What is the risk of falls associated with the use of Seroquel (quetiapine) in elderly patients?

Seroquel (Quetiapine) Significantly Increases Fall Risk in Elderly Patients

Quetiapine poses a substantial fall risk in elderly patients through multiple mechanisms including orthostatic hypotension, sedation, and motor instability, and should be used with extreme caution or avoided when safer alternatives exist. 1

Primary Fall Risk Mechanisms

Quetiapine directly causes falls through three main pathways:

• Orthostatic hypotension occurs due to α1-adrenergic antagonist properties, with syncope reported in 1% of treated patients versus 0.2% in placebo groups 1
• Somnolence is particularly pronounced during the initial 3-5 day dose-titration period, affecting 16-57% of patients depending on indication (compared to 4-15% with placebo) 1
• Motor and sensory instability combined with postural hypotension creates a direct pathway to falls and subsequent fractures 1

The FDA label explicitly states: "Atypical antipsychotic drugs, including quetiapine, may cause somnolence, postural hypotension, motor, and sensory instability, which may lead to falls and, consequently, fractures or other injuries." 1

Evidence from Clinical Guidelines

Multiple high-quality guidelines identify antipsychotics, including quetiapine, as significant fall risk factors:

• The American Geriatrics Society (2001) identified psychotropic medications as having an odds ratio of 1.7 for falls, ranking them among the top modifiable risk factors 2
• The American Academy of Otolaryngology (2017) states that "psychotropic medications such as benzodiazepines are a significant independent risk factor for falls" and notes that fall risk increases with polypharmacy and concurrent use of antidepressants 2
• The Mayo Clinic (2021) specifically lists atypical antipsychotics including quetiapine in their deprescribing table for older adults, noting they worsen cognitive function and should be avoided as pharmacological behavioral control in cognitive disease 2

Special Considerations for Elderly Patients

The fall risk is amplified in geriatric populations through several mechanisms:

• Reduced dose in older patients is mandated due to hepatic impairment and increased sensitivity, yet even at lower doses, sedation and orthostatic hypotension remain problematic 2
• Polypharmacy concerns are critical, as elderly patients with diabetes and other conditions taking multiple medications face exponentially increased fall risk 2
• Anticholinergic effects from norquetiapine (quetiapine's active metabolite) contribute additional cognitive impairment and constipation, further increasing fall risk 1

Practical Management Algorithm

If quetiapine must be used in elderly patients:

1. Start with 25 mg doses (lower than standard) and titrate extremely gradually 2
2. Complete fall risk assessment at initiation and recurrently during long-term therapy 1
3. Monitor orthostatic vital signs regularly, especially after dose adjustments, checking blood pressure supine, immediately upon standing, and after 5 minutes 3
4. Evaluate home safety for high-risk patients and assess gait and balance regularly 3
5. Review all concurrent medications for additive fall risk, particularly other psychotropics, antihypertensives, and anticholinergic agents 2, 3

Critical Warnings

Common pitfalls to avoid:

• Never combine with benzodiazepines - this combination has been associated with fatalities due to oversedation and respiratory depression 2
• Do not use in dementia-related psychosis - FDA black box warning for increased mortality risk, and these patients have the highest fall vulnerability 1
• Avoid abrupt discontinuation - withdrawal symptoms including insomnia and agitation can paradoxically increase fall risk 1

Deprescribing Considerations

The evidence strongly supports deprescribing quetiapine when possible:

• Educational programs to modify prescriber use of such medications have demonstrated reduction in falls 2
• Safe tapering to discontinuation is recommended, especially when there is perceived lack of benefit 2
• Alternative non-pharmacologic interventions (redirection, environmental modifications) should be prioritized over antipsychotic use for behavioral symptoms 2