|

Polypharmacy

Last updated:

Overview

Polypharmacy is the administration of more medicines than are clinically indicated. This is generally, but not restricted to, around 5 or more medicines per day. Some patients will still be at risk of polypharmacy, even if they do not take many drugs. 

Polypharmacy and inappropriate prescribing are risk factors for adverse drug reactions.

Thorough prescription reviews should be carried out to identify adverse drug reactions. One particular consequence of polypharmacy is an increased risk of falls.

Usually, falls can happen due to:

  • Sedation – this slows reaction time and may impair balance
  • Hypotension
  • Arrhythmias e.g. tachycardia, bradycardia, asystole

This section covers some drugs seen in polypharmacy.

Screening

The STOPP and START screening tools are used. They provide evidence-based rules surrounding commonly prescribed drugs.

  • STOPP – Screening Tool of Older Persons Prescriptions
    • Identifies medications where the risk outweighs the benefits and they may be inappropriate
    • These drugs may potentially be inappropriate in people aged 65 or older
  • START – Screening Tool to Alert doctors to the Right Treatments
    • Identifies medications where prescription may provide additional benefits

Approach

When carrying out a prescription review, 7 questions should be asked:

  • What matters to the patient?
    • Explain objectives to the patient through shared decision making
    • What does the patient want?
  • What drugs are essential?
    • Ensure that the patient is educated on what drugs are essential
    • Do some drug therapies need to be increased?
    • Do some drug therapies need to be decreased/stopped?
  • What drugs are unnecessary?
    • Are these drugs meeting the goals and outcomes that matter most to the patient?
    • Can lifestyle changes replace some of these drugs?
    • Are indications valid?
    • Do the benefits outweigh the risks?
  • Are targets being met with these drugs?
    • If not, patient non-adherence may need to be assessed
  • Are these drugs safe?
    • Is the patient at risk of adverse drug reactions?
    • Is the patient experiencing adverse drug reactions?
    • Are any interactions taking place?
  • Are these drugs cost-effective?
    • This should only be considered if the effectiveness, safety, or adherence would not be compromised
  • Is the patient willing and able to take them as indicated?
    • Is the treatment regimen tailored to the patient’s preferences?
    • Does the patient understand the outcome of the prescription review?

Specialist Input

Some medications need expert input before stopping or altering. Examples are:

Cardiovascular Drugs

STOP drugs

The following drugs are potentially inappropriate in people ≥65 years old:

  • Thiazide diuretics:
  • Loop diuretics:
    • Due to the risk of hypokalaemia, hyponatraemia, hypocalcaemia, dehydration, and renal impairment
  • Aldosterone antagonists:
  • Rate-limiting calcium channel blockers (CCBs, verapamil, diltiazem):
    • Due to the risk of hypotension and bradycardia
  • Anti-anginal vasodilators (glyceryl trinitrate spray (GTN), long-acting nitrates, nicorandil):
    • Due to the risk of hypotension and syncope
    • Nicorandil can also cause skin, mucosa, and gastrointestinal ulceration
  • Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs):
  • Amiodarone when used in supraventricular tachycardia:
    • Due to the increased risk of adverse effects compared to other treatment options

START drugs

The following drugs should be considered in people ≥65 years old where no contraindication exists:

  • Antihypertensive therapy
  • Beta-blockers or calcium-channel blockers for stable angina
  • Beta-blockers for chronic heart failure
  • ACE inhibitors for chronic heart failure or diabetes with renal disease
  • Statins as part of primary/secondary prevention of cardiovascular disease

Respiratory Drugs

STOP drugs

The following drugs are potentially inappropriate in people ≥65 years old:

  • Antimuscarinic drugs (ipratropium and tiotropium):
  • Prolonged courses of systemic corticosteroids:
    • Due to the potentially unnecessarily increased risks of adverse effects

START drugs

The following drugs should be considered in people ≥65 years old where no contraindication exists:

  • Beta2-agonist or antimuscarinic bronchodilators:
  • Inhaled corticosteroids:
  • Long-term oxygen therapy:
    • For COPD when criteria are met
  • Spacer device:
    • For effective inhaler administration

Gastrointestinal Drugs

STOP drugs

The following drugs are potentially inappropriate in people ≥65 years old:

  • Drugs that may cause constipation (e.g. opioids, anticholinergic drugs, oral iron, verapamil) and antimotility drugs
  • Metoclopramide:
  • Domperidone:
    • Avoid if being used for anything other than nausea/vomiting
    • Avoid if the patient has serious underlying heart conditions
    • Avoid if the patient takes medication known to cause QT prolongation or inhibit CYP3A4

START drugs

The following drugs should be considered in people ≥65 years old where no contraindication exists:

  • Proton pump inhibitors (PPIs):

Nervous System Drugs

STOP drugs

The following drugs are potentially inappropriate in people ≥65 years old:

