GLP-1 Depression Warning: Weight-Loss Drugs May Carry Suicide Risk

Weight loss drugs such as semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) continue to set record sales. Most people assume that the side effects of medicines prescribed for weight loss or diabetes are mainly linked to digestive woes such as nausea, vomiting or diarrhea. But a new safety alert from Australia warns that drug regulators there are issuing a GLP-1 depression warning for these hugely popular medications. What do you need to know? What other drugs may trigger depression or suicidal thoughts?

Why Did Australia Issue a GLP-1 Depression Warning?

In the US we call our drug regulator the Food and Drug Administration (FDA). In Australia they call it the Therapeutic Goods Administration (TGA). The TGA has just issued a new class-wide drug safety warning for:

“high-profile medicines used to treat diabetes and obesity”

Here is how the TGA of Australia is warning its populace:

“We have updated the product warnings for GLP-1 and dual GIP/GLP-1 receptor agonists for two separate safety issues (see below). This relatively new and high-profile class of medicines is used to treat type 2 diabetes mellitus and/or obesity.

Medicines in the GLP-1 RA class currently marketed in Australia are:

• Ozempic (semaglutide)
• Wegovy (semaglutide)
• Saxenda (liraglutide)
• Trulicity (dulaglutide)
• Mounjaro (tirzepatide)”

According to the TGA, regulators received dozens of reports of suicidal ideation, as well as suicide attempts and significant mood disturbances, among people taking these medications. While officials stress that causality has not been proven, the agency is concerned enough to require updated warnings across the entire GLP-1 class. Doctors are urged to closely monitor patients for depression, suicidal thoughts, and unusual behavior changes.

Not the First GLP-1 Depression Warning!

If the Australian GLP-1 depression warning sounds vaguely familiar, it should. Europe’s EMA (European Medicines Agency) has been investigating similar reports since 2023. In the U.S., the FDA has received hundreds of voluntary reports of psychological side effects associated with GLP-1 drugs, although it has not yet required new warnings.

In the US, semaglutide is marketed as a diabetes medicine under the familiar brand name Ozempic. Check the official prescribing information and you will find no reference to depression or suicide. The same exact semaglutide is also marketed under the familiar brand name Wegovy for weight loss. Search the official prescribing information for Wegovy and you will discover this:

• “Suicidal Behavior and Ideation: Monitor for depression or suicidal thoughts. Discontinue WEGOVY if symptoms develop.”

“Suicidal Behavior and Ideation:

“Suicidal behavior and ideation have been reported in clinical trials with other weight management products. Monitor patients treated with WEGOVY for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue WEGOVY in patients who experience suicidal thoughts or behaviors. Avoid WEGOVY in patients with a history of suicidal attempts or active suicidal ideation.”

“Advise patients to report emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Inform patients that if they experience suicidal thoughts or behaviors, they should stop taking WEGOVY”

Patients are warned:

“You should pay attention to any mental changes, especially sudden changes in your mood, behaviors, thoughts, or feelings. Call your healthcare provider right away if you have any mental changes that are new, worse, or worry you.”

Do you not find it peculiar that the maker of Wegovy would bend over backwards to warn about depression and suicide but not say a word about either for the identical drug Ozempic? I find that strange. Why hasn’t the FDA found it strange?

The Australian TGA Issued a GLP-1 Depression Warning for “medicines used to treat diabetes and obesity.”

Are Americans overlooking a potentially dangerous mental health signal in our rush to embrace GLP-1 drugs in general?

Why GLP-1 Drugs Might Affect Mood:

GLP-1 drugs act in the gut and brain to reduce appetite, regulate blood sugar and alter reward pathways. That means the brain is very much involved in how these drugs work.

Researchers have not yet shown a clear biological mechanism that links GLP-1 agonists to depression or suicidal thoughts. However, individual case reports tell a compelling story.

Here are two examples published in the journal Frontiers in Psychiatry, Aug. 29, 2023:

• A man who had been “optimistic, active, efficient, and had many interests” developed severe depressive symptoms one month after starting semaglutide.

• A 40-year-old woman with controlled recurrent depression experienced a relapse after beginning semaglutide. She also “developed fatigue, slowing of mind, increased need for sleep, and recurrence of suicidal ideation.”

• In both cases, depression lifted after discontinuing the drug.

Such cases don’t prove cause and effect. They do, however, underscore the need for vigilance.

GLP-1 Depression Warning… But GLP-1s Aren’t Alone

The truth is that hundreds of medications — not just weight-loss drugs — can cause or worsen depression. Yet this possibility is rarely discussed during office visits. I wonder how many people who get a prescription for Wegovy are asked about or cautioned about mood disturbances.

