Is Lyrica (pregabalin) as effective as Gabapentin in controlling seizures in patients with a history of epilepsy?

Pregabalin (Lyrica) is NOT as protective against seizures as Gabapentin

Based on the available evidence, pregabalin and gabapentin demonstrate comparable efficacy for seizure control in drug-resistant focal epilepsy, with no significant superiority of either agent. However, neither drug is recommended as a first-line or second-line agent for acute seizure management or status epilepticus in current treatment guidelines.

Evidence for Comparative Efficacy

Direct Head-to-Head Comparison

• A randomized controlled trial directly comparing pregabalin to gabapentin found no significant difference in seizure reduction between the two medications 1
• The median percentage change from baseline was -58.65% for pregabalin versus -57.43% for gabapentin, with the Hodges-Lehman estimated median difference of 0.0 (95% CI -6.0 to 7.0) 1
• Both drugs showed unexpectedly high response rates in this trial, raising questions about generalizability 1

Efficacy as Add-On Therapy

• Pregabalin at doses of 150-600 mg/day demonstrates significant efficacy as adjunctive therapy for drug-resistant focal epilepsy, with responder rates (≥50% seizure reduction) approaching 50% at 600 mg/day 2
• A Cochrane review confirmed pregabalin's efficacy as add-on treatment, showing participants were significantly more likely to achieve ≥50% seizure reduction compared to placebo (RR 1.95% CI 1.40 to 2.72) 3
• When compared to gabapentin as add-on therapy, pregabalin showed no significant difference in achieving 50% or greater seizure reduction (RR 0.96,95% CI 0.82 to 1.12) 3

Comparison to Other Antiepileptic Drugs

• Pregabalin was significantly more effective than lamotrigine in one trial (RR 1.47,95% CI 1.03 to 2.12) but significantly less effective than levetiracetam for achieving seizure freedom (RR 0.50,95% CI 0.30 to 0.85) 3

Clinical Context and Limitations

Role in Treatment Algorithm

• Neither pregabalin nor gabapentin appears in current status epilepticus treatment guidelines as first-line, second-line, or third-line agents 4
• For acute seizure management, benzodiazepines remain first-line treatment, followed by valproate, levetiracetam, fosphenytoin, or phenobarbital as second-line agents 4, 5, 6
• Both pregabalin and gabapentin are reserved for chronic management of drug-resistant focal epilepsy as adjunctive therapy, not for acute seizure control 2, 3

Tolerability Considerations

• Both pregabalin and gabapentin share similar adverse effect profiles, with the most common being dizziness, somnolence, ataxia, and weight gain 2, 7
• Pregabalin at 600 mg/day shows higher withdrawal rates due to adverse effects compared to placebo (RR 2.60,95% CI 1.86 to 3.64) 3
• The safety profiles were comparable between pregabalin and gabapentin in direct comparison 1

Evidence Quality Issues

• The direct comparison trial between pregabalin and gabapentin had atypical response rates that limit generalizability 1
• Most pregabalin trials were short-term (12 weeks), and longer-term data are needed for clinical decision-making 2, 3
• All included studies were sponsored by Pfizer, representing high risk of funding bias 3

Practical Recommendations

• For patients with drug-resistant focal epilepsy requiring add-on therapy, pregabalin and gabapentin can be considered equivalent options based on the lack of significant efficacy differences 1
• Choice between the two should be based on individual patient factors such as dosing convenience (pregabalin can be dosed twice daily vs gabapentin's three times daily), cost, and insurance coverage 7
• Neither drug should be used for acute seizure management or status epilepticus, where evidence-based protocols favor benzodiazepines, valproate, levetiracetam, or fosphenytoin 4, 5, 6