Why do some anti depressants make you gain weight?

I'm taking Cymbalta for the second time around, and my first time I found it actually caused me to LOSE weight, because (once the initial adjustment was over) my urge to munch was gone. Kind of looking forward to that, honestly. :P Though I have heard that some folks lose their appetite altogether and have to force themselves to eat, so it can be a little dangerous.

Zoloft, however - don't even get me started! I gained so much weight on that stuff, it's not even funny.

Speaking of SSRI's. Why are some more related to weight gain than others? I mean you can't just say it ups serotonin and thus making you happier and more carefree so you end up eating more....because say paxil is associated with more weight gain than others, yet they both affect serotonin. But if both affect serotonin, than shouldn't they have the same affect on weight? Do they affect metabolism in some other way? Thyroid? Digestion?

Any thoughts on the matter would be really helpful. Any ideas?


Thanks for reading.

Pharmacologiest/Neuroscientist/Science Geek here

Serotonin does more than regulate happiness. As you already know, it's a neurotransmitter, and... well... neurotransmitters signal from one neuron to another. Your physiological response depends entirely on which circuits are being activated at any given time. Serotonin can and does regulate mood... but it also can help regulate appetite, interest in sex... and... lots of things

Selective Serotonin Reuptake Inhibitors, therefore, promote weight gain because they increase appetite. They don't change metabolism directly, but they can help regulate how much you sleep, how interested you are in exercise, and so on... which therefore regulates calorie burn indirectly. This can also effect weight gain or loss.

Why do SSRIs differ in how much they effect weight gain or loss? Well... Even within the same class, all pharmacological agents differ from one another in how they're absorbed, how they're metabolized, how they act on their target proteins in the brain, whether they have other 'off target' effects and so on. Certain agents might be in the same family, yet they can have different pharmacological profiles and therefor different over-all effects. Paxil tends to be anti-anxiolytic (anxiety), probably due to its interactions with something other than Serotonin re-uptake pumps and is one of the worst for weight gain because of those anti-anxiolytic effects. Calm = less calorie burn.

To complicate matters even further... genetic differences can determine how a certain person responds to a certain drug...

I took citalophram for eight months and I put on nearly a stone with no change to diet or exercise. I'm a nutritionist and personal trainer and I know that nothing contributed to it life style wise except for insomnia....

Anti depressants slow everything in the body. However what is important here is that you can live a normal life! Weight gain is not the be all and end all. I personally just felt like a zombie and exhausted on it. I felt much better when I came off and controlled the depression dietary wise.

Hugs for you all who are struggling there is light at the end of the tunnel. When going through hell... Keep on walking x

Edit: I have been off them for two years, I have only just started to move some of the weight I gained. I read this when I was taking them and saved it : Don't let people tell you that you can just have willpower or exercise more. The drug is messing with your metabolism and your appetite. It's not in your head. If you're vulnerable to this side effect mere "willpower" is unlikely to help.

I gained a large amount of weight on zoloft. Lost it all, but some of it is creeping back (after 7 years), so I'm back at it.

Would I have gained it if I had monitored diet and exercise? I don't know, and after all this time I don't know if I was eating more and moving less. I was working hard to lose the weight towards the end of my tme on the drug, though, and it sure wasn't budging until I stopped taking it.

I would add to people who say "you just need to be more careful what you eat and get some exercise", you may not be familiar with clinical depression. It's not just feeling sad. It's a sense of despair that is so deep and overwhelming it makes looking after yourself virtually impossible. No one chooses it, and it's not an excuse. It's just how it is for people.

If I have to choose between gaining weight and being depressed, I'd rather be heavier and able to live a normal, healthy life. It's worth it.

I took citalophram for eight months and I put on nearly a stone with no change to diet or exercise. I'm a nutritionist and personal trainer and I know that nothing contributed to it life style wise except for insomnia....

Anti depressants slow everything in the body. However what is important here is that you can live a normal life! Weight gain is not the be all and end all. I personally just felt like a zombie and exhausted on it. I felt much better when I came off and controlled the depression dietary wise.

Hugs for you all who are struggling there is light at the end of the tunnel. When going through hell... Keep on walking x

Edit: I have been off them for two years, I have only just started to move some of the weight I gained. I read this when I was taking them and saved it : Don't let people tell you that you can just have willpower or exercise more. The drug is messing with your metabolism and your appetite. It's not in your head. If you're vulnerable to this side effect mere "willpower" is unlikely to help.

