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Attitudes towards prescribing cognitive enhancers among primary care physicians in Germany Franke, Andreas G; Papenburg, Carolin; Schotten, Elena; Reiner, Peter B; Lieb, Klaus Jan 8, 2014

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RESEARCH ARTICLE Open AccessAttitudes towards prescribing cognitiveenhancers among primary care physiciansin GermanyAndreas G Franke1,2*, Carolin Papenburg1, Elena Schotten1, Peter B Reiner3 and Klaus Lieb1AbstractBackground: Primary care physicians are gate keepers to the medical system having a key role in givinginformation and prescribing drugs to their patients. In this respect they are involved in claims of patients/clients forpharmacological Cognitive Enhancement (CE). Therefore, we studied the knowledge of primary care physiciansabout CE and their attitudes toward prescribing CE drugs to healthy subjects.Methods: A self-report paper-and-pencil questionnaire and case vignettes describing a hypothetical CE drug weresent out to all 2,753 registered primary care physicians in Rhineland Palatine, Germany. 832, i.e. 30.2% filled in thequestionnaire anonymously.Results: 96.0% of all participating physicians had already heard about CE. However, only 5.3% stated to be veryfamiliar with this subject and 43.5% judged themselves as being not familiar with CE. 7.0% had been asked by theirclients to prescribe a drug for CE during the last week, 19.0% during the last month, and 40.8% during the last year.The comfort level to prescribe CE drugs was very low and significantly lower than to prescribe sildenafil (Viagra®).Comfort level was mainly affected by the age of the client asking for prescription of CE drugs, followed by theavailability of non-pharmacological alternatives, fear of misuse of the prescribed drug by the client and the missingindication of prescribing a drug.Conclusions: Although a relatively high proportion of primary care physicians have been asked by their clients toprescribe CE drugs, only a small proportion are well informed about the possibilities of CE. Since physicians are gatekeepers to the medical system and have a key role regarding a drugs’ prescription, objective information should bemade available to physicians about biological, ethical and social consequences of CE use.Keywords: Cognitive enhancement, Primary care physician(s), Prescription drug(s)BackgroundPrimary care physicians play a crucial role in prescribingdrugs. In many jurisdictions they are the first individualswho have to be contacted by the general public when a pre-scription is sought. Regarding covering costs by the healthcare system, in the United Kingdom patients have to registerat a primary care physician who gives referrals to specialists.In Germany, patients can chose and change their primarycare physician who gives referrals; however, patients havethe opportunity to contact a specialist directly. In the UnitedStates, patients are able to obtain an appointment with aspecialist without a referral from a primary care physician.As such, depending on the national health care system,primary care physicians act more or less as “gatekeepers”for the medical system. Even if prescription drugsagainst somatic disorders are the most prevalently pre-scribed drugs among primary care physicians (e.g. non-steroidal anti-inflammatories, beta-blockers, etc.), theyfrequently are contacted for advice and counselling formental disorders [1]. With particular reference to thephenomenon of pharmacological cognitive enhancement(CE), Hotze and colleagues found that two thirds of sur-veyed primary care physicians received requests for* Correspondence: afranke@uni-mainz.de1Department of Psychiatry and Psychotherapy, University Medical CentreMainz, Untere Zahlbacher Str. 17, D – 55128 Mainz, Germany2University of Neubrandenburg, University of Applied Sciences, Brodaer Str. 2,D – 17033 Neubrandenburg, GermanyFull list of author information is available at the end of the article© 2014 Franke et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedicationwaiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwisestated.Franke et al. BMC Family Practice 2014, 15:3http://www.biomedcentral.com/1471-2296/15/3“medicine or services that the physicians considered tobe for enhancement rather than therapy” monthly and12.0% at least daily. This survey among a random sampleof 1,500 practicing physicians from the American MedicalAssociation (AMA) Masterfile found that 37.0% of theparticipants stated that they prescribed what they viewedas medicine for enhancement at least monthly and 4.0% atleast daily [2].The group of substances used by healthy subjects forCE purposes consists of over-the-counter- (OTC-) drugs(e.g. Ginkgo biloba, caffeine tablets, etc.) as well as illicitand prescription drugs. Among the drugs that require aprescription are stimulants such as methylphenidate(MPH) and amphetamines (AMPH) such as AdderallW,as well as other drugs such as modafinil, anti-dementiadrugs, beta-blockers, and antidepressants for mood en-hancement (ME) [3-6]. In Germany, the prescriptionvolume of MPH, indicated for attention deficit hyper-activity disorder (ADHD), has risen from 20 milliondaily doses in 2003 to 58 million daily doses in 2012which is hardly to explain with the increase of diagnosesof ADHD; the prescription volume of Atomoxetin, how-ever, is stable for the last years [7].Bergström and Lynöe found that more than 80.0% of300 surveyed primary care physicians in Sweden wereconvinced that CE drugs should not be covered by thehealth insurance system and individuals should paythemselves for CE