The 2023 Study in Frontiers in Pharmacology: A 2023 study in Frontiers in Pharmacology examined gabapentin or pregabalin exposure using Taiwan’s National Health Insurance Research Database.

• The Studies Conclusion: That study included more than 200,000 patients and reported a higher risk of dementia among patients exposed to gabapentin or pregabalin compared with matched non-exposed patients. The risk increased with higher cumulative defined daily doses.
• The Study’s Significance: It suggests a dose-response relationship which is highly valuable evidence for plaintiffs because if higher exposure is associated with higher risk, a strong argument can be made that the relationship is far less likely to be a random occurrence of gabapentin and cognitive decline.
• The Core Logic: If a factor truly causes an outcome, increasing the amount of that factor (the dose or exposure) should logically increase the severity or likelihood of the outcome (the response).
• The Bradford Hill Criteria: In epidemiology, this is one of the classic guidelines used to evaluate if an association is causal rather than just a coincidence.
• Statistical Significance: While a simple correlation can sometimes happen by pure chance, a consistent, step-by-step upward trend across multiple levels of exposure is mathematically much harder to attribute to a random fluke.

The 2022 Study in Frontiers in Pharmacology: This study analyzed older adults with normal cognition using data from the National Alzheimer’s Coordinating Center.

• The Study’s Results: Researchers found a link between gabapentin initiation and certain neurocognitive and functional declines, including changes in Clinical Dementia Rating scores and functional measures. The study also found increased falls in a subgroup.
• The Study’s Conclusion: The study concluded by noting that:” Gabapentin initiation was significantly associated with deleterious neurocognitive changes among older adults with initially normal cognition. Further studies are needed to examine the risk/benefit of prescribing gabapentin in older adult. “ Oh G, Moga DC, Fardo DW and Abner EL (2022) The association of gabapentin initiation and neurocognitive changes in older adults with normal cognition. Front. Pharmacol. 13:910719. doi: 10.3389/fphar.2022.910719 (emphasis added).

The Significance of Off Label Use of Gabapentin

• Off Label Prescribing: As noted above, Gabapentin was approved by the FDA for seizures and postherpetic neuralgia. However, many patients were prescribed the medication off label for chronic back pain, general neuropathy, anxiety, insomnia, migraines, fibromyalgia, and other conditions.
• Risk Benefit Calculation: This is significant because patients taking gabapentin for epilepsy may face a very different risk-benefit calculation than a patient taking it for routine low back pain. Seizures can be life-threatening. Postherpetic neuralgia can be severe.
• Limited Benefit with Potential Cognitive Risks: However, chronic back pain is often treated with multiple therapies, and if gabapentin provides limited benefit for some patients while carrying potential cognitive risks, the warning and prescribing decision becomes more important.
• Previous Fins for Off Label Promotion: In 2004, Warner-Lambert agreed to pay $430 million to resolve criminal and civil allegations tied to illegal promotion of Gabapentin for unapproved uses. Federal prosecutors described a national off-label marketing campaign that included promotion for conditions not approved by the FDA.
• Neurontin’s Off-Label Marketing History: The previous settlement did not include potential gabapentin and cognitive decline but does provide a valid argument that the rampant off label prescribing made gabapentin so widely used also exposed patients to risks they were not adequately warned about.