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Clinical medication review and falls in older people

What does the evidence base tell us and how can we optimise delivery of pharmaceutical care?



What does the evidence base tell us and how can we optimise delivery of pharmaceutical care?



Nuttan Tanna FRPS FFRPS MRPharmS DComP PhD
on behalf of the LNWHT Research group
Trish Winn Msc Nursing
Sunder Chita MPhil (Evaluation Public Health Services}
Krishan Ramdoo MBCh
Clare Batten MA MBBS FRCP
London North West Healthcare NHS Trust, Imperial College, School of Science & Medicine, London, UK
In 2012, the World Health Organisation reported ‘falls’ as the second leading cause of accidental or unintentional injury deaths worldwide.1 Injuries received from unintentional falls result in death, disability, nursing-home admission and direct medical costs.2
Although certain interventions can reduce falls, for example, exercising regularly or having medicines reviewed to reduce side effects and interactions, implementation at the community level remains limited and additional measures are needed to promote widespread adoption.2–4
Community setting 
Community dwelling older individuals are a large group identified as at high risk of future falls and injuries.5 Many are subsequently admitted into intermediate care facilities. Gillespie et al6 reviewed the interventions for preventing falls in older people living in the community, including 159 trials with 79,193 participants.
The most common interventions tested were exercise as a single intervention (59 trials) and multi-factorial programmes (40 trials). Kannus et al7 suggest that a multi-factorial intervention for elderly people is more effective than its single intervention counterpart since ‘causes and risk factors of falling are usually multiple with striking intra-individual (fall to fall) and inter-individual variation’.
Gillespie et al6 found that multi-factorial interventions which included individualised risk assessment reduced rate of falls but not risk of falling. Trials looking at medication review did not demonstrate benefit but a prescribing modification programme also involving primary care physicians and their patients significantly reduced risk of falling. It was also noted6 that gradual withdrawal of psychotropic medication reduced rate of falls but not risk of falling.
Care facilities and hospitals setting 
A recent Cochrane Database review8 assessed the effectiveness of interventions designed to reduce falls by older people in care facilities and hospitals. A total of 43 randomised controlled trials with 30,373 participants in care facilities were included in this systematic review, with the authors noting that despite the large number of trials, there was limited evidence to support any one intervention. Rate of falls were calculated as falls per person year with risk of falling classified as the number of people falling (fallers) in each group.
Results from 13 trials testing exercise interventions in care facilities were inconsistent; exercise programmes seem to increase falls in frail residents in nursing homes, but reduce falls in people in intermediate care facilities. For multi-factorial interventions in care facilities, both the rate of falls and risk of falls showed a trend towards possible benefit. Multi-factorial interventions9 usually include medication review, but published literature does not define a process for a structured clinical medication review. The British Geriatric Society10 recommends that evidence-based medication reviews should be conducted for older people with frailty, suggesting use of STOPP START criteria11,12 as the basis for this process.
Considering trials for specific medicines, Cameron et al8 noted that vitamin D supplementation was effective in reducing the rate of falls, but not the risk of falling. Bjelakovic et al13 reported findings from their updated Cochrane review where the objective was to assess the beneficial and harmful effects of vitamin D supplementation for prevention of mortality in healthy adults and adults in a stable phase of disease. Including 56 trials with 95,286 participants providing usable data on mortality, the authors noted that vitamin D3 may decrease mortality in elderly people living independently or in institutionalised care, but there was a need for further evidence from randomised, placebo-controlled trials in this area.
With this background in mind, we report findings from a literature search to assess the current evidence base for clinical medication review and falls risk.
Literature review
A Pubmed database literature review was undertaken in July 2014, using search strategy terms ‘elderly’, ‘falls’ and ‘medicines’, with selection criteria including review of all abstracts in English, followed by examination of selected publications and any relevant cited references within selected publications, critiqued by three members of the research group. Including the search term ‘older’ in the search strategy did not elicit any further publications of relevance.
