The Y in Psychiatry

E11 - Even More Potentially Impotent Side Effects from the Antidepressants - Part 2

• NguyenInDoubt • Season 1 • Episode 11

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Join Dr. Amayo and Dr. Handratta as they dive into the dark yet enlightening side effects of conventional antidepressants. From weight gain to sexual side effects and hyponatremia, this lively conversation unpacks the mechanisms, challenges, and potential solutions. Get ready for a dose of medical insight with a dash of humor in this must-listen episode.

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Thanh:

Very. That's true. That's so true. Yeah. Like in Vietnam, there's literally a word is now where if you say it, it literally means. Um, this is an event that you're going to go to where you're going to drink and eat a lot of like little aperitifs with like a bunch of people around getting rowdy. And there's a word for that? Yes. Welcome to the Y in Psychiatry!

Dr. Amayo:

Hi, this is Dr. Amayo C/L fellow.

Thanh:

Where we delve into the intricate nuances of psychiatric topics.

Dr. Handratta:

My name is Dr. Handratta attending psychiatrist. I did my residency from University of Connecticut and then I did my fellowship from Georgetown University in consultation and liaison.

Thanh:

Each episode features interview style discussions that explore the intersection of the mind medicine and the human experience. Together we'll uncover the hidden why and the groundbreaking discovery shaping the psychiatric landscape. So grab a seat, warm beverage, tune in, and let's embark on this journey to unlock the mysteries of the human psyche. Only on The Y in Psychiatry.

Dr. Amayo:

Okay, welcome to the Y in psychiatry. Today will be our second episode on side effects with conventional antidepressants. And today we'll be focusing on the weight gain, the sexual side effects hyponatremia and withdrawal side effects. As usual, I'm your host, Dr. Amayo. And with me, we have the guru, Dr. Handratta. Say, hi, sir.

Dr. Handratta:

Hi. How are you guys doing?

Dr. Amayo:

Okay so one, especially for my patients that identifies as female, one of the biggest question they ask me is if they're gonna gain weight with the medication I sometimes use styles and try to see which SSRI is more likely to cause weight gain And so I guess my question is why does antidepressants in general cause weight gain?

Dr. Handratta:

That's a good question, Because this is a question that people usually ask. So the mechanism behind weight gain with antidepressants is that antidepressants that block the serotonin 5HT-2C receptors. Are more likely to gain weight because this particular receptor is present in your hypothalamus, the area of the brain that controls your feeding and metabolism. There's an area called arcuate nucleus. So when you block the 5HT-2C receptor, you can increase the appetite. Second is when you block the histamine receptors can also increase the appetite. So any medication that blocks the 5HT-2C and histamine receptors are more likely to cause weight gain. For example, your mirtazapine. And if you look at antipsychotics, your olanzapine that does that. Clozapine does that. Quetiapine does that. So that's why these medications are more likely associated with weight gain.

Dr. Amayo:

And is it just the 5HT-2C or it has to be a combo 5HT-2C and histamine?

Dr. Handratta:

Either one.

Dr. Amayo:

And doing both would make it even worse, like Razin does Both.

Dr. Handratta:

Yes.

Dr. Amayo:

And with the histamine, the blocking of the histamine receptors, is that also associated with the hypothalamus arcuate nucleus, or is that a different mechanism?

Dr. Handratta:

So it's, it is actually, everything actually basically ends up there.

Dr. Amayo:

Okay.

Dr. Handratta:

Because hypothalamus Exactly. Which is something that controls your feeding as well as your metabolism.

Dr. Amayo:

And just one more question. So in depression, there's a loss of appetite and there's a weight loss associated with depression. Is it the same mechanism with the hypothalamus, arcuate nucleus that's affected?

Dr. Handratta:

So in patients with depression, so there are different reasons actually why patients can lose weight. So sometimes actually the depression is because of an inflammatory condition and there's an increase in the cytokines. So increase in the inflammatory cytokines itself can cause decrease in the appetite. So patients who have inflammatory reaction like cancer, rheumatoid arthritis, you have too much cytokines. So cytokines can cause something called sickness behavior. And the way you differentiate sickness behavior from depression is that the two things that are very typical of sickness behavior is anorexia and psychomotor retardation. Another reason, what I think, which may or may not be true, is that serotonin actually works on receptors depending upon the concentration. So when you have a low amount of serotonin binds to the 5HT-1 A receptors. When you have a little bit high, it binds to 5HT2A. When you have too much serotonin binds to 5HT2C receptors So when serotonin So when serotonin is too low, it might be the five HT one receptor that gets affected.

