Medicines and Falls – Guidance on Causes and Risks (Version 1 – July 2015)

All patients should have their drug burden reviewed with respect to its propensity to cause falls. The history should establish the reason the drug was given, when it started, whether it is effective and what its side effects have been. An attempt should be made to reduce the number and dosage of medications, where possible. Ensure they are appropriate and not causing undue side effects.

Falls can be caused by almost any drug that acts on the brain or on the circulation. Usually the mechanism leading to a fall is one or more of: • sedation, with slowing of reaction times and impaired balance • hypotension, including orthostatic (postural) hypotension • bradycardia, tachycardia or periods of asystole

Falls may be the consequence of recent medication changes, but are usually caused by medicines that have been given for some time.

Red: High risk: can commonly cause falls alone or in combination Amber: Moderate risk: can cause falls, especially in combination Yellow: Lower risk: can possibly causes falls, particularly in combination

Drugs acting on the brain (aka psychotropic drugs) There is good evidence that stopping these drugs can reduce falls (1).

Taking such a medicine roughly doubles the risk of falling. There are no data on the effect of taking two or more such medicines at the same time. (2)

Sedatives, antipsychotics and sedating antidepressants cause drowsiness and slow reaction times. Some antidepressants and antipsychotics also cause orthostatic hypotension.

DRUG CLASS EXAMPLES EFFECT Sedatives: Benzodiazepines Chlordiazepoxide, clonazepam, Drowsiness, slow reactions, diazepam, lorazepam, impaired balance. nitrazepam, oxazepam, Caution in patients who have temazepam been taking them long term.

Sedatives: Z-Drugs Zaleplon, zopiclone, zolpidem Drowsiness, slow reactions, impaired balance.

Sedating antidepressants Amitriptyline, clomipramine, All have some alpha-receptor (tricyclics and related dosulepin, doxepin, imipramine, blocking activity and can cause drugs) lofepramine, nortriptyline, orthostatic hypotension. trimipramine All are also histamine-H2 blockers and cause drowsiness, Mianserin, mirtazapine, impaired balance and slow trazodone reaction times.

Monoamine Oxidase Inhibitors Isocarboxazid, phenelzine, Now seldom used. All (except tranylcypromine moclobemide) can cause severe orthostatic hypotension.

SSRI antidepressants Citalopram, escitalopram, In population studies, cause falls fluoxetine, paroxetine, sertraline as much as other antidepressants. (See below).

Several population studies have shown that SSRIs are consistently associated with an increased rate of falls and fractures, but there are no prospective trials. The mechanism of such an effect is unknown. They cause orthostatic hypotension and bradycardia but only rarely as an idiosyncratic side effect. They do not normally sedate but can impair sleep quality.

SNRI antidepressants Duloxetine, venlafaxine As for SSRIs but also commonly cause orthostatic hypotension.

Drugs for psychosis and Chlorpromazine, fluphenazine, All have some alpha-receptor related conditions haloperidol, olanzapine, blocking activity and can cause quetiapine, risperidone, orthostatic hypotension. trifluoperazine Sedation, slow reflexes, loss of balance.

Opiate (and opioid) analgesics Codeine, dihydrocodeine, Drowsiness, slow reactions, fentanyl, morphine, oxycodone, impair balance, cause delirium, tramadol

Anti-convulsants Phenytoin May cause permanent cerebellar damage and unsteadiness in long term use at therapeutic dose. Excess blood levels cause unsteadiness and ataxia.

Anti-convulsants Carbamazepine, phenobarbital Drowsiness, slow reactions. Excess blood levels cause unsteadiness and ataxia.

Anti-convulsants Gabapentin, sodium valproate Some data suggest an association with falls.

Anti-convulsants Lamotrigine, levatiracetam, Insufficient data to know if these pregabalin, topiramate newer agents cause falls, but it appears less likely

Parkinson’s disease: Pramipexole, ropinirole Can cause orthostatic Dopamine agonists hypotension and delirium. (See below)

Parkinson’s disease: Selegiline Causes orthostatic hypotension. MAOI-B inhibitors (See below).

The association between drugs for Parkinson’s disease and falls is difficult to quantify as orthostatic hypotension is part of the disease state and falls are common. In general only if orthostatic hypotension is definitely considered drug-related should medication be changed.

Anti-muscarinics Orphenadrine, procyclidine, Dizziness, blurred vision, trihexyphenidyl confusion.

Anti-dementia drugs: Donepezil, galantamine, Dizziness, bradycardia, syncope, AChEIs rivastigmine muscle spasm.

