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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 13 of 13. This is the beginning of the thread.
Posted by Marty on August 5, 2008, at 19:39:36
5-HT2c is supposed to be the major culprit in the antidepressant sexual side effects. Fluoxetine is often reported has been one of the worst antidepressant when it comes to sexual side effects. Agreed ? .. now I stumble upon this:
"Have you ever given a dose of fluoxetine (Prozac) to a patient and had them have an activation? Fluoxetine is the only other drug that has powerful 5HT2C antagonist properties; in fact, fluoxetine has more powerful antagonist properties than reuptake blocking properties."Source: " Schizophrenia: From Circuits to Symptoms
Stephen M. Stahl, MD, PhD. Improving Mood and Cognition: Serotonin 2C and 1A"URL:
http://www.medscape.com/viewarticle/484929_5If Prozac is one of the most potent 5-HT2C and end up being one of the worst at the sexual level then ... there's way more to the story than just 5-HT2C .. Any thoughts ?
/\/\arty
Posted by rjlockhart '05 on August 5, 2008, at 23:55:26
In reply to Fluoxetine = 5-HT2c Potent antagonist ? ..confused, posted by Marty on August 5, 2008, at 19:39:36
I used to rerember alot of this nuerological stuff, i havent posted in years.
Just a vague memory, Serotonin for some reason decreases sex drive. Dopamine increases it.
I'll have to catch up, all my files in my head got lost.
rj
Posted by SLS on August 6, 2008, at 5:04:00
In reply to Fluoxetine = 5-HT2c Potent antagonist ? ..confused, posted by Marty on August 5, 2008, at 19:39:36
Hi Marty.
> If Prozac is one of the most potent 5-HT2C and end up being one of the worst at the sexual level then ... there's way more to the story than just 5-HT2C .. Any thoughts ?
None.
:-)
However, that was a great bit of snooping, Marty. Thanks.
Hmm. Perhaps at therapeutically relevant dosages, 5-HT kicks off the Prozac and replaces it on the 5-HT2c receptor?
How much do you suppose activating 5-HT2a receptors might disrupt sexual function? If it does, then that would be another avenue that by which a biphasic effect might occur.
Stahl is really something.
- Scott
Posted by Marty on August 6, 2008, at 9:29:58
In reply to Re: Fluoxetine = 5-HT2c Potent antagonist ? ..confused, posted by rjlockhart '05 on August 5, 2008, at 23:55:26
> I used to rerember alot of this nuerological stuff, i havent posted in years.
---
You know the saying: "Use it or loose it" :)
> Just a vague memory, Serotonin for some reason decreases sex drive. Dopamine increases it.
---
Yes. and 5-HT2c receptor when stimulated too much is the major mechanism by which the serotonin system inhibit sexuality. That why about half the tried AD induced sexual dysfunction antagonize 5-HT2c and the other half are dopaminergic.
> I'll have to catch up, all my files in my head got lost.
---
You feel you should and need to ? Simply because you like psychopharmacology or/and because it would help you figure out what's next to try ?/\/\arty
Posted by JayBTV2 on August 6, 2008, at 10:20:57
In reply to Re: Fluoxetine = 5-HT2c Potent antagonist ? ..confused » rjlockhart '05, posted by Marty on August 6, 2008, at 9:29:58
I don't think 5-ht2c is the problem w/ SSRI sexual side-effects. Based on the fact that the new drug Agomelatine (Valdoxan) is supposed to a 5-ht2c antagonist and it _doesn't_ have the same sexual side-effect issues as most SSRIs.
See: http://www.ncbi.nlm.nih.gov/pubmed/18480691 :
A double-blind comparison of sexual functioning, antidepressant efficacy, and tolerability between agomelatine and venlafaxine XR.
Kennedy SH, Rizvi S, Fulton K, Rasmussen J.Department of Psychiatry, University of Toronto, and University Health Network, 200 Elizabeth Street, Toronto, Ontario, Canada. sidney.kennedy@uhn.on.ca
Impaired sexual function is associated with major depressive disorder in the untreated state and is often more prevalent during antidepressant therapy, which frequently results in poor treatment compliance. In this double-blind, multicenter study, the effects of agomelatine (an MT1 and MT2 agonist and 5HT-2C antagonist) and venlafaxine XR on sexual function were compared using the Sex Effects Scale in depressed patients. A total of 276 male and female patients received either agomelatine (50 mg) or venlafaxine XR (titrated to a target dose of 150 mg/d) for 12 weeks. Those who were sexually active at baseline (n = 193) and those who, in addition, achieved remission (n = 111) were defined a priori for analyses of change in sexual function. Treatment-emergent sexual dysfunction was significantly less prevalent among patients who received agomelatine, and venlafaxine XR was associated with significantly greater deterioration on the Sex Effects Scale domains of desire and orgasm. Both treatments resulted in equivalently high rates of remission (agomelatine, 73%; venlafaxine XR, 66.9%), although fewer patients in the agomelatine group discontinued treatment because of adverse events (agomelatine, 2.2%, vs venlafaxine XR, 8.6%). Agomelatine seems to be an efficacious antidepressant with a superior sexual side effect profile compared with venlafaxine XR, although superiority to placebo was not evaluated in this trial.
