Pregabalin dependence, withdrawal, suicidality and psychosis reports: A disproportionality analysis of the Australian adverse events database.

Aims: Globally, Australia has the highest per capita consumption rate of pregabalin, commonly prescribed for neuropathic pain. Emerging evidence suggests pregabalin may be associated with the onset or recurrence of several potentially life-threatening psychiatric events in some individuals.

Methods: We conducted disproportionality analyses using case reports involving adverse events related to dependence, withdrawal, suicidality and psychosis, submitted to Australia's Therapeutic Goods Administration between 2005 and 2024. Reporting odds ratios (RORs) were calculated to determine whether these adverse events were disproportionately reported for pregabalin compared to all other drugs in the database and to an active comparator group of other neuropathic pain drugs (gabapentin, duloxetine and amitriptyline).

Results: Compared to all other drugs in the database, pregabalin showed strong signals of disproportionate reporting for drug abuse and dependence (ROR = 13.53, 95% confidence interval [CI]: 12.12, 15.10), drug withdrawal (ROR = 6.76, 95% CI: 4.99, 9.15), suicide and self-injury (ROR = 12.40, 95% CI: 10.71, 14.36), and psychosis and psychotic disorders (ROR = 5.81, 95% CI: 4.99, 6.76). When compared to other neuropathic pain drugs, the signal of disproportionate reporting remained for drug abuse and dependence (ROR = 1.38, 95% CI: 1.17, 1.62) and psychosis and psychotic disorders (ROR = 1.26, 95% CI: 1.002, 1.57), albeit with less pronounced effects.

Conclusions: Adverse events related to drug dependence and psychosis are reported to the Australian pharmacovigilance database at a higher rate for pregabalin compared to other drugs, including other neuropathic pain drugs, signalling a potential concern that warrants further investigation.