The People's Perspective on Medicine

Losartan and Suicide? Another ARB (Sartan) Concern

Canadian scientists have found a link between losartan and suicide that also implicates similar drugs such as irbesartan or valsartan.
Elderly woman pensioner measures the blood pressure itself.

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.

Another Day Another Losartan Recall | Can We Trust the FDA?

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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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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Citations
  • Mamdani M et al, "Association between angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and suicide." JAMA Network Open, Oct. 16, 2019. doi:10.1001/jamanetworkopen.2019.13304
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I have been taking Losartin for several years. Lately, I have brain fog. Could it be from the Losartin or just my age (79)?
I have heard medications can cause brain fog as well as stress. Taking Lisinapril caused me to have an irritated throat and dry coughing.

I have been taking telmisartan (micardis) for more than 10 years. All the evidence pointed to this being one of the best meds for hypertension. However, I almost always notice a depressed feeling for about 2 hrs after taking this drug.

I have been taking ACE (verapamil) and ARB (losartan) for a long time now. I am 64, and it has been at least 10 years. My BP is controlled.

Suicidal ideation has never been an issue for me, though I have experienced reactive depression. I have a lot of optionality in my life, and my socioeconomic status is very acceptable to me. I vacated an engineering career and now labor in a botanical garden. Lots of nature and exercise. So I have a number of powerful negative risk factors.

In my experience as a clinical psychologist, I have noticed that patients with a preexisting mood disorder seem to develop more profound symptoms after beginning medications for high blood pressure. They have reported greater feelings of depression, thoughts of self harm, and loss of interest in usual activities.
I wonder if the medications show this effect primarily with people who have a latent or co-existing depressive disorder?

Thank God, some actual scientific evidence!!! I have experienced terrible anxiety and depression on Losartan potasium. And along with it, anger issues. Maybe, now the doctors will listen to us!

I have been taking atenolol for several years when it became unavailable. I was switched to metoprolol. After taking it for about 6 months, I realized I was feeling depressed. I mentioned it to my cardiologist and asked if it could be the metoprolol. He said yes, definitely. That med crosses the blood/brain barrier. Fortunately, atenolol is available again, so I am taking it again. Definitely made a difference. I also take losartan and amlodipine, but no problems with them. My BP is very well controlled.

Been on losartan for about ten years. Depression has been present and now worse…I am always wondering why and how this is happening. I can see how someone would choose suicide now. Perhaps it is partially because of the losartan. I could not tolerate the lisinopril.
Hummmmm?

They all seem to have significant issues. I got off Ace inhibitors & beta blockers because of the cough & lung issue side effects (I’m asthmatic) & now on ARB. Can’t win with these.

I was on Ace Inhibitors for years until the ‘cough’ forced a change. The Arb I am on is at the highest limit. It is not as effective or age and other factors make it difficult to control my bp. So many other factors can contribute to anxiety and depression that it would be hard to say the Arb carries some fault in that. However, so many other good things are in my life that I don’t feel depressed most of the time.

I have not had this problem with losartan (25 mg) over the two years I have been taking it. I’m 71 and in good health. Lisinopril did not control my blood pressure as well, but will talk to my cardio doc at next visit. Thanks for sharing the latest info on this and other health issues. You provide a valuable service. Julie R.

I’m 83. I’ve taken 80 mg Sandoz-Telmisartan for more than 13 years, 84 mg aspirin, and 20 mg Crestor daily, after angina attack and one heart stent insertion. I’ve been upbeat ever since. My cardiologist added 5mg Eliquis to replace aspirin and 12.5 mg Metaprolol-L twice daily (8 a.m. and 8 p.m.) in the last 60 days. Dr. just declared I’m in excellent health, despite mild A-Fib/irregular heartbeats detected 2 months ago. A near-vegetarian, low sodium diet and regular exercise, with body mass below 24 since angina attack, keeps me active; feel fine. Swim 30- 45 minutes, &/or do aqua-fit 3X/week, walk, garden and bike regularly, I’m very happy!

I have been taking 50 mg of losartan & 2.5 mg Amlodipine daily for about 10 years. The meds replaced a diuretic I had severe side effects from. I am 69, male and “retired” 2 yrs ago due to stress / burnout & my wife had health issues including 2 major surgeries in year 1. My BP is under control but my anxiety, depression is not. For the first time in my life suicidal ideation is an issue. I blamed the stress but now worry about the Losartan effect based on this study.

It sounds like you have a lot to deal with. It could be those circumstances rather than the medication that is causing your stress and depression. You might want to discuss this with a psychologist as well as your prescribing doctor to see how to resolve the issue before switching medications.

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