Methylphenidate (Ritalin) – does use by ‘healthy’ students matter?

In their report in the Telegraph, @Josiensor and Rosa Silverman discuss implications of a survey from Cambridge which notes that so-called 'smart' drugs continue to be used by students to try to improve their academic performance, with methylphenidate (Ritalin) a common choice.

Why should this be of public interest?

Methylphenidate has been in use since 1960 for treating ADHD, with effects mainly considered to be improvement in attention and concentration. It is used to treat a number of rare syndromes involving abnormalities in chemical transmission in the brain. The drug is also reported to be in widespread use by students in the UK, the US and elsewhere in the hope that it will improve studying, learning and exam performance.
 

1.    Does it work? Studies of possible effects on studying and learning are typically short-term and usually based on artificial tests – ie not usually test possible benefits of the drug what students may be trying to learn, or effects on the types of exams students may be sitting. Evidence compared to placebo of benefits or risks appears limited to studies lasting 4 weeks or less.

The evidence of benefits from methylphenidate in apparently healthy students is disappointing. For example, in a study in health young volunteers there was a reported benefit from the 1^st dose for a spatial (3D) task and for planning, but not for attention or fluency. However even these effects were not sustained: with a second dose, spatial task performance was less good; ie there was little evidence of sustained benefit on repeat use of the drug and possible evidence that performance might be worse. And one of the side effects is insomnia – fatigue could also therefore be an indirect reason why performance might be impaired by the drug. There are also reports by users that with the drug, too much focus on details may make it difficult both to complete an assessment and to consider a broad enough range of issues to give a complete answer.

2.    Is use of methylphenidate any different from using caffeine? Because of the lack of convincing evidence of benefit from methylphenidate and concerns about serious risks, methylphenidate is not approved for use in the absence of specified medical conditions – e.g. ADHD. As for other drugs, the balance between risk and benefit must be considered by prescriber and user. In the event of any benefit for studying from the drug, others not using it are put at a disadvantage. In contrast caffeine is widely available for those who chose to use it. Too much caffeine, or sensitivity to caffeine can cause troublesome symptoms, including anxiety, tremor, sleep disturbance and palpitations. 

3.    Risks of methylphenidate Potential risks may be serious and include serious cardiac and psychiatric disorders. This has lead to important restrictions by regulatory authorities such as the FDA on use of the drug, even when the drug is medically indicated. 

Withdrawal symptoms of methylphenidate can include psychosis, depression and irritability.

Risks of the drug may be greater if there are medical problems, in particular if the user has a medical history of cardiovascular or psychiatric problems. Use without clinical advice may mean that important underlying conditions are not identified, for example high blood pressure, disorders of heart rhythm, and psychiatric risk; and potential important interactions with other drugs (including other stimulants) may not be considered. For example: 

-      alcohol can delay clearance of the drug from the body, increasing risk of adverse effects; 

-      concurrent use of stimulants such as caffeine would be expected to increase risk from methylphenidate of serious disorders of heart rhythm.

4.    What about access to the drug from internet pharmacies? For the above reasons, licensed pharmacies would not supply methylphenidate in the absence of specified medical conditions. Unlicensed internet pharmacies should be avoided. The quality of medicines is not reliable, with serious risk of being supplied poorly active or counterfeit or contaminated medicines. And medical contra-indications need to be identified and discussed to minimize the risk of preventable serious adverse effects.

5.    Fairness and coercion There are also a number of ethical concerns including:

a)    the need to protect students and others from using so-called ‘smart drugs’ in response to pressure to compete, both in exams and in professional life; 

b)    being fair to other students who do not have access to the drug, or do not wish to use what may be a medically harmful pharmacological aid to improving performance in examinations or to meeting challenges at work.

