Illustration by David Cutler
Illustration by David Cutler

A ‘smart’ approach to performance drugs

An increasing prevalence of the use of cognitive-enhancing substances, or so-called “smart drugs,” among healthy people has raised concerns among internists and medical ethicists.

A substantial proportion of patients and future doctors may be giving new meaning to the phrase, “Work smarter, not harder.”

In recent years, studies have pointed to an increasing prevalence of the use of cognitive-enhancing substances, or so-called “smart drugs,” among healthy people. And while physicians have their druthers when it comes to the off-label prescribing of smart drugs to patients who want to increase their cognitive performance, the concept, while perfectly legal, has raised concerns among internists and medical ethicists.

“What are people actually trying to do with these drugs, become something more than human?” asked Daniel P. Sulmasy, MD, PhD, MACP, professor of biomedical ethics at Georgetown University in Washington, D.C. “To that extent, there's a question about what role physicians ought to play in trying to do that if we are doctors who treat the illness of human beings.”

Use of smart drugs

The most popular prescription smart drugs are stimulants and include mixed amphetamine salts (Adderall) and methylphenidate (Ritalin, Concerta), which are indicated to treat attention-deficit/hyperactivity disorder (ADHD), as well as modafinil (Provigil), which is indicated to treat narcolepsy, sleep apnea, and shift-work sleep disorder.

Neurologist Anjan Chatterjee, MD, professor at the University of Pennsylvania and chief of neurology at Pennsylvania Hospital in Philadelphia, said two very different groups of people appear to be most likely to seek out smart drugs: 1) people in competitive “winner-take-all” environments and 2) people with boring, mind-numbing jobs.

Those in the first camp generally don't even care about how much it makes them better, said Dr. Chatterjee. “As long as it makes them a little better than the next person, they're willing to do it,” he said. At the other extreme, taking a stimulant might mean getting “into a zone,” making time fly during mundane tasks, such as washing dishes, said Dr. Chatterjee.

Although the true incidence of off-label use of smart drugs is unknown, survey studies have focused on academic populations to estimate the prevalence of use. For example, in a longitudinal study of 1,253 undergraduate students at the University of Maryland, about 62% reported being offered prescription stimulants at least once, and 31% reported using a prescription stimulant for nonmedical purposes, according to results published in 2012 in the Journal of American College Health. The most common source of prescription stimulants used in this way was a friend with a prescription.

“It's certainly very prevalent on college campuses. I think some of this parallels the increase in the diagnosis of ADHD and the prescription of these substances and therefore the increased availability of these substances from peers,” said Cathy J. Lazarus, MD, FACP, professor of medicine at Tulane University School of Medicine and Louisiana State University (LSU) School of Medicine in New Orleans.

Dr. Lazarus got involved in the study of smart drugs when a second-year medical student approached her with concerns about peer behaviors she was witnessing. “She told me that she would see students exchanging Adderall in the library,” she said.

Dr. Lazarus and her coauthors looked into the issue by conducting an online survey of 1,115 medical students at four universities in Chicago. Overall, 18% reported using prescription stimulants at least once, while 11% reported use during medical school, according to results published in 2013 in the Journal of General Internal Medicine. Psychostimulant use was significantly correlated with male gender and the use of barbiturates, ecstasy, and tranquilizers.

“What I'm hearing from my own students is that this is still going on,” said Dr. Lazarus, who is also associate dean for student affairs at LSU.

Modafinil use has also increased in recent years. One study found that the number of patients receiving the drug increased almost 10-fold from 2002 to 2009, with on-label use increasing by less than threefold while off-label use ballooned by more than 15-fold, according to a 2013 research letter published in JAMA Internal Medicine.

The internist's response

Although long-term data on the safety and efficacy of smart drugs in healthy populations are not robust, there is some evidence of risks and benefits.

Amphetamine salts and methylphenidate carry black-box warnings about cardiovascular risks and dependence, but Dr. Chatterjee said that two large retrospective studies have since found no increased incidence of cardiac events, at least in adolescents and young adults.

In terms of dependence, he said that in his experience, patients who take these drugs don't typically try to escalate their dose, as is often seen in those addicted to pain medications. “I will tell people that it's OK to take a drug holiday; it might actually be better in the long run in terms of just keeping themselves sensitized. … Most patients are OK with that and will try that. I don't get the sense that people are seeking the drug for anything other than what it helps them accomplish,” Dr. Chatterjee said.

Another risk of these drugs is that they may precipitate psychosis or temporarily mask an underlying psychiatric issue that should be treated with other drugs, according to Dr. Sulmasy, who recounted caring for a patient who was using the drugs in an attempt to stay up all night and study for tests as an undergraduate before having a psychotic break. “These things do have side effects,” he said. “They're not candy, and everybody ought to be aware of that.”

Especially among young people and college students, internists should ask about patients' use of smart drugs, Dr. Lazarus recommended. “I would ask, ‘Are you using any drugs to help you study or to help you perform? Are you taking anything that hasn't been prescribed to you personally?’” she said.