drugs [8]. In a web-based survey of212 primary care physicians throughout the UnitedStates and Canada, Banjo and colleagues found thatnearly 2/3 of the participants had already read articlesabout CE in the public or scientific media and yet justover half rated themselves as not being familiar with thetopic of CE [9].Previous studies on CE found large differences inprevalence rates for CE use ranging from > 1 – 20%among students [10-19]. Using the Randomized Re-sponse Technique (RRT) which guarantees an especiallyhigh degree of privacy, anonymity, and confidentiality,we found in German students a one-year prevalence rateof 20.0% for the use of “pharmaceuticals or illegal drugswhich you cannot buy in a drug-store and which werenot prescribed to you to treat a disease”. [11]. An an-onymous online survey by the journal “Nature” depicteda lifetime prevalence rate of 20.0% for prescription drugssuch as beta-blockers, modafinil and methylphenidate(MPH), stressing that MPH is the most popular substanceused for CE [20]. Another study by our group using RRTamong surgeons revealed a lifetime prevalence rate of19.9% for the use of prescription and illicit drugs for CEpurposes and a lifetime prevalence rate of 15.1% for theuse of prescription antidepressants for ME [21].The present study presents data on the knowledge of,attitudes towards, familiarity with, frequency of beingasked for, and comfort levels with prescribing CE drugsby primary care physicians in Germany.MethodsParticipants and procedureEnvelopes with paper-and-pencil questionnaires weresent out in June 2011 to all registered primary carephysicians (n = 2,753) in Rhineland Palatine, a state inWest Germany with about four million inhabitants. Par-ticipants were asked to complete the questionnaire an-onymously and to return it in an anonymous, addressedand pre-paid envelope within one month. Physicianswho did not answer were identified using a code, calledtwice via telephone and asked to send back the question-naire. Those who did not possess the questionnaire anymore were sent the questionnaire again. Participants alsohad the option of returning the questionnaires via emailor fax.The first wave of completed questionnaires were re-ceived between July and September 2011. Afterwards,the questionnaires were returned according to the orderof the telephone calls.530 physicians responded immediately by sendingback their questionnaire (first response rate: 19.3%), 302responded after telephone calls (second response rate:11.0%) resulting in a total response rate of 832 (30.2%).AssessmentsThe questionnaire was based on the one used by Banjoand colleagues [9]. At the beginning of the questionnaireparticipants had to read a short paragraph which pre-sented an introduction of CE which summarized a lon-ger introduction section of Banjo and colleagues becauseof reduced space on the paper-and-pencil questionnairecompared to the online method by Banjo and colleagues.The paragraph introduced CE drugs to be “substanceswhich are used with the purpose to enhance one’s owncognition and that CE drugs have been developed forthe treatment of cognitive decline (e.g. dementia in eld-erly people) or cognitive disturbance in younger subjects(e.g. attention deficit hyperactivity disorder, ADHD)”.Furthermore, primary care physicians were described as“having a key role in prescribing drugs [for CE]. Beyondthat [primary care physicians] are physicians who getdirectly into contact with patients. Thereby, [you] arethe central link between drug developments and pre-scribing these developed drugs to patients”.Subsequently and identical to the original question-naire of Banjo and colleagues, the second part of theintroduction section reviewed briefly the following: “Re-search shows that normal decline in cognitive functionin healthy individuals becomes evident in the later yearsof the fourth decade of life (late 30’s). Widely acceptedas a normal part of aging, this cognitive decline is not aFranke et al. BMC Family Practice 2014, 15:3 Page 2 of 10http://www.biomedcentral.com/1471-2296/15/3disease and moreover is distinct from the prodromiccognitive decline that precedes dementia. In a society inwhich one’s cognitive abilities are important determi-nants of self-esteem and respect from one’s peers, thenormal cognitive decline of aging can be disturbing”.Identical to Banjo and colleagues we asked for demo-graphic data (age, gender). Beyond Banjo and colleagues,we asked for family status, hours worked per week andwhether respondents were living with or without chil-dren based on the assumption that these factors couldbe associated with the dependent variables describedbelow.Furthermore, a question probing knowledge of CE, thesource of knowledge about CE drugs, and the frequencybeing asked for a prescription of CE drugs developed byour group was asked. This was followed by a question offeeling familiar (very familiar, somewhat familiar and notfamiliar) with CE drugs.A hypothetical case vignette was introduced identicalto Banjo and colleagues: In this vignette, a hypotheticalprescription drug approved for CE in healthy adults wasintroduced to the participants. The CE drug was charac-terized to be effective, safe and without remarkable ad-verse events. In order to assess the impact of patientsgiving reasons for requesting the drug upon physicianattitudes, we presented three scenarios: a 25-year oldgraduate student seeking to cope with the stress ofgraduate school, a 45-year-old employee hoping to im-prove productivity, and a 65-year-old individual feelingconcerns about his ability to perform everyday activities.Then, physicians were