With the exception of one individual, all respondents provided information on their care of patients having a medical indication for methylphenidate. Almost 25% of the respondents gave a positive answer. 75% of them said that their patients were adults and 53% had children under their care. When comparing the four cities the greatest difference was between Munich and Halle (cf. Table 2).

14% of the respondents had already been confronted with a situation in which they were asked to prescribe methylphenidate without a medical indication. The highest prevalence was in Munich (31%) and the lowest in Halle (4%). One doctor from Munich (no. 1) added a handwritten note (“or I wasn’t aware of it”) in reference to additional unperceived cases, and one doctor from Frankfurt (no. 181) was certain concerning this regard (“definitely one female addict”) (cf. Table 3). When evaluating the questionnaires, it was assumed the doctors who checked “No, I have never had that, but I have heard of such cases from colleagues” also marked “No, I have never encountered it” as well. 44% (n = 14) of

the doctors who had already encountered a request to prescribe methylphenidate without medical indication answered the previous question by stating that they also treat patients with indicated methylphenidate.

63% of the doctors who stated they had been asked to prescribe methylphenidate without medical indication had encountered the situation three times at maximum. A doctor from Frankfurt was asked regularly about once a month (cf. Table 4).

The majority of the inquiries (84%) was adults requesting a prescription for themselves. 29% of the inquiries were made by adults for their child. Four doctors?three from Munich?were confronted with both situations. In Munich, the number of inquiries “for themselves” (n = 20) was higher than the average (cf. Table 5).

About 50% of the adults asking for a prescription for themselves were known patients and about 50% were unknown new patients. No major differences were found between the various cities (cf. Table 6). Three additional notes were made by hand:

ñ “Filling in for a colleague” (no. 35)

ñ “Acquaintance!” (no. 73)

ñ “Female colleague” (no. 113)

83% of the adults who requested a methylphenidate prescription for themselves were between 20 and 40 years of age.

Two third of the adults who wanted a prescription for their child were known patients and one third unknown patients. Additionally, one note was added by hand: “a colleague” (no. 52).

The most frequent reasons given for a prescription request without indication were “ADHD in adults?but not proved by documents” (42%) and “The drug is needed for learning and tests” (38%). In Munich, eleven out of 22 patients requested a prescription due to adult ADHD, not proved by documents (cf. Table 7). Additionally, two notes were added by hand:

ñ “X) So that he doesn’t always fall asleep during the opera” (no. 96)

ñ “Tiredness during the day” (no. 223)

Most doctors (65%) said that, in this situation, they did not prescribe methylphenidate because they would not give prescriptions without indication. About 10% examined the person. Altogether 29% issued a prescription to patients (cf. Table 8). Two notes were added by hand regarding “other reasons”:

1) A medical examination in order to verify whether the request is justified by a medical indication; 2) Called the alleged primary physician to ask whether the patient has a medical indication for methylphenidate; 3) Referred the patient for clarification to a psychiatrist; 4) Stated that I do not issue prescriptions without indication; 5) Stated that I cannot write prescriptions for narcotic drugs; 6) I wrote a prescription for the patient.

ñ “Rejected as blood donor” (no. 192)

ñ “Alternative suggestion Vigil (Modafinil)” (no. 223)

20% of all participants made use of the possibility to comment at the end of the questionnaire. Most comments were written by doctors from Augsburg (27%). All additional notes made by the doctors and which were not related to a specific question are also evaluated below. Almost 40% of the doctors thought they were the wrong person for the survey?eg. due to their specialization or due to the fact that they do not prescribe methylphenidate on principle. Further reasons given were as follows:

ñ University: Illegal market by parents whose children take methylphenidate because of an ADHD diagnosis but with a break at the weekend (doctor from Munich)

ñ Very popular with students?passing exams without Ritalin® virtually impossible

ñ Nowadays social demands (school, job) are extremely high

ñ Young people do not want to stop taking Ritalin®-despite cardiac side effects?since they experienced an improvement in scholastic achievements

ñ Ritalin® is prescribed too often and too quickly?in the meantime also for adults

ñ Germany/USA in comparison with Scandinavian countries: epidemic extents of the ADHD diagnoses (lack of sport, ‘Regulative (lifestyle) therapy’², empathic and normal family situation)

ñ Doubts about effectiveness of Ritalin® therapy

ñ More a problem for child and youth psychiatry

ñ Too often unqualified persons comment on Ritalin®-misuse

The studies were published in the years 2000 to 2015, and the earliest data collection was in 1992. When looking at students in general (cf. Table 9), lifetime prevalence of methylphenidate misuse varied from 0.8% [21] to 16.6% [22] . An average lifetime prevalence of 6.9% was calculated on the basis of seven studies [21] - [28] . The one-year prevalence ranged from 1.5% [29] to 7.3% [30] . An average one-year prevalence of 3.8% was calculated on the basis of three studies [23] [29] [31] .