A major study in (JAMA, June 12, 2018) analyzed medication use among more than 26,000 adults. The investigators found:

• 7% of people taking just one drug linked to depression reported significant depressive symptoms.

• Over 15% of those taking three or more such drugs were depressed.

In fact, researchers identified over 200 medications that list depression or suicidal thoughts as possible adverse effects.

Here are some that may surprise you.

Common Drugs That Might Trigger Depression

(Please keep in mind that this may be a very rare potential side effect. Most people will not experience mood disturbances, but forewarned is forearmed.)

Blood pressure medicines:

• Atenolol, metoprolol (beta blockers)

• Enalapril, quinapril (ACE inhibitors)

Acid-suppressing drugs:

• Omeprazole, esomeprazole, lansoprazole

Pain relievers:

• Tramadol, ibuprofen

Hormones:

• Estradiol, ethinyl estradiol

• Levonorgestrel (Plan B)

Neurological drugs:

• Gabapentin

• Lamotrigine

• Topiramate

Psychotropic medications:

• Fluoxetine, paroxetine

• Alprazolam, diazepam

• Trazodone, zolpidem (Ambien)

Others:

• Cyclobenzaprine (muscle relaxant)

• Finasteride (for hair loss or prostate enlargement)

• Corticosteroids (prednisone)

Most people — and many clinicians — don’t realize that common medicines can darken mood, sap motivation, or even lead to intrusive, frightening thoughts.

When Drugs Cause Severe Depression:

Drug side effects pose a dilemma for doctors. On the one hand they are encouraged to “first do no harm.” But all medications have the potential to cause complications.

It is neither practical nor desirable to warn patients about every potential adverse reaction. That’s why physicians have to be selective in choosing which information they share with patients.

Research suggests, however, that health professionals may need to be more attentive to an often-ignored drug side effect: severe depression.

Why Doctors Often Miss Drug-Induced Depression:

Clinicians are trained to consider disease before drug side effects. But this bias can cause harm. When a patient becomes depressed, physicians may assume:

• It’s situational

• It’s psychological

• It’s a new psychiatric condition

• It requires an antidepressant

But adding a new drug on top of the one causing trouble can create even more complications.

What to Do If You’re Feeling Down on a GLP-1 Drug (or Any Medication)

If you are taking Ozempic, Wegovy, Mounjaro, Saxenda, Trulicity, or any medication and notice troubling mood changes, here’s what we recommend:

1. Take your symptoms seriously.

Depression, despair, or intrusive thoughts are not “side effects to push through.”

2. Tell your prescriber immediately.

Describe your symptoms plainly. Say you are concerned about a possible drug-induced reaction.

3. Never stop a medication on your own.

Stopping some drugs abruptly can be dangerous.

4. Ask whether a dose change or drug holiday is safe.

Sometimes reducing the dose gradually or switching to an alternative solves the problem.

5. Involve family or friends.

They may notice behavior changes before you do.

6. If you have suicidal thoughts, seek help immediately.

Call or text 988 in the U.S., or your local country’s suicide crisis hotline.

What About the GLP-1 Depression Warning?

Should physicians, pharmacists and patients take the Australian GLP-1 depression warning seriously? We started hearing whispers about depression and/or suicidal thoughts back in August, 2023. That is when NBC News asked:

“Should Ozempic come with a warning about a risk of suicidal thoughts?”

The lead paragraph stated:

“Following reports of self-injury and suicidal thoughts among a small number of people who’ve taken Ozempic or Wegovy in Europe and the United Kingdom, health regulators there are investigating whether the drugs carry a risk of these side effects.”

According to the author, Aria Bendix, the EMA (European Medicines Agency) was reviewing 150 reports reports of potentially serious psychological side effects.

Ozempic has no warning about either depression or suicidal ideation in the official prescribing information. As mentioned above, Wegovy has a clear warning.

NPR Reports on Possible Mental Health Side Effects (Sept. 21, 2023):

You can listen or read a report by Sydney Lupkin about Ozempic on All Things Considered at this link .

She describes the case of Jenny Kent who developed mental health problems while on this drug for type 2 diabetes:

“I was just constantly in a state of being overwhelmed,” says Kent. “So my response to that was just I was just crying all the time. Sobbing, crying … I still didn’t put it together, so I kept … taking my injections.”

Sydney goes on to describe the EMA’s investigation into 150 reports of suicidal thoughts associated with semaglutide.

