Antidepressants and Weight Gain

Question: Why do antidepressants cause weight gain?  Is there any way to lose weight on them?

Answer: Apparently, since talking fairly openly about my own mental issues I’ve sort of become the go-to guy on this topic for many people.  Which is only potentially overwhelmed by the influx of questions or Facebook PM’s I get about women’s periods right now.

Let me say up front that neuropsychiatry and all of this is not my primary field nor area of expertise and absolutely don’t claim that it is.    At the same time, the neurochemistry of eating behavior is a long time interest and there is certainly crossover between the topics which is why I feel comfortable enough writing about this.  Anyhow.

I couldn’t really answer the first question simply as asked since some anti-depressants are just as likely to cause weight loss as weight gain.  Much of it depends on the type of medication you’re talking about and the context as always.  So let me look at a few different types of medications and how they might or might not impact on this.

I’m also not going to try to be comprehensive and get into all of the other potential drugs such as bipolar treatment drugs such as lamictal (what I’m on), depakote, etc.  This is just about anti-depressants and I’ve probably missed a class of them somehow.

Serotonin Based Antidepressants and Weight

I don’t claim to know the full history of antidepressant medications but I believe that serotonin based drugs were one of them. Serotonin is one of three primary neurochemicals in the brain and is involved in things like mood, eating, hunger and especially carbohydrate cravings.  They can work through different mechanisms but a common one is the specific serotonin-reuptake inhibitor or SSRI.  Prozac, Celexa, Lexapro and others are a few examples.

In short, what these drugs do is prevent the normal reuptake of serotonin from between the nerve space.  This keeps the serotonin signal going longer and this is part of how these drugs are thought to work.  One thing that’s always been a little bit odd is that even though these drugs immediately raise serotonin, the antidepressant effects tend to be delayed, about 4 weeks.  A lot of different ideas have been thrown out including a rewiring on the brain.  This might be mediated by cortisol and Brain Derived Neurotrophic Factor (BDNF) or a change in receptor density.

In any case, SSRI are known for causing both weight gain and weight loss.  Why?

Part of it is that there isn’t really one kind of depression or response to it.  I detailed my own pattern of depression previously but it kind of has two phases.  In the first I sleep like 16 hours per day and don’t have the energy to do much.  Including eat.  In the second, I am functional but tend to self-medicate with carbohydrates (which raise serotonin in the brain).

And that’s kind of the answer.  In some types of depression, the person is just too exhausted to do anything, including eat, shower or get out of bed.  SSRI’s can give them the energy to do these things, including eating.  They gain weight.  I’d note that there is an odd phenomenon with some anti-depressants in that they can increase the risk of suicide in some folks.  I’m sure there’s more going on here but I suspect it’s the same mechanism.  Even if you want to kill yourself, when you can’t get out of bed, you just don’t have the energy.  Once you start to feel better but aren’t not depressed, now you have the energy to go through with it.

But the opposite can be true.  If you have a type of depression where you are self-medicating with carbohydrates, the SSRI may help to blunt that effect.  Weight loss occurs.

Basically, it’s a matter of context.  Moving on

DA/NE Based Antidepressants and Weight

Although SSRI’s were one of the most used antidepressants, it became fairly clear that all forms of depression were not related to serotonin.  The other two primary neurochemicals dopamine (DA) and norepinephrine (NE) also play a role. And there are drugs that work essentially like the SSRI class of drugs in that they inhibit the reuptake of those neurochemicals.

This is importance because DA is heavily involved in the reward pathways of the brain (Note for the nitpickers: I am full aware that reward is related to more than DA, that opiods are involved and the whole liking and wanting thing are separate.  I am trying to keep this a little less technical so don’t bother me.)

All drugs of abuse raise DA and highly palatable foods do too (Trivia: when you diet, brain DA goes down and animals are more likely to addict to drugs when that happens).  The obese may have a malfunctioning reward/DA system (this gets complicated as both under and over-activity may be involved) and I think you can see where this is going.  If someone has low DA levels, they may be more likely to overeat certain foods and increasing the DA signal could potentially offset this.

In that vein, one of the DA/NE drugs, Wellbutrin was repurposed to help with quitting smoking as Buproprion.  Same drug, same mechanism, same purpose.  By maintaining the DA signal that smoking no longer is, quitting becomes easier.  Same basic thing with food here.

Tricyclic Antidepressants and Weight

Though they don’t seem to be in common use anymore, tricyclics actually hit serotonin and norepinephrine and work as reuptake inhibitors of both neurochemical.  And they were associated with a fairly constant weight gain.  I’m not sure why and since they aren’t used much anymore, that’s all I’ll say.

MAOI Antidepressants and Weight

MAOI stands for monoamine oxidase inhibitor.  Monoamine oxidase is an enzyme which causes the breakdown of serotonin, dopamine and norepinephrine and this is just a different approach to raising their levels, in this case by blunting their breakdown.  MAOI seem to have different effects on bodyweight with one causing weight gain and others not.  So there is no consistent pattern (and this is common with these drugs).

The Atypical Antipsychotics and Weight

Although not strictly an anti-depressant there is a class of drugs called atypical antipsychotics (mainly an antipsychotic drug as the name would suggest) that are sometimes used and these can be very very very nasty.  They tend to work by blocking signalling at the DA, NE and serotonin receptors and given what I wrote above, you can maybe see why that would be a problem.   As well, given the central role in those neurotransmitters in other aspects of physiology, these drugs are known to cause an almost pre-diabetic state.

But there also appears to be an effect through the histamine system.  Another system in the brain (also involved in allergic type reactions), histamine signalling is involved in body weight regulation.  And some of the earlier atypicals seem to have blocked histamine signalling (I may have deleted it but I had an old Q&A about chronic anti-histamine use and body composition) and this is apparently part of the problem.

I say part since newer drugs such as Lotuda (lurasidone, a third generation anti-psychotic) don’t appear to cause weight gain (or may cause weight loss) and this is due to a lack of blocking the histamine receptor as other drugs do.  Some of the actual weight loss may be due to switching from a previous drug that caused weight gain, mind you.  So it may not be a direct effect here.

I should mention that some evidence has found that myo-inositol may help to offset the weight gain that occurs with earlier generation atypicals and might help with the weight gain that occurs with those compounds.   It looks like a pretty high dose of 12-18 g/day is used psychiatrically but I will be damned if I can find much more information than that or the original papers (only numbers were given) on the topic.

Anti-Epileptic and Mood Stabilizers and Weight

Although not strictly antidepressants, there are also the class of drugs that happen to control both epilepsy and act as mood stabilizers for bipolar.  Some of these clearly cause weight gain, the drug I’m on (Lamictal/Lamotrogine) is weight neutral (thank goodness) and others cause weight loss. So once again it’s kind of all over the map.

In any case I think you can see how this is really a difficult question to answer since it has no answer.  Some drugs are more likely to cause weight gain than others, there seems to be some individual response, the mechanisms behind the weight gain seem to vary considerably.

So far as the second question in terms of can weight be lost on the drugs, if it occurs.  Well that would also seem to depend.  The only real ways that most antidepressants have to really impact on weight gain or weight loss is through appetite or activity.  And most of them seem to impact mostly on the appetite end of things although atypicals may also reduce activity levels.  This make sense given their impact on the same systems in the brain that play a controlling role in appetite and hunger.  But the same general lifestyle changes should be effective.  For atypical anti-psychotics, myo-inositol may be very worth considering.


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