Abstract
Purpose
Potentially inappropriate prescribing is common in older people presenting to hospital with acute illness in Ireland. The aim of this study was to determine if this phenomenon is unique to Ireland or whether it is a more widespread problem in hospitals across Europe.
Methods
Prospective data were collected from 900 consecutive older patients admitted to six university teaching hospitals (150 patients per centre) in Geneva (Switzerland), Madrid (Spain), Oostende (Belgium), Perugia (Italy), Prague (Czech Republic) and Cork (Ireland). Age, gender, comorbidity, cognitive status, prescription medicines taken before admission and baseline haematological, biochemical and electrocardiographic data were recorded. STOPP and Beers’ criteria were applied to detect potentially inappropriate medicines (PIMs). START criteria were applied to detect potentially inappropriate prescribing omissions (PPOs).
Results
The overall PIM prevalence rate was 51.3% using STOPP criteria, varying from 34.7% in Prague to 77.3% in Geneva, and 30.4% using Beer’s criteria, varying from 22.7% in Prague to 43.3% in Geneva. Using START criteria, the overall PPO prevalence rate was 59.4%, ranging from 51.3% in Cork to 72.7% in Perugia. Polypharmacy predicted the presence of PIMs using STOPP criteria [with >10 medications: odds ratio (OR) 7.22, 95% confidence interval (CI) 4.30–12.12, p < 0.001] and Beers’ criteria (with >10 medications: OR 4.87, 95% CI 3.00–7.90, p < 0.001). Increasing co-morbidity (Charlson Index ≥2) and age ≥85 years significantly predicted PPOs.
Conclusion
Potentially inappropriate drug prescribing and the omission of beneficial drugs are highly prevalent in acutely ill hospitalized older people in six European centres.
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Funding
The Health Research Board of Ireland (Clinical Research Training Fellowship CRT/2006/029) and the Czech Ministry of Health Internal Grant Agency (NS/10029-4/2008) provided financial support for this study.
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Appendices
Appendix 1: Beers’ criteria for potentially inappropriate medication use in older adults
A. Independent of diagnoses or conditions
Propoxyphene and combination products |
Indomethacin |
Pentazocine |
Trimethobenzamide |
Muscle relaxants and antispasmodics: methocarbamol, carisoprodol, chlorzoxazone, metaxalone and cyclobenzaprine and oxybutinin (do not consider extended release oxybutinin) |
Flurazepam |
Amitriptyline, chlordiazepoxide–amitryptiline and perphenazine–amitryptiline |
Doxepin |
Meprobamate |
Doses of short-acting benzodiazepines: doses greater than lorazepam 3 mg; oxazepam 60 mg; alprazolam 2 mg; temezepam 15 mg; triazolam 0.25mg. |
Long-acting benzodiazepines: chlordiazepoxide, chlordiazepoxide–amitryptiline, clidinium–chlordiazepoxide, diazepam, quazepam, halazepam and chlorazepate |
Disopyramide |
Digoxin (should not exceed 0.125 mg daily, except when treating atrial arrhythmias) |
Short-acting dipyridamole. Do not consider the long-acting dipyridamole (which has better properties than the short-acting in older adults) except with patients with artificial heart valves |
Methyldopa and methyldopa-hydrochlorothiazide. |
Reserpine at doses >0.25 mg |
Chlorpropamide |
Gastrointestinal antispasmodic drugs: dicyclomine, hyoscyamine, propantheline, belladonna alkaloids and clinidium–chlordiazepoxide. |
Anticholinergics and antihistamines: chlorpheniramine, diphenhydramine, hydroxyzine, cyproheptadine, promethazine, tripelennamine and dexchlorpheniramine |
Diphenhydramine |
Ergot mesyloids and cyclandelate |
Ferrous sulphate >325 mg/day. |
All barbiturates (except phenobarbital) except when used to control seizures. |
Meperidine |
Ticlopidine |
Ketorolac |
Amphetamines and anorexic agents |
Long-term use of full-dosage, longer half-life, non-COX selective NSAIDs: naproxen, oxaprozin and piroxicam. |
Daily fluoxetine |
Long-term use of stimulant laxatives: bisacodyl, cascara sagrada, and neoloid except in the presence of opioid analgesic use. |
Amiodarone |
Orphenadrine |
