Abstract
Using a prescription-survey linkage dataset for 4506 people aged ≥50 years from six general practices, the null hypothesis that multiple drug prescribing was not associated with changes in health over a 3-year time-period was investigated. There was a significant trend in the adjusted association between higher levels of multidrug therapy and deterioration in both physical and psychological health over a 3-year time period. The study highlights the potential need for assessing drug prescribing in terms of overall health.
Keywords: comorbidity, drug utilisation review, polypharmacy, quality of life
INTRODUCTION
One of the key interventions in reduction of disease risk and progression are drug therapies. Polypharmacy in general practice is high,1 especially in older populations, and routine drug use has been further formalised by chronic disease management approaches. These changes have been part of the larger public health initiative aimed at the reduction of disease-specific complications and mortality, but there have been few attempts at investigating the overall health benefits of multiple drug therapies in older populations.2,3
There has also been scientific debate in relation to the implications of multiple drug treatments in the management of chronic disease such as ischaemic heart disease, and it has been postulated that a polypill might be developed to maximise the benefit and adherence.4 What is less clear is whether the use of multiple drug regimens in general practice has any beneficial or detrimental effects on overall health at the population level, and specifically in relation to change over a longer-term time period.
METHOD
This secondary dataset is drawn from a large population-based postal survey, conducted in six general practice populations of individuals aged ≥50 years, at baseline, with a follow-up using the same health questionnaire at 3 years.
For 4506 patients who had consented, individual health survey data were linked to their general practice records, which included drug prescription data over a 5-year period. The total 5-year time-period for review of clinical data covered the 2 years before the baseline questionnaire survey in 2001 and the 3 years in between baseline and follow-up questionnaires.
Definitions of 3-year change in health
The Short Form-12 (SF-12) questionnaire summarised physical and psychological health status for each study participant.5 Change in health was calculated by subtracting the baseline score from the 3-year follow-up score, with negative scores indicating relative deterioration and positive scores indicating a relative improvement in health. The change scores were then dichotomised about the mean change for the study populations in respect of physical and psychological scores separately, and, using a 2 × 2 table approach, four groups were constructed: (i) controls d – physical and psychological health better; (ii) group a – physical health worse/psychological health better; (iii) group b – psychological health worse/physical health better; and (iv) group c – physical and psychological health worse (Table 1).
Table 1.
Health change over 3 years in the population of individuals aged ≥50 years.
| Number (%)a | Definitionb | Mean change (standard deviation) | |
|---|---|---|---|
| Control group d | 1022 (23) | Physically better | PCS +4.5 (5.39) |
| Psychologically better | MCS +5.4 (6.53) | ||
| Case group a | 1266 (28) | Physically worse | PCS –7.8 (6.05) |
| Psychologically better | MCS +7.5 (7.47) | ||
| Case group b | 1378 (31) | Physically better | PCS +6.1 (6.01) |
| Psychologically worse | MCS –8.6 (7.16) | ||
| Case group c | 840 (19) | Physically worse | PCS –8.0 (6.64) |
| Psychologically worse | MCS –8.5 (6.90) | ||
Figures in brackets are percentages of the overall study group (n = 4506).
Based on the Physical Component Summary (PCS) and the Mental Component Summary (MCS) scores from the SF-12 questionnaire.
Multidrug measures
Linked prescription data for the study population were obtained from general practice records and these data were based on British National Formulary (BNF) codes. Within each BNF chapter there is a hierarchical structure, which details different drugs for the same disease indication or for different classes of drugs within the specific body system.6 The definition of multidrug therapy was based on overall counts at the second hierarchy by: ‘number of drugs prescribed for an individual including different drugs for the same disease, but not including repeat prescription for the same drug in the same time period’.
How this fits in
Multiple drugs prescribing in general practice populations is high, but whether this benefits overall health is unknown. Higher levels of drug prescribing were associated with deterioration in physical and combined physical and psychological health. The study highlights the potential need for assessing prescribing in terms of overall health.
Statistical analyses
Baseline survey measures of health, using the respective study population mean values, were dichotomised SF-12 scores for physical and psychological health. Baseline drug counts in the 2-year time period before the survey were dichotomised about the mean and in the 3-year follow-up period counts were categorised into four groups: (i) 1 to 4 prescribed drugs; (ii) 5 to 7 drugs; (iii) 8 to 11 drugs; and (iv) 12 drugs and over. Associations between the four categories of overall drug counts and the three health-change case groups compared to controls were separately assessed using logistic regression methods with 95% confidence intervals (CIs).
RESULTS
There was a significant and increasing strength of association between higher drug counts and worse physical and psychological health compared to the lowest counts group (trend P<0.001). The adjusted figures were: category two, odds ratio (OR) 1.55 (95% CI = 1.2 to 2.1); category three, OR 2.25 (95% CI = 1.7 to 3.1); and category four, OR 2.91 (95% CI = 2.0 to 4.2).
There was a significant and increasing strength of association between higher drug counts and worse physical health compared to the lowest counts group (trend P = 0.025). The adjusted figures were: category two, OR 1.24 (95% CI = 0.97 to 1.6); category three, OR 1.42 (95% CI = 1.1 to 1.9); and category four, OR 1.64 (95% CI = 1.2 to 2.3) (Table 2).
Table 2.