asked how comfortable they feltprescribing the hypothetical CE drug on a Likert scale(comfort level with anchors at 1 = very uncomfortableand 7 = very comfortable). Subsequently, participantswere asked for the reasons that determined their com-fort level.Afterwards, we probed physicians’ attitudes towardsprescribing the hypothetical CE drug and three otherdrugs sometimes considered to be enhancers: sildenafil,modafinil, and MPH. Using the same Likert scale weasked for their comfort level to prescribe these drugs toa 40-year-old person reporting symptoms consistentwith the label indications for each drug.The study was approved by the local Ethics Committee(Landesärztekammer Rhineland Palatine No. 837.321.08(6318)). Participation was explained to be optional; par-ticipants gave informed consent by returning thequestionnaire.Statistical analysisStatistical analyses were performed using SPSS 17.0.Means are given with corresponding standard deviation(mean ± SD) and Pearson-Clopper confidence intervals(95% CI). Questions were analyzed using stepwise forwardmultiple logistic regression analysis with a selection levelof 0.05. For evaluation of the results of the logistic regres-sion analysis we used pseudo-R squared (Nagelkerke).ResultsParticipants’ characteristicsDemographic data of the participating 832 physicians(= 100.0%) are given in Table 1.Table 1 Participants´ characteristicsParticipants (total) N = 832 (100.0%)GenderMale 567 (68.1%)Female 259 (31.1%)No answer 6 (0.7%)AgeYears (Mean ± SD) 30.0 – 81.0 years (54.3 ± 8.2)30 – 39 40 (4.8%)40 – 49 196 (23.5%)50 – 59 318 (3.2%)60 – 69 240 (28.9%)70 – 79 11 (1.3%)80 – 89 1 (0.1%)Family statusMarried 734 (88.2%)Divorced 49 (5.9%)Single 28 (9.4%)Widowed 12 (1.4%)No answer 8 (1.0%)ChildrenParticipants living with children 487 (58.5%)Participants living without children 330 (39.7%)No answer 15 (1.8%)Certificate of Added Qualification:Yes 504 (60.6%)No 328 (39.4%)No answer 0 (0.0%)Years working as a physician(Mean ± SD)4.0 – 55.0 years (26.3 ± 8.5)Years working in an own officeoutside of a hospital setting(Mean ± SD) 0.5 – 47.0 years (18.6 ± 9.3)Living in a town (> 100.000) 114 (13.7%)Living in a small town/village(< 100.000)548 (65.9%)Estimated hours of work (per week)(Mean ± SD):8.0 – 103.0 hours (50.2 ± 14.5)Demographic data of participants. Means are given with standard deviation(Mean ± standard deviation (SD)).Franke et al. BMC Family Practice 2014, 15:3 Page 3 of 10http://www.biomedcentral.com/1471-2296/15/3Knowledge about CE and familiarity with this topicKnowledge about CEIn total, 96.0% (n = 799 of 832) physicians had alreadyheard about the use of substances of any kind for CE.29.1% (n = 242 of 832) had heard about CE by friends orrelatives and 33.2% (n = 276 of 832) by colleagues. 71.2%(n = 592 of 832) were informed by print media (newspa-pers, magazines), 33.8% (n = 281 of 832) by digital media(TV, internet), and only 4.0% (n = 33 of 832) had not yetheard about CE.Logistic regression analysis revealed that knowledgeabout CE was associated with the location of the doc-tors’ office: Primary care physicians having their office innon-urban areas had heard about CE by colleagues sig-nificantly more often than those whose offices were incities (p = 0.019; OR: 0.500; CI: 0.280 – 0.890; pseudo-RSquared: 0.045). Beyond that, the more years physiciansworked in their office outside of the hospital setting, thegreater their knowledge about CE derived from printmedia (p = 0.014; OR: 1.047; CI: 1.009 – 1.086; pseudo-RSquared: 0.031), and the more their general knowledgeabout CE (apart from the source of knowledge)(p = 0.018; OR: 0.957; CI: 0.923 – 0.993; pseudo-RSquared: 0.071). There were no associations betweenknowledge about CE and the following characteristics ofthe participants: gender, age, family status, living withchildren, having an additional Certificate of AddedQualification nor hours of work per week.Physicians’ knowledge about individual substances forthe purpose of CE differed substantially (see Table 2):MPH was the most widely known substance for CE,whereas caffeinated products, Ginkgo biloba as well asantidementia drugs were known only by about twothirds of the surveyed participants.Being familiar with CEOnly 5.3% (n = 44 of 821) of all participants stated thatthey were very familiar with the topic of CE, 49.9%(n = 415 of 821) stated that they were somewhat familiarwith CE and 43.5% (n = 362 of 821) stated that they werenot familiar with CE.Regarding feeling familiar with CE, there were noassociations found for gender, age, years working in one’sown doctor’s office, working as a physician, hours ofwork per week, living with children, having an additionalCertificate of Added Qualification, doctor’s office beinglocated in a city or family status.Frequency of being asked by patients to prescribe a drugfor CERegarding the estimated frequency of being asked by cli-ents to prescribe a drug for CE purposes, 99.3% (n = 826of 832) answered this question. 