%110 agree with this statement.

I know all too well the effect of drugs on metabolism and appetite. I was on zyprexa, 10mg, for eight years. In that time I gained over 80 pounds. I tried and tried and TRIED to limit my calories, I exercised, and NOTHING helped. I would try and wean myself off the zyprexa, but I couldn't. I was also on Prozac.

I'm at the point now where I can take a quarter of the dose that I used to take of zyprexa, and I switched from Prozac to wellbutrin. I am literally watching the pounds melt off me. It's awesome. I can limit my calories and not be starving all the time. I have energy to exercise.

So in short, they mess with you in many ways. No scientific data to back that up, I just know it did with me.

Oh, and my sister is on Remeron, and it's making her gain massive amounts of weight. I've seen her eat. She never used to eat like she does now.

On Paxil, I went from 135 to 180 over 2 years. I began tracking calorie input and pretty much no matter what I did, the weight came on. I was also unable to exercise during this time due to massive reconstruction of my left leg; but at the end it was clear that the drug was at the bottom of the gain.

I went off Paxil and started losing, again without being able to exercise.

SSRI's are notorious for gain, nobody really knows why. I did crave carbs and sweets while on it. The previous generation of anti-depressants - Elavil was the most frequently prescribed - was also associated with significant weight gain.

I have a similar response to prednisone, a steroid, which I've been on now for 5 weeks. I've gained 12 pounds. Just stopping now, thank heavens.

Wellbutrin is the only anti-depressant that is not necessarily associated with weight gain; however like all antidepressants not everyone is helped by it.

My take on SSRIs (and benzos like Xanax if anyone takes this for anxiety attacks) is that they simply make you not care about anything - so you may be inclined to sleep, eat whatever, lay on the couch, drink more, etc..

I have been on Zoloft and Klonopin for depression and anxiety for 10 years. I feel like these drugs have made me indifferent and have robbed me of my personality. Actually, the side effects have caused more problems for me than anything. I am currently working with my doc and a naturopath to wean off of Zoloft and Klonopin. My goal is to get off this garbage because I have felt like a zombie for years.

Maybe I really need the Zoloft - not sure yet but I am going to try to get off of it because the less meds, the better in my opinion.

Paxil was the worst for me. I liked how it made me not care about anything, but I took it for six months in 1999 and put on 30 lbs. I quit that drug and the weight dropped off.

Paxi caused me to gain a lot of weight and it would not come off no matter what I did, I could have starved myself and it wouldn't have budged. The dr told me it wasn't Paxil there was no way it was Paxil as soon as I went off I dropped 20lb almost overnight. I dont know how it does it but it does it!

Pharmacist here

The fact of the matter is - no one understands exactly why some antidepressants cause weight gain and others do not. The brain is pretty much a soup of chemicals and each separate chemical performs a huge variety of different actions dependent on what molecule it is interacting with on a neuron. We know antidepressants work by affecting levels of neurotransmitters, like dopamine, serotonin, and norepinephrine, and know how some of these neurotransmitters work in several instances. However, how those neurotranmistters work in every single cell of the body is not understood, so slightly affected the levels of one versus another can have wide and varying affects throughout your entire body's chemistry.

Just as a for instance with the widely varying chemical effects in the body - in the kidneys there is an enzyme called angiotensin-converting enzyme. A class of drugs blocks this chemical from working, and through a complex pathway works to lower your blood pressure. However, this same enzyme ALSO exists in your lungs, but there it's called bradykininase. When you take one of these medications, some people start coughing for no reason because the drug is blocking this same chemical from doing its job in two completely different parts of the body.

Much of this can be paralleled with the neurotransmitters that affect your depression, but there is so much that we just do not understand with how they affect all of the systems of the body. Serotonin for example also acts as a regulator of your bowels. For the time being, unfortunately, the answer to your question is globally, "We don't know!"

Just going on personal experience from 10 years of on/off/on various anti-depressants (Paxil, Zoloft, Lexapro, Wellbutrin)...everyone has a different reaction to different drugs. If the weight gain bothers you that much, use objective measurements to help you out. How much are you eating? How much are you sleeping? How hard/often are you exercising? And the worst part is that you may have to compensate additionally to counter the drugs.

