• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
- - - - -

SSRI (escitalopram) Robustly Decreases Dopaminergic Transmission - How to reverse?

ssri lexapro escitalopram dopamine vta motivation

  • Please log in to reply
7 replies to this topic

#1 TheHardProblem

  • Guest
  • 2 posts
  • 0
  • Location:USA

Posted 08 December 2015 - 04:17 AM


I'm currently on 10mg of lexapro (escitalopram) for social anxiety and OCD. I was on it a few years ago and it helped turn my life around in letting me socialize with others with much more moderate (normal) levels of anxiety, but my grades tanked, I developed an insatiable appetite for sugar and junk food, and generally went from an "over achieving neurotic" to a "sociable clown."

 

I can't consciously tell if the reduced focus on grades was due to a more general reduction in anxiety from the SSRI about my future that was previously causing me to stay up nights fretting over school work making sure I was getting it all done, or because of possible "cognitive impairment" in the realm of motivation/concentration impairment that may have come about as a side effect from the escitalopram SSRI.

 

Back on it now, I've noticed a similar  and very welcomed decrease in social anxiety, but also a more general reduction in existential anxiety, again also in regard to academics that I suspect may partly be due to reduced dopamine transmission caused as a side effect of the SSRI.

 

While SSRI's do not acutely affect dopamine neurotransmission, or have a direct affinity for the receptor, the serotonin/dopamine systems are linked and there is a pretty well regarded study published a few years ago documenting exactly this effect. 

 

Effects of sustained serotonin reuptake inhibition on the firing of dopamine neurons in the rat ventral tegmental area (2009) (Full article)

http://www.ncbi.nlm....les/PMC2674976/

 

And in conclusion, basically found that:

 

"5-HT reuptake inhibition can attenuate the firing activity of DA neurons in the VTA, although only escitalopram does so in a robust fashion. This inhibition might result in suppression of mesolimbic and mesocortical DA neurotransmission. On the one hand, because of the critical role of these DA pathways in the regulation of motivation and reward, such an effect may account, in some patients, for the lack of adequate response to SSRIs."

 

We all know here how important dopamine neurotransmission is to motivation/concentration and general cognitive ability, so I suspect that my "poorer academic performance" whenever taking lexapro is not a coincidence, and may be partly due to inhibited/impaired dopaminergic transmission.  I know several people on these boards and elsewhere have noted a similar "cognitive impairment" or other motivation/memory issues as a side effect of SSRI use. Which leads me to the point of this topic, that I hope may be of interest or use to others here finding themselves in a similar situation, of how to reverse this inhibition of DA in the VTA and mesolimbic pathways?

 

----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

 
 

The authors of the above study were also studying a 5-HT2C receptor antagonist coadminstered with the SSRIs and noted a robust reversal of this dopaminergic inhibition:

 

"When we increased the dose of SB 242084 to 2 mg/kg/d, it completely reversed escitalopram-induced suppression of firing of DA neurons in the VTA."

 

I couldn't personally find any supplements/drugs that were 5-HT2C receptor antagonists (SB 242084), but I was hoping someone on here with more knowledge on this subject might.

 

Or if any others could recommended a better way to reverse dopaminergic inhibition in general, or specifically when occurring as a side effect from ssri administration?

 

A simple solution would be to simply cease SSRI use but it really does have a notable impact in decreasing my social anxiety, allowing me to actually enjoy social experiences and turning me into a relatively sociable person instead of a recluses, quality of life is definitely hugely improved, I would just rather it not be at the cost of intellect or general life motivation/ambition.

 

 


Edited by KYSkud, 08 December 2015 - 04:29 AM.


#2 jaiho

  • Guest
  • 521 posts
  • 12
  • Location:Motherland
  • NO

Posted 09 December 2015 - 05:43 AM

I suspect because SSRIs, in absence of 5HT2C antagonism, increases serotonin transmission to 5ht2c, activating it. hence, reducing DA & NE in the PFC.

