GLP-1 Drugs and Suicidal Thoughts

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In July 2023, the European Medicines Agency initiated an investigation to explore a potential link between GLP-1 receptor agonists, such as Ozempic and Wegovy, and the occurrence of suicidal thoughts and thoughts of self-harm.

The probe is expected to reach its conclusion in November of the same year, however this possibility has many people worried, myself included, especially for those who are already taking these drugs and really don’t want to have to wait so long to find out.

So I conducted my own small literature review to see what the current evidence says about these types of thoughts and the use of GLP-1 agonists.

How serious is the EMA probe?

Firstly, how serious is this probe? The specific drugs under investigation are:

• dulaglutide (Trulicity)
• exenatide (Byetta and Bydureon)
• liraglutide (Saxenda and Victoza)
• lixisenatide (Adlyxin)
• semaglutide (Wegovy, Ozempic, or Rybelsus)

However, it’s not just about these specific medications; it could have broader implications. See, there are many other drugs being developed that also fall into the GLP-1 agonist category. So, the results of this investigation could potentially impact those future medications too.

Now, the European Medicines Agency, or EMA for short, is the scientific agency responsible for evaluating and overseeing medicines for both humans and animals.

But here’s the thing, the EMA doesn’t have direct regulatory powers like some other organizations. Instead, it acts more like an advisory committee. Its main focus is on scientific evaluation and providing expert opinions about medicines.

So even if the probe reveals some problems and the EMA recommends removing a medication like Ozempic or Wegovy from the market, it doesn’t mean they’ll be yanked off the shelves right away.

The EMA’s recommendations are valuable and play a vital role in decision-making, but it’s the regulatory bodies, like the FDA, that have the final say. They’ll take the EMA’s scientific assessments into account, but they’re the ones who ultimately decide what to do with the medications.

Reasons for the probe?

Why did the EMA decide to launch this probe in the first place? The review was prompted by reports of suicidal thoughts and self-injury in people using liraglutide and semaglutide medicines, which came to the attention of the Icelandic medicines agency.

So far, authorities have collected about 150 reports of possible cases, which is indeed a cause for concern.

GLP-1 agonists and suicidal thoughts

Are there direct links?

Currently, suicidal thoughts and behaviors are not listed as a side effect on any GLP-1 agonists. Studies done on these drugs that examined the effectiveness and safety of these drugs have not directly found any significant increases in these types of thoughts.

However, these studies were not designed to actually examine the link between these types of thoughts and GLP-1 agonist use.

Plus, they often excluded patients who were already at risk of depression or experiencing such thoughts and behaviors.

We do have one study that specifically looked at a GLP-1 agonist called liraglutide and its potential risk of causing suicidal thoughts and behaviors.

The results showed that there was a slightly higher occurrence in those using liraglutide, compared to those using a placebo. About 0.3% of patients experienced them with liraglutide use, while only 0.1% experienced them in the placebo group.

Now, this might sound concerning at first, as it appears to be a three-fold increase while using liraglutide.

However, when the researchers followed up and assessed patients’ mental health using something called the Patient Health Questionnaire (PHQ-9), they found no significant differences between the two groups. As a result, the researchers concluded that there wasn’t really any cause for concern.

Then there was another cohort study in the UK that also seemed to back this up. They found that GLP-1 agonist use was not associated with an increased or decreased incidence of depression or self-harm when compared to those using another type of medication called the sulfonylureas, another commonly used drug for diabetes.

Are there indirect links?

So current studies don’t seem to show any real correlation between these types of thoughts and behaviors and GLP-1 agonist use.

But do GLP-1 agonists have any effects on the brain or psychiatric conditions that could impact individuals who struggle with these types of thoughts and behaviors?

Actually, there are. However, instead of being problematic, the evidence would suggest that GLP-1 agonists may actually be helpful. You see, depression and bipolar are by far the most common psychiatric conditions associated with suicide.

Several studies have suggested that GLP-1 agonist medications could have a neuro-protective effect and might even be beneficial for patients dealing with depression. How so? Well, these medications seem to improve cognitive function in individuals with depression.

Some studies even suggest that GLP-1 agonists could potentially reduce the risk of anxiety and depression. In fact, they’ve been considered as possible antidepressants, although not all studies fully support this idea.

For people with mood disorders like bipolar disorder, GLP-1 agonists might offer some positive effects too. There’s a hypothesis that these medications could improve cognitive function in adults with mood disorders and even become a viable treatment for these conditions.

But hold on, it’s essential to consider the whole picture. The studies examining these effects often focused on older and weaker GLP-1 agonists like liraglutide or dulaglutide, not necessarily the more recent ones like Ozempic and Wegovy.

We need more data on the newer drugs to draw more definitive conclusions. Nevertheless, from my small literature review, I don’t see anything that raises a cause for concern.

