Supplementary Data

PLEASE NOTE: The very long list of references supporting each of the revised STOPP & START
criteria is too large to include in the present paper. The full list of these references is
available on the journal website http://ageing.oxfordjournals.org as Appendix 1 and
Appendix 2. In the same website, Appendix 3 shows the new STOPP criteria; Appendix 4
shows the new START criteria.

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Appendix 3: Screening Tool of Older Persons’ Prescriptions (STOPP) version 2.
The following prescriptions are potentially inappropriate to use in patients aged 65 years
and older.

Section A: Indication of medication

1. Any drug prescribed without an evidence-based clinical indication.

2. Any drug prescribed beyond the recommended duration, where treatment duration is
well defined.

3. Any duplicate drug class prescription e.g. two concurrent NSAIDs, SSRIs, loop diuretics,
ACE inhibitors, anticoagulants (optimisation of monotherapy within a single drug class
should be observed prior to considering a new agent).

Section B: Cardiovascular System

1. Digoxin for heart failure with normal systolic ventricular function (no clear evidence of
benefit)

2. Verapamil or diltiazem with NYHA Class III or IV heart failure (may worsen heart failure).

3. Beta-blocker in combination with verapamil or diltiazem (risk of heart block).

4. Beta blocker with bradycardia (< 50/min), type II heart block or complete heart block (risk
of complete heart block, asystole).

5. Amiodarone as first-line antiarrhythmic therapy in supraventricular tachyarrhythmias

(higher risk of side-effects than beta-blockers, digoxin, verapamil or diltiazem)

6. Loop diuretic as first-line treatment for hypertension (safer, more effective alternatives
available).

7. Loop diuretic for dependent ankle oedema without clinical, biochemical evidence or
radiological evidence of heart failure, liver failure, nephrotic syndrome or renal failure (leg
elevation and /or compression hosiery usually more appropriate).

8. Thiazide diuretic with current significant hypokalaemia (i.e. serum K+ < 3.0 mmol/l),
hyponatraemia (i.e. serum Na+ < 130 mmol/l) hypercalcaemia (i.e. corrected serum calcium
> 2.65 mmol/l) or with a history of gout (hypokalaemia, hyponatraemia, hypercalcaemia and
gout can be precipitated by thiazide diuretic)

9. Loop diuretic for treatment of hypertension with concurrent urinary incontinence (may
exacerbate incontinence).

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10. Centrally-acting antihypertensives (e.g. methyldopa, clonidine, moxonidine, rilmenidine,
guanfacine), unless clear intolerance of, or lack of efficacy with, other classes of
antihypertensives (centrally-active antihypertensives are generally less well tolerated by
older people than younger people)

11. ACE inhibitors or Angiotensin Receptor Blockers in patients with hyperkalaemia.

12. Aldosterone antagonists (e.g. spironolactone, eplerenone) with concurrent potassium-

conserving drugs (e.g. ACEI’s, ARB’s, amiloride, triamterene) without monitoring of serum
potassium (risk of dangerous hyperkalaemia i.e. > 6.0 mmol/l – serum K should be
monitored regularly, i.e. at least every 6 months).

13. Phosphodiesterase type-5 inhibitors (e.g. sildenafil, tadalafil, vardenafil) in severe heart
failure characterised by hypotension i.e. systolic BP < 90 mmHg, or concurrent nitrate
therapy for angina (risk of cardiovascular collapse)

Section C: Antiplatelet/Anticoagulant Drugs

1. Long-term aspirin at doses greater than 160mg per day (increased risk of bleeding, no
evidence for increased efficacy).

2. Aspirin with a past history of peptic ulcer disease without concomitant PPI (risk of
recurrent peptic ulcer ).

3. Aspirin, clopidogrel, dipyridamole, vitamin K antagonists, direct thrombin inhibitors or

factor Xa inhibitors with concurrent significant bleeding risk, i.e. uncontrolled severe
hypertension, bleeding diathesis, recent non-trivial spontaneous bleeding) (high risk of
bleeding).

4. Aspirin plus clopidogrel as secondary stroke prevention, unless the patient has a coronary
stent(s) inserted in the previous 12 months or concurrent acute coronary syndrome or has a
high grade symptomatic carotid arterial stenosis (no evidence of added benefit over
clopidogrel monotherapy)

5. Aspirin in combination with vitamin K antagonist, direct thrombin inhibitor or factor Xa

inhibitors in patients with chronic atrial fibrillation (no added benefit from aspirin)

6. Antiplatelet agents with vitamin K antagonist, direct thrombin inhibitor or factor Xa

inhibitors in patients with stable coronary, cerebrovascular or peripheral arterial disease (No
added benefit from dual therapy).

7. Ticlopidine in any circumstances (clopidogrel and prasugrel have similar efficacy, stronger
evidence and fewer side-effects).

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8. Vitamin K antagonist, direct thrombin inhibitor or factor Xa inhibitors for first deep
venous thrombosis without continuing provoking risk factors (e.g. thrombophilia) for > 6
months, (no proven added benefit).