Additional tables contain information about the prevalence of MPH misuse within the following groups: students in different healthcare professions, school children, civilian population and “Nature”³ readers, patients in an ADHD treatment center and adults with a methylphenidate prescription, adolescents with suspected alcohol and/or drug problems and students/persons with neuroenhancement (cf. Tables 10-14).

Three studies found a higher likelihood of MPH misuse among males [32] [33]

[35] . 84% to 74% of the people with MPH misuse are white [24] [31] . With regard to size of cities and MPH misuse, no correlation was found [21] . A higher lifetime prevalence of MPH misuse was found specifically among people who are

younger than the age of 24 [23] . Negative results at school/university increased the probability of MPH misuse [21] . 33% of the patients with ADHD diagnosis had taken more than the recommended dose of methylphenidate at least once [26] . MPH misuse correlated with a higher abuse potential of other substances, such as nicotine, alcohol, marihuana, ecstasy and cocaine [16] [31] [43] .

Next to relatives, the peer group is the main influencing factor [25] [33] .

Depending on the study, the main reason for illicit use was the wish to increase alertness with percentages between 68.9% to 100% and is followed by the desire to be able to study better, improve concentration, improve grades and stamina in party situations [23] [35] . Gender had no influence on the reasons mentioned above and 79% of the consumers used MPH with no qualms [23] . It was regarded as a legitimate action when doctors, pilots and soldiers take drugs in special situations and when bearing great responsibility [48] .

The most important source of supply (55.7% to 100%) were friends and acquaintances [16] [21] [24] [27] [28] . In total, 90% of the people received methylphenidate free of charge [27] . 58% of the students who misuse stimulants

thought it was easy to obtain them [23] .

91% of methylphenidate consumers experienced insomnia as a side effect, and many consumers mentioned palpitations, headache, lightheadedness/drowsiness, anxiety as well as flashing, nausea and vomiting [35] . The danger of addiction to Ritalin® was regarded as lower than when taking illegal drugs [48] . Due to their own experience with misuse, 16% of medical students would prescribe stimulants more thoughtlessly in future [36] .

The response rate of doctors from Augsburg and Munich was astonishingly high (both 61%) as was the response rate from Frankfurt (50%) and Halle (53%). This relatively high response rate would seem to indicate that this topic is of great interest and relevant. All handwritten notes?eg. very interested in the results, offer to keep in contact also by phone?confirm this observation.

Almost a quarter of the respondents had patients in their care with a medical indication for methylphenidate. The highest prevalence was among doctors in Munich. Due to the relatively small number of participants, this study is not a representative study; however, other studies have already indicated regional differences in the frequency of ADHD diagnoses and MPH prescriptions [54] . According to these studies, ADHD diagnoses in Bavaria in 2011 were 20% above the German average, and MPH prescriptions were even 24% above average [54] . By comparison, respondents from Frankfurt and Halle had much lower prevalence with 14% or rather 12%. These results are confirm data already collected [54] . In Hesse (specifically Frankfurt) and Saxony-Anhalt (specifically Halle an der Saale), ADHD diagnoses and MPH prescriptions were both below national average [54] . In this study, a difference was noted between Munich and Augsburg (both Bavaria). The observation at the federal state level does not explain these differences. In regard to Bavaria, the data at the district level indicate that district levels in particular near Würzburg (Lower Franconia) were the cause of high rates at the federal state level (Reliably ambulatory F90 diagnoses: 10.92/1000 persons; MPH prescriptions: 5.08/1,000 persons) [54] . Between the district levels Augsburg and Munich, there were only marginal differences in 2011 [54] . The different size of cities, with a estimated higher substance misuse in big cities, may also be one possible explanation. However, the data of 14,000 German children from 2003 to 2006 showed that?regarding to the size of residence?no significant difference in ADHD prevalence could be found [55] .

When doctors had patients in their care with medical indication for methylphenidate, most of these patients were adults. This is quite remarkable as methylphenidate has only been approved for the treatment in adults since 2011 [5] . One respondent (no. 209) complained that too often and too quickly even adults received a prescription. Even against the already mentioned background of the substantial and rapid increase in the number of prescribed methylphenidate for adults, further studies might confirm this hypothesis.

