Download HealthEast medication and suspected delirium

High-Alert Medications and Suspected Delirium
Background information and research related to these tables:
 A wide range of medications and medication issues may contribute to delirium
o Inappropriate dosing
 Too high- for example: digoxin toxicity
 Too low- for example: uncontrolled pain may lead to delirium
o Drug-drug interactions
o Drug-disease interactionsi
 Studies demonstrate increase risk in cancer patients on opioids
 Studies demonstrate delirium risk is decreased in post-surgical patients when pain is control
o Inappropriate drug selection
 Increased drug sensitivities in the elderly
 Potential pathophysiology of delirium based on specific neurotransmitters ii:
 Excess of dopamine
 Depletion of acetylcholine
 GABA, serotonin, endorphins and glutamate also play a role
 Many medications maybe suspect, but few are consistently associated with the development of delirium. iii
o According to one critical review, psychoactive medications appear to be involved in delirium cases in
15-75% of cases
o Drugs were considered a definite cause of delirium in only 2-14% of cases
o Those cited in the critical review include:
 Opioids
 Corticosteroids
 Benzodiazepines
o Other medications mentioned but not consistently cited include:
 Anticholinergics
 NSAIDs
 Chemotherapeutic agents
o There are not many well designed studies examining drug-induced delirium
 The studies have conflicting results
 The studies vary in regards to design and analysis
 Benzodiazepines and antipsychotics noted significant results in a study
 Anticholinergics, anticonvulsants, antidepressants, antiemetics, antiparkinsonians,
corticosteroids, H-2 antagonists, and NSAIDs were not significantly associated with delirium
in any study noted in the critical review
 These studies lack defined controls and numerous variables; therefore, results may not
reliably be compared to infer significant findings.
o Critical review conclusions: the currently available epidemiologic evidence of an association of
psychoactive medications and delirium is rather weak.
High risk medications specific to the elderly (The Beers Criteria):
 Why the Beers Criteria is importantiv
o The Beers criteria are based on expert consensus developed through extensive literature reviews
identifying medications that may potentially inappropriate in older adults
o Centers for Medicare and Medicaid (CMS) adopted the Beers Criteria in July 1999 for nursing home
regulation.
o Studies examining the use of medications found on the list indicate increased provider/facility costs
and increased inpatient, outpatient and emergency visits.
o The Beers Criteria was last update via an expert panel examining current literature and professional
surveys in 2002
Information about this table- Medications Implicated in Drug-Induced Delirium i
 This in not an all encompassing list; these are medications consistently mentioned in delirium literature
 Just because a patient may be on one or more of these meds, it does not mean it is the absolute cause of delirium
 Medication sensitivity and effect vary greatly from patient to patient, and delirium cases should encompass the
patient’s entire medical picture (disease condition, environment, medications, etc.)
Table A- Medications Implicated in Drug-Induced Delirium
Medication Class
Benzodiazepines
Medication
Medication Class
Antidepressants
Amitriptyline 
Desipramine 
Doxepin 
Imipramine 
Protriptyline 
Mirtazapine 
Fluoxetine
Paroxetine
Sertraline
Lorazepam
Diazepam
Clonazepam
Alprazolam
Triazolam
Clorazepate
Opioids
Fentanyl *
Meperidine *
Morphine *
Medication
Dopaminergic Agents
Corticosteroids
Amantadine
Levodpa
Bromocriptine
Prednisone
NSAIDs
Diclofenac
Ibuprofen
Sulindac
Indomethacin
Salicylic acid
Ketoprofen
Antihypertensives
Enalapril
Captopril
Lisinopril
Reserpine
Clonidine
Methyldopa
Nifedipine
Verapamil
Atenolol
Metoprolol
Propranolol
Antipsychotics
Clozapine * 
Fluphenazine
Haloperidol
Loxapine
Olanzapine 
Perphenazine
Quetiapine 
Risperidone
Thioridazine 
Ziprasidone
Antiarrhythmics
Anticholinergics
Atropine 
Benztropine 
Scopolamine 
Tolterodine 
Antimicrobials
Amiodarone
Lidocaine
Quinidine
Tocainide
Tobramycin
Bactrim
Linezolid
Other Agents
Antiasthmatics
Theophylline
Anticonvulsants
Phenytoin
Acetazolamide
Lamotrigine
Pregabalin
Valproic Acid*
Digoxin