Guanethidine |
Guanadrel |
Cyclandelate |
Isoxsurpine |
Nitrofurantoin |
Doxazosin |
Methyltestosterone |
Thioridazine |
Mesoridazine |
Short-acting nifedipine |
Clonidine |
Mineral oil |
Cimetidine |
Ethacrynic acid |
Dessicated Thyroid |
Amphetamines (excluding methylphenidate hydrochloride and anorexics) |
Oetrogens only (oral) |
B. Considering diagnoses or conditions
Disease or condition | Potentially inappropriate drug |
---|---|
Heart failure | Disopyramide and high sodium content drugs |
Hypertension | Phenylpropanolamine hydrochloride, pseudoephedrine, diet pills, amphetamines |
Gastric or duodenal ulcers | NSAIDS and aspirin (>325 mg) (coxibs excluded) |
Seizures or epilepsy | Clozapine, chlorpromazine, thioridazine and thiothixene |
Blood-clotting disorders or anticoagulant therapy | Aspirin, NSAIDs, dipryidamole, Ticlodipine and clopidgrel |
Bladder outflow obstruction | Anticholinergics and antihistamines, gastrointestinal antispasmodics, muscle relaxants, oxybutinin, flavoxate, antidepressants, decongestants and tolterodine |
Stress incontinence | α-blockers, anticholinergics, tricyclic antidepressants (imipramine hydrochloride, doxepin hydrochloride and amitryptiline hydrochloride) and long-acting benzodiazepines |
Arrhythmias | Tricyclic antidepressants (imipramine hydrochloride, doxepin hydrochloride and amitryptiline hydrochloride) |
Insomnia | Decongestants, theophylline, methylphenidate, MAOI’s and amphetamines |
Parkinson’s disease | Metoclopramide, conventional antipsychotics and tacrine |
Cognitive impairment | Barbiturates, anticholinergics, antispasmodics, muscle relaxants and CNS stimulants: dextroamphetamine, methylphenidate, methamphetamine, pemolin |
Depression | Long-term benzodiazepine use, methyldopa, reserpine and guanethidine |
Anorexia and malnutrition | CNS stimulants: dextroamphetamine, methylphenidate, methamphetamine, pemolin and fluoxetine |
Syncope or falls | Short to intermediate acting benzodiazepine and tricyclic antidepressants (imipramine, doxepin and amitryptiline hydrochloride) |
SIADH/hyponatraemia | SSRIs: fluoxetine, citalopram, fluvoxamine, paroxetine and sertraline |
Seizure disorder | Bupropion |
Obesity | Olanzapine |
COPD | Long-acting benzodiazepines: chlordiazepoxide, chlordiazepoxide–amitryptiline, clidinium–chlordiazepoxide, diazepam, quazepam, halazepam and chlorazepate. β-blockers: propanolol |
Constipation | Calcium channel blockers, anticholinergics, tricyclic antidepressants (imipramine hydrochloride, doxepin hydrochloride, amitriptyline hydrochloride |
Appendix 2: STOPP (Screening Tool of Older People’s potentially inappropriate Prescriptions)
The following prescriptions are potentially inappropriate in persons aged ≥65 years of age
A. Cardiovascular system
-
1.
Digoxin at a long-term dose >125 μg/day with impaired renal function (estimated glomerular filtration rate <50 ml/min) (increased risk of toxicity).
-
2.
Loop diuretic for dependent ankle oedema only, i.e. no clinical signs of heart failure (no evidence of efficacy, compression hosiery usually more appropriate).
-
3.
Loop diuretic as first-line monotherapy for hypertension (safer, more effective alternatives available).
-
4.
Thiazide diuretic with a history of gout (may exacerbate gout).
-
5.
Non-cardioselective beta-blocker with COPD (risk of bronchospasm).
-
6.
Beta-blocker in combination with verapamil (risk of symptomatic heart block).
-
7.
Use of diltiazem or verapamil with New York Heart Association (NYHA) Class III or IV heart failure (may worsen heart failure).
-
8.
Calcium channel blockers with chronic constipation (may exacerbate constipation).
-
9.
Use of aspirin and warfarin in combination without histamine H2 receptor antagonist (except cimetidine because of interaction with warfarin) or proton pump inhibitor (high risk of gastrointestinal bleeding).
-
10.
Dipyridamole as monotherapy for cardiovascular secondary prevention (no evidence for efficacy).
-
11.
Aspirin with a past history of peptic ulcer disease without histamine H2 receptor antagonist or proton pump inhibitor (risk of bleeding).
-
12.
