Multiple drugs a minefield for older patients

Many common drugs do little good and some harm. With careful pruning you can lift quality of life without increasing mortality.

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While the use of medicines in older people is improving, too many are still prescribed too many medications with too little evidence of benefit.  

The Australian Commission on Safety and Quality in Health Care’s National Medicines Symposium on Tuesday focused on inappropriate polypharmacy in older people, medicines-related harm and deprescribing.  

Professor Libby Roughead, director of the Quality Use of Medicines and Pharmacy Research Centre at the University of South Australia, said ABS data showed the average Australian 75 and over was on eight medications, with around a third taking 10 or more.  

She said quality use of medicines (QUM) had begun in the 1980s as a consumer-driven movement before becoming government policy then a national strategy, which was last revised 20 years ago.  

In 1998 the first “add-on” therapy was approved for diabetes, where a drug was added instead of exchanged for one that wasn’t working, and we entered the era of polypharmacy.  

“We need many more effective structures for dealing with multimorbidity and polypharmacy,” Professor Roughead said.  

“Deprescribing has emerged as one focus to deal with this, and there are many good resources developed, but they’re not yet in routine practice, and they’re not yet integrated with some of our other resources, such as product information.” 

Steve Waller, advisor to the ACSQHC on medication without harm (the WHO’s third patient global safety challenge, launched in 2017) said medication reviews in aged care facilities were increasing, but there were three areas needing improvement: documenting and reporting adverse drug reactions; generating and distributing current medicines at clinician handover; and including information on de-escalation and cessation of medicines in all consumer medicines information.  

In other positive news, high-risk medicine stewardship was expanding – e.g. insulin poisonings were down despite increasing prevalence of diabetes, and opioid dispensing and unintentional opioid deaths were also down; and antipsychotics prescribing was decreasing among GPs.  

The perils of polypharmacy 

Professor Jennifer Martin, RACP president and a clinical pharmacologist, said multiple drugs could interact not only with each other but with a patient’s diseases, and with drugs that were not always declared to clinicians: supplements, complementary medicines and medicinal cannabis – the last of which could cause psychosis in older people.  

She said some of the most commonly prescribed drugs in older people had poor evidence of efficacy in that population, namely statins and antihypertensives.  

“It’s really important that we actually look at the evidence that we have for the use of these in the older population, because for most of them, we have no evidence,” Professor Martin said.  

“Just as we can’t assume little children will respond to a medication that adults will, we can’t assume an older person is going to respond to a medication as a middle-aged adult – someone that’s been studied in the clinical trial – might respond.” 

Older people, who were excluded from most trial cohorts but were assumed to function the same as younger adults, had “completely altered physiology” that affected pharmacokinetics and pharmacodynamics, including containing less water, less muscle mass, more lipid, decreased renal excretion, slowed liver function and a less responsive of the baroreceptor reflex.  

She said drugs were being used that had little benefit, but they all had toxicity, some of which went unrecognised amid a patient’s other physical or cognitive problems.  

Professor Martin had in her own experience seen three patients on statins develop rhabdomyolysis and die. 

“Our pharmacy colleagues are often much better at looking for drug-drug interactions, not just because of the software, but for the way pharmacists think about the way we use medications. As doctors, we’re good at thinking about drug-disease interactions, but we don’t always consider the effect of other drugs’ concentrations when we add a new drug into the system.” 

There was also drug duplication. It was “not uncommon” for a drug to be dispensed once under its generic name and once under a brand name, particularly where paper systems were still being used.  

In a more subtle form of duplication, different drugs could be blocking the same or similar receptors: “An example of this would be an older person [being prescribed] an opioid, a drug that blocks histamine receptors, a drug that blocks dopamine and serotonergic receptors, and you’re left there thinking, there’s not much that’s actually signalling in that poor patient’s brain.” 

Polypharmacy could make drugs ineffective. In Parkinson’s, prescribers needed to know when a dopamine agonist and antagonist (for psychosis) might just be cancelling each other out, and at what concentration an agonist could turn into an antagonist.  

For adverse events, she said, the biggest culprit drugs were antibiotics (resistance), analgesics (especially gabapentinoids and opioids), anticoagulants, antihistamines, antipsychotics, anticonvulsants, cardiovascular drugs and diabetic drugs.  

Professor Martin said when prescribing for older adults, consider these six points:  

• Continuous review – harms and benefits 
• Are non-drug options possible? 
• Check if dose is correct 
• Start low and go slow 
• Think “drugs” before making a new diagnosis 
• Keep the meds list short: one on, one off  

She encouraged prescribers to make use of pharmacologists and pharmacists, and to ask patients what they wanted: they often preferred mental sharpness as they neared the end of life, even if it meant living with some pain, and not to have their senses dulled.  

Deprescribing to the rescue 

The symposium then turned its focus to solutions. 

Professor Sarah Hilmer, a pharmacologist, geriatrician and chair of the NSW Therapeutic Advisory Group (NSWTAG), said deprescribing – an Australian term – was important for three reasons: the lack of clinical evidence for many drugs’ efficacy in older people, the risks of interactions, and person-centred care.  

“Surveys done nationally and internationally with older people and their carers say very clearly that 85 to 90% of people would be very happy to stop one of their medicines if their doctors said that they could,” Professor Hilmer said.  

It wasn’t just the number of medications, she added.  

The Drug Burden Index, which Professor Hilmer developed with her student, now consultant pharmacist Dr Lisa Kouladjian-O’Donnell, measures a person’s exposure to drugs with sedative and anticholinergic activity and hence the functional burden of a person’s medicines.  

Dr Kouladjian O’Donnell also developed and validated the G-MEDSS deprescribing tool.  

“The higher your drug burden index, the more likely you are to have impaired physical function, falls, delirium, frailty, wind up in hospital, see your GP and to die, and this is independent of the number of medicines you’re taking,” Professor Hilmer said. 

The potential harms of deprescribing were an adverse withdrawal reaction, the return of the underlying condition and pharmacokinetic and pharmacodynamic effects on other drugs; the benefits were reduced treatment burden and adverse events.  

Withdrawing an inappropriate drug could slightly decrease mortality in people aged 65-79, Professor Hilmer said.  

Studies on deprescribing antihypertensives had shown that between 20% and 85% will remain normotensive after six months.  

Deprescribing psychotropics improved cognition and behaviour and reduced the risk of falls without an increase in mortality.  

And when statins were withdrawn in people thought to be in their last year of life, “there’s no change in their mortality and a trend towards improved quality of life”. 

“What’s really important to note is that in all of these studies, medicines are weaned gradually, often over months, and there was no increased risk of adverse withdrawal events reported,” Professor Hilmer said.  

“So deprescribing is an important part of prescribing for older people… people do not like to rattle when they walk and are very willing to talk about deprescribing with their doctors.”