I will say that before I started Paxil, I was probably in the best shape of my life...20 lbs lighter than I am now. I worked out religiously. Almost neurotically...2 hrs/day for 5 days/week. When I started Paxil, I soon didn't care about working out. Ironically, I was more at peace with myself and happier with myself, and didn't care if I wasn't in great shape. I enjoyed life, enjoyed food, and eventually it took a lot more alcohol to gain wait. When I was working out, I was getting the endorphin rush from it, which was motivation to keep working out. On the drugs, that lull from not working out wasn't there...so I didn't work out nearly as much.

Eventually, i went off the drugs. Nothing really happened weight-wise, until I started caring about the weight. I think it was at least a year or two after stopping that I decided to start running. The endorphin rush kicked in, the running became addictive, and the weight fell off. About a year ago, started up on Zoloft. Urge to workout decreased, weight came back. I never really noticed a change in my appetite volume-wise, but I did notice that I cared less about eating quality foods. The Zoloft has also affected my sleep patterns, which I'm betting will also impact metabolism.

I'm sure age and lifestyle has contributed as well, but there has been a direct effect from the drugs. My advice is to regulate your behavior and enlist a loved one to help be an impartial observer. It may be harder to lose weight, but it's not impossible.

Okay hopefully I can make this not too medical for you but SSRI is a class of drug used to treat depression, anxiety, and other mood type disorders. A drug class is just pretty much what the drug does like anti-hypertensive drug but because you don't know what SSRI's really are if you aren't in the medical field it seems like a type of drugs. Because there are many drugs in this class of drugs, they all have there own side effects good vs bad. Hopefully you understand the point I am trying to get across.

Hello, I have a medical degree and have taught psychiatry, neuroscience and pharmacology at Cambridge and Manchester Universities, although I quit being a clinician and a lecturer to set up a business. I also have taken quite a few different antidepressants in my time.

For what seems like a very simple question there is quite a complex answer. I will try and explain it with as little medical jargon as possible.

1. No-one knows exactly why. It is likely there are many mechanisms involved, but researchers have worked out some of those.

2. If you give 100 people Prozac (as an example). some will gain weight and others will lose it. One drug does not necessarily have the same effect on everyone as we all have different genetics. Genetics can alter the way a drug is processed by the body and the molecular consequences on a cerebral neuron (brain cell).

3. Depression causes reduced appetite and so consequently when people recover many gain the weight back again.

4. Although SSRI is supposed to stand for selective serotonin re uptake inhibitors the reality is they are not 100% selective. They also have an effect on other receptors that are present in the brain. For example:



Secondary binding properties of SSRIs

Citalopram (Celexa) most selective serotonin reuptake inhibitor

Escitalopram (Lexapro) most selective serotonin reuptake inhibitor


Fluoxetine (Prozac) least selective serotonin reuptake inhibitor
norepinephrine reuptake
dopamine reuptake
serotonin-2C receptors
cytochrome P450 2D6
cytochrome P450 3A4


Paroxetine (Paxil) muscarinic cholinergic receptors (most potent blocker of muscarinic receptors among the SSRIs)
histamine H1 receptors
nitric oxide synthase
cytochrome P450 2D6


Sertraline (Zoloft) dopamine reuptake (more potent dopamine uptake inhibitor than other SSRIs)
norepinephrine reuptake
sigma receptors

As the above demonstrates, some ADs also block the histamine H1 receptor and the muscarinic receptor (Paxil is worst for this). Blocking both these receptors is a cause of weight gain, hence why Paxil is one of the worst culprits when it comes to piling on the pounds.


5. Another factor in SSRI weight changes is timing. On average when someone starts an SSRI they will lose weight for a few weeks and then start gaining. By the end of year one on average someone on SSRIs will be 5 lbs heavier. No-one understands why this is, but my personal guess is it is because the side effects of nausea are worst at the start to treatment as the body gets accustomed to taking the drug.


6. The last thing to remember is neuroscience and neuropharmacology are rapidly advancing areas of medical research (hence why I chose to be come a research scientist in these disciplines) . The truth is we probably know less than half of the reasons people react differently to psychopharmcological drugs, but in the coming years our understanding will increase rapidly.

They don't make you gain weight.

They can effect you in terms fo making you more tired and lowering how many calories you burn. Or make you more hungry and cause you to eat more.

If you track your activity, and calories... you'd be fine.

Agree, I'm a psych nurse and previous was on citalopram for five years. If you eat well, and exercise more, you shouldn't gain weight. This is the advice we give to our patients.