Methylphenidate use among medical students at Ben-Gurion University of the Negev

Introduction

Methylphenidate (MPH) is a mild CNS stimulant that acts on the brain stem arousal system and cortex. Short- and long-acting formulations of MPH are FDA approved for use in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy.[1] In Israel, it is the most common drug for treatment of ADD/ADHD sold under the brand names Ritalin^®, Ritalin-SR^®, Ritalin-LA^® and Concerta^®.

Lately there has been a significant increase in awareness of ADD/HD in adults. At the same time, a significant increase in the diagnosis of the disorder in adults has resulted in higher rates of MPH treatment. The number of MPH prescriptions issued in Israel for patients above 18 has increased over four folds between the years 2008 and 2012.[2]

At the same time, it seems that the adult “off-label” use of MPH is also on the rise mainly due to the perceived cognitive improvement.[3] Yet, its affect on healthy individuals is not clear, and its ability to bring improvement in cognitive functions was never proved. Both of these trends are particularly evident among academics, where many students attempt to obtain ADD/HD diagnosis, while others simply obtaining MPH prescription for “off–label” use.

Studies estimated the prevalence of MPH off-label use in about 1.5-8% of students.[45] Even a higher rate of the use was shown among medical student and dental students in the USA where up to 20% reported taking a stimulant medication.[6789] There is a sense, therefore, that the use of a cognitive enhancer in this population might be higher than in the general student population.

In this study we tried to evaluate the use of MPH among medical students in Ben Gurion University (BGU) in the Negev and evaluate the association between MPH use and self-report of ADD symptoms.

Materials and Methods

Statistical analysis

Statistical analysis was done using SPSS version 18. The results are presented as the mean (SD) for continuous variables and for the total subjects (the percentage of total subjects) for categorical data. The T-test was used for comparing continuous variables and the Chi-square test was used for categorical data, augmented by Fisher's exact test, if needed. We used the Mann–Whitney test for the comparison of variables not distributed normally and were presented as median and interquartile range (IQ range). Cumulative incidence of MPH use before academic studies and throughout medical school was calculated and is presented in Figure 1. A Venn diagram [Figure 2] was created in order to demonstrate the relation among positive ASRS score, ADHD formal diagnosis and MPH use. The two-tailed P < 0.05 was considered significant.

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Figure 1

The distribution of onset times and the cumulative incidence of drug use in each phase of medical school

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Figure 2

The intersection of the three main diagnoses of the study's participants: Students diagnosed with ADD, students with positive ASRS test and students who consume methylphenidate regularly. Note that only 13 students were ASRS positive and diagnosed with ADD

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Results

The response rate was 96%, with 229 total responses from among the 260 students who received the questionnaire form. None of the questionnaires was disqualified. The respondents age was 26.42 ± 2.75 and 96 were males (43.2%). One hundred and five students were in their pre-clinical years (years 1–3), comprising 45.9% of the cohort, while the remaining 114 students were in their clinical studies (years 4–6). Out of the 229 students included in the analysis, 39 had taken MPH at least once, while 198 did not use MPH. Out of the MPH users, 31 had taken MPH during the year prior to the study and were considered active users, while 8 students had not used MPH during the 12 months prior the survey.

Cumulative incidence of MPH use throughout medical school is demonstrated in Figure 1, which shows the distribution of onset times of drug use at each phase of medical school. It is notable that the major increase in the use rate was prior to the medical school and during other academic studies (4% raise). In the first year, about 6% of the students use MPH, during medical school the rates climb gradually with a significant increase in the third year, from 10% to 14%. By the end of the sixth year we can see a usage rate of 18%.

A Venn diagram presented in Figure 2 shows the intersection of the three main groups among the study's participants: Students diagnosed with ADD; students with positive ASRS test; and students who use MPH regularly. Twenty-two students had formal ADD diagnosis and 52 students had positive ASRS-S score, yet only 13 students were ASRS positive and diagnosed with ADD. The 39 users are presented in the circle below with 20 of them diagnosed with ADD (out of which 13 also had positive ASRS-S score) and 7 more had a positive ASRS-S score but no formal ADD diagnosis.

Baseline characteristics of those who used MPH during the last 12 months are depicted in Table 1. Active MPH users were older, compared with non-active ones (28.13 ± 3.45 vs. 26.14 ± 2.52 respectively, P = 0.001) and self-estimated their grades in the previous year lower than those who did not use MPH (81.31 ± 5.93 vs. 85.72 ± 5.08, respectively, P < 0.001). More students who used MPH during the last 12 months had previous higher education experience prior to commencing medical school studies (45.2% vs. 17.4%, P < 0.001).

