New News About Science News / Weight Loss and SSRIs

Sarah Zhang has an article on The Atlantic about the latest analysis regarding the new crop of obesity drugs and what researchers are learning about how they work.

The nutshell version of the article might be that scientists were right about HOW the drug works but more research is finding they were wrong about WHERE it works. Drugs like Ozempic and Wegovy, known as GLP-1 drugs, supply a hormone to the patient’s system that mirrors the hormone the human gut generates to create a “full” sensation. The medications on the market delivery a much larger, longer lasting dose of that same hormone to mimic the signal sent by the hormone generated in the gut.

What research is finding is that the hormone generated in the gut is a much shorter acting variety - a half-life of minutes. The dose provided by these new drugs is much larger and longer lasting (a half-life of several days) AND primarily acts on the brain directly, leaving those higher levels in the brain.

There are many functions within the brain with receptors for GLP-1 and many areas that produce it. Scientists and doctors are finding patients taking these drugs for weight loss also find it curbs other appetites as well.

It took a long time for scientists to appreciate the extent of GLP-1 in the brain, Karolina Skibicka, a neuroscientist at Penn State, told me. (snip) Since then, in a series of clever experiments using rodents, scientists have been able to show that GLP-1 drugs likely act on the brain. They don’t seem to work, for example, to suppress appetite in mice whose brain GLP-1 receptors have been genetically erased. Moreover, the effects of GLP-1 extend beyond food: Rodents given the drugs will drink less alcohol and use less cocaine. Anecdotally, too, people on GLP-1 medications have reported spontaneously quitting drinking, smoking, shopping, and other addictive and compulsive behaviors.

Here’s where this new science has potentially MASSIVE impacts on public health.

If you’ve been paying attention lately, you’ll notice there are a LARGE number of massively obese people in America. Look on YouTube for videos of public crowds at outdoor concerts in the 1970s versus 2020s and the contrast is striking. Until now, one dominant theory as to why obesity has skyrocketed involves the skyrocketing share of heavily processed foods Americans eat, especially those utilizing high fructose corn syrup. That makes some sense.

However, another key change in the health realm over the last fifty years has been a skyrocketing share of Americans being prescribed anti-depressants - the category of drugs termed selective serotonin reuptake inhibitors or SSRIs. These medications have a crucial side effect in a large portion of the patients taking them… An immediate spike in body weight. In my extended-family experience, three different people were prescribed SSRIs and IMMEDIATELY began gaining serious weight – in one case, ten pounds per month – while on the medication.

Of course, SSRIs pose two other critical problems. First, most (all?) of these drugs have no defined “off-ramp.” They aren’t curing the chemical conditions that are CAUSING depression or anxiety, they simply alter the chemical balance as long as they are taken to temporary mask the original problem. That means very few patients take these drugs for a few months, reach a mental health equilibrium, then STOP taking the SSRI. They remain on the SSRI indefinitely. For YEARS.

The second problem is for some patients, SSRIs don’t continue to work indefinitely. A patient may be prescribed a drug, finally land on an appropriate dose for their level of symptoms after a few weeks / months of adjustments with their doctor, then remain at that dose for months, maybe years. Then, out of the blue, the drug may simply stop working. Like a light switch, in a matter of a day or two. This can cause the patient to “crash” back into an acute condition of depression or anxiety and trigger a flurry of conversations with the doctor to identify another alternative and re-balance dosage levels on that new drug.

But for as many months or years that one of these SSRIs was prescribed, the patient may be continuing to gain weight. Or, they may have plateaued at some higher weight and now cannot drop the weight regardless of how they try to eat or exercise. I’m pretty sure the average person who became 50 to 100 pounds overweight would experience many NEW reasons to be depressed – appearance, joint pains, inability to exercise, skyrocketing blood pressure, diabetes, heart issues, etc.


This new news about how these weight loss drugs seem to be actually affecting the body to work seems to suggest a new strategy for doctors and patients. First, any patient prescribed anti-depressants who immediately begins exhibiting consistent weight gain should probably also be prescribed one of these GLP-1 drugs. If a patient is of normal weight but begins adding 5-10 pounds per month while on an SSRI, that additional weight will create health problems equally damaging to the patient over time as the mental health issues. This is ESPECIALLY true when SSRIs are being prescribed to people as young as 10-12 years old. To become massively obese in childhood is literally an early death sentence.

