How exactly do SSRI's make you fat?

[((Vibe))]

As stated in the title, I imagine it's probably not known for sure, but would like to hear some thoughts on the matter.

Also curious how nortiptyline does this as well. And/or if the mechanism through which TCA's/SSRI's/SNRI's make someone fat is related or the same.

[GhostfaceKillah]

I've never looked into this much, but whenever it is mentioned, my first reaction is correlation vs causation. Treating someone who is depressed with a medication that relieves their symptoms is likely to have a profound effect on diet and activity. I would love to see some well designed studies posted that attempt to control for these confounding factors.

[kassem23]

Overdosing --> induces apathy --> eating frenzy commences --> feeling better, then worse, and the cycle continues.

[Tussmann]

Ex Dubio pooped on this topic somewhere. Search some key terms and you're sure to find it.

[superfob]

Isn't there something about increasing serotonin and decreasing norepinephrine signaling that causes weight to increase?

After going on the SSRI, I have put on weight, and it definately does not have to do with feeling better and eating more, or even feeling worse and eating more. If anything I am eating less and have less of an appetite, and I have increased in weight. I was coming from a highly anxious state, and I think the anxiety/high norepinephrine signaling was keeping the weight down. I had to eat a lot of food to maintain my weight.

[puerco911]

How exactly do SSRI's make you fat?

hmm....not for me, i lost fat (like 10lbs) on lexapro....stops me from binging on carbs for mood support

[Ex Dubio]

As stated in the title, I imagine it's probably not known for sure, but would like to hear some thoughts on the matter.

Also curious how nortiptyline does this as well. And/or if the mechanism through which TCA's/SSRI's/SNRI's make someone fat is related or the same.

It's kind of a loaded question, since it presupposes that SSRIs induce weight gain. If one looks only at the better SSRIs (escitalopram, sertraline, and perhaps fluoxetine), most trials show no effect -- either positive or negative -- on weight. The trials that have shown weight gain typically failed to correct for the fact that depression itself often causes weight loss; thus cessation of depressive symptoms and resumption of a normal [American] diet can easily cause weight gain. There are some individuals who gain weight on SSRIs, but others also lose weight, and it's not clear if any of this is related to the pharmacology per se.

Strictly speaking, 5-HT signaling should have appetite-suppressing properties, particularly acutely.

As to TCAs, that is much easier to answer. Nortriptyline antagonizes adrenergic, cholinergic, and histaminergic pathways. All three of these pathways contribute to short-term and, to a lesser extent, long-term appetite restriction, and so antagonizing them easily leads to increases in appetite. Do note that notriptyline should be the mildest of the common TCAs in this regard, as it is far less anticholinergic/antihistaminergic than amitriptyline, and also has pro-adrenergic effects.

Overdosing --> induces apathy --> eating frenzy commences --> feeling better, then worse, and the cycle continues.

Kind of depends on the type of apathy. True anhedonia is often accompanied by a lack of interest in food.

Isn't there something about increasing serotonin and decreasing norepinephrine signaling that causes weight to increase?

Decreasing NE, at least acutely, tends to increase appetite. But increasing 5-HT tends to decrease appetite.

After going on the SSRI, I have put on weight, and it definately does not have to do with feeling better and eating more, or even feeling worse and eating more. If anything I am eating less and have less of an appetite, and I have increased in weight. I was coming from a highly anxious state, and I think the anxiety/high norepinephrine signaling was keeping the weight down. I had to eat a lot of food to maintain my weight.

There is virtually no mechanism by which an SSRI could change your RMR by more than +- 100 kcal/day. (And even that is doubtful...) You are either eating more, exercising less, or fidgeting (i.e. NEAT) less. NEergic signaling does contribute to RMR somewhat (this is why EC works beyond mere appetite restriction), but the contribution is quite small.

[((Vibe))]

Wow. Impressed as always, Ex Dub. Thanks for the detailed response/answer.

[morganpmiller]

I never had a decrease in appetite on sertraline. In fact, my appetite was ravenous at times. I have bipolar, so that may be a reason why. I have know several people to report weight gain on SSRIs. Whether this was due to a change in appetite or life style, or something else, who knows. I do believe, that while on sertraline, and just sertraline, I seemed to be more likely to go through periods where I would indulge in things that caused weight gain, without being as sensitive to the negative effects on how I would normally feel. So, maybe SSRIs can make some people feel so good that they are more likely to not feel bad, psychologically or pshysiologically, after shoving poisionous crap down their throats. Just a thought.

[Ex Dubio]

I never had a decrease in appetite on sertraline. In fact, my appetite was ravenous at times. I have bipolar, so that may be a reason why. I have know several people to report weight gain on SSRIs. Whether this was due to a change in appetite or life style, or something else, who knows. I do believe, that while on sertraline, and just sertraline, I seemed to be more likely to go through periods where I would indulge in things that caused weight gain, without being as sensitive to the negative effects on how I would normally feel. So, maybe SSRIs can make some people feel so good that they are more likely to not feel bad, psychologically or pshysiologically, after shoving poisionous crap down their throats. Just a thought.

