Pain Medicine 2015; 16: 696–705 Wiley Periodicals, Inc.
PAIN & AGING SECTION Original Research Article Do Male and Female General Practitioners Differently Prescribe Chronic Pain Drugs to Older Patients? Aida Lazkani, PharmD,* Tiba Delespierre, PhD,* Linda Benattar-Zibi, MD,† Philippe Bertin, MD, PhD,‡ Emmanuelle Corruble, MD, PhD,§ Genevie`ve Derumeaux, MD, PhD,¶ Bruno Falissard, MD, PhD,** Francoise Forette, MD, PhD,†† Olivier Hanon, MD, PhD,‡‡ Celine Piedvache, Master of Science,* and Laurent Becquemont, MD, PhD* *Pharmacology Department, Faculty of Medicine ParisSud, University Paris-Sud; Assistance Publique^pitaux de Paris, Ho ^pital Bice ^tre, Le Kremlin Bice ^tre, Ho † France; Department of Geriatry, Medical Director of ORPEA/CLINEA Hospitals, Puteaux, France; ‡ Rheumatology Department, Limoges University Hospital, Limoges, France; §INSERM U 669, University ParisSud, Faculty of Medicine Paris-Sud, Department of ^tre University Hospital, Assistance PubPsychiatry, Bice ^ ^tre, France; lique–Hopitaux de Paris, Le Kremlin Bice ¶ Cardiovascular Functional Exploration, Louis Pradel Hospital, Hospices Civils de Lyon, Bron, France; **Faculty of Medicine Paris-Sud, Biostatistics Department, INSERM U 669, University Paris-Sud, Assistance ^pitaux de Paris, Ho ^pital Paul Brousse, Le Publique-Ho †† ^ Kremlin Bicetre, France; Department of Gerontology, University Paris Descartes, National Foundation of Gerontology, Paris, France; ‡‡Geriatrics Department, University Paris Descartes, EA 4468, Assistance ^pitaux de Paris, Ho ^pital Broca, Paris, France Publique-Ho Reprint requests to: Laurent Becquemont, MD, PhD, ^pital Bice ^tre, 78, Centre de Recherche Clinique, Ho ne ral Leclerc, 94275 LE KREMLIN BICETRE rue du Ge Cedex, France. Tel: 133.1.45.21.35.77; Fax: 133.1.45.21.36.51; E-mail: laurent.becquemont@ bct.aphp.fr Author contributions: Lazkani A: Study design, data analysis, manuscript preparation. Becquemont L:
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Study design, data analysis, manuscript preparation. Delespierre T: Study design, dataanalysis, manuscript preparation. Benattar-Zibi L: Study design, manuscript revision and approval of final version for publication. Bertin P: Study design, manuscript revision and approval of final version for publication. Corruble E: Study design, manuscript revision and approval of final version for publication. Derumeaux G: Study design, manuscript revision and approval of final version for publication. Falissard B: Study design, manuscript revision and approval of final version for publication. Forette F: Study design, manuscript revision and approval of final version for publication. Hanon O: Study design, manuscript revision and approval of final version for publication. Piedvache C: Data analysis, manuscript revision and approval of final version for publication. Conflict of interest: Lazkani A: No conflict of interest. Becquemont L: Received consulting fees from SanofiAventis, Pfizer, Servier and lecture fees from Genzyme, GlaxoSmithKline, Bristol-Myers Squibb and Merck Sharp and Dohme. Close family member working at Sanofi France. Delespierre T: No conflict of interest. Benattar-Zibi L: No conflict of interest. Bertin P: Received consulting fees from Sanofi-Aventis, Pfizer, Ethypharm, Reckitt-Benkiser and speaking fees from Genevrier, Roche, Bristol-Myers Squibb, Merck Sharp and Dohme. Corruble E: Received consulting fees from Servier, Lundbeck, Sanofi-Aventis, BristolMyers Squibb, Eisai. Derumeaux G: Received consulting or speaking fees from Actelion, BoehringerIngelheim, Pfizer, Sanofi-Aventis, and Servier, Research grant from Actelion and Astra Zeneca. Falissard B: Received consulting fees from Sanofi-Aventis, €nenthal, Lilly, HRA, Servier, Roche, AstraZeneca, Gru Boeringher-Ingelheim, Bayer, Novartis, Genzyme, Stallergenes, Daiichi, Otsuka, Bristol-Myers Squibb. Forette F: Received consulting or speaking fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Eisa€ı,
GP Gender and Chronic Pain Prescriptions ExonHit, Pierre Fabre, Ipsen, Janssen-Cilag, Lilly, Lundbeck, Novartis, Merck Sharp and Dohme, Merz, Pfizer, Roche, Sanofi-Aventis, Servier, SchwarzPharma, Specia, Warner-Lamber, Wyeth. Hanon O: Received consulting or speaking fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer, Eisa€ı, ExonHit, Janssen-Cilag, Lundbeck, Novartis, Pfizer, Sanofi-Aventis, Servier. Piedvache C: No conflict of interest.
Introduction Chronic pain is a serious health problem with a prevalence between 25% and 76% in older adults living in the community [1]. Several studies report that achieving adequate pain management in older people is a complex issue because of age-related changes in pharmacokinetics and pharmacodynamics [2,3]. Besides these alterations in drug response, additional factors also appear to be important when treating pain in older adults, such as cognitive status, physical function, and psychological well being [4–7].