=================================================Agomelatine description from Wiki:
Agomelatine (Valdoxan, Melitor) is chemical compound that is structurally closely related to melatonin. Agomelatine is a potent agonist at melatonin receptors and an antagonist at serotonin-2C (5-HT2C) receptors, tested in an animal model of depression (forced swimming test in rodents). It is concluded that the antidepressant-like activity in this model most probably involves a combination of both its melatonin agonist and 5-HT(2C) receptor antagonist properties.
Posted by Marty on August 6, 2008, at 11:30:19
In reply to Re: Fluoxetine = 5-HT2c Potent antagonist ? ..confused, posted by JayBTV2 on August 6, 2008, at 10:20:57
> I don't think 5-ht2c is the problem w/ SSRI sexual side-effects. Based on the fact that the new drug Agomelatine (Valdoxan) is supposed to a 5-ht2c antagonist and it _doesn't_ have the same sexual side-effect issues as most SSRIs.
---
Hi, I respect your opinion, but I have to disagree with your rationale. Your logic is flawed because most AD with sexual side effects induce those because they STIMULATE 5-HT2c because of their reuptake inhibiion mecanism of action (more serotonin in the synaptic cleft "pushing buttons" more often.. 5-HT2c receptor being such button).... Agomelatine being a 5-HT2c ANTAGONIST, it REDUCE THE STIMULATION of the 5-HT2c receptor (the button is less frequently pushed).Your logic implying that Agomelatine act the same way on 5-HT2c as the other antidepressants is thus flawed. They act in opposite ways. In fact Agomelatine could be proposed as an antidote for sexual side effect induced by other antidepressants, theorically that is.
That said can't wait for that Agomelatine to be approved. (damn FDA)
/\/\arty
Posted by rjlockhart '05 on August 6, 2008, at 19:38:10
In reply to Re: Fluoxetine = 5-HT2c Potent antagonist ? ..confused » JayBTV2, posted by Marty on August 6, 2008, at 11:30:19
Note of Logic: dont someone down when i have never said anything to you, i was giving you information.
Thanks
rj
Posted by Marty on August 6, 2008, at 23:51:45
In reply to Re: Fluoxetine = 5-HT2c Potent antagonist ? ..confused, posted by rjlockhart '05 on August 6, 2008, at 19:38:10
> Note of Logic: dont someone down when i have never said anything to you, i was giving you information.
>
> Thanks
>
> rj
---
Hi Rj,I dont get what you mean. Did I told you something wrong ? If you're feeling so then I'm sorry and I invite you to explain me what I've done and to who. Babblemail or here is okay for that I intend to 'stay civil' in any case.
/\/\arty
Posted by JayBTV2 on August 7, 2008, at 11:41:14
In reply to Re: Fluoxetine = 5-HT2c Potent antagonist ? ..confused » JayBTV2, posted by Marty on August 6, 2008, at 11:30:19
> Hi, I respect your opinion, but I have to disagree with your rationale. Your logic is flawed because most AD with sexual side effects induce those because they STIMULATE 5-HT2c because of their reuptake inhibiion mecanism of action (more serotonin in the synaptic cleft "pushing buttons" more often.. 5-HT2c receptor being such button).... Agomelatine being a 5-HT2c ANTAGONIST, it REDUCE THE STIMULATION of the 5-HT2c receptor (the button is less frequently pushed).
>>The title says " Fluoxetine = 5-HT2c Potent antagonist". That's why I assumed the two were similar. Are they both antagonists? Or was there a typo?
Either way I'm not too interested in the mechanics of why SSRIs cause sexual side-effects.
Like you I'm just waiting on Agomelatine and I'm glad that it works and doesn't cause these problems :)
Happy Thursday...
-Jay
Posted by bleauberry on August 7, 2008, at 19:08:08
In reply to Fluoxetine = 5-HT2c Potent antagonist ? ..confused, posted by Marty on August 5, 2008, at 19:39:36
>
> 5-HT2c is supposed to be the major culprit in the antidepressant sexual side effects. Fluoxetine is often reported has been one of the worst antidepressant when it comes to sexual side effects. Agreed ? .. now I stumble upon this:Actually no, not agreed. While all ssris had sexual side effects with me, prozac was by a long shot the friendliest.
>
> "Have you ever given a dose of fluoxetine (Prozac) to a patient and had them have an activation? Fluoxetine is the only other drug that has powerful 5HT2C antagonist properties; in fact, fluoxetine has more powerful antagonist properties than reuptake blocking properties."5ht2c antagonism blocks the effects of serotonin at that receptor, which is actually a good thing for sex, not a bad thing. Downstream effects as a result include release of more DA, NE, and 5ht. Levels of all 3 neuros increase in the brain from prozac but not from other ssris.