7.0% (n = 58 of 826)stated that they had been asked at least once during thelast week, 19.0% (n = 157 of 826) during the last month,and 40.8% (n = 337 of 826) during the last year. 9.4%(n = 78 of 826) of the physicians had been asked morethan one year ago and only 23.7% (n = 196 of 826) indi-cated that they had never been asked to prescribe a drugfor CE by healthy subjects.Comfort levels of primary care physicians to prescribe drugsa) Comfort levels regarding three scenariosComfort levels to prescribe CE drugs to individualsof certain characteristics (25-year old graduatestudent seeking to cope with the stress of graduateschool, 45-year-old employee hoping to improveproductivity, 65-year-old individual feeling concernsabout his ability to perform everyday activities) wererated by using a 7-step Likert scale with anchors at1 (= feeling very uncomfortable) and 7 (= feelingvery comfortable).Figure 1 shows differences regarding the comfortlevel to prescribe a drug to the 25-year-old graduatestudent, the 45-year-old-worker and the 65-year-oldindividual. Means of the comfort levels were: 1.7 ±1.4 regarding the 25-year-old graduate student,2.1 ± 1.5 regarding the 45-year-old-worker and 3.4 ±Table 2 Percentage of primary care physicians who knowthe respective substance as a drug which can be used forCE or MEPrescription drugs % NMPH (e.g. RitalinW, ConcertaW, etc.) 79.7 663Ready-made AMPH tablets (e.g. AdderallW, DexedrineW, etc.) 47.8 398Atomoxetine (StratteraW) 23.3 193Modafinil (ProvigilW, VigilW) 32.1 267Antidementia drugs (e.g. AriceptW, EbixaW/ AxuraW, etc.) 61.9 515Illicit drugs:Illicit AMPH (e.g. Speed, etc.) 49.0 408Ecstasy 38.1 317Cocaine 42.8 356Other illicit psychoactive drugs 20.9 174OTC-drugsCoffee 66.8 556Coca ColaW (or similar) 60.5 503Caffeinated Drinks/ Energy Drinks (e.g. Red BullW) 64.7 539Caffeine tablets (CoffeinumW) 61.1 508Ginkgo biloba 59.1 492Ephedrine 31.7 264Antidepressants for MEAntidepressants (e.g. ProzacW, CipralexW, ZoloftW, etc.) 42.3 352AMPH = amphetamines; CE = cognitive enhancement; ME =moodenhancement; MPH =Methylphenidate; OTC = over the counter.Franke et al. BMC Family Practice 2014, 15:3 Page 4 of 10http://www.biomedcentral.com/1471-2296/15/32.0 regarding the 65-year-old individual. Comfort levelsto prescribe were significantly higher regarding the65-year-old-individual compared to the 25-year-oldgraduate student and to the 45-year-old-employee.Logistic regression analysis revealed no significantinfluence regarding the tested dependent variables(age, hours of work per week, etc.) for all threescenarios.b) Factors influencing comfort levels in prescribingCE drugsTable 3 gives factors affecting physicians’ comfortlevel to prescribe a CE drug to impaired but healthypatients being 25, 45 or 65 years old. For statisticalanalysis see Table 3.c) Comfort levels to prescribe a potential CE drug likemodafinil or methylphenidate as compared tosildenafilPhysicians were asked how comfortable they feltprescribing sildenafil, MPH, Modafinil, or thehypothetical CE drug as described above to a40-year-old person reporting symptoms consistentwith the label indications for each drug using a7-step Likert scale with anchors at 1 (= feeling veryuncomfortable) and 7 (= feeling very comfortable).Figure 2 shows comfort levels of 4.2 ± 2.0 regarding thecomfort level to prescribe ViagraW, 2.0 ± 1.5 to prescribeModafinil, 1.7 ± 1.3 to prescribe RitalinW and 2.3 ± 1.6 toprescribe a potential CE drug.There were significant differences between the dispos-ition of the physicians to prescribe the different types ofdrugs. Physicians felt significantly more comfortable inprescribing ViagraW then prescribing modafinil, RitalinWor the hypothetical CE drug. In addition physicians feltmuch more comfortable in prescribing the hypotheticalenhancer than choosing modafinil or RitalinW.With respect to comfort levels of physicians regardingthe prescription of sildenafil, modafinil, MPH or a hypo-thetical CE drug, logistic regression analysis revealedthat male primary care physicians felt significantly morecomfortable prescribing sildenafil than female physicians(p = 0.003; OR: 0.463; CI: 0.159 – 0.767; pseudo-RSquared: 0.026) as well as primary care physicians havingtheir doctor’s office in a city showed a higher comfortlevel for prescribing sildenafil (p = 0.048; OR: 0.321; CI:0.003 – 0.640; pseudo-R Squared: 0.026). Regardingcomfort levels of prescribing sildenafil, there were noassociations with age, years working as a physician, yearsworking in one’s own doctor’s office, hours of work perweek, family status, living with children, and the locationof one’s own doctor’s office.Regarding modafinil, male primary care physicians andphysicians having their office in a city felt more comfort-able prescribing modafinil (p = 0.001; OR: 0.573; CI:0.227 – 0.918 and p = 0.010; OR: 0.484; CI: 0.118 –0.850; pseudo-R Squared: 0.045 respectively). There wereno associations with age, years worked as a physician,years worked in own doctor’s office, hours worked perweek, family status, living with children, location of doc-tor’s office.For MPH and the hypothetical CE drug, we found thesame positive association with male physicians as withFigure 1 Differences regarding comfort level to prescribe a drug to a 25-year-old graduate student, a 45-year-old-worker and a65-year-old individual. Means of the comfort levels were calculated using Likert scales.Franke et al. BMC Family Practice 2014, 15:3 Page 5 of 10http://www.biomedcentral.com/1471-2296/15/3sildenafil and modafinil (MPH: p = 0.030; CI: 0.040 – 0.786;OR: 0.413, pseudo-R Squared: 0.029; hypothetical CE drug:p = 0.034; CI: 0.028 – 0.682; OR: 0.354, pseudo-R Squared:0.035). Further associations were not found for MPH aswell as the putative CE drug (MPH: age, years worked as aphysician, years working in one’s own doctor’s office, hoursworked per week, family status, living with children, add-itional Certificate of Added Qualification, location of doc-tor’s office. Putative CE drug: age, years worked as aphysician, hours worked per week, family status, living withchildren, additional Certificate of Added Qualification, loca-tion of doctor’s office).DiscussionThis study investigated knowledge of, attitudes towards,familiarity with, frequency of being asked for prescrip-tions for, and comfort levels with prescribing CE drugsamong 832 primary care physicians in Germany. Thestudy showed an especially high knowledge level regard-ing CE among the participating subjects with MPHbeing the most widely known substance for CE. In con-trast to this high knowledge level, only 5.3% of thephysicians stated that they were very familiar with CE,and 43.5% described themselves as being not familiarwith the subject. 