What is the falls risk associated with bupropion (antidepressant) and mirtazapine (antidepressant)?

Falls Risk with Bupropion and Mirtazapine

Mirtazapine carries a higher risk of falls compared to bupropion, with mirtazapine being associated with increased somnolence and mortality risk in elderly patients, while bupropion has a lower overall falls risk profile except for a specific risk of backward falls in geriatric patients. 1, 2

Comparative Falls Risk Profile

Mirtazapine

• Associated with higher mortality risk compared to SSRIs like sertraline (adjusted Hazard Ratio 1.16,95% CI 1.05-1.29) 1
• Causes significant somnolence and sedation, which increases falls risk 3
• Results in higher weight gain than other antidepressants like sertraline, trazodone, or venlafaxine 3
• After 90 days of use, may have lower risk of falls and fractures compared to sertraline, but initial risk is higher 1

Bupropion

• Generally has lower sedative effects compared to most antidepressants 3, 4
• Rarely causes orthostatic hypotension, which is a common mechanism for falls with other antidepressants 4
• Has a unique risk profile of causing backward falls in elderly patients, possibly due to dopaminergic effects in the basal ganglia 2
• May increase falls risk when used as augmentation therapy in elderly patients with depression 5

Mechanism of Falls Risk

1. Sedation and Impaired Alertness:

   • Mirtazapine causes marked sedation with daytime drowsiness 3
   • Bupropion has minimal sedative effects 3, 4

2. Orthostatic Hypotension:

   • Mirtazapine can cause orthostatic changes
   • Bupropion rarely causes clinically significant orthostatic hypotension 4
   • Orthostatic blood pressure changes during treatment are a significant risk factor for falls 5

3. Neurological Effects:

   • Bupropion may cause parkinsonian-like symptoms in some elderly patients, leading to backward falls 2
   • This effect is likely due to bupropion's dopaminergic activity 2

Risk Factors That Increase Falls Likelihood

• Age: Elderly patients (>65 years) are at higher risk 1, 6
• Memory impairment: Significantly increases falls risk during antidepressant treatment 5
• Polypharmacy: Combination of psychotropic medications substantially increases falls risk 3, 7
• Treatment initiation: First 6 weeks of treatment represent a high-risk period (53% of falls occur during this time) 5
• Long-term care setting: Residents in these facilities have particularly high falls risk 1

Clinical Recommendations

1. Medication Selection:

   • Consider bupropion over mirtazapine when falls risk is a primary concern, especially for long-term use 4, 1
   • Be cautious with bupropion in elderly patients with parkinsonian symptoms or gait instability 2

2. Monitoring Protocol:

   • Implement increased monitoring during the first 6 weeks of treatment with either medication 5
   • Regularly assess orthostatic blood pressure changes throughout treatment 5
   • Monitor for daytime drowsiness with mirtazapine 3

3. Risk Mitigation:

   • Use the lowest effective dose, especially in elderly patients 7
   • Avoid combining either medication with benzodiazepines or other psychotropic medications that increase falls risk 3, 7
   • Consider non-pharmacological interventions for depression when falls risk is very high 7

Special Considerations

• In patients with cognitive impairment, bupropion may be preferable due to lower sedative effects, but monitor closely for parkinsonian symptoms 2, 5
• For patients requiring nighttime sedation, mirtazapine's sedative effect may be beneficial if taken at bedtime, but daytime drowsiness should be monitored 3
• In patients with history of falls, consider orthostatic blood pressure monitoring before and during treatment 5

Remember that untreated depression itself is associated with increased falls risk, so appropriate treatment selection rather than avoidance of treatment is recommended 4.