Second, one member of my family started Wegovy in November and described the impact the drug had on appetite. Within four hours of the first shot, the prior chronic HUNGRY signal turned off “like a light switch” and has never returned. I found that “like a light switch” description interesting because this family member has also gone through a series of SSRIs over the last 20 years and used that same metaphor to describe the feeling when one of those meds just stopped working. Coincidence? It’s starting to sound like these drugs all impact the same chemical processes in many of the same brain centers. Perhaps these new GLP-1 drugs should be prescribed INSTEAD of SSRIs for some patients.

This is total conjecture on my part and I know nothing about medicine. However, it seems unlikely that America has an epidemic of OBESITY and an epidemic of mental health conditions that have resulted in MILLIONS being prescribed drugs that TRIGGER extreme obesity in millions of patients and that those two problems are unrelated. The cost of the current approach for treating these problems is draining the coffers of employers and the government alike and the approach isn’t solving the problem. There are literally hundreds of billions of dollars to save if a better solution to both of these problems can be found that doesn’t reinforce both problems. Not to mention millions of lives that would be much improved.



Great post. I don’t have anything to add but if you haven’t checked it out already, you may enjoy the Huberman Lab podcast. He’s had several episodes on brain chemistry. It is surprising how much is known, but there are some straight deep mysteries how it all works.


Real Food™ is the best drug! :heavy_check_mark:

The Captain :slightly_smiling_face:

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Absolutely! There are about one billion people on the planet who would benefit from a prescription for Wegovy or Mounjaro.

(long LLY)

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WTH there is a relationship between drugs and obesity. I do not know the chemistry of it but that relationship is known.

In my own case late nights, eating out, not cooking, and junk food. No other way to put it.

I am losing weight again with Noom. In the last month I have lost 8.5 pounds. As a guy with a very good diet these days I do indulge my pleasure every night with a cannoli and MCD ice cream. Noom does not believe in denying pleasure eating. Denial of self does not last. One reason if you come off the weight loss drug the pleasure aspect will overwhelm then the weight is gained back.

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I have never been on Prozac nor been depressed.

The weight gain is common. I think it is under counted when people are on these drugs for decades.


If I may add what I think is a significant factor: wealth. Yes, even among the “poor”, they are still well off enough to be buying lots and lots of highly processed, not-especially-nutritious junk food. I’d add “laziness” as a subcategory to “wealth”, as I’m sure there are many fewer “Mom cooked meals” in favor of “TV dinners or similar”.

(I would also argue that the issue is worse the further down the economic ladder you go. Having watched what people put in their carts, I think I could make a reasonable scientific paper comparing “bottom size” to “processed food in cart” were I to take a survey in most any supermarket.)

And in fact if you look at the simple metric of “fruits and produce” square footage to “boxed food” at WalMart food stores (which have a giant slice of supermarket sales, probably skewing lower socioeconomic) I think you’d find a correlation there as well, especially if you compared that ratio to supermarkets of a generation or two ago.

Yes, I’m sure this issue has many moving parts, but overall I’d put “nutrition”, as provided to and consumed by American consumers, right up there in the “causes” department.


Indeed…but, for the most part, only if Bogus/Craptaculous Food ™ is responsible for the need for drugs in the first place.

By most accounts the Obesity Epidemic is/was caused by Bogus/Craptaculous Food If that is true then Real Food is the cure. An ounce of prevention…

The Captain


" However, it seems unlikely that America has an epidemic of OBESITY and an epidemic of mental health conditions that have resulted in MILLIONS being prescribed drugs that TRIGGER extreme obesity in millions of patients and that those two problems are unrelated. "

Great post, it does seem very likely that this is a feature of the health “care” drug makers, not a bug.

I do some long workouts for fun, the longest this winter was doing a 50k ( just under 32 miles ) xc ski trek. Took a little over 3 hours. I swear I had no feeling of hunger afterwards, had to consciously force myself to eat something. It’s like that on 90 minute or 2 hour workouts, too. Not sure what is going on inside the body, but the hunger pangs are definitely stifled afterwards.

I fully realize that some people need to go the prescription drug route, but they need to go in with eyes fully wide open. Not remotely implying that all of health care is based on profit motive, but it is definitely a driving force in the industry.

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SSRIs have another side effect: loss of orgasm.

This problem can persist even after the SSRI is discontinued.

When I became depressed after my mother’s death I took Wellbutrin, which acts on dopamine instead of serotonin, because of this well-known problem of SSRIs.



Not quite caused by…the individuals themselves have to choose to reach out, grab said comestibles and cram them into their pie hole, no?

There are still some folk around who, in spite of sharing the same Lifestyle Landscape as those who’ve chosen/still choose to do this, manage not to eat themselves fat.