See also
June 2009: Opposing opinions in the British Medical Journal from John Harris and Anjan Chatterjee

September 2011: Methylphenidate and delayed puberty
July 2012: Methylphenidate for Parkinson's disease
November 2012: Commentary in the Guardian by William Leith: Ritalin before an exam fails the test of common sense 
June 2013: Cautionary report in from Canada on methylphenidate use and learning in  ADHD

Tuberculosis, Bel Ami and the Belle Epoque

Guy de Maupassant

@HealthMed Maupassant's 1885 book Bel Ami concerns the rise to wealth and influence of ex-soldier Georges Duroy, son of a poor rural family. Themes which still have a topical international resonance include the power of the press, foreign wars, corruption in business and government, and stock market insider trading. The anti-hero's success is largely due to the power of the wives of the rich, through their husbands, or direct involvement in political intrigue. A major subplot in Bel Ami is the impact of tuberculosis - estimated to cause the death of between 1 in 4, and 1 in 7 of the population in the mid 19th Century. In Bel Ami, Forestier, a wealthy publisher, develops rapid serious lung involvement, coughing blood, becoming breathless, and fevered. His early death provides a key opportunity for Duroy to enter formally into society.

Belle Epoque France was the outcome of cultural and economic flourishing during the latter part of 19th Century. An obvious question is what people at that time thought about tuberculosis. They knew that is was a serious and often deadly disease: Forestier's rapid death is anticipated as a matter of fact by Clothilde, a faithful companion of Duroy. An important academic view was that the 'soil'' - individual susceptibility - played a major role in the likelihood of developing consumption. There are several apparent similarities between those perceptions and public reaction to the epidemic of HIV-AIDS which emerged in the early 1980s. Tuberculosis was known as consumption because of its wasting effect. The term in translation dates back at least to Hippocrates in 460BCE: the Ancient Greeks used the term phthisis (wasting away) to describe the commonest disease of their time.  This was echoed by the description 'slim disease' for a wasting disorder which emerged in rural Uganda in the early 1980s, strongly associated with infection with the HTLV-III, and thus recognized to be a feature of HIV-AIDS. A major cause of weight loss in HIV-AIDS is associated opportunistic infections such as tuberculosis - a clear illustration of the importance of the impact of impaired host defence on development of a disease.

 

At the time of publishing Bel Ami, Maupassant was ill with syphilis. Not a socially acceptable disease to reflect in a literary work - although ample opportunity for this to be acquired by Maupassant's  anti-hero Duroy and passed on to his high society conquests. The concept of the risk of progressing from a 'night with Venus to a lifetime with Mercury' emerged shortly after the 1494 siege of Naples. In an epic poem of 1530, the Veronese doctor poet Girolamo Fracastoro refers to use of mercury as a possible cure for the disease. And its late effects were well known to Shakespeare, with examples in his play 'Timon of Athens'. One of Fracastoro's many contributions to science and medicine was the idea that certain diseases are spread by particles. In the 1600s, early inventors of microscopy went on to confirm the existence of minute particles. Antoni van Leewenhoek was the first to report single-cell micro-organisms, in 1676 correspondence to the Royal Society, which, after initial scepticism, then confirming his findings, made him a member in 1680. 

A dramatic change in medical thinking and knowledge about tuberculosis occurred in the early 1880s. In 1881, French doctor Louis Landouzy gave a series of influentual lectures on causes of consumption, including speculation that routes of transmission could included infected dust, milk and meat. And in 1882, the Prussian pathologist Robert Koch was the first to describe the causative tubercle bacillus, supported by his formulation in 1884 with Friedrich Loeffler of 4 postulates about the evidence needed to confirm disease causation by microbes. This direct work on the germ theory of disease had been anticipated 350 years before by Frascatoro. Koch's investigations and discoveries in relation to tuberculosis lead to his receipt of the 1905 Nobel Prize in Physiology and Medicine.

The timing of publication in 1885 of Maupassant's novel Bel Ami is therefore of special interest, following 3 years after Koch's discovery. There is no explicit recognition in Bel Ami of the resulting logic for isolating patients with what later became called 'open' tuberculosis - when the TB germs are free to travel from the lungs through the air to nearby contacts. However the move of Forestier to a remote house may have served both to give him a quiet place to convalesce or die, and tacitly to isolate him from at risk friends.

Modern parallels to the public response to tuberculosis in the Belle Epoque range from reactions such as fear, concern and denial for mystery illnesses with no cause known (e.g. pre-HIV 'slim disease'), the response of the public to those affected by HIV-AIDS, before the emergence of effective treatment; and responses to the many types of cancer without known cause, and other  reasons for premature illness and mortality, for example - sudden cardiac death syndromes in young athletes and older adults, despite many advances in diagnosis and treatment.