Drugs Aging (2014) 31:453–459 DOI 10.1007/s40266-014-0169-1
SHORT COMMUNICATION
Prescription of Addictive and Non-Addictive Drugs to Home-Dwelling Elderly Inger Cathrine Kann • Christofer Lundqvist Hilde Lura˚s
•
Published online: 20 May 2014 Springer International Publishing Switzerland 2014
Abstract Background Complex medical conditions are frequent among seniors, and their medical treatment represents a challenge. Older patients have a high rate of consumption of prescription drugs, greater risks of medication interactions, and a higher likelihood of side effects. Many common drugs used by the elderly also have addictive potential. Prescription patterns involving general practitioners (GPs) are not sufficiently known. Objective Our objective was to examine the regular GP role in the prescription of addictive and non-addictive drugs to home-dwelling older people in Norway. Design The study was designed as a panel data study. Setting Data on all prescription drugs dispensed at pharmacies to patients 70 years and older from the Norwegian Prescription Database were merged with data on GPs and GPs’ patient lists from the Regular General Practitioner Database. The dataset included 624,308 patients and 4,520 GPs in the period from 2004 to 2007.
I. C. Kann C. Lundqvist (&) H. Lura˚s Health Services Research Centre (HØKH), Akershus University Hospital, PO Box 95, 1478 Lørenskog, Norway e-mail: [email protected] I. C. Kann e-mail: [email protected] H. Lura˚s e-mail: [email protected] C. Lundqvist H. Lura˚s Institute of Clinical Medicine, University of Oslo, Campus Ahus, Oslo, Norway C. Lundqvist Department of Neurology, Akershus University Hospital, Lørenskog, Norway
Outcome measures Outcome measures included quantities of addictive and non-addictive drugs prescribed and dispensed per patient by the regular GP, other GPs, non-GP specialists, and hospital doctors; the number of prescribers per patient; and time trend over the observation period. Results On average, 319 defined daily doses of medication were prescribed per quarter to an older patient, 6 % of which were classified as possibly addictive medications. Of all drugs, 72 % were prescribed by the patients’ regular GP, 77 % of addictives and 71 % of non-addictives. Drug quantities prescribed increased with multiple prescribers and did so to a greater extent for addictives than for nonaddictives. Time trends show an increasing number of prescribers and increasing drug quantities over the observation period. Conclusion The regular GP prescribes the major portion of non-addictive and, especially, addictive medications to older patients and thus holds a key role in the coordination of prescriptions to this group. Focusing on the role of the GP is important in view of the increasing time trends.
1 Introduction Older people are the population group in Norway with the highest consumption of prescription drugs [1]. Complex medical conditions are frequent among old people, and their medical treatment presents many challenges. With increasing age, the human body undergoes several changes that can influence the way drugs affect the body. Also, as Milton et al. [2] state in their review, ‘‘Older people are more sensitive to the effects of some drugs, especially those that act on the central nervous system.’’ Thus, both the increased morbidity and the natural changes in the human body with age make it more likely for older patients
454
to experience adverse drug reactions [3–5]. Several reports suggest the prevalence of hospital admissions associated with adverse drug reactions to be as high as 11 % in this group [6–8]. Between 19 and 40 % of older patients are shown to receive medication suggested to be inappropriate [9–13]. Chronic pain, insomnia, and anxiety are common problems in this population, and drugs with suggested addictive potential are frequently prescribed to the elderly [14]. Many addictive drugs are listed as high-risk drugs for elderly patients according to Norwegian criteria [13]. In addition, the misuse and abuse of prescription drugs with addictive potential has become a growing problem among older people [15]. For these reasons, the prescription of addictives to this population deserves further attention and awareness. However, this is a challenge as it is well known that addicted patients may not wish to disclose full information about their medication usage to all prescribers. Specific characteristics associated with medication addiction in the elderly may make the detection of addiction-like behaviors in this population even more difficult [14, 15]. Due to these complicating factors, the coordination of drug therapies for older people may represent a considerable challenge. A Canadian study [16] reported that 70 % of the senior population had more than one prescribing physician, while 5 % had more than five. In a study from Denmark of 75 year olds living in their own homes, 31 % received drugs from two or more physicians, and 25 % of these medications were used without the knowledge of the patient’s regular general practitioner (GP) [4]. Norway has about 18,000 active prescribing physicians, about 4,000 of whom at any one time are GPs. The listpatient system of 2001 formalized the relationship between GPs and patients. One important aim was to increase the medical quality in primary care by giving the GP the responsibility for coordinating the medical treatment [17]. The GP has a unique ‘spider-in-the-web’ position in relation to most elderly patients and has the overall task of providing a more holistic, organ-integrative approach. The objective of the present study was to examine the role of the regular GP in the prescription of addictive and non-addictive drugs to home-dwelling seniors in Norway.
I. C. Kann et al.
Practitioner Database (RPD). The dataset consisted of 41 million prescription observations and 7,958,068 patient observations, and included 624,308 patients and 4,520 GPs during the years 2004–2007. 2.2 Data Acquisition Data from the NorPD is based on electronic registration of every prescription collected at pharmacies in Norway. NorPDis a state-run registry, and all pharmacies are compelled to register all their prescriptions as they are dispensed. We were given access to the total registry covering the years 2004–2007 for all patients over 70 years of age in Norway. Patients and prescribers are given a unique code in the registry, which means that all prescriptions by the same prescriber as well as all prescriptions to one single patient may be followed over time. Based on the NorPD data alone, it is not possible to identify whether or not the prescriber is the patient’s regular GP. We have therefore merged the prescription data from NorPD with the data of registered GPs from the RPD database in order to be able to identify for each prescription if the prescriber was the patient’s regular GP. For each of the included patients, the amounts of medication respectively prescribed by the regular GP, by other GPs, and by non-GP specialists and hospital doctors were calculated separately. The variables of interest were aggregated over quarters. Amounts were measured in units representing the average daily maintenance dose for a drug used for its main indication in adults (defined daily doses [DDDs]), according to the World Health Organization (WHO) Collaborating Centre for Drug Statistics Methodology [18]. Drugs defined as addictive are listed in Table 1. 2.3 Outcomes Main outcomes were as follows: •
Quantities of addictive and non-addictive medication prescribed and dispensed per patient in DDDs, by the regular GP, other GPs, non-GP specialists, and hospital doctors. Secondary outcomes were as follows:
2 Methods
• •
2.1 Setting and Participants Data from the Norwegian Prescription Database (NorPD) of all prescription drugs dispensed at pharmacies to homedwelling patients over 70 years of age was merged with data on GPs and their patient lists from the Regular General
•
Number of prescribers per patient. Percentage of the population that receives prescriptions from at least three or at least five physicians within a quarter. Percentage of the population that receives at least 1, 30, or 90 DDD of addictive drugs within a quarter.