Alcohol
withdrawl
Lithium *
* Documented incidence from clinical trials
 Medications that have anticholinergic effects
which can be associated with cognitive impairment
The Beer’s Criteria and fairly commonly medications iv,v
Drug
Propoxyphene and combinations
Indomethacin
Pentazocine
Trimethobenzamide
Muscles relaxants and
antispasmodics
Flurazepam
Amitriptyline
Doxepine
Meprobamate
Specific dosing of
benzodiazepines
 Lorazepam > 3 mg
 Oxazepam > 60 mg
 Alprazolam > 2 mg
 Temazepam > 15 mg
 Triazolam > 0.25 mg
Long-acting benzodiazepines
 Chlordiazepoxide
 Diazepam
 Quazepam
 Halazepam
 Chlorazepate
Disopyramide
Digoxin
Short-acting dipyridamole
Methyldopa
Reserpine > 0.25 mg
Chlorpropamide
GI antispasmodics
 Dicyclomine
 Hyoscyamine
 Belladonna alkaloids
 Clidiniumchlordiazapoxide
Anticholinergics/Antihistamines
 Chlorpheniarmine
 Diphenhydramine
 Hydroxyzine
Concern
Demonstrates analgesic effects similar to
acetaminophen with adverse effects of
narcotics
Produces most CNS effects of the
NSAID class
Narcotic with several CNS effects:
confusion and hallucinations
Poor antiemetic effects; potential for
EPS
Poorly tolerated in elderly;
anticholinergic effects; increase fall risk
Severity Rating
Low
High
High
High
High
Extremely long half-life cause prolonged
side effects of sedation and falls
Potent anticholinergic; sedating
Potent anticholinergic; sedating
Highly addictive anxiolytic
Doses ranging higher than those
suggested demonstrate little benefit with
increased side effects compared to
smaller doses
High
Long half-life produces prolonged
sedation and increased risk for falls
High
Particular antiarrhythmic may induce
heart failure in elderly; also
anticholinergic effects
Closely monitor renal clearance and
levels to prevent toxicity
Potential for orthostatic hypotenstion;
long-acting formulation only in those
with prosthetic heart valves
Bradycardia; may potentiate depression
May induce depression, impotence,
sedation, orthostatic hypotension
Long half-life may prolong
hypoglycemia
Increased anticholinergic effects;
efficacy uncertain
High
Potent anticholinergic
High
High
High
High
Low
Low
High
Low
High
High
 Cyproheptadine
 Promethazine
Diphenhydramine
Ferrous Sulfate > 325 mg/day
Barbiturates (except
Phenobarbital)
Meperidine
Ticlopide
Ketorolac
Amphetamines
Long-term use of NSAIDs
Bisacodyl
Amiodarone
Fluoxetine (daily dosing)
Nitrofurantoin
Doxazosin
Methyltestosterone
Short acting nifedipine
Clonidine
Mineral oil
Cimitidine
Ethacrynic acid
Estrogens only agents
Confusion and sedation; use lowest
possible dose in allergic reactions
High doses not dramatically absorbed;
constipation greatly increased
Highly addictive; harmful side effects
High
Advantage over other analgesics
questionable; increased side effects
No more efficacious than aspirin for
clots; more side effects
Use (especially long-term) associated
with GI side effects
Addictive; Induce hypertension, angina,
and myocardial infarction
GI bleeds, renal failure, high blood
pressure, heart failure
Long-term use may exacerbate bowel
dysfunction
May prolong QT interval; questionable
efficacy in elderly
Long half-life may prolong CNS
stimulation, sleep disturbances, agitation
Renal impairment
Hypotention; anticholinergic effects
Prostatic hypertrophy; cardiac issues
Hypotension; constipation
Hypotension; CNS effects
Risk for aspiration and other side effects
Increased CNS effects (confusion); drug
interactions
Hypertension; fluid imbalances
Evidence of carcinogenic potential and
lack of cardio-protective effects in
elderly women
High
Low
High
High
High
High
High
High
High
High
High
Low
High
High
Low
High
Low
Low
Low
Notes:
Abbreviations: CNS- central nervous system; NSAIDs- nonsteroidal anti-inflammatory drugs; EPS- extrapyramidal
symptoms
Anticholinergic effects- may effect several different systems; most notable effects include: ataxia, dry mouth and
eyes, blurred vision, constipation, tachycardia, light-headedness urinary retention, confusion, and agitation.
References:
i
Borovick and Fuller. Drug-Induced Diseases: Prevention, Detection, and Management: 2nd ed. ASHP 2010;
Chapter 15: Delirium.
ii
Girard TD, et al. Crit Care 2008; 12(Suppl 3): S3
iii
Gaudreau JD, et al. Psychosomatics 2005; 46(6): 302-316
Fick DM, et al. Arch Intern Med 2003; 163: 2716-2724
v
PA-PSRS Patient Safety Advisory 2005; Vol 2(4)
iv