A 2007 critical systematic review14 looked at all original articles examining medication use as a risk factor for falls or fall-related fractures in people aged 60 years or older. Findings were reported from 28 observational studies and one randomised controlled trial, with the number of participants in the trials ranging between 70 and 132,873. The outcome measure was a fall in 22 studies and a fracture in seven studies. The main group of drugs associated with an increased risk of falling were psychotropics, including benzodiazepines, antidepressants, and antipsychotics (Table 1). Antiepileptics and drugs that lower blood pressure were weakly associated with falls. Limitations included need for improvement in the quality of observational studies, as many did not have a clear definition of a fall or target medicines, or prospective follow-up. The researchers also noted that many drugs commonly used by older persons are not systematically studied as risk factors for falls.
Gnjidic et al15 studied the optimal discriminating number of concomitant medications that were associated with geriatric syndromes, functional outcomes, and mortality in their study population of community-dwelling older men. They validated this as the use of five or more medications, accepted as the current definition of poly-pharmacy, and found this to be helpful in estimating the medication-related adverse effects for frailty, disability, mortality, and falls. An observational study in older men living in the community16 found that a self-reported history of falls in the previous 12 months was independently associated with number of medicines taken (odds ratio (OR) =1.06; 95% CI 1.02, 1.09) and use of one or more potentially inappropriate medicines (PIMs) (OR=1.23; 95% CI 1.04, 1.45).
Use of one or more PIMs had a correlation with hospital admission (hazard ratio (HR) = 1.16; 95% CI 1.08, 1.24), while potential under-utilisation was associated with cardiovascular events (HR=1.20; 95% CI 1.03, 1.40), with this study finding that both medication over-use and under-use occur frequently among older men and may be harmful. Nishtala et al17 undertook a large multi-database study that evaluated impact of polypharmacy and exposure to Drug Burden Index (DBI) medicines, with exposure defined as quantification of each individual’s cumulative exposure to anticholinergic and sedative medicines. Both criteria were independently associated with fall-related hospitalisations, frequency of GP visits, and risk of mortality. DBI drugs were associated with fall-related hospitalisations with an incidence rate ratio (IRR) of 1.56 (95% CI = 1.47–1.65) and greater number of GP visits (IRR 1.13; 95% CI = 1.12–1.13).
An Australian study18 reported findings from a retrospective analysis of pain control management and found that some 90% of residents in aged care facilities (ACF) were prescribed analgesics. A total of 2057 residents (28.1%) were taking regular opioids. Only 50% of those taking regular opioids received regular paracetamol at doses of 3–4 g/day. The concurrent use of sedatives was high, with 48.4% of those taking regular opioids also taking an anxiolytic/hypnotic. With the risk of falls and fractures increased by concurrent use of opioids and sedatives, the widespread use of these drugs in a population already at high risk was concerning. There is a need to optimise the prescribing and administration of regular paracetamol as a first-line and continuing therapy for pain management in ACF residents, to potentially improve pain management and reduce opioid requirements. Another study19 evaluated the prevalence of adverse drug events in an acute geriatric setting over a six-month period and reported a rate of 12.7% (n=313; mean age 84.8).
Cardiovascular (39%), psychotropic (36.6%) and opiate (7.3%) medicines were involved most frequently. The adverse events that occurred most frequently were bleeding (28.6%), falls (14.3%), and sleepiness (9.5%), with the authors noting that these could have been ‘prevented’ in 31% of cases. Preventability in this study was determined by assessment of inadequacy with standards of care, medication-related factors (excluding contra-indication) and use of standard lists of harmful medication in the elderly.  A French retrospective case control study20 reported that 50% of falls occurred in patients in their first week after hospital admission, with these classified as severe in 16% cases.