Dr. Amayo:

And that's the other receptors that's the one we want?

Dr. Handratta:

Which is an auto receptor but these receptors are also present in arcuate nucleus.

Dr. Amayo:

Oh, okay. Yeah.

Dr. Handratta:

But the thing that actually makes more sense in my head is actually the cytokines.

Dr. Amayo:

That's interesting.

Dr. Handratta:

Anhedonia too, right? Like patients usually have decreased reward, so they have little satisfaction actually with eating. So that might be another reason actually that yeah, food is not palatable.

Dr. Amayo:

And it could just be lack of motivation

Dr. Handratta:

Lack of motivation. Exactly.

Dr. Amayo:

To even do those life sustaining like activities

Dr. Handratta:

Exactly. Because you are actually, as we know from our previous lectures, that you get stuck in the default mode. Default mode just, and you don't use a central executive network, which is actually tells you, which is close to the sensory motor area, which tells you, Hey, let's go to the kitchen and make food and go to the restaurant and cook get some food or order it online. Yeah.

Dr. Amayo:

Okay, so just I wanna summarize for the weight gain the main culprit is the 5HT-2C receptors and the histamine uh receptors and those will affect your hypothalamus arcuate nucleus, which controls appetite. That's that and any SSRI that block those receptors might increase your chance of gaining weight. Do we know any do you know which ones are particularly notorious mirtazapine.

Dr. Handratta:

It blocks the 5HT-2C receptor. You've got citalopram and escitalopram that has an antihistamine property to it. So these are some of the medication which are more likely to cause weight gain. Paroxetine too, actually hits these receptors. But the weight gain, if you look at it with paroxetine, once patient gains weight, it doesn't reach a plateau. They keep on gaining weight. Whereas with citalopram and escitalopram, they gain weight and then they reach a plateau.

Dr. Amayo:

And I'm guessing, so Prozac and Sertraline are less

Dr. Handratta:

They're less likely. Fluoxetine and Sertaline are less likely cause weight gain?

Dr. Amayo:

Okay. So sexual side effects. That's another one that I find with specific population. And this way are usually my young males that are concerned about that. Yeah.

Dr. Handratta:

So sexual side effects is another thing that we worry about. Do depression itself can actually cause decrease in the sexual function. Yes. So that's actually the major, cause I always educate them, my patients saying that, Hey, depression itself can cause this. Let's start an antidepressant and see how you do. With the psychotherapy, I always combine antidepressants, psychotherapy together Right now there are some antidepressants which are more likely to cause sexual side effects than other majority of the antidepressants will cause it. If they hit the serotonergic system, stimulation of the 5HT-1A receptor is more likely associated with premature ejaculation

Dr. Amayo:

And, from just our recent talk, the 5HT-1A, it seems like it leads, it doesn't need as much serotonin coverage to be hit. So almost any, anything you give that's hits serotonin would hit the 5HT1A.

Dr. Handratta:

And then when you stimulate the 5HT-2C receptor, you cause delayed ejaculation.

Dr. Amayo:

And this is the same 5HT-2C that is the culprit for weight gain.

Dr. Handratta:

Yes. So when you block those 5HT-2C, you cause weight gain. When you stimulate, you actually cause delayed ejaculate

Dr. Amayo:

So when you block it, weight gain, stimulated. Okay. And SSRIs can do both.

Dr. Handratta:

SSRIs can actually stimulate 5HT-2C because if you increase the amount of serotonin, if you flood the system with serotonin we know that 5HT-2 C receptor is a low affinity receptor. So when there's too much serotonin, it goes in, binds to 5HT-2 C, right? So when you have serotonin, the first receptor to be saturated is 5HT-1 A, followed by 5HT-2 A, and then 5HT-2 C.

Dr. Amayo:

And um, how can I help with that? So with my patients, if they have the sexual side effects I know from. Sometimes I had Bupropion or I had sildenafil. Is there anything I can do without giving them more meds? Is there anything I can do with the medication itself besides stopping it?