Aspirin at dose >150mg day (increased bleeding risk, no evidence for increased efficacy).
-
13.
Aspirin with no history of coronary, cerebral or peripheral arterial symptoms or occlusive arterial event (not indicated).
-
14.
Aspirin to treat dizziness not clearly attributable to cerebrovascular disease (not indicated).
-
15.
Warfarin for first, uncomplicated deep venous thrombosis for longer than 6 months duration (no proven added benefit).
-
16.
Warfarin for first uncomplicated pulmonary embolus for longer than 12 months duration (no proven benefit).
-
17.
Aspirin, clopidogrel, dipyridamole or warfarin with concurrent bleeding disorder (high risk of bleeding).
B. Central nervous system and psychotropic drugs.
-
1.
Tricyclic antidepressants (TCAs) with dementia (risk of worsening cognitive impairment).
-
2.
TCAs with glaucoma (likely to exacerbate glaucoma).
-
3.
TCAs with cardiac conductive abnormalities (pro-arrhythmic effects).
-
4.
TCAs with constipation (likely to worsen constipation).
-
5.
TCAs with an opiate or calcium channel blocker (risk of severe constipation).
-
6.
TCAs with prostatism or prior history of urinary retention (risk of urinary retention).
-
7.
Long-term (i.e. >1 month), long-acting benzodiazepines, such as chlordiazepoxide, fluazepam, nitrazepam, chlorazepate and benzodiazepines with long-acting metabolites, such as diazepam (risk of prolonged sedation, confusion, impaired balance, falls).
-
8.
Long-term (i.e. >1 month) neuroleptics as long-term hypnotics (risk of confusion, hypotension, extra-pyramidal side effects, falls).
-
9.
Long-term neuroleptics ( >1 month) in those with parkinsonism (likely to worsen extra-pyramidal symptoms)
-
10.
Phenothiazines in patients with epilepsy (may lower seizure threshold).
-
11.
Anticholinergics to treat extra-pyramidal side-effects of neuroleptic medications (risk of anticholinergic toxicity).
-
12.
Selective serotonin re-uptake inhibitors (SSRIs) with a history of clinically significant hyponatraemia (non-iatrogenic hyponatraemia <130 mmol/l within the previous 2 months).
-
13.
Prolonged use (> 1 week) of first generation antihistamines i.e. diphenydramine, chlorpheniramine, cyclizine, promethazine (risk of sedation and anti-cholinergic side effects).
C. Gastrointestinal system
-
1.
Diphenoxylate, loperamide or codeine phosphate for treatment of diarrhoea of unknown cause (risk of delayed diagnosis, may exacerbate constipation with overflow diarrhoea, may precipitate toxic megacolon in inflammatory bowel disease, may delay recovery in unrecognized gastroenteritis).
-
2.
Diphenoxylate, loperamide or codeine phosphate for treatment of severe infective gastroenteritis, i.e. bloody diarrhoea, high fever or severe systemic toxicity (risk of exacerbation or protraction of infection)
-
3.
Prochlorperazine (stemetil) or metoclopramide with parkinsonism (risk of exacerbating parkinsonism).
-
4.
PPI for peptic ulcer disease at full therapeutic dosage for >8 weeks [earlier discontinuation or dose reduction for maintenance/prophylactic treatment of peptic ulcer disease, oesophagitis or gastroesophageal reflux disease (GORD) as indicated].
-
5.
Anticholinergic antispasmodic drugs with chronic constipation (risk of exacerbation of constipation)
D. Respiratory system.
-
1.
Theophylline as monotherapy for COPD (safer, more effective alternative; risk of adverse effects due to narrow therapeutic index)
-
2.
Systemic corticosteroids instead of inhaled corticosteroids for maintenance therapy in moderate-severe COPD (unnecessary exposure to long-term side-effects of systemic steroids).
-
3.
Nebulized ipratropium with glaucoma (may exacerbate glaucoma).
E. Musculoskeletal system
-
1.
Non-steroidal anti-inflammatory drug (NSAID) with a history of peptic ulcer disease or gastrointestinal bleeding, unless with concurrent histamine H2 receptor antagonist, PPI or misoprostol (risk of peptic ulcer relapse).
-
2.
NSAID with moderate-severe hypertension (moderate: 160/100–179/109 mmHg; severe: ≥180/110 mmHg) (risk of exacerbation of hypertension).
-
3.
NSAID with heart failure (risk of exacerbation of heart failure).
