Angiotensin Receptor Blockers and the Risk of Suicide: An Exercise in the Critical Examination of a Case-Control Study

Angiotensin receptor blockers (ARBs), used in the treatment of hypertension, may modulate neurotransmission in the central nervous system. One previous very small case-control study had suggested that ARBs increase the odds of suicide. In a recent, large, population-based, nested case-control study conducted in Ontario, Canada, completed suicide was associated with significantly increased odds of an ARB prescription during the 100 days preceding the suicide; in this analysis, confounding by indication was reduced by comparing ARB exposure with angiotensin-converting enzyme inhibitor exposure. The results of this new study were widely disseminated in the scientific and mass media. However, at least some of the data presented in the study appeared implausible, and at least one important calculation was incorrect. Furthermore, important subgroup analyses were not conducted. These incongruities diminish the confidence of the reader in the data and in the analyses presented in the study. A generous conclusion is that, at best, ARB use is a marker of suicide risk that merits examination in studies that include a follow-up, in which absolute risks and dose-dependent and treatment duration-dependent effects can be examined. A parsimonious conclusion is that there is no association proven between ARB exposure and suicide.