Can Pregabalin (Lyrica) cause diastolic hypotension?

Pregabalin and Diastolic Hypotension

Pregabalin can cause diastolic hypotension, particularly in patients with cardiovascular risk factors or when used at higher doses. This side effect should be carefully monitored, especially during initiation of therapy.

Evidence for Pregabalin-Associated Hypotension

Pregabalin has been associated with several cardiovascular effects, including hypotension. The evidence shows:

• Pregabalin can cause fluid retention, which may contribute to cardiovascular effects including hypotension 1
• Small nocturnal dose increments of medications like dopamine agonists can effectively diminish adverse effects including postural hypotension 1, suggesting a similar approach may be beneficial with pregabalin
• Recent research indicates pregabalin has a higher risk of cardiovascular adverse events compared to gabapentin, likely due to its greater potency in binding to the α2δ subunit of L-type calcium channels 2

Risk Factors for Pregabalin-Induced Hypotension

Several patient factors increase the risk of experiencing hypotension with pregabalin:

• Advanced age (elderly patients are more sensitive to hypotensive effects of medications) 1
• History of cardiovascular disease (particularly significant in pregabalin users) 2
• Concomitant use of other medications that can cause hypotension (antihypertensives, sedatives, etc.) 1
• Renal impairment (leads to drug accumulation) 3
• Heart failure or reduced ejection fraction 3, 4

Monitoring Recommendations

When prescribing pregabalin, the following monitoring approach is recommended:

• Baseline assessment of cardiovascular function before initiating therapy 3
• Regular blood pressure monitoring, especially during dose titration 3
• Orthostatic vital signs (measuring blood pressure and heart rate while lying down and standing) 5
• Assessment for peripheral edema, which may precede more serious cardiovascular effects 4
• More frequent monitoring in patients with risk factors or taking other medications that can cause hypotension

Management of Pregabalin-Induced Hypotension

If hypotension occurs:

1. Consider dose reduction or slower titration
2. Administer pregabalin at bedtime to minimize symptomatic hypotension
3. Evaluate for and address fluid status
4. In severe cases, temporary discontinuation may be necessary
5. Consider alternative medications for neuropathic pain if hypotension persists

Comparative Risk with Other Medications

Recent evidence suggests that pregabalin carries a higher cardiovascular risk compared to gabapentin:

• A 2025 study of Medicare beneficiaries found that pregabalin was associated with a 48% higher risk of heart failure hospitalizations or emergency department visits compared to gabapentin (AHR 1.48,95% CI 1.19-1.77) 2
• This risk was even higher (85% increased risk) in patients with a history of cardiovascular disease 2
• Both pregabalin and gabapentin have been associated with increased risk of adverse cardiovascular events with long-term use 6

Clinical Implications

When treating neuropathic pain in patients with cardiovascular risk factors:

• Start with lower doses of pregabalin and titrate slowly
• Consider gabapentin as an alternative, particularly in patients with cardiovascular disease history
• For diabetic neuropathic pain specifically, duloxetine may be considered as an alternative first-line agent, though it also carries cardiovascular risks 1
• Carefully weigh the benefits of pain control against potential cardiovascular risks, especially in elderly patients or those with existing cardiovascular conditions

Conclusion

Clinicians should maintain awareness of the potential for pregabalin to cause diastolic hypotension, particularly in vulnerable populations. Proper monitoring and dose adjustment can help mitigate this risk while still providing effective pain management.