Anticholinergic Burden

Anticholinergic burden is the cumulative antimuscarinic effect of all drugs a person takes. It causes confusion, delirium, memory impairment and hallucinations through central effects, and dry mouth, constipation, urinary retention, blurred vision, tachycardia and angle-closure glaucoma through peripheral effects. Scoring scales rate each drug from 0 to 3, and a total of 3 or more is clinically significant.

Mechanism. Blockade of muscarinic receptors reduces acetylcholine signalling, particularly at M1 receptors in cortex and hippocampus. It also directly opposes cholinesterase inhibitors, so donepezil is blunted by an anticholinergic.

Susceptibility. Dementia, chronic kidney disease, a leaky blood-brain barrier in acute illness, older age and low body weight raise vulnerability.

Highest score (3). Amitriptyline, imipramine, clomipramine, paroxetine, chlorphenamine, promethazine, hydroxyzine, oxybutynin, tolterodine, solifenacin, darifenacin, hyoscine, olanzapine, clozapine, quetiapine, chlorpromazine and trihexyphenidyl.

Score 1 drugs. Furosemide, warfarin, metoprolol, digoxin, prednisolone, codeine and haloperidol contribute little alone but add up when several are taken together.

Alternatives by indication.

• Overactive bladder: mirabegron 25 mg orally once daily, increased to 50 mg daily after 4 to 8 weeks if needed; check blood pressure, avoid when systolic pressure is 180 mmHg or over; maximum 25 mg daily if creatinine clearance 15 to 29 mL/min or moderate hepatic impairment.
• Depression or anxiety: sertraline 25 mg orally once daily for 1 week, then 50 mg.
• Allergy: loratadine 10 mg orally once daily.
• Nausea: ondansetron 4 mg orally every 8 hours as needed, after QTc check.
• Chronic obstructive pulmonary disease: inhaled ipratropium has low systemic absorption and is usually acceptable.

Special groups. In Parkinson disease and Lewy body dementia, avoid all strong anticholinergics and use quetiapine only at the lowest dose when an antipsychotic is unavoidable. In dementia treated with a cholinesterase inhibitor, an anticholinergic should rarely be added.

Withdrawal. After prolonged use, reduce tricyclic antidepressants, paroxetine and antimuscarinic bladder drugs by about 25% every 1 to 2 weeks to avoid cholinergic rebound with nausea, sweating, anxiety and insomnia.

Monitoring. Record the total score at each review, cognition and delirium screen, bowel pattern, post-void residual volume (retention is likely when over 200 mL), intraocular symptoms and heart rate. Repeat 4 weeks after any change.

Renal and hepatic. Accumulation is greater when creatinine clearance is under 30 mL/min, so use the lowest dose of any unavoidable agent.

Approach. Remove the highest-scoring drug without a firm indication first, replace it with a drug from the alternatives listed, then reassess the total score.

Common errors. Adding an antimuscarinic bladder drug for incontinence caused by a diuretic or constipation, giving an antihistamine for sleep, and treating anticholinergic constipation with more laxatives alone.

Referral and escalation. Refer for specialist review when the score stays 3 or more after review, when cognitive decline continues after removal, or when urinary retention requires catheterisation.