Dr. Handratta:

So antidepressants, which are more likely to be associated sexual side effects is fluoxetine sertraline, and venlafaxine, are the highest incidence of sexual side effects, the one that is associated with very low risk of sexual side effects is vortioxetine and vilazodone. So those are the two which basically I switch to. Actually the patient is complaining of sexual side effects with most of those you can add, you can switch to buproprion if the patient has depression, right? Bupropion is more effective. The patient has anorgasmia like decreased desire for sexual activity, right? You can add buspirone, which is a partial agonist at 5HT-1 A receptor. You can actually use something that blocks the 5HT-2 C receptor that delay ejaculation like il, right? Some literature will also say that skip a dose of antidepressant, the day you are planning actually a sexual activity.

Dr. Amayo:

So I wonder how skipping a day would work then.

Dr. Handratta:

So the skipping a day basically with a very short half-life. You basically deplete the serotonin system, so you can actually look, paroxetine and fluvoxamine are more notorious actually for withdrawal as well as venlafaxine. So I basically stay away from that. Skipping a dose. Yes. Yeah. I guess

Dr. Amayo:

the next one would be the hyponatremia. I think that's an interesting one, how SSRIs can, increase your chances of hyponatremia.

Dr. Handratta:

So hyponatremia is another side effects. But hyponatremia is more likely to happen in patients who are elderly. The elderly patients have a decrease in the global filtration rate. So that is a reason why they're at more risk for hyponatremia. Hyponatremia is also a risk, especially in post-surgical patients because of the stress that they go through. Because stress nausea, vomiting, pain can increase your a ADH production. But antidepressants actually, the way it causes hypo natia is a little bit different. So SIADH is a syndrome of inappropriate, ADH production. So in SIADH, there will be an alteration in the ADH, but according to the data, what antidepressant does is that it directly stimulates the vasopressin receptor. Your collecting ducts where ADH works. Which is called as a V2 receptors. V2. Yes because ADH is also called vasopressin. So antidepressants by attaching to these V2 receptors, they usually stimulate the second messenger system and they increase the attachment of aquaporin channels, and that actually leads to the reabsorption of water from the collecting duct and diluting your system and that's causing hyponatremia. So it's also called as a syndrome of inappropriate anti diuresis instead of SIADH. Because your ADH is not involved here, the antidepressants will directly go and stimulate those V2 receptors in your collecting duct.

Dr. Amayo:

And is that what ADH does? Stimulate the V2 receptors to cause more increase in aquaporin. And so the serotonin or the SSRIs goes and basically pretends to be ADH.

Dr. Handratta:

Exactly

Dr. Amayo:

And so there's not an increase in ADH it's just the SSRIs are pretending to be it.

Dr. Handratta:

Yeah, exactly right. Instead of increasing the ADH, the ADH level will be low actually, these patients, so you can't test.

Dr. Amayo:

I just wanna summarize the two we just did. So for the sexual side effects, the reason is because of 5HT-1 A and 5HT-2 C. And it's interesting to note that it's a simulation of the 5HT-2 C, that will lead to

Dr. Handratta:

delayed ejaculation.

Dr. Amayo:

Delayed ejaculation. Yes. And the 5HT-1 A will lead to anorgasmia.

Dr. Handratta:

So 1A will lead to premature ejaculation.

Dr. Amayo:

Premature ejaculation. Yes. 5HT-2 C will lead to delayed ejaculation. Yes. And that's important to note because blocking a 5HT-2 C will lead to weight gain

Dr. Handratta:

And I think you are also right actually, Dr. Amayo, like stimulating a 5HT2-C can also lead to anorgasmia. Because when you stimulate the 5HT-2 C, you decrease the amount of dopamine in your reward center of the brain.

Dr. Amayo:

So stimulator 5HT-2 C will give you both delayed ejaculation and anorgasmia. And so that's why we get those sexual side effects. And then for hyponatremia the issue is the SSRI pretends to be ADH stimulates stimulates the V2, increase aquaporin channel, and now we are taking in more water, and elderly patients and people that, that going a lot stress are at risk for this. So it's. I think we have time, even though we have one more draw side effects. I think we can touch that another time. And that's it for today's session. Thank you. Joining us.

Katrina Wachter:

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People on this episode

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Isiomah Amayo, MD

Host
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Dr. Hendratta

Co-host