Losartan and Suicide? Another ARB (Sartan) Concern

Over the last 15 months, millions of blood pressure pills called ARBs have been recalled due to contamination with nitrosamines. Many people with hypertension worried about a possible increased risk of cancer linked to drugs like valsartan. Now there is another concern with this class of medications. A study in JAMA Network Open (Oct. 16, 2019) has found an association between ARBs like losartan and suicide. Is there reason for concern?

What Are ARBs?

ARB stands for angiotensin receptor blocker. These are drugs like candesartan, irbesartan, losartan, olmesartan, telmisartan and valsartan. You probably noticed that they all have “sartan” as part of the suffix of each drug.

They work by interfering with the action of a natural chemical called angiotensin II. If this vasoconstrictor cannot reach its receptors, blood vessels dilate and blood pressure comes down. You can learn more about the way ACE inhibitors and ARBS work at this link.

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ARBs are among the most prescribed antihypertensive medications in the country. That’s largely because they are perceived to cause fewer side effects than their cousins, the ACE inhibitors (ACEIs) that include drugs like lisinopril, enalapril or ramipril.

Losartan and Suicide: Real or Imaginary?

In the new study, Canadian researchers analyzed data collected between 1995 and 2015. People were 66 years of age or older and were taking either ARBs or ACE inhibitors. They compared 964 older adults who died by suicide with 3,856 matched controls. The investigators found that exposure to ARB-type blood pressure medications was linked to a higher risk of death by suicide compared with exposure to ACE inhibitors.

Why Do This Research?

The investigators explain why they undertook this study:

“…recent data suggest that users of ARBs, but not ACEIs, may have an increased risk of suicide compared with nonusers. The objective of our study was to examine the association between suicide and exposure to ARBs compared with ACEIs.”

The potential mechanism involves the chemical angiotensin II (AII). Most primary care physicians, internists and cardiologists think about this chemical in terms of blood vessel constriction. But it also affects the brain.

The authors of the new study offer this complicated explanation:

“The mechanisms by which ARBs or ACEIs might impart differential risks of suicide are unknown. As noted earlier, higher levels of AII may increase levels of substance P, which may, in turn, promote stress and anxiety… Another possible explanation for a higher risk of suicide among users of ARBs is associated with the upregulation of AII and resulting unopposed stimulation of AII type 2 receptors. These effects have been associated with nuclear factor–κB pathway activation, a process increasingly recognized as being involved in the pathophysiology of mood disorders.”

We know that’s an in-the-weeds hypothesis.

Here is what an accompanying editorial (JAMA Network Open, Oct. 16, 2019) has to say about this:

“There is a body of evidence indicating that angiotensin has a role in modulating brain activity, behavior, and possibly, mood…”

The author of the editorial concludes:

“To summarize, 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 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.”

The authors of the original study suggest that since the two classes of medication have similar effectiveness, clinicians may want to favor ACE inhibitors over ARBs when possible.

What has been your experience with ARBs or ACEIs? Please share your thoughts in the comment section below.

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