The secondary outcomes relate to the literature where many prescribers and the use of addictive drugs are
Prescription of Addictive and Non-Addictive Drugs to the Elderly
455
Table 1 List of drugs here defined as ‘addictive drugs’ based on medications with marketing authorization in Norway and classified as narcotics by the Norwegian Medicines Agency ordered according to group in the Anatomical Therapeutic Chemical Classification System [18] N01 Anaesthetics
N02 Analgesics
N01AH01: Fentanyl
N02A Opioids:
N03AA02: Phenobarbital
N05BA01: Diazepam
N01AH02: Alfentanil
N02AA01: Morphine
N03AE01: Clonazepam
N05BA04: Oxazepam
N01AH03: Sufentanil N01AH06: Remifentanil
N02AA03: Hydromorphine N02AA05: Oxycodone
N01AX03: Ketamine
N03 Antiepileptics
N05B Anxiolytics/sedative/stimulants
N05BA12: Alprazolam N05BE01: Buspirone
N02AA59: Codeine
N05CD02: Nitrazepam
N02AB01: Ketobemidone
N05CD03: Flunitrazepam
N02AB02: Pethidine
N05CD08: Midazolam
N02AB03: Fentanyl
N05CF01: Zopiclone
N02AC54: Dextropropoxyphene
N05CF02: Zolpidem
N02AE01: Buprenorphine
N05CM02: Chlomethiazole
N02AG01: Morphine-scopolamine
N06BA01: Amphetamine N06BA04: Methylphenidate
N02AG02: Ketobemidone and spasmolytics
N07BC01: Buprenorphine N07BC02: Methadone
N02AX02: Tramadol N02CA72: Ergotamine
considered to pose a risk in medication of people aged over 70 years [19, 20]. In the literature, there exists no commonly agreed threshold defining what level may be ‘too high’ or ‘too many’. The limits of at least 30 and at least 90 DDD and the threshold of three and five prescribers quarterly were chosen arbitrarily.
data are anonymous registry data, and cannot be traced to human subjects.1
3 Results 3.1 Prescribed Quantities
2.4 Statistics and Analytical Procedures All Norwegians aged 70 years and older who were registered with a GP as of 1 January 2004 were included. New individuals entered the dataset from the quarter in which they reached 70 years of age, and individuals exited the dataset when they died or were no longer registered with a GP. On average, each individual was observed for 12.7 quarters of the total observation period of 16 quarters. The reported means represent the average level over the observation period. The material covers the whole population, and therefore confidence intervals (CIs) or p values are not reported. All analyses were conducted in STATA version 10 (StataCorp LP, College Station, TX, USA). 2.5 Ethics This study was reviewed by, and received all necessary approvals from, The Norwegian Directorate for Health and Social Affairs and The Norwegian Data Inspectorate. The
Quantities of addictive and non-addictive drugs prescribed by different physician groups (regular GPs, other GPs, and non-GP and hospital specialists) are shown in Table 2, demonstrating an increase in the prescription of both addictives and non-addictives over the study period. The average quantity of drugs prescribed and dispensed per list patient over the 4-year period was 319 DDDs per quarter; 6.0 % of prescribed drugs were classified as addictive. In the analyses for each prescriber group, the patient’s regular GP prescribed 6.3 % addictives, other GPs 6.6 %, and non-GPs and hospital specialists 4.2 %. The patient’s regular GP prescribed 72 % of all medications; other GPs were responsible for 8 %, and non-GP specialists and hospital doctors accounted for 20 %. The regular GPs prescribed a larger proportion of addictives than of non-addictives (77 vs. 71 %, 95 % CI 0.7699–0.7701 and 0.7099–0.7104, Fig. 1). The prevalence of having prescriptions for addictive drugs, and having at least 30 and at least 90 DDD addictives 1
Since this is a meta-study using non-personally identifiable data, the approvals are sufficient according to Norwegian regulations.
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Table 2 Average amount of drugs prescribed per patient by different physician groups and number of prescribers per patient Variable
2004
2005
2006
2007
Mean 2004–2007
% change from 2004 to 2007
From regular GP
196.3
209.1
219.2
232.5
214.3
15.5
From other GPs
22.7
22.9
24.5
25.4
23.9
10.7
From non-GP specialists and hospital doctors
57.0
61.0
63.7
65.3
61.7
12.7
Total
276.0
292.9
307.3
323.1
299.8
14.6
From regular GP From other GPs
13.7 1.7
14.4 1.7
14.8 1.8
15.2 1.8
14.5 1.7
9.7 8.2
From non-GP specialists and hospital doctors
2.5
2.8
2.8
2.8
2.7
9.7
Total
17.9
18.9
19.4
19.8
19.0
9.6
1.2
7.6
Non-addictive drugs, number of DDDs
Addictive drugs, number of DDDs
Number of prescribers Average number of prescribers quarterly
1.2
1.2
1.2
1.3
Patient observationsa (N)
1,990,590
1,985,899
1,991,429
1,990,150
DDD defined daily doses, GP general practitioner a
Total number of patient observations over the period 2004–2007 = 7,958,068
Fig. 1 Proportion of medications prescribed to patients by their regular GP, other GPs, non-GP specialists, and hospital doctors: (a) addictive drugs; (b) nonaddictive drugs. GP general practitioner
a
b
8%
9% 14%
71%
77%
Regular GP Other GPs Non−GP specialists and hospital doctors
quarterly, is shown in Table 3. This prevalence also increased over time. The percentage increase was larger for the higher cut-offs (30 and 90 DDDs per quarter) than for just the presence of addictive drugs. For the higher cut-offs, the GPs prescribed a larger proportion of the drugs. 3.2 Number of Prescribers The average number of prescribers per patient was 1.2 per quarter, and the average number increased over the study
21%
Regular GP Other GPs Non−GP specialists and hospital doctors
period (Table 2). The quantities of drugs prescribed increased with the number of prescribers (Fig. 2), and this increase was more notable for addictive drugs than for non-addictives (Fig. 2). A patient with more than five prescribing physicians received 295 % more DDDs of non-addictive drugs and 530 % more DDDs of addictive drugs than patients with only one prescribing physician. Respectively, 9.7 and 1.2 % of patients had at least three or at least five prescribers in the same quarter (Table 3). The prevalence of multiple prescribers increased over the study period as a whole.