Abstract Objective. The aim of this study was to identify the relationship between general practitioner (GP) gender and prescribing practice of chronic pain drugs in older adults. Design. Cross-sectional observational study. Setting. GPs in private practice throughout France. Subjects. Two hundred and sixty GPs (80.8% male and 19.2% female) enrolled 1,379 (28.4% male and 71.6% female) noninstitutionalized patients over 65 years of age, suffering from chronic pain. Methods. A comparison of prescribing habits between male and female GPs was performed on baseline data with univariate analyses followed by multivariate analyses after taking several confounding factors into account. Results. No significant differences were found when comparing male and female GPs’ prescriptions of World Health Organization step 1, step 2, and step 3 analgesics. Male GPs were more likely than female GPs to prescribe antineuropathic pain drugs (11.3% of patients with male GPs versus 4.8% of patients with female GPs, P = 0.004) and less likely to prescribe symptomatic slow-acting drugs for osteoarthritis (SySADOA) (10.2% of male GPs’ patients versus 18.8% of female GPs’ patients, P = 0.0003). After adjusting for several confounding factors, male GPs were still more likely to prescribe antineuropathic pain drugs (OR 2.43, 95% CI 1.15– 5.14, P = 0.02) and less likely to prescribe symptomatic slow-acting drugs (OR 0.64, 95% CI 0.42–0.97, P = 0.03).
In addition to these patient-related factors which influence the prescription of drugs for older patients, the prescribing habits of general practitioners (GPs) for chronic pain have changed over the last few decades, and in particular opioid prescriptions have become more common [8–11]. Meanwhile, the number of women entering medical school has dramatically increased [12,13], reversing the sex ratio of young MDs starting their career. (In the last century, the majority of physicians were male, whereas in this century female physicians will become the majority.) This predominance of female physicians may further contribute to changes in chronic pain management. Indeed, it has been well established that male and female physicians differ in their communication style and in their behavior during office visits with patients [14–17]. A physician gender difference was also observed in treatment decisions and prescribing habits in a range of therapeutic areas [18–24]. Male and female physicians differ in their use of additional tests; notably, intimate examinations are performed less frequently for patients of the opposite sex [18]. Furthermore, female physicians seem to provide more counseling and immunization services, and perform fewer technical-medical interventions [19,20]. In the treatment of chronic heart failure, physician female gender was found to be an independent predictor of betablocker use [21]. Other studies suggested that female GPs prescribe more psychotropic drugs and ACE inhibitors [22,23] while Davidson et al. reported that high volume prescribers were more likely to be males [24]. However, there is still uncertainty as to whether physician gender could be a potential source of variation in prescribing chronic pain drugs. Therefore, this study aimed to determine whether there is a relationship between physician gender and the manner in which drugs used to treat chronic pain in older patients are prescribed.
Conclusion. Male and female GPs prescribe analgesics in a similar manner. However, male GPs prescribe more antineuropathic pain drugs, but fewer SySADOA.
Methods
Key Words. General Practitioner; Gender; Older Adults; Chronic Pain Drugs
The S.AGE (Sujets AGEs, older subjects) cohort [25] is an ongoing French study of noninstitutionalized patients
Study Design and Data Collection
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Lazkani et al. over 65-year old recruited by GPs all over France which aims to describe the real-life therapeutic care of older adults. This cohort (n = 3434) is composed of three subcohorts of patients suffering from either atrial fibrillation (AF; n = 1072), type 2 diabetes mellitus (T2DM; n = 983), or chronic pain (n = 1379). 260, 213, and 287 GPs were enrolled in the chronic pain, T2DM, and AF subcohorts, respectively. The recruitment of GPs was conducted by mail. The first mailing was sent to all 51,000 GPs working in private practice in France who were born after 1947 (to avoid potential study dropouts related to retirement during the planned 3-year follow up). All of the 760 GPs who accepted to participate were enrolled and then randomized into one of the three S.AGE subcohorts. The 260 GPs randomized in the chronic pain subcohort were asked to enroll between 3 and 10 patients, maintaining a ratio of 1:2 between patients aged 65 to 75 and patients over 75-year old. The clinical trial reference of this study is NCT01065909. GPs entered the patients’ medical data into an electronic case report form. All prescriptions were entered using the