The characteristics of the two groups under study (patients who fell and those who did not) were similar: there were no significant differences in variables such as age, sex, number of medicines or prevalence of hypertension or Parkinson’s disease. Probability of falls increased when the patients used zolpidem (adjusted odds ratio (AOR) 2.59; 95% CI 1.16, 5.81; p=0.02), meprobamate (AOR 3.01; 95% CI 1.36, 6.64; p=0.01) or calcium channel antagonists (AOR 2.45; 95% CI 1.16, 4.74; p=0.02). Payne et al reported data from a larger Scottish retrospective case-cohort study,21 which included over 39,000 patients aged over 65 years.
They found that the period with recent changes in psychotropic and cardiovascular medications was associated with a substantial increase in risk of hospital admission for falls and fractures; with an OR of 1.54 (95% CI 1.17–2.03) and 1.68 (95% CI 1.28–2.22) respectively (Table 1). These findings are in line with work reported by Beer et al16 with correlation both for falls risk and hospital admission with use of potentially inappropriate medicines. Notably Payne et al21 found evidence (p=0.003) for variation in the association between change in different psychotropic medications and admission, with the strongest associations for changes with selective serotonin reuptake inhibitor (SSRI) antidepressants (OR 1.99; 95% CI 1.29–3.08), non-SSRI tricyclic antidepressants (OR 4.39; 95% CI 2.21-8.71) and combination psychotropic medication (OR 3.05; 95% CI 1.66–5.63).
The Australian Longitudinal Study of Ageing22 specifically studied the risk of falls with use of psychotropic medicines. Interestingly, use was associated with increased risk of falls in females (IRR=1.47; 95% CI 1.31–1.64) but not in males (IRR=1.03; 95% CI 0.85–1.26). Use of psychotropic medications was also associated with an increased risk of a fracture in females (relative risk (RR) 2.54; 95% CI 1.57–4.11; p<0.0001) but not in males (RR=0.66; p=0.584; 95% CI 0.15–2.86). In both analyses, body mass index (BMI) was found to be the only confounding variable. After adjusting for BMI, the IRR in females decreased to 1.22 (95% CI 1.02–1.45; p<0.015) for falls and the RR decreased to 1.92 (95% CI 1.13–3.24; p<0.015, ) for fractures.
Medicines optimisation
Gallagher et al11 have validated a comprehensive screening tool that enables the prescribing physician to assess an older patient’s prescription drugs in the context of his/her concurrent diagnoses. Inter-rater reliability is favourable12 with a kappa-coefficient of 0.75 for STOPP and 0.68 for START (Table 2). STOPP (Screening Tool of Older Person’s Prescriptions) encompasses 65 clinically significant criteria for potentially inappropriate prescribing in older people. Each criterion is linked with a concise explanation as to why the prescribing practice is potentially inappropriate.  START (Screening Tool to Alert doctors to Right Treatment) consists of 22 evidence-based prescribing indicators for commonly encountered diseases in older people.
International studies using STOPP criteria worryingly indicate high PIM prevalence rates. A PIM index is calculated by dividing the total number of PIMs by the total number of medications. A UK study23 carried out within an acute hospital setting found that the admission PIM prevalence was 26.7 % (95% CI 20.5–32.9; 52 patients, 74 PIMs). The most common PIM categories on admission were central nervous system and psychotropic drugs, drugs adversely affecting patients at risk of falls and drugs acting on the urogenital system.
The likelihood of having a PIM on admission was doubled in patients receiving more than ten medications compared with those taking fewer (OR 2.3; 95% CI 1.2–4.4; p=0.01). The study reported a discharge PIM prevalence of 22.6% (95% CI 16.7–28.5; 44 patients, 51 PIMs), with a significant reduction of PIMs on discharge (p=0.005). Wahab et al24 assessed the prevalence and nature of pre-admission inappropriate prescribing by using the STOPP criteria in a sample of hospitalised elderly inpatients in South Australia. The total number of pre-admission medications screened during the study period was 949 and the median number of medicines per patient was nine (range 2–28). Overall the STOPP criteria identified 138 PIMs in 60% patients.
