Angiotensin receptor blockers linked to heightened risk of suicide
A study of thousands of individuals in Canada suggests the use of angiotensin receptor blockers (ARBs)—as opposed to angiotensin-converting enzyme inhibitors (ACEIs)—could be linked to an increased risk of suicide and poor mental health.
Both ARBs and ACEIs are common prescriptions for heart patients, first author Muhammad Mamdani, PharmD, MA, MPH, and colleagues wrote in JAMA Network Open, where their work was published Oct. 16. The drugs are used to treat a range of CV diagnoses, including hypertension, heart failure, diabetes and chronic kidney disease, lowering a patient’s blood pressure by modulating their renin-angiotensin aldosterone system.
The problem, the authors said, is that we don’t know a lot about how ARBs and ACEIs affect the renin-angiotensin system, which has been implicated in a host of mood disorders. Both classes of drugs can have anti-inflammatory or neuroprotective effects as an extension of their pharmacological outcomes, but ARBs in particular hold the potential to increase levels of angiotensin II in the brain, which might inadvertently worsen users’ outcomes.
“Because ACEIs and ARBs can cross the blood-brain barrier to various degrees, these drugs may interfere with central angiotensin II activity,” Mamdani et al. wrote. “The effect of these drugs on mental health outcomes, particularly suicide, is of increasing interest because of the bidirectional association between depression and cardiovascular disease.”
The team launched a population-based nested case-control study of 964 subjects and 3,856 matched controls in Ontario, Canada, between 1995 and 2015. Subjects had all died by suicide within 100 days of receiving an ACEI or an ARB, and each participant was matched to four controls for age, sex and presence of hypertension and diabetes. Controls were also exposed to ACEIs and ARBs.
The average age in the population was 76 years, and the overwhelming majority of subjects and controls were men (80%). During the study period, 26% of subjects and 74% of controls were exposed to ARBs, while 18.4% and 81.6% were exposed to ACEIs, respectively.
Compared with ACEI exposure, ARB exposure was tied to a 63% increased risk of death by suicide within 100 days of receiving a prescription. Findings were consistent even after a sensitivity analysis excluded participants with a history of self-harm.
“This is the sort of finding—the identification of a serious but rare adverse drug effect—that could only come from real-world data,” Ira R. Katz, MD, PhD, said in a related JAMA editorial, noting that while Mamdani et al.’s results are “important,” they require further corroboration.
Katz said that moving forward, the team will need to replicate their findings in other populations. But our current healthcare system doesn’t provide incentives to researchers for replicating their results, he said, which makes it difficult to synthesize evidence and ultimately produce solid results.
“The report by Mamdani et al. that ARBs are associated with increases in the risk of suicide in a study using real-world data requires conceptual replication,” the editorialist wrote. “The strength of the methods, the importance of preventing suicide and the number of people exposed to ARBs all support the need to encourage additional studies and to translate the combined findings into guidance about prescribing. To ensure that this occurs in a timely manner, there is a need for incentives and structures that reward replication.”
After graduating from Indiana University-Bloomington with a bachelor’s in journalism, Anicka joined TriMed’s Chicago team in 2017 covering cardiology. Close to her heart is long-form journalism, Pilot G-2 pens, dark chocolate and her dog Harper Lee.