Anatomical Therapeutic Chemical Classification Code. A detailed study protocol was published prior to study initiation [25]. All the analyses for this study were performed on baseline data. Written and signed consent was obtained from all patients before they were enrolled in this study. The study was approved de Protection des Perby the Ethics Committee (Comite sonnes Ile de France XI) in January 2009 and by the French Drug Agency (ANSM) in February 2009. Study Population Two hundred and sixty GPs in the chronic pain study prospectively enrolled 1,379 patients aged 65 years or over and living in France, who were able to understand the goal of the study, registered with a social security scheme or an equivalent insurer, presenting pain lasting more than 3 months and requiring treatment, and who had signed the informed consent form for the study. Patients could not participate if they were residents of a nursing home at the time of inclusion, could not be followed after inclusion (planned move, homeless), or had a short life expectancy (less than 3 months). Patients were recruited between June 2009 and September 2011 and the follow-up of patients was planned for 3 years with visits every 6 months. Physicians were free to prescribe any drug at any dose in the context of this noninterventional study. For patients meeting the inclusion criteria, the following data were collected at baseline [26]: Sociodemographic data including gender, age, place of residence, educational level, socioprofessional category, and marital status. Characteristics of pain: type of pain (mechanical, inflammatory or neuropathic), evolution of pain, intensity (scored using auto and hetero visual analogue scales [VAS]). The VAS is a 10-point scale consisting of a horizontal line going from “no pain” to “worst possible pain” [27]. In the auto assessment, the 698
patient himself assessed the amount of pain he or she felt on the VAS line (0 to 10 points), whereas in the hetero assessment, the GP assessed the amount of pain experienced by the patient. The impact of pain on each of mood, sleep, and walking was separately assessed by the GP in this study by asking patients: “During the week before inclusion, could you please rate from 0 to 4 the impact of pain separately on your mood, sleep and walking?” An auto assessment scale (0 to 4 points) was used for this purpose with 0 indicating no impact of pain on each of the three items and four indicating extremely major impact. The impact of pain on each item was then divided into three categories: no impact [0], small impact [1,2], and major impact [3,4]. General clinical characteristics of patients: BMI (body mass index, kg/m2), smoking habits, alcohol intake. Physical function was assessed using the Activity of Daily Living scale (ADL scale)] initially described by Katz et al. [28] which includes six elements: feeding, bathing, dressing, going to toilet, transferring, and continence. Patients with a score of 6 are considered to be independent, while 0 indicates that the patient is totally dependent. A simplified 4-item Instrumental Activity of Daily Living scale was also used (simplified 4-item IADL scale [29]), which includes: ability to use telephone, mode of transportation, responsibility for own medications, and ability to handle finances. A score of 4 indicates that the patient is independent, while 0 indicates that the patient is dependent. The French-language version of this simplified 4-item IADL scale has been previously validated as a potent predictor of one-year incident dementia [29]. Cognitive function was assessed using the Mini Mental State Examination scale (MMSE [30]) which is a 30-item questionnaire, with a score of 0.20 which is an important factor in older adults) were considered as adjustment variables in multivariate analysis
(11.3% of the patients with male GPs versus 4.8% of the patients with female GPs, P = 0.004). Male GPs used antineuropathic pain drugs in 77% of their patients reporting neuropathic pain, whereas female GPs used these drugs in only 43% of the same patients. Conversely, female GPs prescribed significantly more SySA700
DOA compared with their male counterparts (18.8% of female GPs’ patients versus 10.2% of male GPs’ patients, P = 0.0003). After adjusting for confounding factors which were significant at a threshold of 20% (patient’s gender and
GP Gender and Chronic Pain Prescriptions
Table 3
Chronic pain drugs prescribed according to GP gender Patients Treated by Male GPs N (%)
Patients Treated by Female GPs N (%)
WHO Analgesics
Total N (%)
Step 1 analgesics Step 2 analgesics Step 3 analgesics
500 (36.3) 453 (32.9) 48 (3.5)
419 (35.8) 397 (33.9) 41 (3.5)
81 (38.9) 56 (26.9) 7 (3.4)
Other drugs used for chronic pain Antineuropathic pain drugs 6 analgesics SySADOA* 6 analgesics
142 (10.3) 158 (11.5)
132 (11.3) 119 (10.2)
10 (4.8) 39 (18.8)
P 0.39 0.06 0.92 0.004† 0.0003†
*Symptomatic slow-acting drugs for osteoarthritis. † Significant P value 0.05.
