Mark Walter

15.5 million Americans take gabapentin every year. Prescriptions tripled since 2010. It's now the 5th most prescribed drug in the US. Prescribed for nerve pain, seizures, anxiety, insomnia, restless legs, and increasingly off-label for conditions it was never tested for. A new propensity-matched study of 26,414 chronic pain patients (TriNetX, 2004-2024) found that 6+ gabapentin prescriptions were associated with 29% higher dementia risk and 85% higher risk of mild cognitive impairment. The most uncomfortable finding: adults aged 18-64 showed double the risk. RR 2.10 for dementia. RR 2.50 for MCI. The proposed mechanism: gabapentin binds alpha-2 delta subunits on voltage-gated calcium channels in the CNS. Chronic suppression of calcium signaling may impair synaptic plasticity and hippocampal function, the same pathways that degrade in Alzheimer's. This is observational. Confounding is real. Chronic pain itself raises dementia risk. But with 59 million prescriptions dispensed last year, even a modest signal warrants attention. Talk to your prescriber before making changes.