Prescription of Addictive and Non-Addictive Drugs to the Elderly
457
Table 3 Percentage of the population with at least three and at least five prescribers quarterly, and percentage of patients with at least 1, 30, or 90 defined daily doses of addictive drugs Variable
2004 (%)
2005 (%)
2006 (%)
2007 (%)
Mean2004–2007 (%)
% change from 2004 to 2007
At least three prescribers quarterly
8.9
9.5
10.0
10.4
9.7
16.9
At least five prescribers quarterly
0.8
0.9
1.0
1.0
0.9
26.7
Number of prescribers
Addictive drugs At least 1 DDD quarterly
25.8
24.9
25.8
26.1
26.3
5.8
GP alone at least 1 DDD quarterly
20.5
19.6
20.5
20.6
21.0
5.6
At least 30 DDD quarterly GP alone at least 30 DDD quarterly
15.8 12.4
16.6 13.0
17.0 13.3
17.3 13.6
16.7 13.1
9.6 10.0
At least 90 DDD quarterly
8.1
8.7
9.0
9.3
8.8
15.3
GP alone at least 90 DDD quarterly
6.2
6.7
7.0
7.2
6.8
15.8
Patient observationsa,b (N)
1,990,590
1,985,899
1,991,429
1,990,150
DDD defined daily doses, GP general practitioner a
Each patient observed once each quarter
b
Total number of patient observations over the period 2004–2007 = 7,958,068
a
b
Fig. 2 Average amount of drugs per patient (expressed as DDDs) by number of prescribing physicians: (a) addictive drugs; (b) nonaddictive drugs. DDD defined daily dose, GP general practitioner
4 Discussion Our main results show that regular GPs prescribed the majority of the medication to their registered patients. The proportion prescribed by the patients’ regular GP was higher for addictive than for non-addictive drugs. The average quantities of prescribed drugs per patient increased with increasing numbers of prescribers, and did so to a greater extent with addictive than with non-addictive drugs. An increasing trend in the amount of drugs and the number of prescribers per patient was seen over the observation period.
The data explored in this study are extracted from a national registry of all prescriptions made to the total population of home-dwelling seniors over 70 years old in Norway, which is a considerable strength. Since compliance with prescriptions is a well known problem [21], it is important to note that the dataset includes the prescribed amount dispensed at pharmacies, not just the total amount prescribed. GPs in Norway are not obliged to report to the health authorities when patients move into an institution and receive drugs directly from the institution, which implies that the calculated amounts of drugs may be slightly
458
underestimated in our analyses. Likewise, the patients’ use of over-the-counter drugs is not registered in the database [22]. However, these underestimations only serve to strengthen the significance of our results. Since we do not have any detailed medical information about individual cases included in the study, the definition of medications that we have classified as ‘addictive’ may be criticised. Addiction, in the sense of substance dependence, is a clinical definition that is based not only on the pharmacological characteristics of the substance in question but also on clinical and behavioral patient characteristics and intake pattern over time. The pharmacological definition used here indicates a risk situation especially for older patients, but does not mean that the patient is addicted. The use of the higher cut-off levels such as more than 30 or more than 90 DDDs per quarter may complement the whole picture, which we suggest is alarming. It should be noted that medication listed as addictive here is also listed as a possible inappropriate medication for the elderly based on both its addictive potential and its side effects [13]. The appropriateness of medication should preferably be evaluated in relation to the diagnosis of the patients. This cannot be done here since we lack medical data; however, the high and increasing use of potentially risky medication, including addictives, certainly suggests that further studies with more such clinical data are required. We thus suggest that this category of drugs merits special attention in the medication of older patients. Use of such medication may be necessary for older people (e.g., for treatment of severe pain), but should be carefully evaluated and monitored, preferably by the main prescriber (i.e., the patient’s regular GP). Further clinical studies on prescription medication, addiction, and dependence among older people are necessary to complete the picture. Based on another study using data from NorPD, Kjosavik et al. [22] found that 80 % of psychotropic drugs in the Norwegian population are prescribed by a GP. However, this analysis did not distinguish between prescriptions from the patients’ regular GP and prescriptions from other GPs. Hence, the results are similar to our findings. We found that 30 % of the patients had two or more prescribers, which is in accordance with a study from Denmark that has a similar list-patient system [4]. It is often a general assumption that a major part of the increasing rates of prescription of potent medication to seniors is caused by further involvement of different specialists. We cannot completely refute this, as GP prescription may simply serve to continue prescriptions started by hospital specialists. However, our data clearly show that GPs have a major responsibility of which they need to be aware. Observationally, specialists in geriatrics tend to be
I. C. Kann et al.
among the few specialities that reduce the number of medications for older patients, and further training in geriatrics is one possible intervention that may hold promise. However, in the present study, we had very few prescribers who were specialists in geriatric medicine so we are unable to examine this issue in detail. The proportion of GPs and other specialists, as well as their respective roles, may also vary between healthcare systems, which may need to be considered in comparisons between countries. Empirical evidence indicates that the risk of adverse drug reactions and compliance errors increases with the amount of drugs taken [3, 10, 13, 19, 21]. Hence, our findings of high levels and steadily increasing time-trends of average drug amounts and number of prescribers is a serious concern. When the prescribed amounts were divided into amounts prescribed by the patients’ GPs and those prescribed by other physicians, we observed different patterns for addictive and non-addictive drugs. For both prescriptions by other physicians and prescriptions by the regular GP, a greater increase in addictive drugs was seen with increasing numbers of prescribers. For non-addictive drugs, the quantity prescribed by the regular GP remained almost constant despite an increasing number of other prescribers (Fig. 2). Whether this indicates elements of ‘doctor-shopping’ for addictive drugs, the search for less restrictive doctors by patients with high usages of addictive drugs, or a higher tendency by the GP to continue prescriptions of potent medications introduced by other specialists, is impossible to ascertain.