40.8% of the surveyed primary carephysicians had been asked for a prescription for CE dur-ing the last year followed by 19.0% which had beenasked during the last month and 7.0% during the lastweek. Comfort levels to prescribe CE drugs are lowamong the surveyed physicians and significantly lowerthan to prescribe sildenafil (ViagraW). Another mainfinding is that comfort levels to prescribe a CE drug aremainly affected by the age of the asking subject followedby the availability of non-pharmacological alternatives,fear of misuse of the prescribed drug and the missingnecessity of needing the drug.We demonstrated that nearly all surveyed primary carephysicians (96.0%) reported that they knew about thepossibility of pharmacological CE. This is significantlyhigher proportion than among students in previousTable 3 Reasons that affect attitudes for prescribing CE drugsa) 25-year old graduatestudent seeking to copewith the stress ofgraduate schoolb) 45-year-oldemployee hopingto improveproductivityc) 65-year-old individualfeeling concerns abouthis ability to performeveryday activitiesStatistical analysis(p-value, OR, CI)Availability of non-pharma-cological methodsof achieving the same goals61.5% (n = 512) 52.8% (n = 439) 31.3% (n = 260) p < 0.001; OR: 0.071;CI: 0.039 – 0.127Fear of misuse 60.6% (n = 504) 51.7% (n = 430) 21.8% (n = 181) p < 0.001; OR: 0.056;CI: 0.34 – 0.91Patient does not need the drug 54.3% (n = 452) 43.4% (n = 361) 25.1% (n = 209) p < 0.000; OR: 0.073;CI: 0.048 – 0.112Undermines the values of personal effort 26.9% (n = 224) 19.4% (n = 161) 8.4% (n = 70) p < 0.001; OR: 0.027;CI: 0.15 – 0.49To help patient succeed 13.5% (n = 114) 17.9% (n = 149) 14.8% (n = 123) p = 0.498; OR: 0.141;CI: 0.109 – 0.181Your cultural values 12.3% (n = 102) 11.3% (n = 94) 8.2% (n = 68) p = 0.057; OR: 0.005;CI: 0.001 – 0.014Fear of legal liability 10.1% (n = 84) 7.1% (n = 59) 4.4% (n = 37) p = 0.000; OR: 0.002;CI: 0.000 – 0.014It constitutes a form of cheating 10.1% (n = 84) 6.6% (n = 55) 2.6% (n = 22) p < 0.001; OR: 0.006;CI: 0.002 – 0.020To improve patients’ overall health and wellness 7.5% (n = 62) 14.4% (n = 120) 38.7% (n = 322) p < 0.001; OR: 0.810;CI: 0.063 – 0.103Respect for patients’ Autonomy 6.5% (n = 54) 8.7% (n = 72) 17.2% (n = 143) p = 0.004; OR: 0.042;CI: 0.028 – 0.062To improve daily living 6.1% (n = 51) 13.9% (n = 116) 47.6% (n = 396) p < 0.001; OR: 0.096;CI: 0.075 – 0.122Your religious believes 3.4% (n = 28) 3.6% (n = 30) 2.2% (n = 18) p = 0.625; OR: 0.004;CI: 0.001 – 0.012Patients‘ socio-economic Status 3.0% (n = 25) 6.6% (n = 55) 4.8% (n = 40) p = 0.044; OR: 0.091;CI: 0.057 – 0.193Drug is age-appropriate 1.6% (n = 13) 4.2% (n = 35) 20.7% (n = 127) p < 0.001; OR:0.040;CI: 0.024 – 0.065Reasons affecting attitudes for prescribing CE drugs of the surveyed primary care physicians. Statistical analysis was carried using p-values, odds ratios (OR) andconfidence intervals (CI).Franke et al. BMC Family Practice 2014, 15:3 Page 6 of 10http://www.biomedcentral.com/1471-2296/15/3studies. Two studies among nearly 10,000 students re-veal that about 80% of surveyed students knew aboutthis possibility of CE [12,13,19]. Furthermore, 81.4% ofGerman students stated to know about using substancesof any kind for CE which was significantly higher inuniversity than in high school students [13]. We canonly speculate about the reasons; one reason may be thehigher age of the surveyed primary care physicians goingalong with an increase of professional expertise beingprobably associated with age. In distinction from ourprevious study among students, in this study we werenot able to detect differences regarding sex [13]. Regard-ing stimulants, 39.8% of the students knew about pre-scription stimulants for CE and 57.9% about illicitstimulants for CE [12]. Primary care physicians were lessinformed about the use of illicit stimulants but more in-formed regarding prescription stimulants. Even if thisand previous studies examine the knowledge of CE,there are no comparable data regarding the single sub-stances for CE.Although nearly all physicians had heard about thepossibility of CE, only about half of the physicians feltthey were not familiar with the topic of CE, and only aminority of physicians felt very familiar with CE. Ascompared to Banjo and colleagues, we obtained compar-able results for feeling very familiar with CE (Banjo andcolleagues: 4.0%, present study: 5.7%) [9]. However,Banjo and colleagues reported a higher percentage ofphysicians (57.0% vs. 43.5% in our study) feeling not fa-miliar with CE and a respective lower percentage (39.0%vs. 49.9% in our study) feeling somewhat familiar withCE. We can only speculate about possible causes forthese differences. One might be the different time pointof assessment (2009 in the study by Banjo et al. and2011 in our study) or differences in information systemsbetween Canada and Germany. Another explanation forthe low level of familiarity may be the fact that prescrip-tion drugs for somatic disorders are much more preva-lently prescribed than prescription drugs for CEbelonging to the group of drugs prescribed for mentaldisorders by primary care physicians [1].Compared to Hotze