age, inflammatory and neuropathic pain, pain intensity according to hetero assessment scale, impact of pain on mood and sleep during the week before inclusion, simplified 4-item IADL, MMSE, GP’s age, years in practice, and number of enrolled patients per GP), in addition to GDS which is not significant at 20% but considered as an important confounding factor in older adults, male physicians were still more likely to prescribe antineuropathic pain drugs (OR 2.43, 95% CI 1.15– 5.14, P = 0.02), and less likely to prescribe SySADOA (OR 0.64, 95% CI 0.42–0.97, P = 0.03; Table 4). Additionally, we found no difference between male and female GPs in terms of the prescribed daily doses of analgesics and antineuropathic pain drugs at inclusion (data not shown). Discussion This multicenter observational study aimed to investigate how male and female GPs prescribe different classes of chronic pain medication for noninstitutionalized older adults in France. The results did not reveal any difference in prescriptions between male and female physicians for WHO step 1, 2, or 3 analgesics. This finding concurs with several studies conducted in the general population. Raftery et al. found no difference in analgesic pre-
scription in relation to the gender of the health care provider in the emergency department [34]. Burgess et al. also found that physician gender had no effect on the decision to prescribe a stronger type or higher dose of opioid analgesics in patients suffering from chronic lower back pain [35]. Moreover, Weiss et al. found no difference in the physician’s decision to prescribe analgesics for chronic back pain and kidney stone patients according to physician gender [36]. In a national randomized sampling of certified registered nurse anesthetists, Criste et al. found no difference between male and female providers for pain treatment strategies [37]. However, data from other studies contrast with our findings. Safdar et al. found that female physicians were more likely to prescribe analgesics than male physicians [38]. Veldhuijzen et al. found a significant difference between male and female physicians in their first line treatment choice for lower back pain, with more pharmacological agents prescribed by female physicians as a first line therapy compared with male physicians [39]. Shugarman et al. also reported that the frequency of opioid prescriptions was higher among female physicians [40]. Conversely, some studies found that male physicians prescribed more analgesics than females. In Australia,
Table 4 The relationship between GP gender and prescription of antineuropathic pain and symptomatic slow-acting drugs (SySADOA) at inclusion in univariate and multivariate analyses (male versus female, female as a reference group) Unadjusted OR (95%CI) Antineuropathic pain drugs 6 analgesics SySADOA* 6 analgesics
2.52 (1.29–4.87) 0.49 (0.34–0.72)
P 0.006† 0.0002†
Adjusted OR* (95% CI) 2.43 (1.15–5.14) 0.64 (0.42–0.97)
P 0.02† 0.03†
*Adjusted for gender and age of patient (65–75, 75), inflammatory and neuropathic pain, pain intensity according to the hetero assessment scale, impact of pain on mood and sleep during the week before inclusion by auto-assessment scale, simplified 4item IADL, MMSE, GDS, GP’s age, number of practice years, and the number of patients enrolled per GP. † Significant P value 0.05
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Lazkani et al. Harrison et al. examined the characteristics of GPs who prescribed opioids in general population, and found that male GPs prescribed significantly more opioids than females [9]. In Germany, Glaesmer et al. also reported that male physicians prescribed analgesics more frequently than their female counterparts [41]. In an observational study of 21 Dutch GPs, Feleus et al. found that male physician gender was associated with more medication prescription for nontraumatic complaints of the arm, neck, or shoulder in a general practice [42]. Larue et al. investigated the attitudes of French physicians toward morphine prescription for cancer pain, and found that female physicians tended to prescribe morphine less frequently than their male counterparts [43]. In summary, many studies have found no relation between physician gender and analgesic prescription, which is also the case in our study. Other studies observed more analgesic prescriptions made by female providers while still others reported opposite data. These discrepancies might arise from additional physician-based confounding factors, such as the provider’s ethnicity, specialty, training experience, and geographical location, as recently revealed [33]. Furthermore, the type of pain (acute vs chronic, cancer vs non cancer) and the location of pain frequently varied among these studies, which probably explain the difference in the results concerning the influence of physician gender. In this study, it is rather reassuring that physician gender did not appear to be a significant factor for analgesic drug prescription. Indeed, prescription of analgesic drugs must follow evidence-based guidelines [44,45] based on a codified clinical evaluation that should not be influenced by physician gender.
antineuropathic drug use is far less codified [50]. The fear of prescribing such drugs, known to produce side effects that can alter cognition and mobility in older patients [50,51], might proffer an explanation. Conversely, female physicians prescribed significantly more SySADOA than male GPs. SySADOA are regarded as health food supplements in many countries including the United Kingdom, United States, and Canada while in France they are still considered as drugs, albeit they are generally considered alternative medicine. SySADOA have been reported to be safe, with slow efficacy and a long carry-over effect once treatment is interrupted [52–54]. Several studies reported that female physicians were more likely than males to refer patients for complementary alternative medicine and they were also more likely to provide more preventive services, as well as preventive counseling [55–58]. This could be an explanation for prescribing more SySADOA by female GPs whose patients had a lesser degree of pain. To our knowledge, no data on SySADOA prescriptions according to physician gender are available. This study presents some limitations. First of all, the small number of female physicians may limit the scope of our results, and further studies are needed to confirm our findings. We were not able to take into account all the confounding factors that have been listed which may influence prescribing habits for chronic pain in older patients. For this reason, the observed differences between male and female prescribing practices might be related to unidentified confounding factors. Finally, our observations were obtained from French physicians whose prescribing habits may differ from those of other countries. Conclusion
Although the study patients treated by male physicians presented higher pain levels compared with patients treated by female GPs, they did not receive step 2 or 3 analgesics more frequently. This reluctance to prescribe opioids is probably related to the well-known risks of opioid treatment including fear of patient addiction and physical dependence, as well as potential side effects and an increased risk of death [46–49]. With regard to drugs used in addition to or instead of analgesics, antineuropathic pain drugs and SySADOA prescriptions differed between male and female physicians in the present study. Female physicians prescribed less antineuropathic pain drugs: among patients suffering from neuropathic pain, 43% of those treated by female physicians and 77% of those treated by male physicians received antineuropathic pain drugs. We have no clearcut explanation for this observation. Perhaps one of the possible explanations is that the lower pain scores reported by the patients seen by the female GPs resulted in them prescribing fewer antineuropathic pain drugs than the male GPs. As discussed above, whereas analgesic drug prescription is well defined, 702
Our results suggest no difference between male and female GPs in the prescription of analgesics (WHO steps 1, 2, and 3) to older adults suffering from chronic pain. However, some differences might exist in prescribing behaviors for antineuropathic pain drugs and SySADOA. Our results need to be confirmed in other pharmacoepidemiologic studies performed in different countries where prescribing practices might differ.
