Does solifenacin carry an anticholinergic burden?

Solifenacin and Anticholinergic Burden

Yes, solifenacin carries a significant anticholinergic burden as it is a competitive muscarinic receptor antagonist that can contribute to cumulative anticholinergic effects, particularly in elderly patients.

Mechanism and Anticholinergic Properties

Solifenacin is a competitive muscarinic receptor antagonist that works primarily by blocking M3 receptors in the bladder to treat overactive bladder symptoms 1. While it was developed to be more selective for bladder M3 receptors, it still exhibits anticholinergic properties that contribute to systemic anticholinergic burden:

• It acts as an antagonist at muscarinic cholinergic M1, M2, and M3 receptors 2
• Despite claims of "uroselectivity" in preclinical studies, this selectivity has not been fully validated in clinical trials 2
• Solifenacin can cross the blood-brain barrier 3, which increases its potential for central nervous system effects

Anticholinergic Side Effects

The FDA label for solifenacin clearly identifies several anticholinergic side effects 1:

• Dry mouth (most common)
• Constipation
• Blurred vision
• Heat exhaustion or heat stroke due to decreased sweating
• Urinary retention in susceptible individuals

Anticholinergic Burden in Elderly Patients

The 2021 Mayo Clinic guideline on polypharmacy management specifically addresses anticholinergic burden in older adults 4:

• Overactive bladder agents like solifenacin have strong anticholinergic effects
• These medications are "usually poorly tolerated in aged patients"
• The "anticholinergic burden" from multiple anticholinergic drugs can adversely affect cognition and functionality
• Anticholinergic medications can lead to "a decline in cognition, functional status, and activities of daily living (ADL) scores in older patients"

Cognitive Impact and Dementia Risk

Recent research raises concerns about long-term use of solifenacin in elderly patients:

• A 2022 study noted that "recent population-based studies that assessed the use of anticholinergics or bladder antimuscarinics showed an increased risk of dementia when these drugs were used for a prolonged period" 5
• While short-term clinical studies have shown solifenacin to be relatively safe for cognition, "there are no long-term randomized studies that prove the safety of this drug for the CNS" 5
• The study recommends avoiding prolonged use of solifenacin in elderly patients until its long-term safety is established 5

Clinical Implications

When prescribing solifenacin, clinicians should:

1. Consider the patient's total anticholinergic burden from all medications
2. Be particularly cautious in elderly patients or those with cognitive impairment
3. Consider alternative treatments with lower anticholinergic burden for patients at risk
4. Monitor for anticholinergic side effects, especially cognitive changes in elderly patients
5. Consider dose reduction to 5 mg in patients with severe renal impairment or moderate hepatic impairment 1

Alternative Considerations

For patients where anticholinergic burden is a concern, especially the elderly, guidelines suggest considering β3-adrenoceptor agonists like mirabegron as an alternative with less anticholinergic effects 4.

In summary, solifenacin definitively carries an anticholinergic burden that should be carefully considered, especially in elderly patients or those taking other medications with anticholinergic properties.