Associations between multidrug therapy and health change over a 3-year time period
| Adjusted odds ratio (95% CI) | |||||||
|---|---|---|---|---|---|---|---|
| Drug countsa | Health changee | Unadjusted odds ratio (95% CI) | Age, sex, and deprivation status | Age, sex, deprivation status, and baseline physical and psychological health | Age, sex, deprivation status, and baseline drug counts | Age, sex, deprivation status, baseline physical and psychological health, and drug counts | |
| Better | Worse | ||||||
| Category 1a lowest | 317 | 365 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 |
| Category 2b | 264 | 343 | 1.13 (0.9 to 1.4) | 1.08 (0.9 to 1.3) | 1.22 (0.97 to 1.5) | 1.13 (0.9 to 1.4) | 1.24 (0.97 to 1.6) |
| Category 3b | 258 | 318 | 1.07 (0.9 to 1.3) | 0.99 (0.8 to 1.2) | 1.36 (1.1 to 1.7) | 1.14 (0.9 to 1.5) | 1.42 (1.1 to 1.9) |
| Category 4b highest | 183 | 240 | 1.13 (0.9 to 1.5) | 0.99 (0.8 to 1.3) | 1.55 (1.2 to 2.1) | 1.19 (0.9 to 1.6) | 1.64 (1.2 to 2.3) |
| Category 1b lowest | 317 | 361 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 |
| Category 2c | 264 | 342 | 1.14 (0.9 to 1.4) | 1.08 (0.9 to 1.4) | 1.06 (0.8 to 1.3) | 1.10 (0.9 to 1.4) | 1.05 (0.8 to 1.3) |
| Category 3c | 258 | 371 | 1.26 (1.0 to 1.6) | 1.14 (0.9 to 1.4) | 1.16 (0.9 to 1.5) | 1.18 (0.9 to 1.5) | 1.14 (0.9 to 1.5) |
| Category 4c highest | 183 | 304 | 1.46 (1.2 to 1.9) | 1.26 (0.98 to 1.6) | 1.47 (1.1 to 2.0) | 1.33 (0.98 to 1.8) | 1.44 (1.0 to 2.0) |
| Category 1c lowest | 317 | 199 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 |
| Category 2d | 264 | 213 | 1.29 (0.99 to 1.7) | 1.19 (0.9 to 1.5) | 1.49 (1.1 to 1.9) | 1.49 (1.1 to 1.9) | 1.55 (1.2 to 2.1) |
| Category 3d | 258 | 242 | 1.49 (1.2 to 1.9) | 1.36 (1.1 to 1.8) | 2.09 (1.6 to 2.8) | 2.09 (1.6 to 2.8) | 2.25 (1.7 to 3.1) |
| Category 4d highest | 183 | 186 | 1.62 (1.2 to 2.1) | 1.30 (0.98 to 1.7) | 2.68 (1.9 to 3.7) | 2.68 (1.9 to 3.7) | 2.91 (2.0 to 4.2) |
Drug counts defined as: category 1 (1–4); category 2 (5–7); category 3 (8–11); category 4 (12 and over) in the 3-year interval period.
Cases within this group are people whose physical health was worse but psychological health (SF-12) was better after 3 years.
Cases within this group are people whose psychological health was worse but physical health (SF-12) was better after 3 years.
Cases within this group are people whose physical and psychological health was (SF-12) worse after 3 years.
Same controls for each case group and whose physical and psychological health (SF-12) was better after 3 years.
While the strength of association between higher drug counts and worse psychological health increased (but was weaker), it did not show any significant statistical trend.
DISCUSSION
Summary of main findings
There were high levels of multiple drugs routinely prescribed in the older population of individuals aged ≥50 years from general practice, but such high prescribing was not associated with benefit as measured by change in physical and psychological health over a 3-year time period. Therefore, the possible implications that are generated from these results are either that multidrug therapy may be detrimental to health or that there was an increased prescribing response by clinical practitioners to changing health status.
Strengths and limitations of the study
In terms of testing a hypothesis, this study was drawn from a large population-based cohort and provides an internal comparison (and ‘dose’-relationship) of multidrug counts and its association with health change. The simple drug counts measure does not convey the indication or duration of drug therapies, and whether they were aimed at short-term conditions (for example, antibiotics for infections) or for chronic diseases on an ongoing basis (for example, diabetes or ischaemic heart disease). This approach also does not disentangle the specific drug interactions or adherence issues that might play different roles in influencing health change.7,8
Comparison with existing literature
Previous studies indicate that psychological distress is associated with increased comorbidity,9 and so is likely to be associated with a higher number of prescribed drug therapies. However, the analyses for the group whose psychological health worsened showed that the prescribing response was relatively weaker than for the other two groups. Clinical practitioners also usually prescribe in response to disease diagnosis or symptoms, as opposed to health change,10 and this further indicates the need for a prospective investigation into the effect of multiple drug therapy on long-term health change.
Implications for clinical practice
In conclusion, the study shows that multidrug therapy was associated with worse physical health or combined physical and psychological health over a 3-year period. Baseline health or drug prescribing, or sociodemographic characteristics did not explain these results. The importance of the study findings then relates to whether prescribing should be assessed in terms of overall health assessment or whether multipharmacy should be simply viewed as benefiting specific illness or disease management.
Acknowledgments
An expression of thanks is extended to the patients who took part in the study and the teams who collected the survey and clinical data, and to Peter Croft for his comments on the initial draft of the paper.
Funding body
The author was funded by an NIHR Fellowship (PAS/PDA/03/07/035); project funding was by the Medical Research Council (UK) and the North Staffordshire Primary Care Research Consortium.
Ethical approval
Ethical approval was given by the North Staffordshire Local Research Ethics Committee.
Competing interests
The author has stated that there are none.
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