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PAIN & AGING SECTION Original Research Article Do Male and Female General Practitioners Differently Prescribe Chronic Pain Drugs to Older Patients? Aida Lazkani, PharmD,* Tiba Delespierre, PhD,* Linda Benattar-Zibi, MD,† Philippe Bertin, MD, PhD,‡ Emmanuelle Corruble, MD, PhD,§ Genevie`ve Derumeaux, MD, PhD,¶ Bruno Falissard, MD, PhD,** Francoise Forette, MD, PhD,†† Olivier Hanon, MD, PhD,‡‡ Celine Piedvache, Master of Science,* and Laurent Becquemont, MD, PhD* *Pharmacology Department, Faculty of Medicine ParisSud, University Paris-Sud; Assistance Publique^pitaux de Paris, Ho ^pital Bice ^tre, Le Kremlin Bice ^tre, Ho † France; Department of Geriatry, Medical Director of ORPEA/CLINEA Hospitals, Puteaux, France; ‡ Rheumatology Department, Limoges University Hospital, Limoges, France; §INSERM U 669, University ParisSud, Faculty of Medicine Paris-Sud, Department of ^tre University Hospital, Assistance PubPsychiatry, Bice ^ ^tre, France; lique–Hopitaux de Paris, Le Kremlin Bice ¶ Cardiovascular Functional Exploration, Louis Pradel Hospital, Hospices Civils de Lyon, Bron, France; **Faculty of Medicine Paris-Sud, Biostatistics Department, INSERM U 669, University Paris-Sud, Assistance ^pitaux de Paris, Ho ^pital Paul Brousse, Le Publique-Ho †† ^ Kremlin Bicetre, France; Department of Gerontology, University Paris Descartes, National Foundation of Gerontology, Paris, France; ‡‡Geriatrics Department, University Paris Descartes, EA 4468, Assistance ^pitaux de Paris, Ho ^pital Broca, Paris, France Publique-Ho Reprint requests to: Laurent Becquemont, MD, PhD, ^pital Bice ^tre, 78, Centre de Recherche Clinique, Ho ne ral Leclerc, 94275 LE KREMLIN BICETRE rue du Ge Cedex, France. Tel: 133.1.45.21.35.77; Fax: 133.1.45.21.36.51; E-mail: laurent.becquemont@ bct.aphp.fr Author contributions: Lazkani A: Study design, data analysis, manuscript preparation. Becquemont L:
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Study design, data analysis, manuscript preparation. Delespierre T: Study design, dataanalysis, manuscript preparation. Benattar-Zibi L: Study design, manuscript revision and approval of final version for publication. Bertin P: Study design, manuscript revision and approval of final version for publication. Corruble E: Study design, manuscript revision and approval of final version for publication. Derumeaux G: Study design, manuscript revision and approval of final version for publication. Falissard B: Study design, manuscript revision and approval of final version for publication. Forette F: Study design, manuscript revision and approval of final version for publication. Hanon O: Study design, manuscript revision and approval of final version for publication. Piedvache C: Data analysis, manuscript revision and approval of final version for publication. Conflict of interest: Lazkani A: No conflict of interest. Becquemont L: Received consulting fees from SanofiAventis, Pfizer, Servier and lecture fees from Genzyme, GlaxoSmithKline, Bristol-Myers Squibb and Merck Sharp and Dohme. Close family member working at Sanofi France. Delespierre T: No conflict of interest. Benattar-Zibi L: No conflict of interest. Bertin P: Received consulting fees from Sanofi-Aventis, Pfizer, Ethypharm, Reckitt-Benkiser and speaking fees from Genevrier, Roche, Bristol-Myers Squibb, Merck Sharp and Dohme. Corruble E: Received consulting fees from Servier, Lundbeck, Sanofi-Aventis, BristolMyers Squibb, Eisai. Derumeaux G: Received consulting or speaking fees from Actelion, BoehringerIngelheim, Pfizer, Sanofi-Aventis, and Servier, Research grant from Actelion and Astra Zeneca. Falissard B: Received consulting fees from Sanofi-Aventis, €nenthal, Lilly, HRA, Servier, Roche, AstraZeneca, Gru Boeringher-Ingelheim, Bayer, Novartis, Genzyme, Stallergenes, Daiichi, Otsuka, Bristol-Myers Squibb. Forette F: Received consulting or speaking fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Eisa€ı,
GP Gender and Chronic Pain Prescriptions ExonHit, Pierre Fabre, Ipsen, Janssen-Cilag, Lilly, Lundbeck, Novartis, Merck Sharp and Dohme, Merz, Pfizer, Roche, Sanofi-Aventis, Servier, SchwarzPharma, Specia, Warner-Lamber, Wyeth. Hanon O: Received consulting or speaking fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer, Eisa€ı, ExonHit, Janssen-Cilag, Lundbeck, Novartis, Pfizer, Sanofi-Aventis, Servier. Piedvache C: No conflict of interest.
Introduction Chronic pain is a serious health problem with a prevalence between 25% and 76% in older adults living in the community [1]. Several studies report that achieving adequate pain management in older people is a complex issue because of age-related changes in pharmacokinetics and pharmacodynamics [2,3]. Besides these alterations in drug response, additional factors also appear to be important when treating pain in older adults, such as cognitive status, physical function, and psychological well being [4–7].