Do keep in mind that sertraline is known for having dis-inhibiting properties not shared with the other SSRIs, purportedly due to its sigma-1 antagonism. This sounds like a manifestation of sertraline-related disinhibition.

[morganpmiller]

Do keep in mind that sertraline is known for having dis-inhibiting properties not shared with the other SSRIs, purportedly due to its sigma-1 antagonism. This sounds like a manifestation of sertraline-related disinhibition.

That makes perfect sense. I was thinking about sertraline along those lines, just not functioning well enough to go there. Thanks for bringing attention to that.

[superfob]

Could my weight gain be attributed to atenolol? I've been taking 25 mg every night. Something has been increasing my weight. My diet and activity level have been relatively the same.

[Julez]

Could my weight gain be attributed to atenolol? I've been taking 25 mg every night. Something has been increasing my weight. My diet and activity level have been relatively the same.

PMID:7214722 and PMID:6133659 - some beta blockers decrease t3 and/or increase rt3 levels, but atenolol appears not to, although it did provide some relief for hyperthyroid people. so i dunno. maybe give a try stop it if it's safe to, and see if you drop any.

since your main dysfunction seems to be your hpa axis, i would think about what the ssri might be doing to your hpa.. it could bring your cort. up, or it might be bringing your cort down. with me, if i have less cort, i start filling out right away, and on higher levels of cort. i always drop. and on higher levels of cort i eat much more too.

ive also seen mention that ssris can make thyroid levels either lower or less efficient in some people. (PMID:19583486) but i dont think the effect is signficant.

[essential]

hmm....not for me, i lost fat (like 10lbs) on lexapro....stops me from binging on carbs for mood support

Likewise here, SSRIs always stop me from carb binging both Citalopram and Escitalopram, I'm currently on 20mgs daily of Escitalopram and the leanest I have been in years and motivated.
I think for me the high NE before these caused major anxiety requiring constant loading up on 'ballast' to slow down the rollercoaster.

[bdog527]

Just to toss in another n=1. My uncle went from a very fat person to the leanest he's ever been in his life while taking Lexapro. He is an internal medicine doctor, and is also an advocate of very low dose SSRI. He only takes 2.5mgs. or so a day. But yeah, it completely controls his appetite and has maintained efficacy over years.

[physicus007]

not exactly on topic, but somewhat related

Although it is true that these changes can be explained by adiposity, produced and released
by adipocytes in response to increased fat deposition to regulate body weight, there is intriguing
evidence to support the hypothesis that antipsychotics could induce or exacerbate a leptin resistance
status. Resistance to leptin could generate metabolic conditions resulting in weight gain. Further
research is still needed to clarify the relationship between leptin and antipsychotics. The elucidation
of these potential mechanisms could be important for quantification of patient risk during treatment
with antipsychotics, and can spur development of novel forms of treatment.

full text of review > http://www.hindawi.com/journals/jobes/aip/572848/

[trance2]

My GF took them and basically it helps you not give a fuck about anything, including what you eat. So, you get fat. Weight watchers helps because it keeps you accountable.

[nidhogg]

I am about 1 month in on a 15mg/day mirtazapine course and i have so far gained a whopping 10lbs. I have counted my kcal intake and very rarely(once EOW) do i consume crappy food(chocolate, potato chips etc). I eat approx 2400kcal a day +/- 100. My exercise routine has not changed since i started taking mirta and i counted burning on average 2400kcal a day(averaged over a week).

I used to think people were fooling themselves when blaming the antidepressants for their weight gain but i tell you compulsive eating/increased appetite is definitely not the sole reason. Even though mirtazapine is notorious in its appetite increasing properties from 5HT2 antagonism there has to be more to it. I am not very strict on the micronutrients composition but i am sure of the total calorie intake since ive had about 3 years of experience counting calories on a regular basis

I find mirtazapine particularly interesting in this case, because it antagonizes the adrenergic a2 receptor which regulates liposynthesis. It also increases neurotransmitter release because of it as well as weakly inhibits the NA transporter protein. This would result in increased adrenergic beta activity and increased lipolysis. So it basically tackles fatty weight gain twofold.

Taken all of this in account i yet managed to gain 10lbs in 30 days, hell it souls like bullshit even when i read what i just wrote, but its the truth.

Intra and extracellular water retention comes to mind considering it messes with the HPA axis(glucocorticoids), but i doubt its significant to the extent of massive weight gain.
High serum leptin levels have been reported probably as a biochemical response to the increased appetite.

Strangeness at its finest

[Bill]

I would love to see some well designed studies posted that attempt to control for these confounding factors.

I wouldn't hold my breath

[Johnhopps]

Hi. First time poster here as I am searching for an answer on why ssris cause weight gain. Whenever I take an ssri I gain weight without increasing my calorie intake or reducing excercise . I would lose weight after stopping the med. This, last time prozac caused me to go from a lean 230 to 265. And 20 of those pounds were gained training for a marathon. In 8 months being off the meds I have only been able to get down to 250. No dr can give, me a medical explanation and I bust my ass many days without results . These meds can cause cause weight gain . It isn't just people being lazy and eating poorly because they feel better .