-
4.
Long-term use of NSAID (>3 months) for relief of mild joint pain in osteoarthtitis (simple analgesics preferable and usually as effective for pain relief)
-
5.
Warfarin and NSAID together (risk of gastrointestinal bleeding).
-
6.
NSAID with chronic renal failure (estimated glomerular filtration rate 20–50 ml/min) (risk of deterioration in renal function).
-
7.
Long-term corticosteroids (>3 months) as monotherapy for rheumatoid arthritis or osteorarthritis (risk of major systemic corticosteroid side-effects).
-
8.
Long-term NSAID or colchicine for chronic treatment of gout where there is no contraindication to allopurinol (allopurinol first choice prophylactic drug in gout)
F. Urogenital system
-
1.
Bladder antimuscarinic drugs with dementia (risk of increased confusion, agitation).
-
2.
Bladder antimuscarinic drugs with chronic glaucoma (risk of acute exacerbation of glaucoma).
-
3.
Bladder antimuscarinic drugs with chronic constipation (risk of exacerbation of constipation).
-
4.
Bladder antimuscarinic drugs with chronic prostatism (risk of urinary retention).
-
5.
Alpha-blockers in males with frequent incontinence i.e. one or more episodes of incontinence daily (risk of urinary frequency and worsening of incontinence).
-
6.
Alpha-blockers with long-term urinary catheter in situ, i.e. >2 months (drug not indicated).
G. Endocrine system
-
1.
Glibenclamide or chlorpropamide with type 2 diabetes mellitus (risk of prolonged hypoglycaemia).
-
2.
Beta-blockers in those with diabetes mellitus and frequent hypoglycaemic episodes, i.e. ≥1 episode per month (risk of masking hypoglycaemic symptoms).
-
3.
Oestrogens with a history of breast cancer or venous thromboembolism (increased risk of recurrence)
-
4.
Oestrogens without progestogen in patients with intact uterus (risk of endometrial cancer).
H. Drugs that adversely affect those prone to falls (≥1 fall in past 3 months)
-
1.
Benzodiazepines (sedative, may cause reduced sensorium, impair balance).
-
2.
Neuroleptic drugs (may cause gait dyspraxia, parkinsonism).
-
3.
First generation antihistamines (sedative, may impair sensorium).
-
4.
Vasodilator drugs known to cause hypotension in those with persistent postural hypotension, i.e. recurrent >20 mmHg drop in systolic blood pressure (risk of syncope, falls).
-
5.
Long-term opiates in those with recurrent falls (risk of drowsiness, postural hypotension, vertigo).
I. Analgesic drugs
-
1.
Use of long-term powerful opiates e.g. morphine or fentanyl as first line therapy for mild-moderate pain [World Health Organization (WHO) analgesic ladder not observed].
-
2.
Regular opiates for more than 2 weeks in those with chronic constipation without concurrent use of laxatives (risk of severe constipation).
-
3.
Long-term opiates in those with dementia unless indicted for palliative care or management of moderate/severe chronic pain syndrome (risk of exacerbation of cognitive impairment).
J. Duplicate drug classes
Any regular duplicate drug class prescription, such as two concurrent opiates, NSAIDs, SSRIs, loop diuretics, ACE inhibitors (optimization of monotherapy within a single drug class should be observed prior to considering a new class of drug). This excludes duplicate prescribing of drugs that may be required on a prn (as needed) basis, such as inhaled beta-2 agonists (long and short acting) for asthma or COPD and opiates for management of breakthrough pain.
START: Screening Tool to Alert doctors to Right (i.e. appropriate) indicated Treatments
These medications should be considered for people ≥65 years of age with the following conditions, where no contraindication to prescription exists.
A. Cardiovascular system
-
1.
Warfarin in the presence of chronic atrial fibrillation.
-
2.
Aspirin in the presence of chronic atrial fibrillation, where warfarin is contraindicated, but not aspirin.
-
3.
Aspirin or clopidogrel with a documented history of atherosclerotic coronary, cerebral or peripheral vascular disease in patients with sinus rhythm.
-
4.
Antihypertensive therapy where systolic blood pressure consistently >160 mmHg.
-
5.
Statin therapy with a documented history of coronary, cerebral or peripheral vascular disease, where the patient’s functional status remains independent for activities of daily living and life expectancy is > 5 years.
-
6.
ACE inhibitor with chronic heart failure.
-
7.