and colleagues, the percentage ofprimary care physicians who reported being asked for aprescription of a drug for CE during the last week wasconsiderably lower in our study: 62% in the survey byHotze and colleagues receive requests “to prescribe in-terventions for what they view as enhancement pur-poses” monthly and 12.0% daily as compared to 7.0%during the last week, 19.0% during the last month, and41.0% during the last year in our study presented here.We can only speculate about the reasons for his differ-ence. Age and sex of the participants of the two studiesis comparable (Mean age in our study: 54.3 years, Hotzeet al.: 52.6 years; sex in our study: male: 68.1%, female:31.1%, Hotze et al.: male: 72.0%, female: n.a.). Unfortu-nately, neither Hotze and colleagues nor our study de-scribes the requesting individuals (age, sex, students,workers, etc.). One possibility is that the requesting indi-viduals in the study of Hotze and colleagues had differ-ent characteristics than the requesting individualsremembered by the surveyed primary care physicians inour study. Furthermore, in the introduction section ofFigure 2 Comfort levels to prescribe ViagraW, Modafinil, RitalinW, Cognitive enhancer using Likert scales (comfort level with anchors at1 = very uncomfortable and 7 = very comfortable).Franke et al. BMC Family Practice 2014, 15:3 Page 7 of 10http://www.biomedcentral.com/1471-2296/15/3our questionnaire we defined CE drugs to be “substanceswhich are used with the purpose to enhance one’s owncognition and that CE drugs have been developed forthe treatment of cognitive decline (e.g. dementia in eld-erly people) or cognitive disturbance in younger subjects(e.g. attention deficit hyperactivity disorder, ADHD)”.Hotze and colleagues asked about “how often patientsrequested medicine or services that the physicians con-sidered to be for enhancement rather than therapy” [2].Thus, the definition in our study is much more preciseand tight than in the study of Hotze and colleagues andmay be the main reason for the significantly higherrequesting rates in Hotze and colleagues.Using vignettes of patients requesting a physicians’prescription of a CE drug, we probed participants abouttheir behaviour in case of a healthy 25-, 45- and 65-yearold individual having cognitive problems and thereforeparticipants having a reason for prescribing a CE drug.We found age of the requesting patient/client to be themain factor determining comfort level of the surveyedprimary care physicians. However, even if the aim of allthree scenarios is cognition enhancement, the reasonsfor the requests are different (to cope with stress atgraduate school, improve productivity at work, leadingan active life to counteract subjective cognitive decline).This has to be considered when interpreting that age ofthe requesting person is the decisive associated factor.Further participants’ characteristics were found to playno role (sex, etc.). This is in line with previous results ofBanjo and colleagues who found that the age of therequesting patient/client as being a key determiningfactor [9]. Furthermore, they found the same in case of ahealthy 25-, 45- and 65-year old individual without anycognitive problems and with reasons for requesting a CEdrug [9].We found that fear of misuse, availability of non-pharmacological methods of achieving the same goalsand the fact that the requesting individual does not needthe drug to be the most relevant reasons affecting physi-cians comfort levels of prescribing CE drugs in case ofthe 25-year old college student and the 45-year old em-ployee. These results confirm the results of Banjo andcolleagues [9]. Beyond that, in our study as well as inBanjo and colleagues the factors to improve patient’soverall health and wellness, to improve daily living andthe assumption/fact that the drug is age-appropriatewere the most crucial factors regarding the prescriptionof a CE drug to the 65-year old individual feeling con-cerns about his ability to perform everyday activities.Fear of legal liability as well as the aspect that the use ofCE drugs constitute a form of cheating played a veryminor role in both studies. This is in line with previousresults of our group: In an interview study about reasonsof students justifying their use of stimulants for CEcompared to caffeine we found that legal aspects play avery minor role for them [22]. Interestingly, for studentusers as well as potential prescribers (primary carephysicians) legal aspects play a minor role.The last set of questions was about a comparison ofsildenafil, MPH, modafinil and a hypothetical CE drugprescribing to patients having the label indication. Wefound that the highest comfort level for prescribingthese agents was for sildenafil (comfort level 7 = 13.1%)compared to MPH (comfort level 7 = 1.8%), modafinil(comfort level 7 = 2.5%) and the hypothetical CE drug(comfort level 7 = 1.9%). These results are similar tothose of Banjo and colleagues [9] and show that there issome degree of similarity in transnational attitudes. Fur-thermore, when asked to freely respond on their an-swers, Banjo and colleagues show that the surveyedphysicians stated to be more familiar with sildenafil andthat the latter should have a better safety profile. Furthercomments show the primary care physicians being afraidabout the abuse potential of stimulant drugs.Beyond that, we found that male primary care physi-cians had a higher comfort level to prescribe sildenafil,modafinil, MPH or a hypothetical CE drug to patientshaving an indication for a prescription. This is in linewith previous results by Ponnet and colleagues searchingfor