SSRIs and sexual dysfunction: mechanism?

[whopper]

I just found this out a few weeks ago while studying for USMLE Step III.

And I'm a bit ashamed that I found it out from a test question.

The question from Blueprints for USMLE Step III-Internal Medicine (their question book for the exam, not their general IM book) had a clinical scenario where a psychiatric patient had all the sx of hyperprolactinemia (galactorrhea, decreased sexual desire) and the question asked what was the most likely cause of the effect? The prolactin level was about 50 (I think).

Yeah well I figured I had this nipped in the bud.

The answer obviously was going to be an antipsychotic....

After all prolactinomas usually push prolactin levels above 100, usually over 150.
Atypicals and typicals as we know block dopamine which in turn increase prolactine.

So I check the answer choices--prolactinoma, yeah, expected that wrong answer to be there, but THERE WAS NO ANTIPSYCHOTIC IN THE ANSWER CHOICES.

Well guess what, psyche resident got the psyche question wrong. The answer was fluoxetine.

I never read about SSRIs decreasing dopamine, so I double checked various sources and yes it does do this.

So that got me thinking....
Was the mechanism of sexual dysfunction and SSRIs every established? I never heard of a specific explanation.

Is it because of decreased dopamine? That would make sense. Decreased dopamine --> increased prolactin --> sexual dysfunction.

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[50960]

There is a known downregulation of dopamine secondary to SSRI's. This is why wellbutrin is used to treat SSRI sexual dysfunction.

 

[allosteric1]

I believe the primary problem with SSRI's is their binding to a certain sub-type of serotonin receptor, can't remember which one.

 

[Hurricane]

They also prolong latency to ejaculation, and are sometimes used as a treatment for premature ejaculation.

The mechanism for this isn't known for sure, but may have to do with binding to serotonin receptors on ejaculation generator neurons which have been identified in rodent spinal cords.

 

[whopper]

Well scratch my theory with the dopamine as the primary cause. It could be involved, it may still even by the primary cause, however sertraline (Zoloft) as we know (and for some idiotic reason I forgot to consider this) increases dopamine, yet sertraline still causes the same type of sexual dysfunction as seen in all SSRIs.