ACE inhibitor following acute myocardial infarction.
-
8.
Beta-blocker with chronic stable angina.
B. Respiratory system
-
1.
Regular inhaled beta-2 agonist or anticholinergic agent for mild to moderate asthma or COPD.
-
2.
Regular inhaled corticosteroid for moderate–severe asthma or COPD, where predicted FEV1 <50%.
-
3.
Home continuous oxygen with documented chronic type 1 respiratory failure (pO2 <8.0 kPa, pCO2 <6.5 kPa) or type 2 respiratory failure (pO2 <8.0 kPa, pCO2 >6.5 kPa)
C. Central nervous system
-
1.
L-DOPA in idiopathic Parkinson’s disease with definite functional impairment and resultant disability.
-
2.
Antidepressant drug in the presence of moderate-severe depressive symptoms lasting at least three months.
D. Gastrointestinal system
-
1.
PPI with severe gastro-oesophageal acid reflux disease or peptic stricture requiring dilatation.
-
2.
Fibre supplement for chronic, symptomatic diverticular disease with constipation.
E. Musculoskeletal system
-
1.
Disease-modifying anti-rheumatic drug (DMARD) with active moderate-severe rheumatoid disease lasting >12 weeks.
-
2.
Bisphosphonates in patients taking maintenance oral corticosteroid therapy.
-
3.
Calcium and vitamin D supplement in patients with known osteoporosis (radiological evidence or previous fragility fracture or acquired dorsal kyphosis).
F. Endocrine system
-
1.
Metformin with type 2 diabetes ± metabolic syndrome (in the absence of renal impairment*).
-
2.
ACE inhibitor or angiotensin receptor blocker in diabetes with nephropathy, i.e. overt urinalysis proteinuria or micoralbuminuria (>30 mg/24 h) ± serum biochemical renal impairment (estimated glomerular filtration rate <50 ml/min).
-
3.
Antiplatelet therapy in diabetes mellitus if one or more co-existing major cardiovascular risk factor present (hypertension, hypercholesterolaemia, smoking history).
-
4.
Statin therapy in diabetes mellitus if one or more co-existing major cardiovascular risk factor present.
Appendix 3: Univariate analysis to determine which factors were significantly associated with potentially inappropriate prescribing according to STOPP, Beers and START criteria
Factors | STOPP | Beers’ | START | ||||||
---|---|---|---|---|---|---|---|---|---|
PIM (n = 462) | No PIM (n = 438) | p | PIM (n = 274) | No PIM (n = 626) | p | PIM (n = 535) | No PIM (n = 365) | p | |
Age (years) | 0.906 | 0.746 | 0.005* | ||||||
62–74 | 73 | 74 | 0.657 | 42 | 105 | 0.589 | 73 | 74 | 0.008* |
75–84 | 217 | 203 | 0.31 | 126 | 294 | 0.786 | 245 | 175 | 0.525 |
≥85 | 172 | 161 | 0.883 | 106 | 227 | 0.488 | 217 | 116 | 0.007* |
Gender | 0.007* | 0.097* | 0.034* | ||||||
Male | 161 | 191 | 96 | 256 | 194 | 158 | |||
Female | 301 | 247 | 178 | 370 | 341 | 207 | |||
Dementia | 182 | 140 | 0.02* | 105 | 217 | 0.292 | 194 | 128 | 0.714 |
CCI ≥ 2 | 318 | 280 | 0.119 | 189 | 409 | 0.287 | 388 | 210 | 0.000* |
Number of medications | 0.000* | 0.000* | 0.002* | ||||||
≤5 | 139 | 235 | 0.000* | 68 | 306 | 0.000* | 197 | 177 | 0.000* |
6–10 | 224 | 176 | 0.012* | 142 | 258 | 0.003* | 260 | 140 | 0.002* |
≥11 | 99 | 27 | 0.000* | 64 | 62 | 0.000* | 78 | 48 | 0.554 |
≥1 hospital admission in preceding year | 278 | 239 | 0.089* | 175 | 342 | 0.010* | 321 | 196 | 0.060* |
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Gallagher, P., Lang, P.O., Cherubini, A. et al. Prevalence of potentially inappropriate prescribing in an acutely ill population of older patients admitted to six European hospitals. Eur J Clin Pharmacol 67, 1175–1188 (2011). https://doi.org/10.1007/s00228-011-1061-0
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DOI: https://doi.org/10.1007/s00228-011-1061-0