Almost 15% of the doctors who participated in this survey stated that they had been asked to prescribe methylphenidate without indication. In the four cities mentioned above, the probability of such a non-indicated inquiry (Question 5) was correlated with an additional affirmative answer, whether the same physician had patients in care who had an indication for treatment with MPH (Question 4). Regarding this Munich had the highest correlation. Therefore MPH misuse and ADHD pharmacotherapy could be the two sides of the same coin [22] .

Methylphenidate for the purpose of abuse is almost exclusively obtained from friends and acquaintances [16] [21] [24] [27] [28] . Against this background and knowing from the comparison with the literature that only a small percentage of this drug is prescribed by a doctor, the prevalence discovered in this paper (15%) would seem to be quite high. It must be pointed out that a request and a non-indicated prescription does not automatically go together. As reported in the results, most doctors (65%) rejected those requests. However, the estimated number of prescriptions may be marginally increased, supposing that the case of one respondent (no. 1), who admitted that it was likely that he prescribed methylphenidate without medical indication, but did not recognize it as non-indicated in the situation, is not an isolated case. The results support the assumption that Germans try to obtain the drug from a doctor, but it is fortunately no promising tract.

The questionnaire was also sent to doctors with a specialization in internal medicine. The assumption was that patients may go from one doctor to another in an attempt to obtain methylphenidate from a different source. Numerous notes on the inquiry sheets, however, suggest specialists do not run into this. About half of the doctors who already were asked for methylphenidate without indication also care for patients in which administration was indicated. With this knowledge, a separate survey among doctors with several “methylphenidate patients” in their patient base, would seem to be important. The frequency at which doctors were confronted with non-indicated requests appears to be rather low.

The doctors who participated in this survey were also asked whether adults wanted the drug for themselves or for a child. The result was that 80% of the patients wanted the medicine for themselves, more than 80% of these patients were between 20 and 40 years old. Given the fact that examinations and time pressure among students and young working people are seen as a stress factor, these results are not surprising [15] . The ages between 20 and 40 discovered in this survey also correlates with the age determined in the examined studies on misuse [23] [31] . Against this background, some of the respondents’ notes are very interesting. One doctor (no. 136) thinks that nowadays social requirements of school and jobs are extremely high. Another doctor (no. 47) mentioned the popular intake by students because passing state examinations without Ritalin® is virtually impossible. A cardiologist (no. 68) emphasized that methylphenidate often has cardiac side effects. Nevertheless, young people are unwilling to stop the taking the drug because they want to improve school performance (“Frequent cardiac side effects due to Ritalin-therapy (tachycardia), but they still don’t want to stop taking it because of alleged higher grades”). Due to the numerous and partly serious side effects which were described in the introduction, it is necessary to monitor the patient before and during the phamacotherapy [8] .

Only 10% of the adults with an indicated request had been examined by doctors. It is not clear whether a doctor did not consider or whether the patient refused an examination. It is easy to imagine that a patient suffering from drug misuse strictly refuses an examination. Further studies should deal with this aspect.

The information that an illegal market for methylphenidate exists at the University of Munich is quite alarming. One respondent (no. 13) mentioned the fact that parents of children with ADHD diagnosis do not give their children methylphenidate over the weekend but sell this “saved” drug at the university. To date studies about MPH misuse have indicated an illegal market at schools and universities; however, only university students and school children giving away or selling methylphenidate have been mentioned in these studies [16] [24] [36] [37] [46] [56] . The fact that parents knowingly deprive their children of the drug?which is funded by the health insurance schemes?was not mentioned in any publication. As a consequence, doctors should not only ensure good compliance on the part of the child, but also take into account the danger of interruptions in treatment induced by the parent. The consequences of such interruptions for children?whether in the long or short term?are unknown. The welcome effects of Ritalin® only last for six hours [1] . Possibly numerous and short breaks in therapy are responsible for an increase in typical ADHD symptoms. These symptoms could be misinterpreted by doctors and result in higher doses.

