Use of gabapentinoid treatment and the risk of self-harm: population based self-controlled case series study

Abstract

Objective: To estimate the effect of gabapentinoid treatment on self-harm. Design: A population based self-controlled case series study. Setting: UK Clinical Practice Research Datalink Aurum database linked to the Hospital Episode Statistics and Office for National Statistics databases. Participants: 10 002 adults (aged ≥18 years), with gabapentinoid prescriptions, who had an incident event of self-harm between 1 January 2000 and 31 December 2020. Individual censoring occurred on the date of epilepsy, substance misuse, or cancer diagnosis. Main outcome measures: Crude incidence rates of self-harm in different risk periods: 90 days before gabapentinoid treatment, gabapentinoid treatment period, 14 days after treatment periods, and reference periods were calculated. Conditional Poisson regression derived the incidence rate ratio and 95% confidence intervals (CIs) to evaluate the risk of self-harm in different risk periods, compared with reference period for each individual. Results: 1 503 597 individuals received gabapentinoid prescriptions and 10 002 individuals were included in the analysis. The incidence rate of self-harm per 100 person years was 16.79 (95% CI 16.65 to 16.92) in the 90 days before treatment period, 9.66 (9.62 to 9.70) in the treatment period, 29.60 (29.09 to 30.11) in the 14 days after treatment period, and 6.75 (6.74 to 6.77) in the reference period. The results yielded an increased risk of self-harm during the 90 day period before treatment, with an adjusted incidence rate ratio of 1.69 (95% CI 1.55 to 1.85). The spline based analysis showed that the risk of self-harm declined gradually around the time of treatment initiation and returned to reference level during the treatment period (adjusted incidence rate ratio 1.06 (0.98 to 1.13)). Adjusted incidence rate ratio for self-harm increased within 14 days after treatment cessation (3.02 (2.53 to 3.60)). The findings remained consistent throughout a series of subgroups and sensitivity analyses. Conclusions: The association between gabapentinoids and risk of self-harm seems to be multifaceted: an elevated risk of self-harm is present before initiation of gabapentinoid treatment, which persists during the initial phase of the treatment period, and rises again shortly after treatment discontinuation. These findings do not support a direct effect of gabapentinoid treatment on self-harm but underscore the necessity for close patient monitoring of self-harm throughout the gabapentinoid treatment journey.