Abstract Objective. The aim of this study was to identify the relationship between general practitioner (GP) gender and prescribing practice of chronic pain drugs in older adults. Design. Cross-sectional observational study. Setting. GPs in private practice throughout France. Subjects. Two hundred and sixty GPs (80.8% male and 19.2% female) enrolled 1,379 (28.4% male and 71.6% female) noninstitutionalized patients over 65 years of age, suffering from chronic pain. Methods. A comparison of prescribing habits between male and female GPs was performed on baseline data with univariate analyses followed by multivariate analyses after taking several confounding factors into account. Results. No significant differences were found when comparing male and female GPs’ prescriptions of World Health Organization step 1, step 2, and step 3 analgesics. Male GPs were more likely than female GPs to prescribe antineuropathic pain drugs (11.3% of patients with male GPs versus 4.8% of patients with female GPs, P = 0.004) and less likely to prescribe symptomatic slow-acting drugs for osteoarthritis (SySADOA) (10.2% of male GPs’ patients versus 18.8% of female GPs’ patients, P = 0.0003). After adjusting for several confounding factors, male GPs were still more likely to prescribe antineuropathic pain drugs (OR 2.43, 95% CI 1.15– 5.14, P = 0.02) and less likely to prescribe symptomatic slow-acting drugs (OR 0.64, 95% CI 0.42–0.97, P = 0.03).
In addition to these patient-related factors which influence the prescription of drugs for older patients, the prescribing habits of general practitioners (GPs) for chronic pain have changed over the last few decades, and in particular opioid prescriptions have become more common [8–11]. Meanwhile, the number of women entering medical school has dramatically increased [12,13], reversing the sex ratio of young MDs starting their career. (In the last century, the majority of physicians were male, whereas in this century female physicians will become the majority.) This predominance of female physicians may further contribute to changes in chronic pain management. Indeed, it has been well established that male and female physicians differ in their communication style and in their behavior during office visits with patients [14–17]. A physician gender difference was also observed in treatment decisions and prescribing habits in a range of therapeutic areas [18–24]. Male and female physicians differ in their use of additional tests; notably, intimate examinations are performed less frequently for patients of the opposite sex [18]. Furthermore, female physicians seem to provide more counseling and immunization services, and perform fewer technical-medical interventions [19,20]. In the treatment of chronic heart failure, physician female gender was found to be an independent predictor of betablocker use [21]. Other studies suggested that female GPs prescribe more psychotropic drugs and ACE inhibitors [22,23] while Davidson et al. reported that high volume prescribers were more likely to be males [24]. However, there is still uncertainty as to whether physician gender could be a potential source of variation in prescribing chronic pain drugs. Therefore, this study aimed to determine whether there is a relationship between physician gender and the manner in which drugs used to treat chronic pain in older patients are prescribed.
Conclusion. Male and female GPs prescribe analgesics in a similar manner. However, male GPs prescribe more antineuropathic pain drugs, but fewer SySADOA.
Methods
Key Words. General Practitioner; Gender; Older Adults; Chronic Pain Drugs
The S.AGE (Sujets AGEs, older subjects) cohort [25] is an ongoing French study of noninstitutionalized patients
Study Design and Data Collection
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Lazkani et al. over 65-year old recruited by GPs all over France which aims to describe the real-life therapeutic care of older adults. This cohort (n = 3434) is composed of three subcohorts of patients suffering from either atrial fibrillation (AF; n = 1072), type 2 diabetes mellitus (T2DM; n = 983), or chronic pain (n = 1379). 260, 213, and 287 GPs were enrolled in the chronic pain, T2DM, and AF subcohorts, respectively. The recruitment of GPs was conducted by mail. The first mailing was sent to all 51,000 GPs working in private practice in France who were born after 1947 (to avoid potential study dropouts related to retirement during the planned 3-year follow up). All of the 760 GPs who accepted to participate were enrolled and then randomized into one of the three S.AGE subcohorts. The 260 GPs randomized in the chronic pain subcohort were asked to enroll between 3 and 10 patients, maintaining a ratio of 1:2 between patients aged 65 to 75 and patients over 75-year old. The clinical trial reference of this study is NCT01065909. GPs entered the patients’ medical data into an electronic case report form. All prescriptions were entered using the Anatomical Therapeutic Chemical Classification Code. A detailed study protocol was published prior to study initiation [25]. All the analyses for this study were performed on baseline data. Written and signed consent was obtained from all patients before they were enrolled in this study. The study was approved de Protection des Perby the Ethics Committee (Comite sonnes Ile de France XI) in January 2009 and by the French Drug Agency (ANSM) in February 2009. Study Population Two hundred and sixty GPs in the chronic pain study prospectively enrolled 1,379 patients aged 65 years or over and living in France, who were able to understand the goal of the study, registered with a social security scheme or an equivalent insurer, presenting pain lasting more than 3 months and requiring treatment, and who had signed the informed consent form for the study. Patients could not participate if they were residents of a nursing home at the time of inclusion, could not be followed after inclusion (planned move, homeless), or had a short life expectancy (less than 3 months). Patients were recruited between June 2009 and September 2011 and the follow-up of patients was planned for 3 years with visits every 6 months. Physicians were free to prescribe any drug at any dose in the context of this noninterventional study. For patients meeting the inclusion criteria, the following data were collected at baseline [26]: Sociodemographic data including gender, age, place of residence, educational level, socioprofessional category, and marital status. Characteristics of pain: type of pain (mechanical, inflammatory or neuropathic), evolution of pain, intensity (scored using auto and hetero visual analogue scales [VAS]). The VAS is a 10-point scale consisting of a horizontal line going from “no pain” to “worst possible pain” [27]. In the auto assessment, the 698
