In the Journals

Angiotensin receptor blockers may increase risk for suicide

Patients treated with angiotensin receptor blockers had an increased risk for suicide compared with those treated with ACE inhibitors, according to a study published in JAMA Network Open.

“Given their high prevalence of use, the severity of the outcome and the similar efficacy of these drug classes in treating the same conditions, clinicians may opt for preferential use of ACE inhibitors over angiotensin receptor blockers where possible,” Muhammad Mamdani, PharmD, MA, MPH, director of the Applied Health Research Center at the Li Ka Shing Knowledge Institute at St. Michael’s Hospital in Toronto and associate professor in the department of health policy, management and evaluation at the University of Toronto, and colleagues wrote.

Older patients and controls

Researchers analyzed data from 964 patients (80% men) aged at least 66 years who died by suicide within 100 days of being prescribed an ACE inhibitor or angiotensin receptor blocker.

These patients were matched by sex, age and previous diagnoses of diabetes and hypertension with up to four controls, which totaled to 3,856 controls (80% men). The controls were also exposed to an ACE inhibitor or angiotensin receptor blocker within 100 days of the index date, which was defined as the date of death.

Patients treated with angiotensin receptor blockers had an increased risk for suicide compared with those treated with ACE inhibitors, according to a study published in JAMA Network Open.
Source: Adobe Stock

The median age of both patients and controls was 76 years. Of the patients who died from suicide, 26% were exposed to angiotensin receptor blockers and 18.4% were exposed to an ACE inhibitor. In contrast, 74% of controls were exposed to angiotensin receptor blockers and 81.6% were exposed to ACE inhibitors.

Exposure to angiotensin receptor blockers was linked to an increased risk for death by suicide compared with exposure to ACE inhibitors (adjusted OR = 1.63; 95% CI, 1.33-2). Findings were consistent when patients with a history of self-harm were excluded in a sensitivity analysis (OR = 1.6; 95% CI, 1.29-1.98).

“The mechanisms by which angiotensin receptor blockers or ACE inhibitors might impart differential risks of suicide are unknown,” Mamdani and colleagues wrote. Higher levels of angiotensin II may increase levels of substance P, which may, in turn, promote stress and anxiety. Similarly, animal studies have found that angiotensin II induces panic and stress when injected into stress-sensitive brain structures such as the dorsomedial hypothalamus and amygdala. However, because these effects were reversible after angiotensin II type 1 receptor blockade with an angiotensin receptor blocker, it is unlikely that this is the mechanism associating these drugs with suicide.”

Future research

In a related editorial, Ira R. Katz, MD, PhD, professor of psychiatry and director of the section of geriatric psychiatry at the University of Pennsylvania and director of the Mental Illness Research Education and Clinical Center at Philadelphia VA Medical Center, wrote: “The strength of the methods, the importance of preventing suicide and the number of people exposed to angiotensin receptor blockers 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.” – by Darlene Dobkowski

Disclosures: Mamdani reports he received honoraria for serving on ad hoc advisory boards for Allergan and Novo Nordisk and received an honorarium from Celgene. Katz reports he is an employee of the U.S. Department of Veterans Affairs. Please see the study for all other authors’ relevant financial disclosures.

Patients treated with angiotensin receptor blockers had an increased risk for suicide compared with those treated with ACE inhibitors, according to a study published in JAMA Network Open.

“Given their high prevalence of use, the severity of the outcome and the similar efficacy of these drug classes in treating the same conditions, clinicians may opt for preferential use of ACE inhibitors over angiotensin receptor blockers where possible,” Muhammad Mamdani, PharmD, MA, MPH, director of the Applied Health Research Center at the Li Ka Shing Knowledge Institute at St. Michael’s Hospital in Toronto and associate professor in the department of health policy, management and evaluation at the University of Toronto, and colleagues wrote.

Older patients and controls

Researchers analyzed data from 964 patients (80% men) aged at least 66 years who died by suicide within 100 days of being prescribed an ACE inhibitor or angiotensin receptor blocker.

These patients were matched by sex, age and previous diagnoses of diabetes and hypertension with up to four controls, which totaled to 3,856 controls (80% men). The controls were also exposed to an ACE inhibitor or angiotensin receptor blocker within 100 days of the index date, which was defined as the date of death.

Patients treated with angiotensin receptor blockers had an increased risk for suicide compared with those treated with ACE inhibitors, according to a study published in JAMA Network Open.
Source: Adobe Stock

The median age of both patients and controls was 76 years. Of the patients who died from suicide, 26% were exposed to angiotensin receptor blockers and 18.4% were exposed to an ACE inhibitor. In contrast, 74% of controls were exposed to angiotensin receptor blockers and 81.6% were exposed to ACE inhibitors.

Exposure to angiotensin receptor blockers was linked to an increased risk for death by suicide compared with exposure to ACE inhibitors (adjusted OR = 1.63; 95% CI, 1.33-2). Findings were consistent when patients with a history of self-harm were excluded in a sensitivity analysis (OR = 1.6; 95% CI, 1.29-1.98).

“The mechanisms by which angiotensin receptor blockers or ACE inhibitors might impart differential risks of suicide are unknown,” Mamdani and colleagues wrote. Higher levels of angiotensin II may increase levels of substance P, which may, in turn, promote stress and anxiety. Similarly, animal studies have found that angiotensin II induces panic and stress when injected into stress-sensitive brain structures such as the dorsomedial hypothalamus and amygdala. However, because these effects were reversible after angiotensin II type 1 receptor blockade with an angiotensin receptor blocker, it is unlikely that this is the mechanism associating these drugs with suicide.”

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Future research

In a related editorial, Ira R. Katz, MD, PhD, professor of psychiatry and director of the section of geriatric psychiatry at the University of Pennsylvania and director of the Mental Illness Research Education and Clinical Center at Philadelphia VA Medical Center, wrote: “The strength of the methods, the importance of preventing suicide and the number of people exposed to angiotensin receptor blockers 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.” – by Darlene Dobkowski

Disclosures: Mamdani reports he received honoraria for serving on ad hoc advisory boards for Allergan and Novo Nordisk and received an honorarium from Celgene. Katz reports he is an employee of the U.S. Department of Veterans Affairs. Please see the study for all other authors’ relevant financial disclosures.