Gabapentin users face nearly double the odds of developing depression compared with nonusers, according to a recent study.  

After adjusting for all covariates, the association remained significant, and gabapentin users demonstrated an approximately 80% higher risk of depression. Linear regression results also showed that gabapentin users had an average Patient Health Questionnaire score four points higher than nonusers. Subgroup analyses highlighted that the association was strongest among women (double the risk vs 60% increased risk in men) and those who reported shorter sleep duration—specifically, less than 7 hours a night. Of the factors analyzed, only sleep duration showed a statistically significant interaction with gabapentin use, while all other covariates had nonsignificant interaction effects. The predictive model demonstrated good overall accuracy, with an area under the receiver operating characteristic curve of 0.78.

While gabapentin is prescribed for a variety of indications, including as an adjunctive to traditional antidepressants or to mitigate their side effects, "conflicting evidence suggests that gabapentin is ineffective as a monotherapy for depression and may even exacerbate mood disturbances, particularly with prolonged or high-dose use," noted lead author Hao Zhang, MM, of the Department of Pharmacy at Chengdu Seventh People’s Hospital (Affiliated Cancer Hospital of Chengdu Medical College) in Shuangliu District, Chengdu, Sichuan Province, China, and colleagues.

In the US Food and Drug Administration’s Adverse Event Reporting System (FAERS), 9,951 adverse events were linked to gabapentin, including 1,165 (11.7%) psychiatric events. Among psychiatric reports, suicidal ideation was most frequent (263; 22.6%), whereas insomnia had the highest reporting odds ratio, 32.03. “Gabapentin use is associated with an increased risk of depression. It is crucial for clinicians to monitor patients’ mental health closely when prescribing gabapentin and to provide timely intervention if needed,” continued the authors.

The researchers conducted a population-based cross-sectional study to examine the correlation between gabapentin use and depression. Using data from the National Health and Nutrition Examination Survey (NHANES) and the FAERS between 2011 and 2018, they evaluated whether gabapentin exposure was associated with an increased likelihood of depressive symptoms.

The analysis included 6,397 adults aged 20 years and older from the NHANES after excluding participants with pregnancy, incomplete records, or missing lifestyle data. Gabapentin exposure was based on self-reported prescription medication use within the past month. To align with the Patient Health Questionnaire assessment window, participants who had taken gabapentin for fewer than 14 days were also excluded. Depressive symptoms were assessed using the 9-item Patient Health Questionnaire, with scores of 10 or higher indicating major depression. The researchers used multivariate logistic and linear regression models to adjust for demographic, lifestyle, and clinical factors, including age, sex, race, education, income, physical activity, sleep duration, hypertension, diabetes, and alcohol and caffeine intake. Of all participants, 372 reported gabapentin use, and 419 met the criteria for depression.

There were several limitations in the study. The cross-sectional NHANES design relied on self-reported and observational data, and excluding participants with missing covariates may have introduced bias. The FAERS database, a spontaneous reporting system, is subject to underreporting, misreporting, and incomplete information from varied sources, which can lead to reporting bias. Although both the reporting odds ratio and Bayesian Confidence Propagation Neural Network methods were used to strengthen adverse event signal detection, false-positive findings cannot be excluded. The results reflect an association rather than causation, and because depression is multifactorial, prospective studies are needed to confirm these findings. Limited medication data in both databases also prevented assessment of dose- or duration-dependent effects of gabapentin on depression risk.

The researchers reported no conflicts of interest.

Source: Medicine