patient himself assessed the amount of pain he or she felt on the VAS line (0 to 10 points), whereas in the hetero assessment, the GP assessed the amount of pain experienced by the patient. The impact of pain on each of mood, sleep, and walking was separately assessed by the GP in this study by asking patients: “During the week before inclusion, could you please rate from 0 to 4 the impact of pain separately on your mood, sleep and walking?” An auto assessment scale (0 to 4 points) was used for this purpose with 0 indicating no impact of pain on each of the three items and four indicating extremely major impact. The impact of pain on each item was then divided into three categories: no impact [0], small impact [1,2], and major impact [3,4]. General clinical characteristics of patients: BMI (body mass index, kg/m2), smoking habits, alcohol intake. Physical function was assessed using the Activity of Daily Living scale (ADL scale)] initially described by Katz et al. [28] which includes six elements: feeding, bathing, dressing, going to toilet, transferring, and continence. Patients with a score of 6 are considered to be independent, while 0 indicates that the patient is totally dependent. A simplified 4-item Instrumental Activity of Daily Living scale was also used (simplified 4-item IADL scale [29]), which includes: ability to use telephone, mode of transportation, responsibility for own medications, and ability to handle finances. A score of 4 indicates that the patient is independent, while 0 indicates that the patient is dependent. The French-language version of this simplified 4-item IADL scale has been previously validated as a potent predictor of one-year incident dementia [29]. Cognitive function was assessed using the Mini Mental State Examination scale (MMSE [30]) which is a 30-item questionnaire, with a score of 0.20 which is an important factor in older adults) were considered as adjustment variables in multivariate analysis
(11.3% of the patients with male GPs versus 4.8% of the patients with female GPs, P = 0.004). Male GPs used antineuropathic pain drugs in 77% of their patients reporting neuropathic pain, whereas female GPs used these drugs in only 43% of the same patients. Conversely, female GPs prescribed significantly more SySA700
DOA compared with their male counterparts (18.8% of female GPs’ patients versus 10.2% of male GPs’ patients, P = 0.0003). After adjusting for confounding factors which were significant at a threshold of 20% (patient’s gender and
GP Gender and Chronic Pain Prescriptions
Table 3
Chronic pain drugs prescribed according to GP gender Patients Treated by Male GPs N (%)
Patients Treated by Female GPs N (%)
WHO Analgesics
Total N (%)
Step 1 analgesics Step 2 analgesics Step 3 analgesics
500 (36.3) 453 (32.9) 48 (3.5)
419 (35.8) 397 (33.9) 41 (3.5)
81 (38.9) 56 (26.9) 7 (3.4)
Other drugs used for chronic pain Antineuropathic pain drugs 6 analgesics SySADOA* 6 analgesics
142 (10.3) 158 (11.5)
132 (11.3) 119 (10.2)
10 (4.8) 39 (18.8)
P 0.39 0.06 0.92 0.004† 0.0003†
*Symptomatic slow-acting drugs for osteoarthritis. † Significant P value 0.05.
age, inflammatory and neuropathic pain, pain intensity according to hetero assessment scale, impact of pain on mood and sleep during the week before inclusion, simplified 4-item IADL, MMSE, GP’s age, years in practice, and number of enrolled patients per GP), in addition to GDS which is not significant at 20% but considered as an important confounding factor in older adults, male physicians were still more likely to prescribe antineuropathic pain drugs (OR 2.43, 95% CI 1.15– 5.14, P = 0.02), and less likely to prescribe SySADOA (OR 0.64, 95% CI 0.42–0.97, P = 0.03; Table 4). Additionally, we found no difference between male and female GPs in terms of the prescribed daily doses of analgesics and antineuropathic pain drugs at inclusion (data not shown). Discussion This multicenter observational study aimed to investigate how male and female GPs prescribe different classes of chronic pain medication for noninstitutionalized older adults in France. The results did not reveal any difference in prescriptions between male and female physicians for WHO step 1, 2, or 3 analgesics. This finding concurs with several studies conducted in the general population. Raftery et al. found no difference in analgesic pre-
scription in relation to the gender of the health care provider in the emergency department [34]. Burgess et al. also found that physician gender had no effect on the decision to prescribe a stronger type or higher dose of opioid analgesics in patients suffering from chronic lower back pain [35]. Moreover, Weiss et al. found no difference in the physician’s decision to prescribe analgesics for chronic back pain and kidney stone patients according to physician gender [36]. In a national randomized sampling of certified registered nurse anesthetists, Criste et al. found no difference between male and female providers for pain treatment strategies [37]. However, data from other studies contrast with our findings. Safdar et al. found that female physicians were more likely to prescribe analgesics than male physicians [38]. Veldhuijzen et al. found a significant difference between male and female physicians in their first line treatment choice for lower back pain, with more pharmacological agents prescribed by female physicians as a first line therapy compared with male physicians [39]. Shugarman et al. also reported that the frequency of opioid prescriptions was higher among female physicians [40]. Conversely, some studies found that male physicians prescribed more analgesics than females. In Australia,
