientific or media portrayals. It is reasonable to conclude that some colleagues here described habitual drug use by young people as a new problem that they eventually recommended themselves to study and solve, given appropriate funding [2,15,17]. That psychotropic drugs and other medications are used for nonmedical purposes-think Viagra in a sexual context or painkillers in popular sports-is also not new and has been studied in medical sociology for decades.

Efficacy of neuroenhancement substances.

Since several large pharmaceutical companies have reduced or even completely stopped their investments in psychopharmacological research, the situation for clinical researchers in psychia-try has not become easier [18]. A major difference between pharmacological trials for the treatment of patients and performance enhancement in healthy individuals is the target: Whereas in one group the aim is to alleviate or cure a condition and/or certain symptoms, it is still unclear what a good neuroenhancement drug would actually have to achieve in healthy individuals. In the relatively few experiments with healthy subjects, neuropsychological test batteries are usually used that were developed to document the course of a disease or therapy. Statistically significant improvements in these tests therefore do not allow any conclusions to be drawn as to whether, for example, students in an examination situation or employees in office work would benefit from them. Clinically useful methods do not readily translate to a nonclinical context [17]. In addition, the effect sizes of the cognitive improvements shown in healthy individuals taking stimulants are often rather small and thus of little relevance to everyday life [19,20].

Furthermore, research to improve performance in healthy people faces particular challenges: It is more difficult to justify ethically (cost-benefit trade-off) and to fund because of the funding priorities for basic or clinical research. That is why the samples of the available studies are often small and the substances were only administered for a short time. For these reasons, the results to date are not very representative. Also, adverse long-term side effects in healthy individuals have hardly been studied so far. After reviewing the relevant studies years ago, the authors already drew the preliminary conclusion that no cognitive miracle pills are to be expected in the foreseeable future [2,20,21].

In addition to optimistic speculation that antidementia drugs such as acetylcholinesterase inhibitors would also have beneficial effects for healthy individuals, the discussion centered primarily on the psychostimulants amphetamine, metyhlphenidate, and modafinil. This is surprising insofar as these means are not new discoveries of modern brain research, as is sometimes suggested. Quite the opposite: amphetamine has been known for more than 100 years and methylphenidate was developed as early as the 1940s [22].

Psychostimulants also appear to primarily compensate for fatigue effects in healthy individuals, but they are unlikely to increase overall cognitive performance above initial baseline levels [19,20]. Besides the stimulant-typical increase in vigilance, however, these substances also increase motivation, which can also have a positive effect, albeit indirect, on performance in tests [20]. In addition, there is the mood-enhancing and rewarding effect of all stimulants, which also explains their addictive potential [23]. Stimulants thus do not improve cognitive performance per se in healthy individuals, but they do cause consumers to be more alert, motivated, and in a better mood. In this context, qualitative studies of methylphenidate users who used the substance for learning are also informative. According to their reports, they experienced the learning work as more interesting and they enjoyed it more [24]. However, systematic reviews and meta-analyses confirm the impression that – at least with the currently available means – hardly any pharmacological performance enhancements can be achieved in healthy individuals [8,19,20,25].

Outlook

We assume that the age of a “cosmetic psychopharmacology” has not yet begun and will not begin in the foreseeable future. The discussion in scientific journals as well as in popular science media is mainly characterized by exaggerations and unrealistic expectations. It is also not a new phenomenon in principle that people use medicines outside clinical contexts in order to cope with certain challenges in life. So far, the discussion has mainly benefited clinicians and scientists who have attracted media attention and research funding with this topic. Especially against the background of dwindling resources for clinical research, we even consider this to be an ethical problem: With limited resources, we believe that the treatment of sick people should be given priority over performance enhancement in actually healthy individuals. Furthermore, disappointed expectations fueled by premature promises could have a long-term negative impact on the public image of the scientific branches concerned.

Finally, there remains the question of the role of the physician. In the discussion of cognitive enhancement, it has been argued that the physician’s role is that of a gatekeeper [26]. He or she decides to whom the drugs will be prescribed. However, we believe that the healing mandate should still guide medical action and therefore advise against “cosmetic” prescriptions of stimulants, not least because the long-term side effects in healthy individuals have also remained largely unexplored. If the focus is only on motivational problems of low pathological value that are to be treated with the help of psychostimulants, the question always arises as to in whose interest this is done. This may deprive those affected of the opportunity to critically reflect on their situation and realize, for example, that a certain course of study or a certain profession may not fit their own interests at all.

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InFo NEUROLOGY & PSYCHIATRY 2015; 13(5): 14-18.