Table 1 Baseline characteristic among students who used methylphenidate during the last 12 months and students who did not

Overall, 39 students (17% of our total cohort) had used it at least one time. Among them, 20 (51.3%) had taken MPH according to prescription (“on label”) while 19 (48.7%) had taken the drug without prescription (“off label”). Majority of “off-label” users had taken short-term MPH (52.6%), while most of the “on-label” users had taken both kinds of MPH, namely long and short acting (55%). While 88.9% of “off-label” users had begun to use the drug during their medical school studies, a majority of “on-label” users had started to take MPH during their former academic studies (45%), P = 0.003. When asked regarding their opinion of MPH use among students who had not been diagnosed with ADHD, most of the “off-label” users were indifferent (47.4%), while 55% of “on-label” users opposed drug use among undiagnosed students (P = 0.023) [Table 2].

Table 2 Usage patterns and characteristic among student whom used methylphenidate at least one time

In our cohort, 22 (9.6%) students have a formal diagnosis of ADHD made by a physician. Among the 205 students without formal diagnosis, 39 (19%) had the positive ASRS test (ASRS score four or above). As demonstrated in Table 3, students with a formal diagnosis were by 2 years. older compared with those without the diagnosis Students with ASRS score lower than four self-estimated their academic grades higher (85.79 ± 5.08) than those with ADHD diagnosis (82.76 ± 6.26) and those with ASRS score 4 and above (83.67 ± 5.89), P = 0.035.

Table 3 Comparison between students with and without ADHD diagnosis

Discussion

In this study we attempted to evaluate the prevalence of MPH use among medical students and its relationship to the established and possible ADD/HD diagnosis. Among the study participants, 9.6% reported having a formal ADD/HD diagnosis. ASRS-S questionnaire was positive (four positive answers and above) in 22.7%.

Among the participating students, 13.5% reported using MPH in the past 12 months prior to the study, while 17% reported lifetime use. This is similar to the rate reported[9] among US medical students (20% prevalence of life time use, 15% during medical school), and higher than prevalence reported[8] a few years ago (10.1%) in the USA and the rate among American college students (6.9%). These figures are significantly higher than the reported worldwide prevalence of ADD/HD among adults. Two meta-analyses found the prevalence of AD/HD to be 2.5-4.4%,[1314] and the rate of adults with positive ASRS-S is 8.2% in wide survey conducted in Britain in 2007.[15] Alongside with that, the findings among Israeli students are similar to those recently reported among US medical students, where a 5.5-9% prevalence was reported. It is hard to determine whether the high prevalence of ADD/HD found among medical students indeed represents a higher prevalence of the disorder or reflects higher self awareness to symptoms and greater diagnostic availability.

The effectiveness of MPH as enhancing therapy to improve cognitive abilities in general and academic performance in particular, is still controversial. Several studies examined the effect of MPH on the cognitive function of healthy youth and adults. These studies showed MPH appears to improve performance in novel tasks and attention-based tasks and reduces planning latency in more complex tasks.[16] MPH was not found to be helpful in visual learning and memory.[17] Despite this, it was never demonstrated that MPH improves academic performance. Healthy youth treated with placebo in studies examining the efficacy of MPH, reported improvement in “intellectual energies” and higher efficiency in carrying out tasks, although participants didn’t differ in their performance from the control group of those not taking MPH.[18] It is possible that the expectation effect to functional improvement is able to explain the vast use of the medication.

The ethical perspective of “enhancing medicine” was discussed thoroughly in the medical and popular media and also by the ethical chamber of the Israeli medical association. The consensus is that enhancing medicine is allowed under medical restrictions and close observation following the establishment of the treatment efficacy. The students treated with MPH “off-label” introduce a different situation: Future doctors using supervised medication without prescription or follow-up, based on self diagnosis, without assessment of side effects or treatment efficacy.

The wide use of MPH among medical students is probably related to the competitive environment encouraging and even demanding higher grades. The need to improve their academic abilities leads students to seek enhancing medical treatment. However, many of these students present symptoms of ADD/HD, and it is possible that these students can gain benefit from controlled medical treatment. A proactive diagnostic plan of AD/HD among medical students can identify the students who may benefit from treatment in one hand, and prevent uncontrolled and inefficient use of the drug on the other hand. Moreover, lack of the proven cognitive efficacy benefit associated with MPH makes its “off-label” use by anybody and particularly by future medical doctors highly questionable.

Our study, demonstrating a high prevalence of MPH use among medical students for both medical indication and “off-label” use, has several limitations: It is based on self report and therefore may under represent non-medical use of the drug. The study was conducted in a single institution, making its generalisability limited.

Conclusion

The rate of use of MPH among the medical students in our study is similar to the rate recently reported among US medical students. The prevalence of ADD/HD is higher among students than the estimated prevalence in adults. Proactive diagnosis for ADD/HD and insisting on “on-label” MPH use may help those who may benefit from such a treatment and prevent uncontrolled use. It is necessary to conduct further research about the possible effects of MPH on academic performances of healthy individuals.