According to Ms. Lupkin:

“The FDA hasn’t taken that step. For now, the agency is monitoring the situation. ‘We continue to conclude that the benefits of these medications outweigh their risks when they are used according to the FDA approved labeling,’ spokesperson Chanapa Tantibanchachai said in an email to NPR. She noted that weight-loss drug Wegovy, which contains the same active ingredient as Ozempic, semaglutide, includes a warning about suicidal thoughts on its label.”

Sydney Lupkin goes on to describe an NPR analysis of the FDA’s adverse event reporting system (FAERS). It has apparently received nearly 500 voluntary reports of psychological side effects associated with semaglutide.

We won’t know if this drug for type 2 diabetes and weight loss really causes psychological depression or suicidal thoughts until a well-controlled clinical trial is conducted.

Over-The-Counter Drugs and Depression:

Most of these drugs are prescribed, but some are available over the counter. Proton pump inhibitors, for example, such as esomeprazole (Nexium), lansoprazole (Prevacid) and omeprazole (Prilosec) may all trigger symptoms of depression.

So can the emergency contraceptive levonorgestrel (Plan B). Unfortunately, OTC drug labels contain little information about depression as a side effect.

Are Patients Informed About Drug-Induced Depression?

Even when people take prescription medicines, they may not get information about side effects.

One reader wrote:

“I took the beta blocker propranolol a couple of years ago to slow my heart rate down. The medication worked, but after a week or so I started to sleep more, wanted to be alone and lost interest in cooking and eating.

“I work from home and my job is challenging and exciting. However, after few weeks I didn’t care if there were orders to process and I didn’t want to communicate with customers. I had to force myself to do things that normally I can’t wait to wake up and start my day doing.

“After six months I was really depressed. I spoke to my cardiologist’s nurse, but she said that depression was highly unlikely as a side effect. She said I could safely stop taking propranolol because I was on a very small dose. I skipped a pill for a day and felt like a dark cloud started to lift. I felt happy.

“When I went to my cardiologist and told him what had happened, he said that depression is a very common side effect of beta blockers. Really? Why was that too hard to mention before he put me on it?”

Commonly Taken Meds and Depression:

An NPR report (June 12, 2018) describes it this way:

“The list includes a wide range of commonly taken medications. Among them are certain types of proton pump inhibitors (used to treat acid reflux), beta blockers, anxiety drugs, painkillers including ibuprofen, ACE inhibitors (used to treat high blood pressure) and anti-convulsant drugs.

“’The more of these medications you’re taking, the more likely you are to report depression,’ says study author Mark Olfson, a professor of psychiatry at Columbia University.”

A Close Call with Heartburn Medicine:

Many years ago a reader shared this experience:

“I was stopped at an intersection on an icy day waiting for a sand truck to pass when I almost pulled out in front of him–intentionally.

“When I saw the young man’s face, I said to myself, ‘I cannot do this to him.’ After the truck passed and I drove on, I wondered what in the world was going on. I was not depressed.

“When I arrived home, I was still shaken from what I had almost done. I read the daily newspaper while I ate lunch. The first article in your column that day was from a lady whose husband had committed suicide while taking metoclopramide (Reglan).

“That was the exact same medication my doctor had prescribed for my stomach. I jumped up and emptied that bottle down the toilet and wrote on it in large letters, DO NOT TAKE AGAIN. I thank God and the lady who wrote you that letter.”

Metoclopramide carries a warning that it can cause mental depression and suicidal ideation. Patients should always be cautioned about such a serious complication.

Sometimes a medicine is essential, and any psychological reactions it causes can be handled with another medication. But often, rather than piling one drug with potential side effects up on top of another, it makes sense to re-evaluate the original treatment.

Full Information About Drugs and Severe Depression!

Health professionals must alert their patients about the potential for drug-induced severe depression as a side effect. This is particularly true if people are taking more than one medication.

Please share your own experience with drugs and depression in the comment section below. You may find our free eGuide “Psychological Side Effects” of interest. It can be downloaded from the Health eGuides section of this website. There is also an eGuide to Dealing with Depression.

Bottom Line: GLP-1 Depression Warning Is a Wake-Up Call

Australia’s decision to add a GLP-1 depression warning does not mean these medications should be abandoned. They offer powerful benefits for many people.

But it does mean that patients and clinicians must be alert. Any medication that acts on the brain — even indirectly — can influence mood. And the list of drugs capable of causing depression is far longer than most people realize.

If you suspect a medicine is affecting your mental health, speak up. You deserve to feel well — both physically and emotionally.

If you found this article of value, please share it with friends and family. You have no idea what medicines acquaintances could be taking. They deserve to know if depression could be a potential side effect. This article might help them discover why they are feeling down. Thank you for supporting our work.