Gabapentin and Syncope: Risk Assessment and Management
Gabapentin is not typically associated with causing syncope as a primary adverse effect, but it can contribute to syncope through its effects on the central nervous system, particularly dizziness and somnolence, which may increase fall risk. 1
Mechanism and Risk Factors
Gabapentin can cause significant CNS depression, including somnolence (21% vs 5% placebo), dizziness (28% vs 8% placebo), and ataxia, which may indirectly lead to falls and syncope, especially in vulnerable populations 1
Higher doses of gabapentin (≥600 mg/day) are associated with increased risk of altered mental status, which could contribute to syncope episodes 2
A clear dose-response relationship exists for falls or fractures, with highest risk observed among patients prescribed ≥2,400 mg/day (RR 1.90,95% CI 1.50 to 2.40) 3
Older adults are particularly susceptible to these adverse effects, with a study showing that high-dose gabapentin (>600 mg/day) was associated with a 29% increased relative risk of hospitalization with altered mental status compared to low-dose gabapentin 2
Clinical Considerations
Gabapentin is recommended for neuropathic pain management, including in patients with primary systemic AL-amyloidosis, but should be used with caution in patients with risk factors for syncope 4
When prescribing gabapentin, clinicians should be aware that it can cause significant driving impairment due to somnolence and dizziness, which may reflect the same mechanisms that could lead to syncope 1
The risk of adverse events like dizziness and somnolence appears to be highest during initial titration, with some evidence suggesting these effects may be transient and not necessarily worsen at higher maintenance doses 5
Patients should be carefully monitored when gabapentin is used with other medications with sedative properties due to potential synergistic effects that could increase syncope risk 1
Special Populations at Risk
Patients with cardiac conditions may be at higher risk for syncope when taking medications that can cause dizziness or altered mental status 4
Patients with orthostatic hypotension may experience worsened symptoms if gabapentin causes dizziness or somnolence, potentially leading to syncope 4
Individuals with alcohol use disorder may have elevated baseline risk for falls regardless of gabapentin exposure 3
Management Recommendations
Start gabapentin at low doses (100-300 mg at bedtime or 100-300 mg three times daily) and titrate slowly to minimize adverse effects that could contribute to syncope 4
Consider dose reduction in patients with renal insufficiency, as higher blood levels could increase adverse CNS effects 4
Monitor patients for early signs of dizziness, somnolence, or altered mental status, particularly during dose titration periods 1, 2
For patients who experience syncope or pre-syncope while on gabapentin, consider dose reduction or alternative medications for neuropathic pain 1
Advise patients not to operate complex machinery or drive until they have gained sufficient experience to assess whether gabapentin impairs their abilities 1
Case Reports and Special Situations
There is a case report of gabapentin successfully treating glossopharyngeal neuralgia with cardiac syncope, suggesting that in certain specific neurological conditions, gabapentin might actually help prevent syncope by treating the underlying condition 6
Another case report describes successful management of cough syncope using low-dose gabapentin, indicating that in select cases of reflex syncope triggered by cough, gabapentin might be beneficial rather than harmful 7
While gabapentin is not directly listed as a cause of syncope in major syncope guidelines 4, its known adverse effects of dizziness, somnolence, and altered mental status can increase the risk of falls and syncope, particularly in older adults and at higher doses. Careful dose titration, patient monitoring, and awareness of risk factors are essential when prescribing gabapentin to minimize syncope risk.