One of the things I’ve oftentimes " 'fessed up to" is that, over close to a 4 decade career as a dentist, greater than 95% of my income has been derived from managing diseases that are greater than 95% preventable for greater than 95% of the population. With the full disclosure that the figure should probably be something like 99%. Possibly still slightly ahead of obesity but probably not for much longer. Now I have to say that I have never given a single patient information that could possibly be called a driving force in this state of affairs…i.e that they should start or continue to eat cariogenic snacks like cookies, candies etc or to actively avoid brushing and flossing diligently. I’m reasonably sure that no hygienists or other staff in my employment have either.

I suspect that it’s the same with obesity. It’s not necessary to give out bad advice…folk do stupid things anyway. Even while they’re bellyaching about the pills they’re taking.


I’m exactly like this: I am never hungry for hours after exercise/workouts. Always been that way as long as I can remember. I think we might be relative rarities since virtually of the people I know are the opposite and are quite hungry after working out.

Another thing that is more rare than many others: I am quite hot-natured and like it much cooler than most of my friends and co-workers. I wonder is there is any relationship between these two things…

Strange metabolism or just another uniqueness of life?



"I am never hungry for hours after exercise/workouts. "

I have no medical background at all, but am curious as to what hormone is being released in our bodies that is sending the signal ( or not sending a signal ) that food is not needed. Since there are no side effects to having a sated appetite from this method, the drug companies should maybe pursue that, might be better for the people who are taking the weight loss drugs.

Losing weight and keeping it off is really tough for a lot of people, I hope science can come up with something without side effects for these folks.


One of the things I’ve noticed…and this is from my avocation/side gig asba fitness instructor/personal trainer…is that folk who have gained weight through overeating and Sedentarianism tend to do the “eat less:exercise more” things a bit too enthusiastically. Oftentimes exercising a bit too hard for their fitness levels and prompting all those compensatory behaviors (eating more) to well…compensate.

Blaming the victims? Oh well…

The Captain

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A strong candidate is a metabolite (not a hormone) called N -lactoyl-phenylalanine, or lac-phe for short. It is produced after exercise and is found in other mammals besides humans. The research paper is paywalled but here is a review:

“We estimate that the lac-phe pathway is responsible for about 25% of the anti-obesity effects of exercise,” ‘Anti-hunger’ molecule forms after exercise, scientists discover | News Center | Stanford Medicine.

The assumption is that lac-phe goes to the brain and binds something there. Unfortunately no one knows the details yet, so the commercialization of this is pretty far off. Researchers first have to figure out how it works.

This story is also a good description of how science works. One lab cataloged small molecules that increased in quantity in mice after exercise. There were many that showed a statistically significant increase, with lac-phe being one. They did a similar study in horses and found that lac-phe also increased after exercise in this species, which peaked their interest a bit. Another lab was doing similar studies in humans and heard about the mice data. They shared information and found that exercise induction of lac-phe was common to all these species.

So lac-phe was fed to mice and it decrease their appetite by 30%. This was a statistically significant difference over controls. Genetic modification methods were used to knock out the enzyme that makes lac-phe in mice and this resulted in mice that were statistically fatter than control mice.

And that is where we are at the moment. I put statistically in bold to emphasize the importance of statistics in science, a point that one poster in other threads seems to have a strong disagreement with.


I’d add a bit of human compassion here. As I am getting older and working on becoming more aware of what I eat, I find that preparing healthy meals takes time. The working poor often don’t have the time needed to cook good meals. They work two jobs, have a couple children to care for, and precious little time for anything else.

Obviously, this doesn’t explain everyone, but it does cover a good portion of them. Fast food and pre-prepared meals are all they have time for.

One of the less appreciated advantages of even modest wealth and/or a higher income is the ability to trade money for time. You can spend money to be able to use less if your time. You can pay someone to clean your home instead of spending your time to clean. Or pay to fix your car or home. Or pay to tutor your children or watch them after school instead of supervising their homework yourself. All those things free up time to shop for and cook better quality food.



More on the lac-phe story …

Exercise-Induced N-Lactoylphenylalanine Predicts Adipose Tissue Loss during Endurance Training in Overweight and Obese Humans - PMC(Lac%2DPhe,of%20exercise%20interventions%20in%20humans.

It’s an interesting puzzle piece on the table for sure, and likely to be an interesting molecule among many others that helps to explain individual human responses to exercise and its effects on obesity and its consequences. Not so much about medication induced weight gain…or untreated depression, come to that.