SSRIs and weight

March 20, 2008 10:29 AM

Why do some people lose weight on SSRIs, while other people gain weight, with no changes in food intake or activity level?

I've used various antidepressants in the past and find that I lose weight while on Zoloft, without changing my food intake or activity level. I know that others gain weight on SSRIs. Friends that are on various antidepressants sometimes say that the drugs increase/decrease their appetite and that's why they lose/gain weight, but many say that their food intake does not change and they still gain/lose. In my case I'm sure that neither my intake or activity change because I keep track (somewhat obsessively - one reason I'm on the drugs in the first place.

So my question is, what's the mechanism behind weight/loss gain from antidepressants (why does it happen)? Do SSRIs directly effect one's metabolism, or do they cause you to retain more water, or something entirely different? And why would the effect be different (gaining vs losing) for different people, seemingly on a random basis?

I did a search on pubmed and was surprised that all I really found was one article addressing the topic:

http://www.nature.com/ijo/journal/v25/n10/full/0801729a.html

It talks about corticotropin-releasing hormone but is hardly conclusive. Is this just one of those mysteries?

posted by btkuhn to health & fitness (10 comments total)

I suspect there IS a reason.... we just don't know what it is (yet). Obviously there's much about the human body we still do not know. A lot of medications that are sold have in print somewhere in the pamphlet that comes with them, if you read the whole thing, info that states that the mechanism for how they work is "unknown". It doesn't surprise me that if we don't know why a particular medication works, exactly, that we perhaps also don't know why it effects some people x way and others y way.

IANAD, and this doesn't mean there isn't newer, better info on the mechanics of SSRI's that perhaps you haven't dug up yet, but as a general rule I have noticed this to be true in all my years of discussing various medications with people.
posted by bitterkitten at 10:46 AM on March 20, 2008

The sad fact is that no one really knows why these drugs do the things they do, nor why different people respond to them in such different ways. Fact is, it isn't even understood just why SSRI's help some people who are depressed.

The theory is that they cause a rise in the background level of serotonin, and that's what helps. That's what you'll find in the literature. But the problem with that is that it doesn't affect everyone the same, and though the serotonin level rise happens nearly immediately, it can take weeks before the drugs affect mood -- if they do so at all.

As to side effects, and how varied they are, that too is a complete mystery. Probably it's due to genetic differences, but what those differences are, and how they interact with the drug, is almost completely unknown.

There's basic research going on into those questions right now, and the hope is that eventually a clinically depressed person could give a blood sample for genetic analysis, which would indicate what kinds of drugs would be most likely to be helpful. But we're not there yet, and it could be decades.

Psychiatrists don't like to admit this, but right now treatment of clinical depression is more art than science. Nearly everything that's known about it is the result of serendipity and empirical study. There's damned little solid theory behind it, and that means usually a lot of experimentation is needed for each patient in order to find drugs that work, without unacceptable side effects.
posted by Class Goat at 10:50 AM on March 20, 2008

If AskMefi has taught me one thing about SSRIs is that they have completely different results to different people. A quick review of the archives will show people with crazy high libidos and ones now leading a monastic lifestyle.
posted by mmascolino at 11:05 AM on March 20, 2008 [1 favorite has favorites]

Here's a review of psychotropic drugs and weight changes - http://www.ncbi.nlm.nih.gov/pubmed/16586261?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
These authors note that SSRIs induced only mild weight changes.


And maybe this full article may have something interesting-
http://www.ncbi.nlm.nih.gov/pubmed/15468580?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
They conclude that SSRIs induce mild weight loss initially, and slight gain in the long term.

And here's another interesting one-
http://www.ncbi.nlm.nih.gov/pubmed/9693356?ordinalpos=19&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
"Significantly more weight loss and less weight gain when depressed were found in remitted weight gainers versus nonweight gainers. These findings suggest that weight gain in remitted depressed patients may not necessarily be a pharmacological effect of antidepressants, but may rather be an effect, at least in part, of recovery from depression."


And yet another one-
http://www.ncbi.nlm.nih.gov/pubmed/12585563?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
"Switching agents was the first choice of 61% (214/353) of clinicians for managing SSRI-induced agitation, 93% (339/363) for managing SSRI-associated weight gain. In an effort to manage most SSRI-associated side effects (with the exception of sexual dysfunction and insomnia), the majority of the clinicians responding to our survey opted to switch agents rather than add a specific medication to the existing SSRI."
posted by frankie_stubbs at 11:14 AM on March 20, 2008

There is some evidence that the thermodynamics understanding of weight gain (i.e. that "excessive" calories => weight) is a bit lacking. Given the way that biological systems tend to work via buffers and metabolic plateaus it makes sense that a purely mechanical understanding of body size as relates to eating habits, other habits, and general physical, mental and emotional health may not be sufficient to predict how certain medications will affect certain individuals.

Given that, I am not entirely surprised that SSRIs (mentioned by others here as being prone to being very persnickety in how they work in any individual versus any other) would further muddle our understanding of how body size and metabolism work for us as groups and as individuals.
posted by kalessin at 12:24 PM on March 20, 2008

but may rather be an effect, at least in part, of recovery from depression.
Almost every drug that affects hormonal balance and/or brain chemistry seems to have the potential to induce weight gain as a side effect. I suspect it's not specifically caused by the drug but rather the result of a deep-seated physiological response to the change in your body. It's natural response for the body to conserve and store up energy (fat) in times of distress or rapid change.

In the case of SSRI, I think that's exactly what's happening. Depending on how your body responds to the drug and its affects, it may or may not induce weight gain.
posted by junesix at 12:30 PM on March 20, 2008

i wonder if it doesn't have to do with the fact that a lot of serotonin is produced in the intestine. maybe changing your serotonin levels affects how efficiently you absorb the food you eat.
posted by thinkingwoman at 2:34 PM on March 20, 2008

ThinkingWoman, it doesn't affect serum serotonin levels. What it changes is serotonin levels in the synapses.

Junesix, most of the cases where weight change happens as a result of use of things like antidepressants, it's either because the person's metabolism level changes (up or down; some cause weight loss) or because of affects on apetite.

It's possible that the effect you describe does happen in some cases, but usually there's a more direct effect involved.
posted by Class Goat at 2:39 PM on March 20, 2008

SSRI's have enormously varied effects-- some of the known influences on their effects include the genes for the enzymes in your liver, your life history of stress, the genes in your brain, and your personality. Short answer: no one really knows/ YMMV.

Goat, SSRI's *do* affect serotonin receptors in the gut, where there is actually more serotonin than in the brain. Unless you are shooting your drugs, which I imagine is not the case!
posted by Maias at 3:03 PM on March 20, 2008

I suspect it's the opposite- SSRIs cause the same changes in all our different bodies, but because we are all nuts in our own specific, snowflake-like way, we perceive it differently. Some people are so profoundly messed up that normal is such a departure that they can't take it. If I'm depressed, lethargic and suicidal, for example, and I don't tell anyone I'm suicidal, and my depression and lethargy are cured, I'm going to cheerfully go and kill myself. It's not the drug's problem, it's a tragedy of bad diagnosis and me lying to my doctor.

And I really, really think that if food intake and exercise were measured externally, we'll find that they are directly related, and the SSRI has little to nothing to do with it.

Our brains are excellent pattern recognizers and also excellent at ignoring those patterns when they offend our sense of well being. That's why Cognitive Behavior Therapy works so well- when we are taught to recognize what's really going on, we can change our behavior.
posted by gjc at 7:29 PM on March 20, 2008