5 Conclusion The results indicate that the Norwegian list-patient system, one of the aims of which is that the GP should act as a coordinator in drug prescription to the elderly population, does not impede an increasing trend toward larger amounts of drugs and more prescribers per patient, which are traits associated with higher risks for this group. This seems particularly alarming in the increase of addictive medications, which are suggested to be problem medications for older people. The appropriateness for the prescription of such medication to the elderly needs to be further studied in relation to the relevant health issues and should be considered carefully for individual patients. The GP is responsible for the largest proportions of both addictive and non-addictive prescriptions to older patients and also for the greatest increase over time in prescribed quantities. This implies that attempts to improve coordination further must involve the GPs. How such interventions should be performed to be most effective requires further study.
Prescription of Addictive and Non-Addictive Drugs to the Elderly Acknowledgments The financial support of the Norwegian Research Council is gratefully acknowledged. The South-East Norway Regional health authority is gratefully acknowledged for support to CL. Thanks to the Norwegian Prescription Database (NorPD), Norwegian Social Science Data (NSD), The Norwegian Labour and Welfare Administration (NAV), and Statistics Norway (SSB) for providing data, thus making the analysis possible. These sources are not responsible for data analysis or interpretations. The classification of drugs was performed with the help of pharmacist Vigdis Solberg at the hospital pharmacy enterprise: ‘Sykehusapotekene HF’. The authors affirm that there are no conflicts of interest.
References 1. Sakshaug S, Strøm H, Berg CL, et al. (Ed: Ronning M) Legemiddelforbruk i Norge 2004-2008. The Norwegian Institute of Public Health, 2008. http://www.fhi.no/dokumenter/542314a014. pdf. 2. Milton JC, Hill-Smith I, Jackson SHD. Prescribing for older people. BMJ. 2008;336(7644):606–9. 3. Straand J, Fetveit A, Rognstad S, et al. A cluster-randomized educational intervention to reduce inappropriate prescription patterns for elderly patients in general practice—The Prescription Peer Academic Detailing (Rx-PAD) study [NCT00281450]. BMC Health Serv Res. 2006;6:72. 4. Barat I, Andreasen F, Damsgaard EMS. The consumption of drugs by 75-year-old individuals living in their own homes. Eur J Clin Pharmacol. 2000;56(6–7):501–9. 5. Ziere G, Dieleman JP, Van der Cammen TJM, et al. Selective serotonin reuptake inhibiting antidepressants are associated with an increased risk of nonvertebral fractures. J Clin Psychopharmacol. 2008;28(4):411–7. 6. Kongkaew C, Noyce PR, Ashcroft DM. Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies. Ann Pharmacother. 2008;42(7):1017–25. 7. Einarson TR. Drug-related hospital admissions. Ann Pharmacother. 1993;27(7–8):832–40. 8. Hallas J. Drug related hospital admissions in subspecialities of internal medicine. Dan Med Bull. 1996;43(2):141–55.
459 9. Bregnhoj L, Thirstrup S, Kristensen MB, et al. Prevalence of inappropriate prescribing in primary care. Pharm World Sci. 2007;29(3):109–15. 10. Brekke M, Rognstad S, Straand J, et al. Pharmacologically inappropriate prescriptions for elderly patients in general practice: how common? Scand J Prim Health Care. 2008;26(2):80–5. 11. Fick DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults—results of a US consensus panel of experts. Arch Intern Med. 2003;163(22):2716–24. 12. Liu GG, Christensen DB. The continuing challenge of inappropriate prescribing in the elderly: an update of the evidence. J Am Pharm Assoc (Wash). 2002;42(6):847–57. 13. Rognstad S, Brekke M, Fetveit A, et al. The Norwegian General Practice (NORGEP) criteria for assessing potentially inappropriate prescriptions to elderly patients. Scand J Prim Health Care. 2009;27(3):153–9. 14. Culberson JW, Ziska M. Prescription drug misuse/abuse in the elderly. Geriatrics. 2008;63(9):22–31. 15. Simoni-Wastila L, Yang HK. Psychoactive drug abuse in older adults. Am J Geriatr Pharmacother. 2006;4(4):380–94. 16. Tamblyn R. Medication use in the seniors population: optimization of physician prescribing as a means of preventing drugrelated illness. Can J Aging. 1997;16:147–61. 17. Sandvik H. Evaluering av fastlegeordningen 2001—2005 [Summary in English]. Research Council of Norway 2005. 18. WHO Collaborating Centre for Drug Statistics Methodology. Department of Pharmacoepidemiology at the Norwegian Institute of Public Health 2010. http://www.whocc.no/atc_ddd_ methodology/who_collaborating_centre/. 19. Stewart RB, Cooper JW. Polypharmacy in the aged—practical solutions. Drugs Aging. 1994;4(6):449–61. 20. Green JL, Hawley JN, Rask KJ. Is the number of prescribing physicians an independent risk factor for adverse drug events in an elderly outpatient population? Am J Geriatr Pharmacother. 2007;5(1):31–9. 21. Hemminki E, Heikkila J. Elderly peoples compliance with prescriptions, and quality of medication. Scand J Soc Med. 1975;3(2):87–92. 22. Kjosavik SR, Ruths S, Hunskaar S. Psychotropic drug use in the Norwegian general population in 2005: data from the Norwegian Prescription Database. Pharmacoepidemiol Drug Saf. 2009;18(7):572–8.