The note of a transfusion physician (no. 192) underlines the fact that methylphenidate is a medicine that is not to be underestimated. According to this physician, patients who use methylphenidate are definitely not acceptable as blood donors. Following oral application of an immediate-release preparation, the half-life period in plasma is two to three hours and this value doubles after application of a retard preparation [1] [57] [58] . Thus, drug residues in the blood bag cannot be excluded. According to a transfusion physician of the “Bavarian Red Cross (BRK)”, there were no official guidelines about methylphenidate in particular which were based on studies [59] . Blood donor services have come to internal agreements and followed guidelines written by the Medical Association in cooperation with the German Paul Ehrlich Institute [59] . With regard to donors with medication intake, the Medical Association demands in an upgraded version of 2010 that they will be postponed for an estimated time [60] . The provision of each medicine depends on the pharmacokinetic and indication [60] . The result is that all patients with psychostimulant therapy?which include methylphenidate?are excluded from donating blood [59] . The reason for exclusion is a matter of concern with regard to possible paradox reactions on the recipient’s side [59] . Obviously, this quality requirement regarding stored blood can only be realized in actual practice if there is a relationship of trust between doctors and donors. In the preliminary talk, the donor fails to disclose the use of methylphenidate. But if a blood donor misuses methylphenidate, inhibition level will probably be quite high, and the individual will conceal that he/she takes methylphenidate more frequently.

According to a physician in the Department of Addiction Medicine (no. 76), methylphenidate abuse among his patients had decreased in recent years. He doubted that the importance of methylphenidate had declined, however. His assumption was that more and more “crystal meth”, a methamphetamine, is being consumed. He stated that it was cheaper and much easier to obtain. “Crystal meth” is a substance similar to methylphenidate and causes similar effects [4] . Data released by the police about the development of drug abuse confirm an increasing spread of amphetamines and methamphetamines [61] .

In Germany, the trend to obtain the entrance examination requirement for higher education has become very popular in recent years [62] . 57% of the school leavers completed their secondary education with the requirements for higher education [62] . Obviously, more and more people think that an academic qualification is a “must” to obtain a safe job. Justifications for the improper MPH use illustrate that school children take methylphenidate in order to reach this aim. The reasons mentioned most frequently are as follows: increasing level of attention and concentration, enhancing learning behavior and grades [23] [35] . It would seem likely that there is a connection between a change of school and the highest frequency of ADHD diagnoses around the age of 10 [54] . Therefore, MPH abuse can partly be seen as a consequence of today’s achievement-orientated society.

The number of ADHD diagnoses and MPH prescriptions has been increasing considerably [7] [54] [63] . If the misuse of stimulants is not considered as a separate problem, but as part of the misuse problem of stimulants used to treat ADHD then today’s ADHD therapies should be looked at very critically [23] . Particularly with regard to the updated license for methylphenidate in 2011 with an approval for treatment of adults, a skeptical discussion seems to be of special significance [5] . The possibility of misuse should be taken into account when prescribing methylphenidate [22] .

When comparing the different studies already published, it is quite remarkable that only four of the 34 studies deal with German data, and the majority of studies (n = 20) were conducted in the USA. Moreover, it was primarily university students who were linked to methylphenidate misuse, and, apart from the DAK-health report, virtually no data exists about the working people [7]. It is obvious that?despite the numerous reports in the media?additional data is needed not only about Germany but also about different occupational groups.

Essential differences among students became clear: lifetime prevalence varied from 0.8% [21] to 16.6% [22] . The reason for this could be the different methods of conducting studies. In other words, Franke et al. recognized deviating prevalence in a survey among surgeons on the issue of the neuroenhancement with prescription drugs and illicit drugs depending on the method of questioning [64] . When using an anonymous questionnaire, the life-time prevalence was 9% and when using the random-response-technique (RRT) among the same cohort the prevalence was 20% [64] . Compared to common questioning methods, the RRT provide more reliable data, especially in cases of indiscreet and incriminating questions [65] . None of the studies examined in the present paper used this technique. Hence, it is assumed that there is a high number of unrecorded methylphenidate misuse cases. This fact is underlined by information on differences between data of own misuse and alleged misuse by fellow students [40] .

The methylphenidate misuse seems to be highly associated with the male gender and a Caucasian origin [24] [30] [31] [32] [33] [35] . Furthermore, young adults around the age of 20 as well as college students present themselves as particularly at risk [23] [31] . With this knowledge it is possible to narrow down a group of persons that should be given attention and targeted by preventive measures. It is not surprising that 89% of the Israeli medical students who misuse MPH began misuse at university, because neuroenhancement is more frequently reported by students with higher levels of performance pressure and if the pressure is considered as more burdensome by those students [28] [38] [44] [53] . One can imagine that performance pressure is very common among medical students. This point gain even more significance when knowing that stimulant taking?whether coffee or Ritalin®?is regarded partly only as a way of achieving aims such as good marks [48] . However, they feel better if the results were achieved without enhancers [48] .

Misuse is most likely not more widespread in large cities, as there was, unexpectedly, no difference detectable in regard to the size of cities [21] .