determinants of physicians to prescribe MPH for CEusing the theory of planned behaviour (TPB). Theyfound that gender influenced attitudes towards prescrib-ing MPH for CE, too: Compared to male physicians,female physicians had more negative attitudes towardsprescribing MPH for CE [23]. However, they used avignette presenting a healthy university student and didnot probe for older patients/clients with or without rea-sons/symptoms for a prescription.Finally, primary care physicians have a crucial role ofthe supply of prescription drugs for CE, they are meantto be gatekeepers to the medical system and they are thefirst who are contacted by the general public searchingfor a physicians’ prescription. However, at the presenttime the prescription of CE drugs by primary care physi-cians is much less prevalent than the prescription ofsomatic medication to patients [1].At present primary care physicians have to decidewhat to do on their own regarding CE. Although nearlyall of them reported that they knew about thephenomenon of pharmacological CE there is a lack ofguidelines aimed at primary care physicians. One possi-bility is that the existing guidelines to neurologists foradult and paediatric populations could be adopted. The“Guidance of the Ethics, Law and Humanities Commit-tee” for neurologists provides neurologists with an over-view of ethical, legal, and social issues surrounding CEas well as practical guidance for responding to an adultpatient’s request for CE drugs developed by LarriviereFranke et al. BMC Family Practice 2014, 15:3 Page 8 of 10http://www.biomedcentral.com/1471-2296/15/3and colleagues [24]. These guidelines propose that neu-rologists have no obligation to prescribe CE drugs andmay ethically refuse a prescription. They should exercise“their clinical and ethical judgment to decide whether toprescribe medications for neuroenhancement”. It wouldbe “ethically permissible for neurologists to prescribesuch therapies, provided that they adhere to well-knownbioethical principles of respect for autonomy, benefi-cence, and nonmaleficence” [24].Beyond that, “Ethical, legal, social, and neurodevelop-mental implications” have been developed for pediatric CE[25]. Graf and colleagues stated that prescribing CE drugsto children and adolescents without a neurological diagno-sis is not justifiable. In “nearly autonomous adolescents”this dogma should be weaker, but prescribing CE drugsshould be not advisable “because of numerous social, de-velopmental, and professional integrity issues” [25].These position papers are primarily directed at neurol-ogists, but the conclusions are indeed relevant to pri-mary care physicians as well. What is missing from thediscussion is the development of a more general set ofguidelines that can apply to all physicians – neurologists,primary care physicians, and others – that will assistthem in their decision-making with respect to prescrib-ing CE. Much more data about the phenomenon of CEis needed. At least, medical education and post-graduateeducation of physicians should contain informationabout the pro-cognitive limitations, the fact of pro-cognitive placebo-effects and the relevant side effects aswell as the safety profile of potential CE drugs as well asethical and social implications. Clients claiming for a CEprescription should be elucidated by their physicians.A few questions for further studies arise based uponthe presented data and should be addressed in furtherstudies to inform the debate about CE: We do not knowif the clients asking for a prescription are younger stu-dents needing help to perform better in school and uni-versity or older ones complaining cognitive decline. Thiswould be an important additional piece of informationthat could be used to characterize claims for CE and theprescription of CE drugs. Therefore, further studiesamong primary care physicians should address the ques-tion of characteristics of patients asking for a CE pre-scription. Furthermore, the present study does notassess if the clients ask for a special drug (e.g. MPH)which they want to get prescribed or if they ask for gen-eral pharmaceutical cognitive help. In this respect we donot know what requested primary care physicians doafter having been requested for a prescription. The be-haviour after being asked for a prescription should beaddressed in further studies as well. Beyond that, we didnot ask for interventions primary care physicians doafter being asked for a prescription e.g. counselling re-garding alternative possibilities to enhance cognition ormood and if they explain the small pro-cognitive effectas well as the (dangerous) side effect profile of thepresent drugs. To address these questions and questionsto the close context in case of being asked for prescrib-ing a CE drug may be contents for qualitative research(interview studies) among primary care physicians. Un-fortunately, these questions cannot be addressed by theuse of anonymous questionnaires (neither paper-and-pencil, nor web-based). Therefore, in depth interviews ofprimary care physicians should be done.Some limitations of the study are worth identifying. Ageneral problem of anonymous surveys is the possibilityof misunderstanding questions and the interpretation ofthe questions by the participants. Together with the useof case vignettes this may lead to a certain kind of fuzzi-ness of data obtained. Furthermore, the relevance per-ceived by the participants may influence the answersobtained. The more important aspect regarding under-standing and interpretation of this survey may be the so-cially undesirable behaviour of misusing substances toenhance