SHORT COMMUNICATION
Prescription of Addictive and Non-Addictive Drugs to Home-Dwelling Elderly Inger Cathrine Kann • Christofer Lundqvist Hilde Lura˚s
•
Published online: 20 May 2014 Springer International Publishing Switzerland 2014
Abstract Background Complex medical conditions are frequent among seniors, and their medical treatment represents a challenge. Older patients have a high rate of consumption of prescription drugs, greater risks of medication interactions, and a higher likelihood of side effects. Many common drugs used by the elderly also have addictive potential. Prescription patterns involving general practitioners (GPs) are not sufficiently known. Objective Our objective was to examine the regular GP role in the prescription of addictive and non-addictive drugs to home-dwelling older people in Norway. Design The study was designed as a panel data study. Setting Data on all prescription drugs dispensed at pharmacies to patients 70 years and older from the Norwegian Prescription Database were merged with data on GPs and GPs’ patient lists from the Regular General Practitioner Database. The dataset included 624,308 patients and 4,520 GPs in the period from 2004 to 2007.
I. C. Kann C. Lundqvist (&) H. Lura˚s Health Services Research Centre (HØKH), Akershus University Hospital, PO Box 95, 1478 Lørenskog, Norway e-mail: [email protected] I. C. Kann e-mail: [email protected] H. Lura˚s e-mail: [email protected] C. Lundqvist H. Lura˚s Institute of Clinical Medicine, University of Oslo, Campus Ahus, Oslo, Norway C. Lundqvist Department of Neurology, Akershus University Hospital, Lørenskog, Norway
Outcome measures Outcome measures included quantities of addictive and non-addictive drugs prescribed and dispensed per patient by the regular GP, other GPs, non-GP specialists, and hospital doctors; the number of prescribers per patient; and time trend over the observation period. Results On average, 319 defined daily doses of medication were prescribed per quarter to an older patient, 6 % of which were classified as possibly addictive medications. Of all drugs, 72 % were prescribed by the patients’ regular GP, 77 % of addictives and 71 % of non-addictives. Drug quantities prescribed increased with multiple prescribers and did so to a greater extent for addictives than for nonaddictives. Time trends show an increasing number of prescribers and increasing drug quantities over the observation period. Conclusion The regular GP prescribes the major portion of non-addictive and, especially, addictive medications to older patients and thus holds a key role in the coordination of prescriptions to this group. Focusing on the role of the GP is important in view of the increasing time trends.
1 Introduction Older people are the population group in Norway with the highest consumption of prescription drugs [1]. Complex medical conditions are frequent among old people, and their medical treatment presents many challenges. With increasing age, the human body undergoes several changes that can influence the way drugs affect the body. Also, as Milton et al. [2] state in their review, ‘‘Older people are more sensitive to the effects of some drugs, especially those that act on the central nervous system.’’ Thus, both the increased morbidity and the natural changes in the human body with age make it more likely for older patients
454
to experience adverse drug reactions [3–5]. Several reports suggest the prevalence of hospital admissions associated with adverse drug reactions to be as high as 11 % in this group [6–8]. Between 19 and 40 % of older patients are shown to receive medication suggested to be inappropriate [9–13]. Chronic pain, insomnia, and anxiety are common problems in this population, and drugs with suggested addictive potential are frequently prescribed to the elderly [14]. Many addictive drugs are listed as high-risk drugs for elderly patients according to Norwegian criteria [13]. In addition, the misuse and abuse of prescription drugs with addictive potential has become a growing problem among older people [15]. For these reasons, the prescription of addictives to this population deserves further attention and awareness. However, this is a challenge as it is well known that addicted patients may not wish to disclose full information about their medication usage to all prescribers. Specific characteristics associated with medication addiction in the elderly may make the detection of addiction-like behaviors in this population even more difficult [14, 15]. Due to these complicating factors, the coordination of drug therapies for older people may represent a considerable challenge. A Canadian study [16] reported that 70 % of the senior population had more than one prescribing physician, while 5 % had more than five. In a study from Denmark of 75 year olds living in their own homes, 31 % received drugs from two or more physicians, and 25 % of these medications were used without the knowledge of the patient’s regular general practitioner (GP) [4]. Norway has about 18,000 active prescribing physicians, about 4,000 of whom at any one time are GPs. The listpatient system of 2001 formalized the relationship between GPs and patients. One important aim was to increase the medical quality in primary care by giving the GP the responsibility for coordinating the medical treatment [17]. The GP has a unique ‘spider-in-the-web’ position in relation to most elderly patients and has the overall task of providing a more holistic, organ-integrative approach. The objective of the present study was to examine the role of the regular GP in the prescription of addictive and non-addictive drugs to home-dwelling seniors in Norway.
I. C. Kann et al.
Practitioner Database (RPD). The dataset consisted of 41 million prescription observations and 7,958,068 patient observations, and included 624,308 patients and 4,520 GPs during the years 2004–2007. 2.2 Data Acquisition Data from the NorPD is based on electronic registration of every prescription collected at pharmacies in Norway. NorPDis a state-run registry, and all pharmacies are compelled to register all their prescriptions as they are dispensed. We were given access to the total registry covering the years 2004–2007 for all patients over 70 years of age in Norway. Patients and prescribers are given a unique code in the registry, which means that all prescriptions by the same prescriber as well as all prescriptions to one single patient may be followed over time. Based on the NorPD data alone, it is not possible to identify whether or not the prescriber is the patient’s regular GP. We have therefore merged the prescription data from NorPD with the data of registered GPs from the RPD database in order to be able to identify for each prescription if the prescriber was the patient’s regular GP. For each of the included patients, the amounts of medication respectively prescribed by the regular GP, by other GPs, and by non-GP specialists and hospital doctors were calculated separately. The variables of interest were aggregated over quarters. Amounts were measured in units representing the average daily maintenance dose for a drug used for its main indication in adults (defined daily doses [DDDs]), according to the World Health Organization (WHO) Collaborating Centre for Drug Statistics Methodology [18]. Drugs defined as addictive are listed in Table 1. 2.3 Outcomes Main outcomes were as follows: •
Quantities of addictive and non-addictive medication prescribed and dispensed per patient in DDDs, by the regular GP, other GPs, non-GP specialists, and hospital doctors. Secondary outcomes were as follows:
2 Methods
• •
2.1 Setting and Participants Data from the Norwegian Prescription Database (NorPD) of all prescription drugs dispensed at pharmacies to homedwelling patients over 70 years of age was merged with data on GPs and their patient lists from the Regular General
•
Number of prescribers per patient. Percentage of the population that receives prescriptions from at least three or at least five physicians within a quarter. Percentage of the population that receives at least 1, 30, or 90 DDD of addictive drugs within a quarter.