9. Vitamin K antagonist, direct thrombin inhibitor or factor Xa inhibitors for first pulmonary
embolus without continuing provoking risk factors (e.g. thrombophilia) for > 12 months (no
proven added benefit).

10. NSAID and vitamin K antagonist, direct thrombin inhibitor or factor Xa inhibitors in
combination (risk of major gastrointestinal bleeding).

11. NSAID with concurrent antiplatelet agent(s) without PPI prophylaxis (increased risk of
peptic ulcer disease)

Section D: Central Nervous System and Psychotropic Drugs

1. TriCyclic Antidepressants (TCAs) with dementia, narrow angle glaucoma, cardiac

conduction abnormalities, prostatism, or prior history of urinary retention (risk of worsening
these conditions).

2. Initiation of TriCyclic Antidepressants (TCAs) as first-line antidepressant treatment (higher

risk of adverse drug reactions with TCAs than with SSRIs or SNRIs).

3. Neuroleptics with moderate-marked antimuscarinic/anticholinergic effects

(chlorpromazine, clozapine, flupenthixol, fluphenzine, pipothiazine, promazine,
zuclopenthixol) with a history of prostatism or previous urinary retention (high risk of
urinary retention).

4. Selective serotonin re-uptake inhibitors (SSRI’s) with current or recent significant

hyponatraemia i.e. serum Na+ < 130 mmol/l (risk of exacerbating or precipitating
hyponatraemia).

5. Benzodiazepines for ≥ 4 weeks (no indication for longer treatment; risk of prolonged
sedation, confusion, impaired balance, falls, road traffic accidents; all benzodiazepines
should be withdrawn gradually if taken for more than 4 weeks as there is a risk of causing a
benzodiazepine withdrawal syndrome if stopped abruptly).

6. Antipsychotics (i.e. other than quetiapine or clozapine) in those with parkinsonism or

Lewy Body Disease (risk of severe extra-pyramidal symptoms)

7. Anticholinergics/antimuscarinics to treat extra-pyramidal side-effects of neuroleptic

medications (risk of anticholinergic toxicity),

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8. Anticholinergics/antimuscarinics in patients with delirium or dementia (risk of
exacerbation of cognitive impairment).

9. Neuroleptic antipsychotic in patients with behavioural and psychological symptoms of

dementia (BPSD) unless symptoms are severe and other non-pharmacological treatments
have failed (increased risk of stroke).

10. Neuroleptics as hypnotics, unless sleep disorder is due to psychosis or dementia (risk of
confusion, hypotension, extra-pyramidal side effects, falls).

11. Acetylcholinesterase inhibitors with a known history of persistent bradycardia (< 60

beats/min.), heart block or recurrent unexplained syncope or concurrent treatment with
drugs that reduce heart rate such as beta-blockers, digoxin, diltiazem, verapamil (risk of
cardiac conduction failure, syncope and injury).

12. Phenothiazines as first-line treatment, since safer and more efficacious alternatives
exist (phenothiazines are sedative, have significant anti-muscarinic toxicity in older people,
with the exception of prochlorperazine for nausea/vomiting/vertigo, chlorpromazine for
relief of persistent hiccoughs and levomepromazine as an anti-emetic in palliative care ).

13. Levodopa or dopamine agonists for benign essential tremor (no evidence of efficacy)

14. First-generation antihistamines (safer, less toxic antihistamines now widely available).

Section E: Renal System. The following drugs are potentially inappropriate in older people
with acute or chronic kidney disease with renal function below particular levels of eGFR
(refer to summary of product characteristics datasheets and local formulary guidelines)

1. Digoxin at a long-term dose greater than 125µg/day if eGFR < 30 ml/min/1.73m2 (risk of
digoxin toxicity if plasma levels not measured).

2. Direct thrombin inhibitors (e.g. dabigatran) if eGFR < 30 ml/min/1.73m2 (risk of bleeding)

3. Factor Xa inhibitors (e.g. rivaroxaban, apixaban) if eGFR < 15 ml/min/1.73m2 (risk of

bleeding)

4. NSAID’s if eGFR < 50 ml/min/1.73m2 (risk of deterioration in renal function).

5. Colchicine if eGFR < 10 ml/min/1.73m2 (risk of colchicine toxicity)

6. Metformin if eGFR < 30 ml/min/1.73m2 (risk of lactic acidosis).

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Section F: Gastrointestinal System

1. Prochlorperazine or metoclopramide with Parkinsonism (risk of exacerbating Parkinsonian

symptoms).

2. PPI for uncomplicated peptic ulcer disease or erosive peptic oesophagitis at full
therapeutic dosage for > 8 weeks (dose reduction or earlier discontinuation indicated).

3. Drugs likely to cause constipation (e.g. antimuscarinic/anticholinergic drugs, oral iron,

opioids, verapamil, aluminium antacids) in patients with chronic constipation where non-
constipating alternatives are available (risk of exacerbation of constipation).

4. Oral elemental iron doses greater than 200 mg daily (e.g. ferrous fumarate> 600 mg/day,
ferrous sulphate > 600 mg/day, ferrous gluconate> 1800 mg/day; no evidence of enhanced
iron absorption above these doses).