>
> Source: " Schizophrenia: From Circuits to Symptoms
> Stephen M. Stahl, MD, PhD. Improving Mood and Cognition: Serotonin 2C and 1A"
>
> URL:
> http://www.medscape.com/viewarticle/484929_5
>
> If Prozac is one of the most potent 5-HT2C and end up being one of the worst at the sexual level then ... there's way more to the story than just 5-HT2C .. Any thoughts ?
>
> /\/\artyThe potency as a 5ht2c antagonist is actually sex-friendly. Of course, the serotonin reuptake is powerful enough to over-ride much of it. Due to the 5ht2c antagonism, prozac has been called an atypical ssri.
And to say in a generalized manner that the 5ht2c receptor is responsible for sexual side effects is extremely oversimplified. It just aint that simple. Lots of stuff going on. And a great deal of interplay/interaction/shared duties between other receptors and other neuros.
Posted by Marty on August 7, 2008, at 19:33:00
In reply to Re: Fluoxetine = 5-HT2c Potent antagonist ? ..confused, posted by bleauberry on August 7, 2008, at 19:08:08
> Actually no, not agreed. While all ssris had sexual side effects with me, prozac was by a long shot the friendliest.
---
I'm glad to hear that because Prozac is the only SSRI that I didn't try yet. Many people reported Prozac to be harsher than others while not being as bad as let say Paxil. That would be interesting to start a thread and make a poll in the kind of "What was your best and worst SSRI regarding sex ? and list which one you tried." .. are you aware of a thread on pbabble in the past doing just that ?
> 5ht2c antagonism blocks the effects of serotonin at that receptor, which is actually a good thing for sex, not a bad thing.
---
Yes, I'm well aware of this. That's why I was confused since I thought Prozac was one of the worst regarding sex and since 5-HT2c antagonism is a good thing for sex then I wondered why it wasn't one of the best regarding sex. Now that you mention that you found Prozac to be easier than others I guess that explains my confusion.
> The potency as a 5ht2c antagonist is actually sex-friendly. Of course, the serotonin reuptake is powerful enough to over-ride much of it. Due to the 5ht2c antagonism, prozac has been called an atypical ssri.
---
I was aware it was called an atypical SSRI but I never look into why it was considered atypical. Very interesting. Are you aware if it also antagonize 5-HT2a to a significant level ?> And to say in a generalized manner that the 5ht2c receptor is responsible for sexual side effects is extremely oversimplified. It just aint that simple. Lots of stuff going on.
---
No doubt
/\/\arty
Posted by atmlady on August 7, 2008, at 21:13:16
In reply to Re: Fluoxetine = 5-HT2c Potent antagonist ? ..confused » bleauberry, posted by Marty on August 7, 2008, at 19:33:00
Huh. Well, my (new) pdoc says that I shouldn't just *assume* that I will have sexual side effects from *all* SSRI's, only because I've experienced them with the (only) two I've taken (Effexor and Leapro). I'm having a hard time believing that. What do you guys and gals think? If these two ADs cause sexual side effects for me, should I just keep trying all the SSRI's available? Have I erroneously (or too quickly) jumped to the conclusion that *all* SSRI's will affect me this way, based on the experience of just two SSRI's?
I should have asked him (I always thing of these things when it's too late) whether he's ever actually treated a patient like me, who miraculously found the one perfect SSRI that didn't cause weight gain or sexual side effects, after being on a string of them that did. Personally, I think he's handing me a line, but at least he didn't say, "Gee that's strange, Lexapro isn't associated with weight gain" like my last pdoc did.
Posted by Marty on August 7, 2008, at 22:28:32
In reply to Re: Fluoxetine = 5-HT2c Potent antagonist ? ..conf, posted by atmlady on August 7, 2008, at 21:13:16
> Huh. Well, my (new) pdoc says that I shouldn't just *assume* that I will have sexual side effects from *all* SSRI's, only because I've experienced them with the (only) two I've taken (Effexor and Leapro). I'm having a hard time believing that. What do you guys and gals think? ----
I think it partly depends on how much (severity and extent) you've suffered from those sexual side effects. Lexapro being the SSRI who's usually is the easier on the sexuality and Effexor XR being one of the worst for woman I think your chances of finding one with no sexual side effect are pretty much near ZERO. But med trial being the art (not the science) that it is who knows ? If sexual side effects is your problem I suggest you look at (if it's not already done):- Wellbutrin (not a SSRI, act on dopamine and NE. good for sex and can be added to an SSRI to help a little)
- Tianeptine (not a SSRI, more anxiolitic than Wellbutrin)
- Serzone (SSRI with no sexual side effects)
- Parnate (and old MAOI, good for sex, bad for many other side effects and comes with a diet)
Also there's the antidote game. Example: Cyproheptadine. You can google "sexual side effects +antidote" and find a couple proposed antidotes. It doesn't work for everyone and it's far from being perfect but it has helped some.
Good luck,
/\/\arty
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