The secondary outcomes relate to the literature where many prescribers and the use of addictive drugs are
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Table 1 List of drugs here defined as ‘addictive drugs’ based on medications with marketing authorization in Norway and classified as narcotics by the Norwegian Medicines Agency ordered according to group in the Anatomical Therapeutic Chemical Classification System [18] N01 Anaesthetics
N02 Analgesics
N01AH01: Fentanyl
N02A Opioids:
N03AA02: Phenobarbital
N05BA01: Diazepam
N01AH02: Alfentanil
N02AA01: Morphine
N03AE01: Clonazepam
N05BA04: Oxazepam
N01AH03: Sufentanil N01AH06: Remifentanil
N02AA03: Hydromorphine N02AA05: Oxycodone
N01AX03: Ketamine
N03 Antiepileptics
N05B Anxiolytics/sedative/stimulants
N05BA12: Alprazolam N05BE01: Buspirone
N02AA59: Codeine
N05CD02: Nitrazepam
N02AB01: Ketobemidone
N05CD03: Flunitrazepam
N02AB02: Pethidine
N05CD08: Midazolam
N02AB03: Fentanyl
N05CF01: Zopiclone
N02AC54: Dextropropoxyphene
N05CF02: Zolpidem
N02AE01: Buprenorphine
N05CM02: Chlomethiazole
N02AG01: Morphine-scopolamine
N06BA01: Amphetamine N06BA04: Methylphenidate
N02AG02: Ketobemidone and spasmolytics
N07BC01: Buprenorphine N07BC02: Methadone
N02AX02: Tramadol N02CA72: Ergotamine
considered to pose a risk in medication of people aged over 70 years [19, 20]. In the literature, there exists no commonly agreed threshold defining what level may be ‘too high’ or ‘too many’. The limits of at least 30 and at least 90 DDD and the threshold of three and five prescribers quarterly were chosen arbitrarily.
data are anonymous registry data, and cannot be traced to human subjects.1
3 Results 3.1 Prescribed Quantities
2.4 Statistics and Analytical Procedures All Norwegians aged 70 years and older who were registered with a GP as of 1 January 2004 were included. New individuals entered the dataset from the quarter in which they reached 70 years of age, and individuals exited the dataset when they died or were no longer registered with a GP. On average, each individual was observed for 12.7 quarters of the total observation period of 16 quarters. The reported means represent the average level over the observation period. The material covers the whole population, and therefore confidence intervals (CIs) or p values are not reported. All analyses were conducted in STATA version 10 (StataCorp LP, College Station, TX, USA). 2.5 Ethics This study was reviewed by, and received all necessary approvals from, The Norwegian Directorate for Health and Social Affairs and The Norwegian Data Inspectorate. The
Quantities of addictive and non-addictive drugs prescribed by different physician groups (regular GPs, other GPs, and non-GP and hospital specialists) are shown in Table 2, demonstrating an increase in the prescription of both addictives and non-addictives over the study period. The average quantity of drugs prescribed and dispensed per list patient over the 4-year period was 319 DDDs per quarter; 6.0 % of prescribed drugs were classified as addictive. In the analyses for each prescriber group, the patient’s regular GP prescribed 6.3 % addictives, other GPs 6.6 %, and non-GPs and hospital specialists 4.2 %. The patient’s regular GP prescribed 72 % of all medications; other GPs were responsible for 8 %, and non-GP specialists and hospital doctors accounted for 20 %. The regular GPs prescribed a larger proportion of addictives than of non-addictives (77 vs. 71 %, 95 % CI 0.7699–0.7701 and 0.7099–0.7104, Fig. 1). The prevalence of having prescriptions for addictive drugs, and having at least 30 and at least 90 DDD addictives 1
Since this is a meta-study using non-personally identifiable data, the approvals are sufficient according to Norwegian regulations.
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Table 2 Average amount of drugs prescribed per patient by different physician groups and number of prescribers per patient Variable
2004
2005
2006
2007
Mean 2004–2007
% change from 2004 to 2007
From regular GP
196.3
209.1
219.2
232.5
214.3
15.5
From other GPs
22.7
22.9
24.5
25.4
23.9
10.7
From non-GP specialists and hospital doctors
57.0
61.0
63.7
65.3
61.7
12.7
Total
276.0
292.9
307.3
323.1
299.8
14.6
From regular GP From other GPs
13.7 1.7
14.4 1.7
14.8 1.8
15.2 1.8
14.5 1.7
9.7 8.2
From non-GP specialists and hospital doctors
2.5
2.8
2.8
2.8
2.7
9.7
Total
17.9
18.9
19.4
19.8
19.0
9.6
1.2
7.6
Non-addictive drugs, number of DDDs
Addictive drugs, number of DDDs
Number of prescribers Average number of prescribers quarterly
1.2
1.2
1.2
1.3
Patient observationsa (N)
1,990,590
1,985,899
1,991,429
1,990,150
DDD defined daily doses, GP general practitioner a
Total number of patient observations over the period 2004–2007 = 7,958,068
Fig. 1 Proportion of medications prescribed to patients by their regular GP, other GPs, non-GP specialists, and hospital doctors: (a) addictive drugs; (b) nonaddictive drugs. GP general practitioner
a
b
8%
9% 14%
71%
77%
Regular GP Other GPs Non−GP specialists and hospital doctors
quarterly, is shown in Table 3. This prevalence also increased over time. The percentage increase was larger for the higher cut-offs (30 and 90 DDDs per quarter) than for just the presence of addictive drugs. For the higher cut-offs, the GPs prescribed a larger proportion of the drugs. 3.2 Number of Prescribers The average number of prescribers per patient was 1.2 per quarter, and the average number increased over the study
21%
Regular GP Other GPs Non−GP specialists and hospital doctors
period (Table 2). The quantities of drugs prescribed increased with the number of prescribers (Fig. 2), and this increase was more notable for addictive drugs than for non-addictives (Fig. 2). A patient with more than five prescribing physicians received 295 % more DDDs of non-addictive drugs and 530 % more DDDs of addictive drugs than patients with only one prescribing physician. Respectively, 9.7 and 1.2 % of patients had at least three or at least five prescribers in the same quarter (Table 3). The prevalence of multiple prescribers increased over the study period as a whole.