Anti-dementia drugs: Memantine Commonly causes dizziness and Memantine balance disorders Muscle relaxants Baclofen, dantrolene Drowsiness, reduced muscle tone. (See below).

There are little falls data on muscle relaxants as they tend to be used in conditions associated with falls.

Vestibular sedatives / anti- Cyclizine, metoclopramide, Some alpha-receptor blocking emetics prochlorperazine activity and can cause Phenothiazines orthostatic hypotension. Sedation, slow reflexes, loss of balance.

Vestibular sedatives Betahistine, cinnarazine No data, but sedation likely to Antihistamines contribute to falls.

Antihistamines for allergy Chlophenamine, hydroxyzine, No data, but sedation likely to (Sedating) promethazine, trimeprazine contribute to falls.

Anticholinergics acting on the Oxybutinin, solifenacin, No data, but have known CNS bladder tolterodine effects.

Drugs acting on the heart and circulation

Maintaining consciousness and an upright posture requires adequate blood flow to the brain. This requires adequate pulse and blood pressure. In older people a systolic BP of 110mmHg or less is associated with an increased risk of falls.

Any drug that reduces blood pressure or slows the heart can cause falls (or feeling faint or loss of consciousness or “legs giving way”) (3). In some patients the cause is clear – they may be hypotensive, or have a systolic blood pressure drop on standing. Others may have a normal blood pressure lying and standing, but have syncope or pre-syncope from underlying circulatory disorders.

Alpha receptor blockers Alfluzosin, doxazosin, indoramin, Commonly cause severe (Used for hypertension or for prazosin, tamsulosin, terazocin orthostatic hypotension. prostatism in men).

Centrally acting alpha-2 Clonidine, moxonidine Can cause severe orthostatic receptor agonists hypotension. Sedating.

Thiazide diuretics Bendroflumethiazide, Cause orthostatic hypotension. chlorthalidone, metolazone Muscle weakness due to lowered sodium and potassium plasma levels.

Loop diuretics Bumetanide, furosemide Dehydration causes hypotension. Muscle weakness due to lowered sodium and potassium plasma levels.

Angiotensin converting Captopril, enalapril, lisinopril, Can cause severe orthostatic enzyme inhibitors (ACEIs) perindopril, ramipril hypotension.

Symptomatic hypotension in systolic cardiac failure  ACEIs and beta blockers have a survival benefit in systolic cardiac failure and should be maintained whenever possible.  NICE recommends: stop nitrates, calcium channel blockers and other vasodilators. If no evidence of cardiac congestion, reduce diuretics. If problem persists, seek specialist advice.  The mortality risk from a fall at age 85 is about 1% per fall. The frequency of falls determines the balance between risk and benefit.  Most cardiac failure in older people is diastolic (preserved left ventricular function). ACEIs and beta blockers have little survival benefit in diastolic failure.

Angiotensin receptor Candesartan, irbesartan, Cause less orthostatic blockers (ARBs) losartan, telmesartan, valsartan hypotension than ACEIs but still carry significant risk.

Beta blockers Atenolol, bisoprolol, propranolol, Can cause bradycardia and sotalol hypotension.

Anti-anginals Glyceryl trinitrate (GTN) Commonly cause syncope due to sudden blood pressure drop.

Isosorbide dinitrate/mononitrate, Cause hypotension and nicorandil paroxysmal hypotension

Calcium channel blockers that Amlodipine, felodipine, Cause hypotension and only reduce blood pressure lercanidipine, nifedipine paroxysmal hypotension

Calcium channel blockers Diltiazem, verapamil Can cause hypotension and/or which reduce blood pressure bradycardia and slow the pulse

Other antidysrhythmics Amiodarone, digoxin, flecainide Can cause bradycardia and other arrhythmias. Data on digoxin and falls probably spurious due to confounding by indication.

Author:

Jed Hewitt Chief Pharmacist – Governance & Professional Practice

Based on a document produced by The John Radcliffe Hospital, Oxford (2011).

Approved by the Trust Drugs & Therapeutics Group: July 2015 Date of next review: July 2018

References:

1) Campbell, Robertson et al. J. Am. Geriatric Soc 1999: 47: 850-3 2) Darowski, Chambers & Chambers. Drugs & Aging 2009; 26 (5): 381-395 3) Darowski & Whiting. Reviews in Clinical Gerontology 2011; 21 (2): 170-179 4) Van der Velde et al. J. Am. Geriatric Soc 2007; 55: 734-739 5) Alsop & MacMahon. Postgrad MJ 2001; 77: 403-5