Gabapentinoid use is associated with modestly higher odds of Alzheimer's disease and related dementiasReviewing the Link Between Gabapentin Use and Risk of Developing Dementia

This meta-analysis evaluated the association between gabapentinoid use, specifically gabapentin and pregabalin, and the incidence of Alzheimer's disease and related dementias (ADRD). The study included a large sample size of 325,245 individuals who were prescribed gabapentinoids for neuropathic pain and other chronic conditions. The primary objective was to determine if there is a statistically significant link between these medications and the development of ADRD.

The analysis compared users of gabapentin and pregabalin against non-users or other non-gabapentinoid comparators. While specific dosing protocols were not detailed in the data, the focus remained on the overall association of gabapentinoid use with cognitive outcomes. The study also performed subgroup analyses to assess how the risk of bias and age influenced the observed associations.

The primary outcome revealed that gabapentinoid use was associated with modestly higher estimated odds of ADRD. Specifically, the results showed an Odds Ratio (OR) of 1.28 (95% CI 1.10-1.50; P = 0.002). When the analysis was restricted to studies characterized by a low risk of bias, the association was attenuated, resulting in an OR of 1.23 (95% CI 0.83-1.84). These findings suggest that while a correlation exists, it may be influenced by study quality and other confounding variables.

Secondary outcomes included investigations into the effects of age on the association and the impact of study risk of bias. The attenuation of the effect size in low-risk studies suggests that some of the observed risk in the broader meta-analysis might stem from lower-quality data or specific biases inherent in certain study designs. However, no specific p-values were provided for these secondary outcomes.

Safety and tolerability data, including specific adverse event rates, serious adverse events, or discontinuation rates, were not reported in the analysis. Therefore, the clinical safety profile of gabapentinoids regarding immediate toxicity or acute side effects is not addressed by this specific dataset.

These results contribute to the broader landscape of pharmacotherapies for neurological conditions. While some therapies targeting inflammatory pathways and neurotransmitters have shown cognitive benefits in Alzheimer's patients, this meta-analysis highlights a potential risk associated with common gabapentinoids. The findings do not establish a causal link but provide a basis for cautious clinical decision-making.

The study faced several significant methodological limitations that affect the certainty of the evidence. These include high heterogeneity (I = 90.3%), residual confounding, and confounding by indication. Because of these factors, the overall certainty of the evidence is low. The lack of clear causal inference means these results should be interpreted as an association rather than a direct effect of the medication.

Clinically, these findings suggest that physicians should exercise caution when prescribing gabapentinoids, particularly for off-label uses or in patients requiring long-term management of chronic conditions. Practitioners should weigh the benefits of pain management against the potential risk of ADRD. Further research is needed to clarify the role of confounding by indication and to determine if specific dosages or durations of use influence these outcomes.