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457
Table 3 Percentage of the population with at least three and at least five prescribers quarterly, and percentage of patients with at least 1, 30, or 90 defined daily doses of addictive drugs Variable
2004 (%)
2005 (%)
2006 (%)
2007 (%)
Mean2004–2007 (%)
% change from 2004 to 2007
At least three prescribers quarterly
8.9
9.5
10.0
10.4
9.7
16.9
At least five prescribers quarterly
0.8
0.9
1.0
1.0
0.9
26.7
Number of prescribers
Addictive drugs At least 1 DDD quarterly
25.8
24.9
25.8
26.1
26.3
5.8
GP alone at least 1 DDD quarterly
20.5
19.6
20.5
20.6
21.0
5.6
At least 30 DDD quarterly GP alone at least 30 DDD quarterly
15.8 12.4
16.6 13.0
17.0 13.3
17.3 13.6
16.7 13.1
9.6 10.0
At least 90 DDD quarterly
8.1
8.7
9.0
9.3
8.8
15.3
GP alone at least 90 DDD quarterly
6.2
6.7
7.0
7.2
6.8
15.8
Patient observationsa,b (N)
1,990,590
1,985,899
1,991,429
1,990,150
DDD defined daily doses, GP general practitioner a
Each patient observed once each quarter
b
Total number of patient observations over the period 2004–2007 = 7,958,068
a
b
Fig. 2 Average amount of drugs per patient (expressed as DDDs) by number of prescribing physicians: (a) addictive drugs; (b) nonaddictive drugs. DDD defined daily dose, GP general practitioner
4 Discussion Our main results show that regular GPs prescribed the majority of the medication to their registered patients. The proportion prescribed by the patients’ regular GP was higher for addictive than for non-addictive drugs. The average quantities of prescribed drugs per patient increased with increasing numbers of prescribers, and did so to a greater extent with addictive than with non-addictive drugs. An increasing trend in the amount of drugs and the number of prescribers per patient was seen over the observation period.
The data explored in this study are extracted from a national registry of all prescriptions made to the total population of home-dwelling seniors over 70 years old in Norway, which is a considerable strength. Since compliance with prescriptions is a well known problem [21], it is important to note that the dataset includes the prescribed amount dispensed at pharmacies, not just the total amount prescribed. GPs in Norway are not obliged to report to the health authorities when patients move into an institution and receive drugs directly from the institution, which implies that the calculated amounts of drugs may be slightly
458
underestimated in our analyses. Likewise, the patients’ use of over-the-counter drugs is not registered in the database [22]. However, these underestimations only serve to strengthen the significance of our results. Since we do not have any detailed medical information about individual cases included in the study, the definition of medications that we have classified as ‘addictive’ may be criticised. Addiction, in the sense of substance dependence, is a clinical definition that is based not only on the pharmacological characteristics of the substance in question but also on clinical and behavioral patient characteristics and intake pattern over time. The pharmacological definition used here indicates a risk situation especially for older patients, but does not mean that the patient is addicted. The use of the higher cut-off levels such as more than 30 or more than 90 DDDs per quarter may complement the whole picture, which we suggest is alarming. It should be noted that medication listed as addictive here is also listed as a possible inappropriate medication for the elderly based on both its addictive potential and its side effects [13]. The appropriateness of medication should preferably be evaluated in relation to the diagnosis of the patients. This cannot be done here since we lack medical data; however, the high and increasing use of potentially risky medication, including addictives, certainly suggests that further studies with more such clinical data are required. We thus suggest that this category of drugs merits special attention in the medication of older patients. Use of such medication may be necessary for older people (e.g., for treatment of severe pain), but should be carefully evaluated and monitored, preferably by the main prescriber (i.e., the patient’s regular GP). Further clinical studies on prescription medication, addiction, and dependence among older people are necessary to complete the picture. Based on another study using data from NorPD, Kjosavik et al. [22] found that 80 % of psychotropic drugs in the Norwegian population are prescribed by a GP. However, this analysis did not distinguish between prescriptions from the patients’ regular GP and prescriptions from other GPs. Hence, the results are similar to our findings. We found that 30 % of the patients had two or more prescribers, which is in accordance with a study from Denmark that has a similar list-patient system [4]. It is often a general assumption that a major part of the increasing rates of prescription of potent medication to seniors is caused by further involvement of different specialists. We cannot completely refute this, as GP prescription may simply serve to continue prescriptions started by hospital specialists. However, our data clearly show that GPs have a major responsibility of which they need to be aware. Observationally, specialists in geriatrics tend to be
I. C. Kann et al.
among the few specialities that reduce the number of medications for older patients, and further training in geriatrics is one possible intervention that may hold promise. However, in the present study, we had very few prescribers who were specialists in geriatric medicine so we are unable to examine this issue in detail. The proportion of GPs and other specialists, as well as their respective roles, may also vary between healthcare systems, which may need to be considered in comparisons between countries. Empirical evidence indicates that the risk of adverse drug reactions and compliance errors increases with the amount of drugs taken [3, 10, 13, 19, 21]. Hence, our findings of high levels and steadily increasing time-trends of average drug amounts and number of prescribers is a serious concern. When the prescribed amounts were divided into amounts prescribed by the patients’ GPs and those prescribed by other physicians, we observed different patterns for addictive and non-addictive drugs. For both prescriptions by other physicians and prescriptions by the regular GP, a greater increase in addictive drugs was seen with increasing numbers of prescribers. For non-addictive drugs, the quantity prescribed by the regular GP remained almost constant despite an increasing number of other prescribers (Fig. 2). Whether this indicates elements of ‘doctor-shopping’ for addictive drugs, the search for less restrictive doctors by patients with high usages of addictive drugs, or a higher tendency by the GP to continue prescriptions of potent medications introduced by other specialists, is impossible to ascertain.
