(P-101) A Pharmacovigilance Analysis of Restless Legs Syndrome Treatments and Suicidality

Background: Lifetime suicidal ideation and attempts are prevalent among those with moderate to severe restless legs syndrome (RLS) due to the condition itself and psychiatric comorbidities, but it is unclear whether psychiatric adverse effects associated with RLS treatments are also contributors.

Objectives: To assess disproportionality in adverse drug event (ADE) reports of suicidality and suicide with RLS treatments including dopamine agonists (DAs), gabapentinoids, and select opioids.

Methods: Data from the FDA Adverse Event Reporting System were analyzed from 1995 (year of RLS diagnosis establishment) to Q3/2019. Brand and generic product names were used to extract reports for DAs (i.e., ropinirole, pramipexole, rotigotine), gabapentinoids (i.e., gabapentin, gabapentin ER, pregabalin), and opioids (i.e., oxycodone, methadone, naloxone). Drugs reported with a role of primary or secondary suspect in the ADE were included. Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms were used to identify RLS indication and to define suicidality by reactions of: suicidal ideation, suicidal behaviour, depression suicidal, suicide attempt, and completed suicide. Disproportionality was assessed with proportional reporting ratios (PRR) with restriction to serious reports (i.e., 15-day expedited) and exclusion of cases indicating litigation or from clinical study. PRRs were performed using both the full FAERS population and a population with a RLS indication. Sensitivity analysis examined non-serious reports and cases indicating litigation.

Results: There were 4,543,951 unique ADE reports for the full FAERS population, of which 2,197 reports had an RLS indication. Opioids were excluded from PRR analyses due to low RLS frequency (n=25). In the full FAERS population, gabapentin/gabapentin ER were the only agent to yield a PRR (2.537) with a significant lower 95% confidence interval (CI) (2.185). However, the PRR was not significant when restricted to the RLS population. In sensitivity analysis, both gabapentin/gabapentin ER (lower 95% CI=7.805) and pregabalin (lower 95% CI=2.328) yielded significant PRRs.

Conclusions: This analysis revealed a potential pharmacovigilance signal associated with gabapentin/gabapentin ER and suicidality when examining the full FAERS population but not the RLS population. Sensitivity analysis further revealed a potential signal for pregabalin, but this may be due to reporting bias. Although results were not significant when restricted to the RLS population, risk of suicidal ideation and behavior should be considered in RLS users of gabapentinoid agents.