  • Tricyclic antidepressants (amitriptyline, imipramine, doxepin, dosulepin):
    • May worsen cognitive impairment in dementia
    • May exacerbate glaucoma
    • May increase the risk of arrhythmia (they can cause QT prolongation)
    • May exacerbate or cause constipation or urinary retention
    • May increase the risk of and worsen falls as they can slow reaction rates and impair balance
  • Benzodiazepines (e.g. diazepam, lorazepam, clonazepam, chlordiazepoxide) and Z-drugs (e.g. zopiclone, zolpidem):
    • May increase the risk of and worsen falls as they can slow reaction rates, impair balance, cause confusion, and cause drowsiness
    • May exacerbate respiratory failure, such as those with hypercapnic COPD
  • Antipsychotics (e.g. haloperidol, risperidone, quetiapine, olanzapine, chlorpromazine):
    • May cause extrapyramidal side effects and falls, hypotension, and confusion if used long-term (generally >1 month)
    • May exacerbate Parkinson’s disease or dementia with Lewy bodies – avoid
    • May increase the risk of and worsen falls as they can slow reaction rates, cause sedation, postural hypotension, and impaired balance
    • May increase the risk of stroke 
  • Anticholinergic drugs (e.g. procyclidine):
    • May exacerbate cognitive impairment in dementia
    • Anticholinergic drugs can cause many problematic adverse effects, these are discussed below
  • Selective serotonin reuptake inhibitors (SSRIs):
    • May cause or worsen hyponatraemia due to syndrome of inappropriate ADH release (SIADH)
    • Citalopram and escitalopram can cause QT prolongation and increase the risk of arrhythmia
    • May cause orthostatic hypotension
    • May impair sleep and cause drowsiness
  • Other antidepressants (e.g. mirtazapine and trazodone):
    • May cause drowsiness, impaired balance, and slow reactions
  • First-generation antihistamines (e.g. promethazine, chlorphenamine, and cyclizine:
    • Due to the risk of sedation and anticholinergic side effects – these are discussed below
  • Opiates (e.g. codeine, morphine, and tramadol):
    • May cause drowsiness and impaired balance
    • May cause constipation
    • May exacerbate cognitive impairment in those with dementia
  • Monoamine oxidase inhibitors (MAOIs) (e.g. selegiline, rasagiline, phenelzine, isocarboxazid):
    • May cause profound orthostatic hypotension
  • Older antiepileptic drugs (e.g. phenytoin, carbamazepine, phenobarbitone, sodium valproate, gabapentin):
    • Phenytoin can cause cerebellar damage in long-term + excess phenytoin can cause ataxia
    • Carbamazepine and phenobarbitone can sedate and slow reaction time + excess can cause ataxia
    • Sodium valproate and gabapentin have an association with falls
  • Dopamine agonists in Parkinson’s disease (e.g. ropinirole, bromocriptine, cabergoline, pramipexole):
  • Muscle antispasmodics (e.g. baclofen, dantrolene):
    • Sedation
    • Reduced muscle tone
  • Acetylcholinesterase inhibitors (e.g. donepezil, rivastigmine, galantamine):
    • Bradycardia
    • Syncope

START drugs

The following drugs should be considered in people ≥65 years old where no contraindication exists:

  • Levodopa/dopamine agonists:
    • In idiopathic Parkinson’s disease
  • Non-tricyclic antidepressants (TCAs) (e.g. SSRIs):
    • For depression
    • TCAs carry a higher risk of side effects compared to SSRIs
  • Acetylcholinesterase inhibitors (e.g. donepezil, rivastigmine, galantamine):
  • Opioids:
    • When paracetamol or NSAIDs have been ineffective
  • Laxatives:
    • In patients using opioids regularly

Endocrine Drugs

STOP drugs

The following drugs are potentially inappropriate in people ≥65 years old:

  • Sulfonylureas:
  • Metformin if eGFR <30 mL/min/1.73m2
    • Due to risk of lactic acidosis
  • Pioglitazone:
    • Due to fluid retention and the risk of exacerbating heart failure
  • Oestrogens (e.g. hormone replacement therapy):
    • Due to the risk of venous thromboembolism or endometrial cancer if used without progestogen opposition
  • Any hormone replacement therapy (HRT) in people with:
    • Acute liver disease, as HRT is metabolised in the liver
    • Oestrogen-dependent cancer, as it can worsen the prognosis
    • Undiagnosed postmenopausal bleeding
    • Active thrombophilia or hypercoagulable state due to the risk of venous thromboembolism
    • Active or recent arterial thromboembolic disease (e.g. angina/myocardial infarction)
  • Androgens in the absence of hypogonadism:
    • Due to the risk of androgen toxicity
  • Bisphosphonates:
    • If >5 years of treatment, consider a drug holiday
    • May exacerbate or cause oesophagitis, oesophageal ulcers, oesophageal stricture
  • Bisphosphonates or denosumab:
    • May not be necessary if FRAX score low
  • Denosumab:
    • If patients cannot have regular dental check-ups

START drugs

The following drugs should be considered in people ≥65 years old where no contraindication exists:

  • Vitamin D, calcium, and bisphosphonates:
    • In patients taking long-term systemic corticosteroids, as they offer bone protection
    • Also may be used in patients with osteoporosis

Haematology Drugs

STOP drugs

The following drugs are potentially inappropriate in people ≥65 years old:

  • Aspirin:
    • Due to the increased risk of bleeding, especially if the patient:
  • Any anticoagulant if there is a significant bleeding risk:
    • Such as uncontrolled severe hypertension or increased susceptibility to bleeds
  • Aspirin + clopidogrel as secondary stroke prevention
  • Direct oral anticoagulants (DOACs) and warfarin:
  • Dabigatran:
    • If eGFR is <30 mL/min/1.73m2 due to an increased risk of bleeding
  • Apixaban, edoxaban, and rivaroxaban (factor Xa inhibitors:
    • If eGFR <15 mL/min/1.73m2 due to an increased risk of bleeding

START drugs

The following drugs should be considered in people ≥65 years old where no contraindication exists:

  • Antiplatelets (aspirin, clopidogrel, prasugrel, or ticagrelor):
    • If there is a history of coronary, cerebral, or peripheral vascular disease
  • Anticoagulation:

Genitourinary Drugs

STOP drugs

The following drugs are potentially inappropriate in people ≥65 years old:

  • Alpha1-receptor blockers (e.g. doxazosin, tamsulosin, alfuzosin):
    • Profound orthostatic hypotension
    • Stopping may cause urinary retention in men
  • Alpha-2 receptor agonists (e.g. clonidine, moxonidine):
    • Profound orthostatic hypotension
  • Anticholinergic drugs (e.g. oxybutynin):
    • May exacerbate cognitive impairment in dementia
    • Anticholinergic drugs can cause many problematic adverse effects, these are discussed below
  • Phosphodiesterase-5 inhibitors (e.g. sildenafil, tadalafil):
    • May precipitate cardiovascular collapse in those with severe heart failure and hypotension (<90 mmHg systolic) or those taking nitrates for angina

START drugs

The following drugs should be considered in people ≥65 years old where no contraindication exists:

  • Topical vaginal oestrogen:
    • For symptomatic atrophic vaginitis
  • Alpha1-receptor blockers:
  • 5-alpha reductase inhibitors (e.g. finasteride):
    • For symptomatic benign prostatic hyperplasia where surgery is not considered necessary

Musculoskeletal Drugs

STOP drugs

The following drugs are potentially inappropriate in people ≥65 years old:

  • NSAIDs:
    • Due to the risk of peptic ulcer relapse in people with a history of peptic ulcer disease or gastrointestinal bleeding – offer gastroprotection (a proton pump inhibitor)
    • Peptic ulcer relapse may occur in those taking antiplatelets (especially aspirin), antidepressants (SSRIs, venlafaxine), and corticosteroids without gastroprotection
    • May exacerbate hypertension in severe/uncontrolled hypertension
    • Diclofenac is contraindicated in cardiovascular disease due to the increased risk of thrombotic events
    • May risk renal failure in people with an eGFR <50 mL/min/1.73m2
    • May increase the risk of gastrointestinal bleeding in people taking anticoagulants
  • Long-term colchicine or NSAIDs if there is no contraindication to allopurinol:
    • This is generally >3 months
    • The risk of colchicine toxicity is increased if eGFR <10 mL/min/1.73m2
  • Long-term corticosteroids (>3 months) for rheumatoid arthritis:
    • Due to the risks of adverse effects associated with corticosteroids

START drugs

The following drugs should be considered in people ≥65 years old where no contraindication exists:

  • Allopurinol:
    • For gout prophylaxis
  • Disease-modifying antirheumatic drugs (DMARDs):
    • Under specialist guidance where indicated
  • Folic acid:
    • If patients are taking methotrexate
  • Gastroprotection (proton pump inhibitors):
    • In people taking drugs that increase the risk of peptic ulcers (e.g. SSRIs, venlafaxine, antiplatelets, and corticosteroids)

Ophthalmic Drugs

STOP drugs

The following drugs are potentially inappropriate in people ≥65 years old:

  • Non-selective beta-blockers (e.g. timolol):
    • Increased risk of bradycardia, heart block, heart failure, or bronchoconstriction in susceptible people

START drugs

The following drugs should be considered in people ≥65 years old where no contraindication exists:

Anticholinergic Burden

Anticholinergic drugs are often used to treat many conditions such as overactive bladder, COPD, asthma, Parkinson’s disease, vertigo, and nausea. These medications can cause:

  • Dry mouth
  • Blurred vision
  • Urinary retention
  • Constipation
  • Drowsiness
  • Headache
  • Nausea
  • Vomiting
  • Palpitations 
  • Confusion and angioedema in rare cases

Anticholinergic burden is the overall effect of a patient taking one or more drugs with anticholinergic activity.  Excess use and long duration of use in people >65 years of age increases the risk of dementia, along with their adverse effects being more profound.

Medications are given an ACB (anticholinergic burden) score. A higher score indicates a higher anticholinergic burden.

ACB 0ACB 1ACB 2ACB 3
MirabegronTramadolCetirizineTolterodine
DomperidoneCodeineSertralineOxybutynin
WarfarinProchlorperazineFesoterodine
HydrocortisoneDarifenacin
PrednisoloneChlorphenamine
NifedipineAmitriptyline
MirtazapineSolifenacin

Author