There was a strong association between MPH misuse and ADHD diagnoses. It appears that persons with a MPH prescription are given to misuse methylphenidate more often [26] [50] [51] . Perhaps this increased likelihood persists after the end of therapy. Half of the university students with a stimulant prescription in the past, were still taking the drug for the purpose of neuroenhancing at the time of the survey [42] . Based on this awareness, a potential misuse after a pharmacological therapy in patients with ADHD should be considered.

It is assumed that a pharmacological therapy with the psychostimulant methylphenidate?above all because of certain similarity to amphetamine and cocaine?could function as a gateway drug [32] . Looking at the high correlation between MPH misuse and misuse of other substances such as marijuana, ecstasy and cocaine, the hypothesis does not appear to be unfounded [16] [31] [43] . It should be noted that an influence in the opposite direction is also conceivable, so that persons with experience of abuse are more likely to use methylphenidate [66] .

The peer group turned out to be the most important influencing factor [33] . Typically, a peer group has a leader with a strong and accepted influence, resulting in the high conformity of the group [67] . A study with a view to students with pharmacological neuroenhancement showed the influence of the peer group and also a division concerning the transfer of information. On the one hand, there is a well-informed group which supports or at least tolerates neuroenhancement and partly practices it themselves; on the other hand, there are students who are skeptical about the topic [68] . The result is two information systems that are completely independent of each other wherein students who take NE avoid critical discussions [68] . Kwan et al. were able to show in their study on the subject of the influence of a substance abusing peer leader on group members, who are vulnerable to misuse, that the risk in this situation declines for women and increases for men [69] . Moreover, this is a revealing point since the majority of the abusing students are male [32] [33] [35] . These findings are of central importance to initiate education programs as far as possible within the peer group and even gender-specific programs can possibly be beneficial.

The fact that the taking of a stimulant by physicians, pilots or soldiers is viewed in certain situations and at a high level of responsibility as legitimate, may have alarming consequences on the professional environment [48] . The issue of doping in sports is strictly regulated by the World Anti-Doping Agency (WADA), and methylphenidate is on the list of prohibited substances [70] . At a major computer fair (Gamescom) with contest prizes of a million Euros and more, drug testing was carried out for first time in 2015 for prescription drugs (Ritalin®, Adderall®) [71] . Nevertheless, there is no equivalent regulation in the working world. When considering soldiers, surgeons or brokers, the question arises of whether “doping” should be accepted?unlike in the case of sports?and what acceptance says about a society. These are not speculations about the future. US army flight surgeons are already obligated indirectly to take dexedrine during missions [72] .

One third of the students who misuse general stimulants are afraid of “brain dopers” [25] . Mental performance will become even more important to future generations. Out of the concern that classmates might be being given methylphenidate by their parents, it is possible that some parents will feel compelled to give methylphenidate to their own children in order to give them the best opportunities [47] .

Methylphenidate is primarily obtained from friends and acquaintances [16] [21] [24] [27] [28] . They usually have a valid prescription, therefore greater efforts are important to raise patient compliance [16] [46] . In the case of stimulant therapies, treating physicians bear a great responsibility with regard to weighing use and risks and should be aware of possible overdose and/or diversion [29] [34] . Special care and strict controls must be taken for patients with illicit substance use in the past [50] . Furthermore, physicians should bear in mind that patients may simulate ADHD symptoms in order to receive a stimulant prescription [24] . Physicians need additional training to be able to identify those patients [46] . Novak et al. also argue for additional monitoring programs on prescription drugs or strict penalties for lax prescribing practices [46] . More generally, wide-ranging prevention measures?which involve parents and fellow students?are required [34] . Early programs focusing on middle-school children and thus before the usual starting age, would be beneficial [32] . De Santis et al. note that it gets exponentially heavier to get in touch with students due to increasing widespread stimulant misuse (20-30% at most of the US universities) [73] . Mainly in regard to the aspect of financial constraints, it would be more promising to look for the small share of “distributors” (2-4% at most of the US universities) [73] .

Emanuel et al. detected common psychostimulant misuse among medical students and argued for further studies on side effects, clinical implications and the intake during the years as an assistant doctor [36] . Nearly one fifth of medical students would prescribe stimulants more thoughtlessly to their own patients in future; consequently, further scientific consideration is needed [36] . Data on widespread misuse among surgeons, collected by Franke et al., need closer examination [64] . Although certain students assume that an intake in special situations, eg. as by a surgeon, is legitimate, critical analyses with regard to the risks posed by intake are lacking [48] . It is to be considered that a surgeon operating under the effect of drugs overestimates his or her capabilities, this can quickly pose an increased risk to patients [64] .