Section G: 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
corticosteroids and effective inhaled therapies are available).

3. Anti-muscarinic bronchodilators (e.g. ipratropium, tiotropium) with a history of narrow

angle glaucoma (may exacerbate glaucoma) or bladder outflow obstruction (may cause
urinary retention).

4. Non-selective beta-blocker (whether oral or topical for glaucoma) with a history of

asthma requiring treatment (risk of increased bronchospasm).

5. Benzodiazepines with acute or chronic respiratory failure i.e. pO2 < 8.0 kPa ± pCO2 > 6.5
kPa (risk of exacerbation of respiratory failure).

Section H: Musculoskeletal System

1. Non-steroidal anti-inflammatory drug (NSAID) other than COX-2 selective agents with
history of peptic ulcer disease or gastrointestinal bleeding, unless with concurrent PPI or H2
antagonist (risk of peptic ulcer relapse).

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2. NSAID with severe hypertension (risk of exacerbation of hypertension) or severe heart
failure (risk of exacerbation of heart failure).

3. Long-term use of NSAID (>3 months) for symptom relief of osteoarthritis pain where
paracetamol has not been tried (simple analgesics preferable and usually as effective for
pain relief)

4. Long-term corticosteroids (>3 months) as monotherapy for rheumatoid arthrtitis (risk of

systemic corticosteroid side-effects).

5. Corticosteroids (other than periodic intra-articular injections for mono-articular pain) for
osteoarthritis (risk of systemic corticosteroid side-effects).

6. Long-term NSAID or colchicine (>3 months) for chronic treatment of gout where there is
no contraindication to a xanthine-oxidase inhibitor (e.g. allopurinol, febuxostat) (xanthine-
oxidase inhibitors are first choice prophylactic drugs in gout).

7. COX-2 selective NSAIDs with concurrent cardiovascular disease (increased risk of

myocardial infarction and stroke)

8. NSAID with concurrent corticosteroids without PPI prophylaxis (increased risk of peptic
ulcer disease)

9. Oral bisphosphonates in patients with a current or recent history of upper gastrointestinal

disease i.e. dysphagia, oesophagitis, gastritis, duodenitis, or peptic ulcer disease, or upper
gastrointestinal bleeding (risk of relapse/exacerbation of oesophagitis, oesophageal ulcer,
oesophageal stricture)

Section I: Urogenital System

1. Antimuscarinic drugs with dementia, or chronic cognitive impairment (risk of increased

confusion, agitation) or narrow-angle glaucoma (risk of acute exacerbation of glaucoma), or
chronic prostatism (risk of urinary retention).

2. Selective alpha-1 selective alpha blockers in those with symptomatic orthostatic

hypotension or micturition syncope (risk of precipitating recurrent syncope)

Section J. Endocrine System

1. Sulphonylureas with a long duration of action (e.g. glibenclamide, chlorpropamide,

glimepiride) with type 2 diabetes mellitus (risk of prolonged hypoglycaemia).

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2. Thiazolidenediones (e.g. rosiglitazone, pioglitazone) in patients with heart failure (risk of
exacerbation of heart failure)

3. Beta-blockers in diabetes mellitus with frequent hypoglycaemic episodes (risk of

suppressing hypoglycaemic symptoms).

4. Oestrogens with a history of breast cancer or venous thromboembolism (increased risk of

recurrence).

5. Oral oestrogens without progestogen in patients with intact uterus (risk of endometrial
cancer).

6. Androgens (male sex hormones) in the absence of primary or secondary hypogonadism

(risk of androgen toxicity; no proven benefit outside of the hypogonadism indication).

Section K: Drugs that predictably increase the risk of falls in older people

1. Benzodiazepines (sedative, may cause reduced sensorium, impair balance).

2. Neuroleptic drugs (may cause gait dyspraxia, Parkinsonism).

3. Vasodilator drugs (e.g. alpha-1 receptor blockers, calcium channel blockers, long-acting
nitrates, ACE inhibitors, angiotensin I receptor blockers, ) with persistent postural
hypotension i.e. recurrent drop in systolic blood pressure ≥ 20mmHg (risk of syncope, falls).

4. Hypnotic Z-drugs e.g. zopiclone, zolpidem, zaleplon (may cause protracted daytime
sedation, ataxia).

Section L: Analgesic Drugs

1. Use of oral or transdermal strong opioids (morphine, oxycodone, fentanyl,

buprenorphine, diamorphine, methadone, tramadol, pethidine, pentazocine) as first line
therapy for mild pain (WHO analgesic ladder not observed).

2. Use of regular (as distinct from PRN) opioids without concomitant laxative (risk of severe
constipation).

3. Long-acting opioids without short-acting opioids for break-through pain (risk of

persistence of severe pain)

Section N: Antimuscarinic/Anticholinergic Drug Burden

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Concomitant use of two or more drugs with antimuscarinic/anticholinergic properties (e.g.
bladder antispasmodics, intestinal antispasmodics, tricyclic antidepressants, first generation
antihistamines) (risk of increased antimuscarinic/anticholinergic toxicity)