The most frequent PIM was for opiates prescribed in patients with recurrent falls (12.3%). The other two culprit medicines were benzodiazepines in fallers (10.1%) and proton pump inhibitors prescribed for peptic ulcer disease for long-term at maximum doses (9.4%). The number of medications being taken had a positive correlation with pre-admission PIM use (ρ=0.49,
STOPP START tool criteria
Medication review for patients may be undertaken by various health professionals. A randomised control trial25 assessed the effect of clinical medication review undertaken by a pharmacist for elderly people living in care homes. This included 661 residents aged 65 years and over, on one or more medicines. The study found that GPs did not review most care home patients’ medication. Medication changes initiated and proposed by the pharmacist were usually accepted, with a reduction in number of falls, but without any changes to overall drug costs.
In addition, there were no significant changes in consultations, hospitalisations, mortality, standardised Mini Mental State examination or Barthel scores (the Barthel Index consists of ten items that measure a person’s daily functioning, specifically the activities of daily living).
Wilcock et al26 utilised community pharmacists to collate data for their cross sectional survey which included a study population of 581 residents recruited from 18 UK residential homes. They found that the use of psychotropic drugs was common, and observed a trend for increase in prescribing rates as compared with data from a previous survey in 2001. There was limited use of calcium and vitamin D supplements, which have the potential for reducing morbidity associated with falls.
Although use of both calcium and vitamin D had increased significantly (8.3% in 2005 vs. 2.1% in 2001), overall this was relatively low, with an 8% usage level in this at-risk population (Table 3). In their paper on prevention of falls and consequent injuries in elderly people, Kannus et al7 discuss the traditional approach often used for prevention of bone fracture injury with focus on prevention and treatment of osteoporosis. The aims are to maximise peak bone mass and prevent ongoing bone loss with regular exercise, calcium and vitamin D and treatment of osteoporosis with pharmacological medicines.9
Service development in the UK NHS has included pharmacist-led, multidisciplinary team-supported, medication management clinics that focus on osteoporosis, falls and fracture prevention.27 The pharmaceutical care approach28,29 utilised in these clinics within the secondary care setting, provide a structured framework to help identify polypharmacy issues and ensure safe and efficacious medication usage by patients. Assessment of compliance and adherence with medication taking30 is undertaken by the pharmacist, with patients encouraged to raise their medication and health- related concerns, and where the aims are to agree to an ongoing management plan.
Medication review
Limitations for the findings reported from this review include study of publications identified via a search utilising only the PubMed database. Our work was undertaken as a quick, time-limited, preliminary fact-finding exercise to understand what the current evidence base is for clinical medication review and falls in older people. Readers may find that the findings reported in this paper provides useful knowledge, and that our work helps inform wider database searches and helps inform more research activity in this area.
Tables 1–3 highlight the main knowledge generated from this review. In clinical practice elderly fallers often have numerous comorbidities and are on multiple medicines. It is important to remember that for delivery of effective pharmaceutical care, elderly people with age related deficits may benefit more from discontinuation and de-prescribing of some of their medications. This decision needs to be made considering all the medicines taken, and especially when the elderly patient reports side effects, and not reserved for medicines on the STOPP list and defined as causing adverse events.
This paper reports the current knowledge of the evidence base for clinical medication review and falls in the elderly.  Both medication over-use and under-use occur frequently and may be harmful. Many drugs commonly used by older persons have not been systematically studied as risk factors for falls.  The STOPP START tools, validated for assessment of potentially inappropriate prescribing in the elderly, offer the possibility of provision of a structured clinical medication review to patients. There is a need for more research on the impact of these interventions on both the rates of falls and risk of falls in the elderly.
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Key points
  • Many drugs taken by older persons have not been systematically studied as risk factors for falls.
  • Both medication over-use and under-use occurs frequently
  • Medication over-use or under-use in older persons may be harmful.
  • Number of medications taken is positively correlated with hospital pre-admission and PIM (potentially inappropriate medicine) use.
  • Elderly people with age related deficits may benefit more from de-prescribing of some of their medicines.



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