Citation

Napoli AA, Wood JJ, Coumbis JJ, Soitkar AM, Seekins DW, Tilson HH. J. Int. AIDS Soc. 2014; 17.

Copyright

(Copyright © 2014, Holtzbrinck Springer Nature Publishing Group - BMC)

DOI

10.7448/IAS.17.1.19214

PMID

unavailable

Abstract

OBJECTIVE: To assess the potential association of selected antiretrovirals (ARVs), including efavirenz, with suicidality.

DESIGN: Retrospective analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS), by performing a Multi-Item Gamma Poisson Shrinker (MGPS) disproportionality analysis.

METHODS: MGPS disproportionality analysis, a technique to identify associations between drugs and adverse events, was performed using cumulative data from the FAERS database collected up to August 2012. This method yields an Empirical Bayesian Geometric Mean score and corresponding 90% confidence interval (EB05, EB95). EB05 scores ≥2 were pre-defined as a signal for a potential drug-event association. The FAERS database includes spontaneous adverse-event reports from consumers and healthcare professionals. All FAERS reports of suicidality (including suicidal ideation, suicide attempt and completed suicide or a composite of these) in patients taking efavirenz (as single agent or in fixed-dose combination), atazanavir, darunavir, etravirine, nevirapine and raltegravir were identified. A number of parallel analyses were performed to assess the validity of the methodology: fluoxetine and sertraline, antidepressants with a known association with suicidality, and raltegravir, an ARV with rhabdomyolysis and myopathy listed as "uncommon" events in the US-prescribing information.

RESULTS: A total of 29,856 adverse event reports were identified among patients receiving efavirenz, atazanavir, darunavir, etravirine, nevirapine and raltegravir, of which 457 were reports of suicidality events. EB05 scores observed for the composite suicidality term for efavirenz (EB05 =0.796), and other ARVs (EB05 =0.279-0.368), were below the pre-defined threshold. Fluoxetine and sertraline gave EB05 scores for suicidality >2. Raltegravir gave EB05 scores >2 for myopathy and rhabdomyolysis.

CONCLUSIONS: The pre-determined threshold for signals for suicidality, including suicidal ideation, suicide attempt, completed suicide and a composite suicidality endpoint, was not exceeded for efavirenz and other ARVs in this analysis. Efavirenz has been associated with suicidality in clinical trials. Further studies that adjust for confounding factors are needed to better understand any potential association with ARVs and suicidality. © 2014 Napoli AA et al; licensee International AIDS Society.

Language: en

Keywords

Humans; United States; human; suicide; Suicide; epidemiology; suicidal ideation; Suicidality; drug use; suicide attempt; HIV; rhabdomyolysis; completed suicide; major clinical study; retrospective study; fluoxetine; pathophysiology; sertraline; efavirenz; HIV Infections; analytic method; myopathy; postmarketing surveillance; Product Surveillance, Postmarketing; antiretrovirus agent; nevirapine; monotherapy; empirical research; Article; Bayes theorem; statistics and numerical data; Anti-Retroviral Agents; atazanavir; raltegravir; Benzoxazines; Antiretroviral; etravirine; Efavirenz; geometry; darunavir; benzoxazine derivative; Disproportionality; efavirenz plus emtricitabine plus tenofovir disoproxil; Food and drug administration adverse event reporting system; Medical Dictionary for Regulatory Activities; multi item gamma poisson shrinker; Multi-Item gamma poisson shrinker.