cognition which can be regarded to be comparableto the use of drugs for physical enhancement. Answeringquestions regarding such a stigmatizing subject – even ifthe survey is anonymous – may lead to socially desired an-swers depicting a bias of the present data.The sample of primary care physicians of Rhineland-Palatine is large, but is neither representative of Germanynor other countries. Furthermore, the response rate was30.2%. This response rate of only 1/3 means a selectionbias. We can only speculate about the reasons of nonresponding to the questionnaire (e.g. lack of time, feelingthat the topic is not important, socially non-desired opin-ions, etc.). These aspects make it difficult to generalizefrom the results.Beyond that, the logistic regression analysis was themost appropriate method to analyse the data of this sur-vey study. However, several times ORs are quite close to1.0 and the analysis of pseudo-R Squared are smallerthan 0.1 which limits the explanatory power of theanalysis.ConclusionThe data presented in this study confirm and extendprevious studies of physician attitudes towards prescrib-ing enhancement pharmaceuticals to physicians inGermany. Given the different social, legal and medicalcontexts in Germany, the present results are importantin demonstrating that the general trends of physician at-titudes towards enhancement are relatively stable: physi-cians view themselves as gatekeepers and are generallyless comfortable prescribing CE for younger populationsthan for older individuals. Despite these observations,the study highlights the need for further education ofphysicians about the biological, ethical, and socialFranke et al. BMC Family Practice 2014, 15:3 Page 9 of 10http://www.biomedcentral.com/1471-2296/15/3consequences of CE use, and suggests that an organizedinternational effort for outreach to physicians is bothappropriate and timely.AbbreviationsAMA: American Medical Association; AMPH: (Prescription) Amphetamine(s);AQ: Anonymous questionnaire; ADHD: Attention deficit/hyperactivitydisorder; CE: (Pharmacological) cognitive enhancement; CI: Confidenceinterval; ME: (Pharmacological) mood enhancement; MPH: Methylphenidate;OR: Odds ratio; OTC: Over the counter; RCT: Randomized controlled trial;RRT: Randomized response technique; SD: Standard deviation; TPB: Theory ofplanned behaviour.Competing interestsAll authors declare to have no competing interests.Authors’ contributionsAGF, KL and PBR participated in the conception and design of the study.AGF, CP and ES monitored data collection. AGF, KL, CP analysed andchecked the data calculation. All authors participated in data interpretation,drafting, and revising the manuscript. All authors read and approved thefinal manuscript.Authors’ informationAGF, ES, CP and KL belong to the Department of Psychiatry andPsychotherapy, University Medical Centre Mainz, Germany. KL is a Professorfor Psychiatry and Psychotherapy and the the head of the Department ofPsychiatry and Psychotherapy. AGF is a research fellow at the Departmentfor Psychiatry and Psychotherapy and has recently received a Professorshipfor Medicine in Social Work and Education at the University ofNeubrandenburg; ES and CP are doctoral students of the Department ofPsychiatry and Psychotherapy. PBR is a Professor for Neuroethics at theUniversity of British Columbia (UBC), he is trained in neurobiology ofbehavioral states and the molecular underpinnings of neurodegenerativedisease. He focuses his research in the area of neuroethics at the NationalCore for Neuroethics at the UBC in Vancouver (Canada).AcknowledgementsThe authors would like to thank the staff of the Institute of MedicalBiostatistics, Epidemiology and Informatics (IMBEI) of the University MedicalCenter of the Johannes-Gutenberg University Mainz for the mathematicalsupport of the statistical analysis.Financial project funding: German ministry of Research and Education(BMBF) No. 01GP0807 (2009 – 2011). The BMBF had no influence on thecontent of this manuscript.Author details1Department of Psychiatry and Psychotherapy, University Medical CentreMainz, Untere Zahlbacher Str. 17, D – 55128 Mainz, Germany. 2University ofNeubrandenburg, University of Applied Sciences, Brodaer Str. 2, D – 17033Neubrandenburg, Germany. 3National Core for Neuroethics, University ofBritish Columbia, 2211 Wesbrook Mall, Koerner Pavilion, Room S 124Vancouver, British Columbia, Canada.Received: 17 September 2013 Accepted: 2 January 2014Published: 8 January 2014References1. Laux G, Kühlein T, Gutscher A, Szecsenyi J: Versorgungsforschung in derHausarztpraxis. Ergebnisse aus dem CONTENT-Projekt 2006–2009. Heidelberg:Springer-Verlag; 2010.2. Hotze TD, Shah K, Anderson EE, Wynia MK: "Doctor, would you prescribe apill to help me… ?" a national survey of physicians on using medicinefor human enhancement. Am J Bioeth 2011, 11(1):3–13.3. 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Larriviere D, Williams MA, Rizzo M, Bonnie RJ: Responding to requests fromadult patients for neuroenhancements: guidance of the Ethics Law andHumanities Committee. Neurology 2009, 73(17):1406–1412.25. Graf WD, Nagel SK, Epstein LG, Miller G, Nass R, Larriviere D: Pediatricneuroenhancement: ethical, legal, social, and neurodevelopmentalimplications. Neurology 2013, 80(13):1251–1260.doi:10.1186/1471-2296-15-3Cite this article as: Franke et al.: Attitudes towards prescribing cognitiveenhancers among primary care physicians in Germany. BMC FamilyPractice 2014 15:3.Franke et al. BMC Family Practice 2014, 15:3 Page 10 of 10http://www.biomedcentral.com/1471-2296/15/3

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