We found that during one year, more then 2/3 of all individuals in a national population received at least one dispensed drug and that a considerable proportion, about 1/4, was exposed to multiple medications, a known potential risk factor for patients' health.
Age and gender
Our findings reveal that multiple medications is not only a relevant issue regarding the elderly but also for other age groups. Thus, 2/3 of all individuals with multiple medications were younger than 70 years of age. Furthermore, there were more individuals with multiple medications in the age group 50–59 than in the age group 80–89, and almost four times as many in the age group 40–49 as in the age group 90 and above.
Our findings that the median number of dispensed drugs for all individuals, 70 years and above was 7, 8, and 9 in the respective 10-year age groups, are in line with previous reports [15, 25].
Multiple medications, being more frequent for females than for males, may partly be explained by the use of sex hormones and modulators of the genital system (ATC G03) among fertile females [26]. When ATC G03 were excluded from our data, the prevalence of multiple medications declined in all age groups above 10 years, but the RR for females for DP ≥ 5 only decreased from 1.5 to 1.4. The increased RR among females vs. males for multiple medications is in line with previous studies [15, 27] and may partly be explained by that females, of all ages, visit a doctor more often than males [28, 29].
The validity of dispensed drugs as an estimator of multiple medications
When dispensed drugs are used as an estimator of drug use and multiple medications, some conditions could cause both over- and underestimations. For a variety of reasons, a certain percentage of all drugs will never be used by patients, resulting in an overestimation of drug use when studying dispensed drugs [26]. On the reverse, the prevalence of drug use and multiple medications may be underestimated, as patients also use other medications than dispensed drugs. Additional sources, such as in-hospital medications, previously filled prescriptions (before the study period), OTC sales, herbal and alternative remedies, gifts and elicit Internet sales contribute to an underestimation of the total consumption of drugs. The absence of in-hospital medications in our data have different impact on different age groups, since the majority of the in-hospital medications is given to elderly individuals.
Among additional sources, OTC-drugs are of special interest, as previous studies have demonstrated a clear association between the use of prescription drugs and OTC drugs [10]. The vast majority of individuals over 65 use OTC drugs regularly [30] and different studies have shown that elderly people regularly use one OTC drug for every 2–3 prescribed drugs [30–32]. Applied on our data e.g., five dispensed drugs should correspond to a total use of seven drugs, OTC-drugs included.
Concomitantly taken multiple medications is a known risk factor for the patient's health. Many dispensed drugs are prescribed to be taken regularly. Some drugs, such as certain analgesics, are meant to be taken temporarily only when needed. Other drugs like antibiotics, are mostly intended to be taken periodically; a quarter of all individuals in Sweden in 2006 received one or more courses of treatment of ATC J01 (Antibacterials for systemic use). Periodically used drugs have different impact on the prevalence of multiple medications in different age groups. Antibacterials for systemic use had a huge impact on the prevalence of multiple medications in the age group 0–9, but only a minor effect on the prevalence in the age groups 70 and above. Antibacterials for systemic use were the most commonly prescribed drugs for individuals in the age group 0–9, but just one of many different used drugs for elderly with multiple medications.
Another source of underestimation of multiple medications in our data was generic duplication of dispensed drugs, recognised as a common problem in health care [4, 7, 33]. We did not evaluate the number of duplicates for each individual, but only calculated the number of dispensed drugs comprised of different substances. If the generic duplicate had been taken into account, it would have resulted in an even larger prevalence of multiple medications.
Methods to estimate multiple medications on a national level
Data of drug utilisation and multiple medications may be available from the prescribers' medical records, pharmacy registers, or from the patient. The medical record may be preferable when to study the actual prescription orders, whereas data from pharmacies provides a better picture of what drug the patient actually received. Data collected from individuals may be closer to the true exposure of drugs, but are empirically associated with both intended and unintended memory failures.
In the present study, we choose a cumulative method [18] and counted all dispensed drugs, subsidized and non-subsidized, for all individuals in all ages during a 12-month period. Thereby, we compensated the monthly variation of dispensed drugs during a year, which in Sweden in 2006 varied by more than 20% between different months.
A 12-month study period also includes all females with prescribed sex hormones (ATC G03). Approximately three quarter of all females with ATC G03 receives these drugs, in contrast to other continually used drugs, for a 12-month period at one single pharmacy visit. A shorter study period, e.g. 3- or 6-month, will capture only a fraction of the number of females with ATC G03.
Our study shows that the length of a study period is essential for the estimation of the prevalence of the drug use and multiple medications, especially for the younger age groups. Compared to a study from Denmark based on a sample from a large regional database over dispensed drugs [8], we found a substantially higher prevalence of drug use and multiple medications in an entire national population. The difference between the results can partly be explained by differences in methods of estimation; in the Danish study were only subsidized prescription drugs and drugs with established DDD included. Other contributing explanations were that DDD per 1,000 inhabitants per day differs substantially between the countries [34], and also that there were 14 years between the two studies, 1994 and 2006. The continued increase in the use of drugs may therefore have influenced the estimates of the prevalence of DP ≥ 1 and DP ≥ 5. Compared to a study, based on interviews with a sample of elderly in Sweden [35], our observed prevalence for the age group was substantially higher. Possible explanations to the difference might be a minor difference in the definition of multiple drug use, and also sample and interview bias. The presented prevalences in three other studies from Sweden, based on individual register data of dispensed drugs [13–15], were close to our findings, with the reservation that the observed "polypharmacy" was not explicitly defined in one of the studies [14].
Clinical relevance and implications
If the drug use and the occurrence of polypharmacy continue to increase, a future challenge for health care will be to treat the resulting side effects. Therefore, the evaluation and reconsideration of the drug therapy, especially for patients who receive drugs via several different doctors, should be a standard procedure before prescribing a new drug. On an individual level, a prescriber seems to need an overview of all the patients medications, including other prescribers and OTC drugs and also earlier dispensed "if needed drugs", to be able to optimize the patient's treatment. Observed multiple medications for an individual should serve as a warning signal, reminding the prescriber that the number of dispensed drugs, together with an uncertain number of drugs from additional sources, may be a risk factor for the patient's health.
Cost effects
The costs associated with drug-related problems have been estimated to have more than doubled between 1995 and 2000 [36]. Moreover, the risk for drug-drug interactions and adverse drug reactions are expected to increase exponentially with the number of drugs consumed [9]. If the current increase in the total drug consumption and multiple medications will continue, there will be a considerable risk of increased primary as well as secondary costs for drug-related problems in the society. The relationship between the prevalence of multiple medications and the cost for drug-related problems remains to be studied.