The mysterious symptom popping up in some GLP-1 users

If you watched the Super Bowl, you might have noticed that a lot of the ads were for weight-loss drugs. Even Serena Williams was selling them. That’s because demand for GLP-1s has skyrocketed over the last year, with users more than doubling from 2024. 

GLP-1s are relatively new and the industry is rapidly expanding, so we’re still learning more about their long-term effects. Users report fatigue and nausea as being quite common during use. But with more people using the drug, more side effects are popping up.

Dr. Sera Lavelle is a clinical psychologist who noticed several of her patients reporting a strange GLP-1 side effect: extreme apathy. She told Today, Explained co-host Jonquilyn Hill that it isn’t quite depression, but more of a “missing spark,” making people lose interest in things they previously loved.

Below is an excerpt of their conversation, edited for length and clarity. There’s much more in the full episode, so listen to Today, Explained wherever you get podcasts, including Apple Podcasts, Pandora, and Spotify.

When did you first start noticing people having a psychological reaction to GLP-1s?

I first started looking into this about a year ago. It was kind of the same conversation with three different patients in the same week, and I started noticing they all had this flat affect. None of them were depressed, but each was saying things like, “Well, what’s the point?” “Maybe I don’t even care about that job promotion.” “I don’t know what it is, but I’m not even excited to go out with my friends.” And these three in particular had been on GLP-1s. And of course, you can’t make an inference based on three people, but it is what motivated me to start looking into more of the psychological effects, particularly around what we do and do not know about how GLP-1s affect dopamine and motivation-seeking behavior. 

The other thing is that there’s a big difference between a person being depressed [versus the GLP-1 side effects], which they have started looking into. Does it affect suicidality and depression? You have to think about depression like, yes, it can be that kind of apathy feeling. However, depression really implies a negative affect: Like, I’m no good, I don’t feel like existing, right? That’s very different than a flatness.

It sounds like it’s not even sadness, it’s just nothing.

The same excitement you might get from, ‘Ooh, I’m going to eat this pizza later,’ or ‘Ooh, I’m going to see my friend later,’ you’re dampening this anticipatory response. So one of the theories in the literature is that it’s not just changing your appetite and metabolism, because, think about it, if it’s also helping gambling and shopping addictions, that can’t be just about metabolism. 

So how are we making sense of this? That it is helping people not eat as much, they’re not getting that food noise, but they’re also not gambling and shopping. And of course we look at all three of those as negative, but what kind of positives might it be dulling? Because again, it doesn’t seem like it’s leading to something clinically diagnosable, like depression, that there’s more of these personal reports coming out of people saying, “I feel flat.”

I wonder how you think of GLP-1s. Is this a net negative? A net positive?

I have to think of it [as] very nuanced. I really hate that people are in the pro or negative GLP-1 camp. I see positives in terms of mental health for some people. I’ve worked with so many people with a history of binge eating disorder that might be a hundred pounds overweight, and it’s not just about them losing weight, looking good or being healthier, but those people have lost all psychological hope that it could ever change. If you are a hundred pounds overweight and you’re extremely upset about it and you’ve given up all hope, I think GLP-1s can be not just this physical lifesaver, but this light at the end of a tunnel for you.

But then we can’t talk about that person the same as the person who struggles with anorexia, who is abusing it because it’s their dream drug. It makes them not think about food. People with anorexia traditionally hate even thinking about food. They hate feeling hungry. It scares them. So if you’re already a hundred pounds, you hear that, oh, now I can take a pill that’s going to make me not think about food or feel hungry at all. To me, that’s a huge problem. So net positive, net negative within society? Probably equal. Whereas I think there’d be a net positive in some populations and a very net negative in others.

There are lots of physiological things we’re still learning about weight gain and weight loss, but the psychological impacts seem just as complex and difficult to manage.

They’re really complicated. Do we as a society think of obesity as strictly metabolic, or do we think of it as strictly psychological, like a binge eating disorder? But what you’re finding even with GLP-1s is that if there is a psychological component to it, that it’s more emotional eating, stress, as opposed to in response to the sight or taste of food, it’s not going to be as effective, and you’re more likely to go back to the same behaviors after going off of them.

If you have a client that’s taking GLP-1s, what’s something you want them to look out for?

I have very mixed feelings about it. There are patients I would recommend going on them for psychological reasons. Sometimes people do need a break from that food noise. It is so overwhelming. However, you want to do a lot of prep work if they’re ever planning on going off of them, because especially a person who’s kind of frantic at the idea of that food noise, of those cravings, thinking something’s wrong with them, if they get them when you go off, that’s going to be, I dunno, two to four times more intense than prior to even going on them. What you’ll find is then if they go off of them, they don’t remember what they were like before and they go, “Oh, see, I was always like this.” And it can then reinforce this idea that there’s something wrong with them. So I think a lot of preparation about going off of them and what it’s going to be like for you when your cravings return, and what are you going to do if those actually feel quite intense, and normalizing the fact that it’s going to be intense so that they know to prepare for that.

Do you ever worry that we’re going to live in a society where, like, 80% of people have that flat sort of nothing feeling?

Could it get so normalized within society that it creates this large impact? I am not willing to be fearful of that. I think it would find its place the way that we had a lot of fear that Prozac would do that to everybody, and maybe it was over-prescribed at a certain point, but it kind of found its place within society. 

I do have concerns about the health impact. Doctors are saying, “Okay, well, take your GLP-1s and this is going to make you less motivated for food, but we somehow expect you to have more motivation to change your diet and to exercise.” If it’s gonna dampen your desire to kind of eat, isn’t it also going to dampen your desire, like that high you get from working out, or that [thought], “Hey, I wanna be healthier, maybe I should go for a salad.” If you think the only reason to eat better is to lose weight and something else is making you lose weight, that might actually give you inherently less motivation to eat better.