Unlike, for example, the use of GLP-1 agonists and thyroid or pancreatic cancer risks, which I would consider a cause of concern.

Correlation with depression?

It’s crucial to take a step back and consider the bigger picture. Patients dealing with diabetes and obesity may have higher risks of depressive and mood disorders.

When it comes to diabetes, multiple studies have consistently shown that there’s an increased risk of depression and suicide in patients with the condition, especially among those with more severe diabetes or additional diseases and disabilities related to diabetes.

When we talk about obesity, the relationship between it and depressive and mood disorders can be a bit more complex. Some studies have found a positive correlation between obesity and these conditions in both adults and adolescents.

However, it’s not as clear-cut as we might think because there are also studies that have found the opposite to be true.

GLP-1 use

So we can’t definitively say that having diabetes or obesity will directly lead to depression or mood disorders, but research does suggest that individuals with these conditions may be at a higher risk of developing these conditions, which may lead to an increased risk of suicidal thoughts and behaviors.

The severity of diabetes or obesity seems to play a role too. Those with more severe forms of these conditions are even more vulnerable.

In type 2 diabetes, GLP-1 agonist medications are not typically the first choice for treatment. We have metformin, which is effective, cheaper, and safer, and it’s usually the initial drug prescribed for diabetics.

GLP-1 agonists come into play as a second-line medication, only if metformin alone doesn’t achieve the desired blood sugar control.

As a result, patients who end up using GLP-1 agonists often have more severe type 2 diabetes, because they require additional medications to manage their condition.

The same goes for managing obesity. Current guidelines recommend using GLP-1 agonists for individuals with higher BMIs, greater than 30, or greater than 27 in the presence of other medical conditions like type 2 diabetes, hypertension, dyslipidemia, sleep apnea, or cardiovascular disease.

These are typically individuals with more severe forms of obesity, who often have other debilitating issues, and require medical intervention such as GLP-1 agonists.

So it might not be the GLP-1 agonist medications themselves that cause an increase in depressive disorders and suicidal thoughts.

Instead, it could be the fact that these medications are consistently used in populations that are already at higher risk of developing these conditions and thoughts. It may just be a matter of correlation rather than causation.

Imagine it like this: If a person with a fever takes a fever-reducing medication and later experiences a headache, we can’t simply blame the medication for causing the headache. It might just be that the headache is caused by the underlying illness that causes the fever.

In the same way, the higher incidence of depression and mood disorders in those using GLP-1 agonists could be related to the severity of their diabetes or obesity, rather than the medications themselves being the direct cause.

Dr. Brian’s thoughts

So based on the current evidence, I don’t believe there’s any indication that these medications have negative effects on mental health.

In fact, the evidence points towards potential benefits. GLP-1 agonists seem to have some neuro-protective properties that could be helpful for individuals dealing with depression and mood disorders.

Now, it’s important to acknowledge the limitations of the current evidence. Most of the studies focus on older GLP-1 agonists, and we still lack enough research and safety information on newer drugs, such as Mounjaro.

That’s why I’m glad that the EMA has taken the initiative to conduct a probe and review the safety of these drugs. Having an independent and authoritative agency like the EMA hold these medications to scrutiny provides a higher level of accountability than relying only on information from the drug manufacturers themselves. We need this kind of vigilance to ensure the well-being of the public.

So if you’re taking a GLP-1 agonist, I don’t see any red flags yet, but you can rest assured, I’ll be actively keeping an eye on the latest developments, and I’ll be ready to provide you with more information once the EMA’s findings are available.

Learn more about

• Preventing suicide: Warning signs and how to help
• Ozempic and Thyroid Cancer
• Ozempic vs Rybelsus vs Saxenda vs Victoza for Weight Loss
• What to Expect With Wegovy
• Comparing other GLP-1 Agonists for Weight Loss
• Other weight loss medications

See also

• 
  Comparing Weight Loss Drugs in 2024
  Ozempic and Mounjaro are highly effective at treating obesity, however there are many other approved and off-label options that also work.
• 
  Bupropion vs Contrave vs Naltrexone
  Contrave is a synergistic combination of buproprion and naltrexone, which can be replicated to some degree using the generics individually.
• 
  New Obesity Drugs in 2024
  New obesity drugs target more than just GLP-1 and do much more than suppress appetite for a more nuanced approach to weight loss.
• 
  Mounjaro: Who Loses the Most Weight?
  White or Asian younger women who use metformin and have lower sugar and lipid levels tend to experience more weight loss with Mounjaro.
• 
  How does Oforglipron compare?
  Orforglipron, Semaglutide, and Danuglipron are oral GLP-1 agonists that are all similar enough that cost may end up being the winning factor.