5 Conclusion The results indicate that the Norwegian list-patient system, one of the aims of which is that the GP should act as a coordinator in drug prescription to the elderly population, does not impede an increasing trend toward larger amounts of drugs and more prescribers per patient, which are traits associated with higher risks for this group. This seems particularly alarming in the increase of addictive medications, which are suggested to be problem medications for older people. The appropriateness for the prescription of such medication to the elderly needs to be further studied in relation to the relevant health issues and should be considered carefully for individual patients. The GP is responsible for the largest proportions of both addictive and non-addictive prescriptions to older patients and also for the greatest increase over time in prescribed quantities. This implies that attempts to improve coordination further must involve the GPs. How such interventions should be performed to be most effective requires further study.
Prescription of Addictive and Non-Addictive Drugs to the Elderly Acknowledgments The financial support of the Norwegian Research Council is gratefully acknowledged. The South-East Norway Regional health authority is gratefully acknowledged for support to CL. Thanks to the Norwegian Prescription Database (NorPD), Norwegian Social Science Data (NSD), The Norwegian Labour and Welfare Administration (NAV), and Statistics Norway (SSB) for providing data, thus making the analysis possible. These sources are not responsible for data analysis or interpretations. The classification of drugs was performed with the help of pharmacist Vigdis Solberg at the hospital pharmacy enterprise: ‘Sykehusapotekene HF’. The authors affirm that there are no conflicts of interest.
References 1. Sakshaug S, Strøm H, Berg CL, et al. (Ed: Ronning M) Legemiddelforbruk i Norge 2004-2008. The Norwegian Institute of Public Health, 2008. http://www.fhi.no/dokumenter/542314a014. pdf. 2. Milton JC, Hill-Smith I, Jackson SHD. Prescribing for older people. BMJ. 2008;336(7644):606–9. 3. Straand J, Fetveit A, Rognstad S, et al. A cluster-randomized educational intervention to reduce inappropriate prescription patterns for elderly patients in general practice—The Prescription Peer Academic Detailing (Rx-PAD) study [NCT00281450]. BMC Health Serv Res. 2006;6:72. 4. Barat I, Andreasen F, Damsgaard EMS. The consumption of drugs by 75-year-old individuals living in their own homes. Eur J Clin Pharmacol. 2000;56(6–7):501–9. 5. Ziere G, Dieleman JP, Van der Cammen TJM, et al. Selective serotonin reuptake inhibiting antidepressants are associated with an increased risk of nonvertebral fractures. J Clin Psychopharmacol. 2008;28(4):411–7. 6. Kongkaew C, Noyce PR, Ashcroft DM. Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies. Ann Pharmacother. 2008;42(7):1017–25. 7. Einarson TR. Drug-related hospital admissions. Ann Pharmacother. 1993;27(7–8):832–40. 8. Hallas J. Drug related hospital admissions in subspecialities of internal medicine. Dan Med Bull. 1996;43(2):141–55.
459 9. Bregnhoj L, Thirstrup S, Kristensen MB, et al. Prevalence of inappropriate prescribing in primary care. Pharm World Sci. 2007;29(3):109–15. 10. Brekke M, Rognstad S, Straand J, et al. Pharmacologically inappropriate prescriptions for elderly patients in general practice: how common? Scand J Prim Health Care. 2008;26(2):80–5. 11. Fick DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults—results of a US consensus panel of experts. Arch Intern Med. 2003;163(22):2716–24. 12. Liu GG, Christensen DB. The continuing challenge of inappropriate prescribing in the elderly: an update of the evidence. J Am Pharm Assoc (Wash). 2002;42(6):847–57. 13. Rognstad S, Brekke M, Fetveit A, et al. The Norwegian General Practice (NORGEP) criteria for assessing potentially inappropriate prescriptions to elderly patients. Scand J Prim Health Care. 2009;27(3):153–9. 14. Culberson JW, Ziska M. Prescription drug misuse/abuse in the elderly. Geriatrics. 2008;63(9):22–31. 15. Simoni-Wastila L, Yang HK. Psychoactive drug abuse in older adults. Am J Geriatr Pharmacother. 2006;4(4):380–94. 16. Tamblyn R. Medication use in the seniors population: optimization of physician prescribing as a means of preventing drugrelated illness. Can J Aging. 1997;16:147–61. 17. Sandvik H. Evaluering av fastlegeordningen 2001—2005 [Summary in English]. Research Council of Norway 2005. 18. WHO Collaborating Centre for Drug Statistics Methodology. Department of Pharmacoepidemiology at the Norwegian Institute of Public Health 2010. http://www.whocc.no/atc_ddd_ methodology/who_collaborating_centre/. 19. Stewart RB, Cooper JW. Polypharmacy in the aged—practical solutions. Drugs Aging. 1994;4(6):449–61. 20. Green JL, Hawley JN, Rask KJ. Is the number of prescribing physicians an independent risk factor for adverse drug events in an elderly outpatient population? Am J Geriatr Pharmacother. 2007;5(1):31–9. 21. Hemminki E, Heikkila J. Elderly peoples compliance with prescriptions, and quality of medication. Scand J Soc Med. 1975;3(2):87–92. 22. Kjosavik SR, Ruths S, Hunskaar S. Psychotropic drug use in the Norwegian general population in 2005: data from the Norwegian Prescription Database. Pharmacoepidemiol Drug Saf. 2009;18(7):572–8.