If an internist uncovers a patient's use of smart drugs, he or she should avoid giving the wrong response. For example, don't say, “Don't you know what you're doing is bad for your health?” Dr. Lazarus advised. “I think we all, hopefully, have learned how to counsel people who might be making choices that we don't agree are necessarily good for their health by helping them recognize that there may be risks associated with it,” she said.

When talking to patients who have expressed interest in giving prescription stimulants a try, Dr. Chatterjee said he encourages them to first implement two behaviors that have important effects on cognition: adequate sleep and adequate exercise. “It's almost like you want people to be like little kids: You run around until you're tired, then you drop off and fall asleep,” he said.

Dr. Sulmasy, who is also a senior research scholar at the Kennedy Institute of Ethics at Georgetown, noted that it isn't clear that these drugs are effective at enhancing cognition in healthy populations. “They may not work very well, and anything that doesn't work very well can have side effects, and we ought not to do something that could harm people without helping them,” he said.

In terms of effectiveness, Dr. Chatterjee said some have proposed that people who take smart drugs may feel that they are performing better than they actually are. “It gives a kind of confidence, and some people suggest that they really should be described as ‘drive drugs' rather than ‘smart drugs,’” he said.

For modafinil specifically, a 2015 systematic review published in European Neuropsychopharmacology found that the drug appears to enhance executive function and variably benefit attention, learning, and memory with few negative cognitive consequences.

The drug appears to act on higher cognitive functions that rely on convergence of information, “which might have allowed research participants to more effectively allocate their cognitive resources to more complex tasks,” said lead author Ruairidh M. Battleday, BM BCh, also a PhD candidate at the Helen Wills Neuroscience Institute at the University of California, Berkeley. However, the studies were conducted in controlled scientific environments, not real-world contexts, and typically only looked at the effects of a single dose, he noted.

Nonetheless, it is clear that many healthy people are using modafinil, added coauthor Anna-Katharine Brem, PhD, head of neuropsychology at the Max-Planck Institute of Psychiatry in Munich, Germany. “This means that with modafinil, as well as with other neuroenhancement methods such as noninvasive brain stimulation, the ethical debate on their use in this manner needs to be pushed forward,” she said.

Ethical implications

There are few ethical guidelines from medical societies about the use of smart drugs.

While no official College policies address the issue specifically, the ACP Ethics Manual (sixth edition, 2012) states that physicians' recommendations should be based on the best available evidence. The Manual also says that promoting patients' welfare and best interests in an increasingly complex health care system “… entails forthrightly helping patients to understand clinical recommendations and make informed choices among all appropriate care options.”

“So the question here would be, is this an appropriate care option for healthy people?” said Lois Snyder Sulmasy, JD, director of ACP's Center for Ethics and Professionalism. “A strong argument would be no, this is outside the goals of medicine.”

One organization that has addressed the use of smart drugs is the American Academy of Neurology, which in 2009 published recommendations about neuroenhancement for adults in its medical journal, Neurology.

Overall, the group concluded that the act of prescribing cognitive-enhancing drugs to adults who request them is ethically and legally permissible in the U.S. and ultimately subject to an individual physician's judgment. (The neurology group went on to release a position paper in 2013 that advises against prescribing cognitive-enhancing drugs in healthy pediatric populations for reasons it said did not apply to autonomous adults who are capable of making their own decisions.)

Dr. Sulmasy, the Georgetown professor, pointed to numerous ethical problems with prescribing smart drugs to healthy people, such as the lack of conclusive data on safety and efficacy and concerns about fairness. “Frankly, like doping in sports, this is cheating,” he said. “The persons who are taking them are trying to gain a competitive advantage over other people, and participating in that, I think, is ethically problematic.”

Dr. Sulmasy said he sees no situation where it would be advisable to prescribe a smart drug off-label to a healthy person. “I simply think we should say that's outside the scope of medicine and not something we could do,” he said.

More and more, medicine appears to be becoming a set of skills that gets sold to consumers, whose preferences set the goals, said Dr. Sulmasy. “I think the profession is just going to see more and more of all these kinds of consumer preference-driven demands, and we need to be clear about setting the boundaries of what medicine is,” he said.

Dr. Chatterjee said that in his group's unpublished research, younger people and early adopters of technology in general seem to be more open about the use of smart drugs. Regardless of the ethical correctness of the practice, “I think more and more people, as they're trained, will feel comfortable prescribing these medications for enhancement purposes,” he said.

In terms of ethical implications for medical education, Dr. Lazarus said that she has concerns about the potential distortion of academic achievement. “It's constant testing and evaluation of performance in medical school. … so the pressure of using it is out there, and the pressure of maintaining your own academic performance, if it's being driven and fueled by the use of these substances, is just going to continue,” she said.

As Dr. Sulmasy sees it, any learner who wants to do his or her best already has the tools to do so: developing good study habits, reading, and learning from role models. “You don't want to be the doctor who's got an MD with an asterisk after it because you didn't really deserve it,” he said, drawing a comparison to certain home run records in baseball.

Considering today's ultra-competitive culture, the drive to be smart doesn't seem to be going away anytime soon, said Dr. Chatterjee. “There is this push toward achievement and accomplishment in a very narrow sense,” he said. “I think there's something out of balance with that, and the increased use of these drugs is an expression of that sensibility.”