Can Lyrica (pregabalin) cause cognitive side effects?

Cognitive Side Effects of Lyrica (Pregabalin)

Yes, Lyrica (pregabalin) can cause significant cognitive side effects including confusion, difficulty with concentration/attention, memory problems, and thinking abnormalities. 1

Evidence of Cognitive Side Effects

Pregabalin's FDA label clearly documents cognitive side effects, including:

• Confusion (reported in 2-7% of patients, dose-dependent)
• Thinking abnormal (primarily difficulty with concentration/attention, reported in 2-9% of patients)
• Amnesia (reported in 2-6% of patients)
• Speech disorder (reported in 1-7% of patients)
• Incoordination (reported in 2-6% of patients) 1

These cognitive effects are dose-dependent, with higher rates at 600 mg/day compared to lower doses.

Research Confirming Cognitive Impairment

A Class I double-blind, placebo-controlled study in healthy volunteers specifically examining cognitive effects found that pregabalin at 600 mg/day for 12 weeks caused:

• Significant negative effects on multiple cognitive measures including:
  • Digit Symbol test
  • Stroop test
  • Controlled Oral Word Association test
• Subjective complaints of neurotoxicity as measured by the Portland Neurotoxicity Scale 2

This high-quality study provides direct evidence that pregabalin negatively impacts cognition even in healthy individuals.

Risk Factors and Vulnerable Populations

Certain populations may be at higher risk for cognitive side effects:

• Elderly patients are particularly vulnerable to cognitive impairment with pregabalin 3
• Patients with renal impairment may experience increased side effects due to reduced clearance 4
• Concomitant use with other CNS depressants can worsen cognitive effects 1

Mechanism of Cognitive Effects

Pregabalin's cognitive side effects likely stem from its mechanism of action:

• As a GABA analogue, it affects neurotransmission in the central nervous system 4
• It inhibits presynaptic excitatory neurotransmitter release by blocking α2δ calcium channels 5
• Animal studies have demonstrated memory impairment with chronic pregabalin administration 6

Clinical Recommendations

When prescribing pregabalin:

1. Start with low doses (25-50 mg at night) and titrate slowly to minimize cognitive side effects 5
2. Monitor for cognitive changes regularly during treatment
3. Consider alternative medications if cognitive side effects emerge
4. Use caution in elderly patients - the American Geriatrics Society recommends avoiding medications with anticholinergic properties and CNS effects in older adults 3
5. Avoid combining with other CNS depressants when possible to prevent additive cognitive impairment 1

Other Common Side Effects to Monitor

Beyond cognitive effects, monitor for:

• Dizziness (21-38% of patients)
• Somnolence (12-28% of patients)
• Peripheral edema (5-12% of patients)
• Weight gain (4-16% of patients)
• Blurred vision (4-12% of patients) 1

Conclusion

When prescribing Lyrica, clinicians should weigh the potential benefits against the risk of cognitive impairment. Patients should be informed about possible cognitive side effects and monitored closely, especially during dose adjustments. Using the lowest effective dose may help minimize these adverse effects while maintaining therapeutic benefit.