Friday Weird Science: Antidepressants affect sexual behavior...but HOW?

I was very pleased to run across this paper a few weeks ago.  I answer a LOT of questions about psychiatric drugs (on blog and IRL), and one of the most frequent ones is "DO antidepressants hurt sexual activity?" and "HOW?"

As for whether they DO, well, yes.  The most popular class of antidepressants, the selective serotonin reuptake inhibitors (SSRIs) definitely has a side effect of reduced sexual function, and other antidepressant classes that target serotonin directly or indirectly do as well.  But what does "reduced sexual function" MEAN?!  Well it can mean reduced libido, delayed ejaculation or orgasm, or inhibiting ejaculation entirely.  This can be a very unfortunate side effect, really affecting how people feel about themselves.  And of course, when you're already DEPRESSED, well it doesn't help much.

(But at least it can prevent this...)

And then people ask me HOW exactly SSRIs change sexual function. And...I don't know. Or I didn't. BUT I DO NOW. And I'm going to share it with you!!!

Hueletl-Soto et al. "Fluoxetine chronic treatment inhibits male rat sexual behavior by affecting both copulatory behavior and the genital motor pattern of ejaculation" Journal of Sexual Medicine, 2011.

Now, while colloquial wisdom has it that all activities of the penis are regulated by...the penis, in fact ejaculation is the result of signaling in two different areas of the central nervous system. At the lower level, there's a spinal generator of ejaculation (SGE) which is a central pattern generator in the lumbosacral portion of the spinal cord (that's your WAY lower back, at the junction between your back and your butt). This area is controlled by the brainstem. But there's also a higher area in the brain itself, a specific ejaculation network including areas like the amygdala, stria terminalis, and parts of the thalamus.

Together, these two pathways control and modulate the two phases of ejaculation, the emission phase and the expulsion phase (I know, it sounds the same, they are in fact different). Basically, when a guy is about to ejaculate, the semen has to come out the same hole that pee usually comes out of (I know this may come as a shock to some men, but women have two different holes for this). So during the emission phase, the neck of the bladder closes off, and semen is dumped into the urethra instead. And during the expulsion phase, the semen meets the outside world. Like this:

So the question becomes: we know that SSRIs affect ejaculation. Do they affect the lower ejaculatory response? The upper one? Neither? Both?

To test this, the authors of the study took a bunch of rats. The rats were "rendered sexually experienced" which sounds like some sort of horrid surgical procedure, but really it was a bunch of hot dates with lovely lady rats. If the rats passed the test with flying colors (first date to ejaculation in less than 15 minutes) they were selected for the study. They then gave them the SSRI fluoxetine (aka Prozac) for 14 days, and threw them in with their charming dates on days 1, 7, and 14, for an hour each time, to see how they fared.

Now rats are some randy little guys. When you put a male rat with a lady for an hour, you judge whether or not he's got ejaculatory dysfunction by how many times he can ejaculate with her. And he's considered to have a problem if he can't make it happen FOUR TIMES in an HOUR. I'm impressed.

So, fluoxetine. Did it work?

You can see that they looked at the number of ejaculations, the number of mounts (gettin' all up ons like you do), how long it took the ejaculate, and how long it took between ejaculations. They also looked at two different doses of fluoxetine. On day 1 they got changes at the highest dose in post-ejaculatory interval (aka, the pillow talk phase), and other measures changed as the drug was given over the two week period. The net result was a significant decrease in some measures of sexual activity (like ejaculations and latency) at the highest dose after 14 days. Though you note it never did stop them trying.

I would like to note that there's no program that can take this data for you. These self-sacrificing scientists were sitting there, watching rats bone through video monitors. The things we do for SCIENCE...

So we've confirmed that fluoxetine is decreasing the rats ability to ejaculate (as for libido, rats are notoriously close mouthed on the subject). But how do we know where that's coming from? To determine this, they took the rats that had received the fluoxetine, waiting two days for the drug to wash out, and then did a spinal transection. This involves exposing the spinal cord, putting recorders on the muscles of the pelvis and the penis itself, and electrically stimulating ejaculation. Needless to say, you don't want to be a volunteer.
(Fig 5 from the paper)

What we've got here are the recordings of the stimulation response in a vehicle treated rat (left) and a fluoxetine treated rat (right). You can see that the fluoxetine treated rats were much less sensitive to the effects of stimulation on the SGE than the vehicle treated rats. It looks like chronic antidepressant treatment here can decrease the sensitivity of the SGE, meaning it reacts less to the same stimulation.

So it appears that some of the effects of antidepressants on sexual activity may be via the lower limb of the ejaculation control centers, the ones in the spinal cord mediated by the brainstem.