Table 4 The relationship between GP gender and prescription of antineuropathic pain and symptomatic slow-acting drugs (SySADOA) at inclusion in univariate and multivariate analyses (male versus female, female as a reference group) Unadjusted OR (95%CI) Antineuropathic pain drugs 6 analgesics SySADOA* 6 analgesics
2.52 (1.29–4.87) 0.49 (0.34–0.72)
P 0.006† 0.0002†
Adjusted OR* (95% CI) 2.43 (1.15–5.14) 0.64 (0.42–0.97)
P 0.02† 0.03†
*Adjusted for gender and age of patient (65–75, 75), inflammatory and neuropathic pain, pain intensity according to the hetero assessment scale, impact of pain on mood and sleep during the week before inclusion by auto-assessment scale, simplified 4item IADL, MMSE, GDS, GP’s age, number of practice years, and the number of patients enrolled per GP. † Significant P value 0.05
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Lazkani et al. Harrison et al. examined the characteristics of GPs who prescribed opioids in general population, and found that male GPs prescribed significantly more opioids than females [9]. In Germany, Glaesmer et al. also reported that male physicians prescribed analgesics more frequently than their female counterparts [41]. In an observational study of 21 Dutch GPs, Feleus et al. found that male physician gender was associated with more medication prescription for nontraumatic complaints of the arm, neck, or shoulder in a general practice [42]. Larue et al. investigated the attitudes of French physicians toward morphine prescription for cancer pain, and found that female physicians tended to prescribe morphine less frequently than their male counterparts [43]. In summary, many studies have found no relation between physician gender and analgesic prescription, which is also the case in our study. Other studies observed more analgesic prescriptions made by female providers while still others reported opposite data. These discrepancies might arise from additional physician-based confounding factors, such as the provider’s ethnicity, specialty, training experience, and geographical location, as recently revealed [33]. Furthermore, the type of pain (acute vs chronic, cancer vs non cancer) and the location of pain frequently varied among these studies, which probably explain the difference in the results concerning the influence of physician gender. In this study, it is rather reassuring that physician gender did not appear to be a significant factor for analgesic drug prescription. Indeed, prescription of analgesic drugs must follow evidence-based guidelines [44,45] based on a codified clinical evaluation that should not be influenced by physician gender.
antineuropathic drug use is far less codified [50]. The fear of prescribing such drugs, known to produce side effects that can alter cognition and mobility in older patients [50,51], might proffer an explanation. Conversely, female physicians prescribed significantly more SySADOA than male GPs. SySADOA are regarded as health food supplements in many countries including the United Kingdom, United States, and Canada while in France they are still considered as drugs, albeit they are generally considered alternative medicine. SySADOA have been reported to be safe, with slow efficacy and a long carry-over effect once treatment is interrupted [52–54]. Several studies reported that female physicians were more likely than males to refer patients for complementary alternative medicine and they were also more likely to provide more preventive services, as well as preventive counseling [55–58]. This could be an explanation for prescribing more SySADOA by female GPs whose patients had a lesser degree of pain. To our knowledge, no data on SySADOA prescriptions according to physician gender are available. This study presents some limitations. First of all, the small number of female physicians may limit the scope of our results, and further studies are needed to confirm our findings. We were not able to take into account all the confounding factors that have been listed which may influence prescribing habits for chronic pain in older patients. For this reason, the observed differences between male and female prescribing practices might be related to unidentified confounding factors. Finally, our observations were obtained from French physicians whose prescribing habits may differ from those of other countries. Conclusion
Although the study patients treated by male physicians presented higher pain levels compared with patients treated by female GPs, they did not receive step 2 or 3 analgesics more frequently. This reluctance to prescribe opioids is probably related to the well-known risks of opioid treatment including fear of patient addiction and physical dependence, as well as potential side effects and an increased risk of death [46–49]. With regard to drugs used in addition to or instead of analgesics, antineuropathic pain drugs and SySADOA prescriptions differed between male and female physicians in the present study. Female physicians prescribed less antineuropathic pain drugs: among patients suffering from neuropathic pain, 43% of those treated by female physicians and 77% of those treated by male physicians received antineuropathic pain drugs. We have no clearcut explanation for this observation. Perhaps one of the possible explanations is that the lower pain scores reported by the patients seen by the female GPs resulted in them prescribing fewer antineuropathic pain drugs than the male GPs. As discussed above, whereas analgesic drug prescription is well defined, 702
Our results suggest no difference between male and female GPs in the prescription of analgesics (WHO steps 1, 2, and 3) to older adults suffering from chronic pain. However, some differences might exist in prescribing behaviors for antineuropathic pain drugs and SySADOA. Our results need to be confirmed in other pharmacoepidemiologic studies performed in different countries where prescribing practices might differ.
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