But that still doesn't define what the MECHANISM is. Fortunately, there's a good hypothesis for the mechanism, though it remains to be tested. We know that low levels of serotonin increase sexual activity, and high levels of serotonin decrease sexual activity. But most serotonin neurons are the brainstem. And so is the SGE. In fact, the spinal cord (and thus the SGE as well) gets a strong dose of serotonergic innervation. So if you're getting serotonin signalling from the brainstem, and this normally increases sexual activity, and then you INCREASE serotonin by adding an SSRI...well you might have the mechanism.

Of course this remains to be tested. You could probably do it by either finding a specific serotonin receptor (there are a LOT) or possibly doing a selective lesion of the serotonin areas and then giving fluoxetine, to see what kind of effects result. In the meantime, now you know what might cause the sexual side effects associated with antidepressant use, you get desensitization of the spinal generator of ejaculation.

Hueletl-Soto, M., Carro-Juárez, M., & Rodríguez-Manzo, G. (2011). Fluoxetine Chronic Treatment Inhibits Male Rat Sexual Behavior by Affecting Both Copulatory Behavior and the Genital Motor Pattern of Ejaculation The Journal of Sexual Medicine DOI: 10.1111/j.1743-6109.2011.02339.x

13 responses so far

  • albert says:

    Wow, the second guy, coming out, in the supermarket and wearing glasses looks identical to Francis Collins. Is he already on vacation?.

  • CyberLizard says:

    This is a subject near and dear to my... um, heart. Yeah, heart. Anyway, as a taker (consumer? swallower?) of prozac, I have definitely noticed a negative impact on my libido. I haven't, however, noticed any problems achieving orgasm. So is what you're saying that the "desensitization of the spinal generator of ejaculation" is also responsible for the greatly reduced desire for sex?

    • scicurious says:

      I would say probably not. I don't actually know. This probably only plays a role in the actual delay in ejaculation experienced by some people (I imagine it's probably a lot of people, just may not be particularly severe).

      • CyberLizard says:

        It's incredibly frustrating how elusive all this anti-depressant stuff is. I mean, I understand why, it just sucks. I wish I had the smarts to figure this stuff out. I guess I'm left in your (and scientist people like you) hands 🙂

  • J Robinowitz says:

    Okay, so that explains what's going on for men (at least in part), but what about for women? SSRIs don't only affect men's ability to ejaculate, they also impact women's ability to orgasm. I'm going to guess that it's not due to the same neural mechanisms. What gives?

    • Katie says:

      I would love to know this too. Am looking down the barrel of a lifetime on fluoxetine and the delayed orgasm/sexual response issue is proving a really difficult one. I'm having real trouble finding any information on how to ameliorate the situation - any information would be so appreciated.

  • Ron says:

    You have the best videos.

  • Padre Angelo says:

    O Face !!!!.

    That's a sin and a psychological disorder but you can always go to confession.... And then you can re-do it all over again... as many times as you want with as many confessions as desired. HAHAHAHAHAHAHA

  • Craig says:

    Now I'm wondering how many times is normal for a human over an hour... I tried tonight and easily reached three but am one of the sufferers of delayed ejaculation and have never reached orgasm with a partner due to lack of stimulation (also possibly due to my masturbation technique). I haven't felt depressed for years but I had an extreme reaction to an SSRI ten years ago that has left me feeling a part of my conscious self missing and have been unable to really enjoy the high of experiencing orgasms or any activity highs unless they happen to be extreme or involving since that time. I had no such problems in my youth or when I was depressed but not on meds. A recent relationship was affected by my condition and so I can relate to "a very unfortunate side effect, really affecting how people feel about themselves."
    I thank all the male rats in the study for taking one (or four or more) for the team.

  • SB says:

    From the headline I was expecting to find information about the effect of antidepressants on women's libido as well.

  • [...] Scicurious on rat studies that clarify how antidepressants interfere with ejaculation [...]

  • Bianca says:

    My boyfriend and I have a great sex life, we keep things interesting, I never say "no" to anything he wants to try and he goes out of his way to make sure I am satisfied (sometimes over 5 satisfactions in one session) but he has been on AD's for the last 10 months or so. He was originally on Wellbutrin and that made him ejaculate one out of 5 times, his doctor recently switched him to selexia (the Wellbutrin wasn't effective with his psychological disorder) and he now doesn't orgasm at all. I know he enjoys himself on the same level, if not more than he used to, I've been extra conscious of him in the bedroom, paying closer attention to his reactions, we talk about what feels good/what doesn't, and no matter what, he just cannot "finish." I don't want him off the meds because they are an essential part of him staying mentally healthy, which is far more important than an orgasm, but I do want to pleasure him in the same way he pleasures me. Are there any exercises or remedies we can try to speed up the process of him being able to live on the meds and not have it disrupt what once was an amazing sex life? Thank you!

  • […] Read more of this, uhm, explicit article on how SSRI’s affect male ejaculatory responses. […]

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