I believe if we had a selective potent 5ht2c antagonist, this would eliminate sexual side effects of SSRIs. Antagonism of 5HT2C downregulates it, and increases dopamine & NE in the PFC.

I have augmented Nortriptyline, a potent inverse agonist of 5ht2c, with SSRIs, my sexual side effects disappeared.

 

The next thing to target in regards to SSRI side effects, is the emotional blunting. Is 5HT1A Autoreceptor downregulation the cause of this? 5HT1A releases oxytocin, our love chemical. Chronic SSRI use downregulates 5HT1A, pre & post synaptic, which is likely why they blunt the feeling of love & emotions.

If we can target 5HT1A & 5HT2C in this way, we can treat depression, anxiety, and have fully functioning sex lives, as well as a wide emotional range to enjoy life to its fullest.


Edited by jaiho, 09 December 2015 - 05:43 AM.


sponsored ad

  • Advert
Advertisements help to support the work of this non-profit organisation. To go ad-free join as a Member.

#3 Ark

  • Guest
  • 1,729 posts
  • 383
  • Location:Beijing China

Posted 09 December 2015 - 06:10 AM

Lexapro is shit imho
  • Agree x 1

#4 justabody

  • Guest
  • 71 posts
  • 5
  • Location:Austin, TX

Posted 09 December 2015 - 09:38 PM

I'd switch to something like Vilazodone or Vortioxetine if you're dissatisfied w/ SSRIs but still need medication, considerably less sexual sides which probably indicates it's less inhibitory on dopaminergic transmission.


Edited by justabody, 09 December 2015 - 09:42 PM.


#5 TheHardProblem

  • Topic Starter
  • Guest
  • 2 posts
  • 0
  • Location:USA

Posted 09 December 2015 - 09:59 PM

The sexual sides aren't a problem, I actually kind of prefer having slightly diminished sensation and the boost in endurance while on an SSRI.

Perhaps dopamine plays a role in the actual desire for sex, but I feel like many of the common sexual sides are the interactions SSRI's have with nitric oxide levels in the penis, while play a crucial role in controlling blood flow.

 

I was assuming augmentation with 5HT2C antagonism, and increasing dopamine transmission in the VTA, would help more generally with motivation when it comes to tasks like work and concentration? Because these are the areas targeted by dopamine agonists like Adderall, and being on SSRI's almost feels like the opposite (reduced concentration/motivation.)

 

I'll look into Vilazodone or Vortioxetine's effets on dopamine transmission and report back here.

 

 

 



#6 justabody

  • Guest
  • 71 posts
  • 5
  • Location:Austin, TX

Posted 09 December 2015 - 10:03 PM

I think Jaiho had a good suggestion with the Nortryptiline. I've read reports on the Dr. Bob forum (I think it was there) with people saying it was great for dysthymia.

I also relate to the aspect of social anxiety being significantly decreased on SSRIs with the expense of feeling sort of robotic. I've been off SSRIs for awhile and it's really worsened my social anxiety.


Edited by justabody, 09 December 2015 - 10:07 PM.


#7 proileri

  • Guest
  • 80 posts
  • 2

Posted 31 December 2015 - 02:17 PM

I've been wondering about the side effects of SSRIs as well. I'm on Lexapro at the moment, and while the serotonin effect seems to help with anxiety and depression, I've noticed a decline in cognitive abilities as well. I wonder if the brain fog / zombie-like sluggish brain sensation is connected to dopamine transmission and such.

 

I've also noticed that Dexedrine seems to rescue the brain function a bit, and it essentially functions as NDRI, if I've understood it correctly. I wonder if Wellbutrin might have similar effect, as it's a NDRI (weak on dopamine, though) and apparently rescues sexual dysfunction as well. 

 

Seems like the first thing to try might be going from Escitalopram to Citalopram - seems to do slightly better on dopamine function.  


Edited by proileri, 31 December 2015 - 03:07 PM.


sponsored ad

  • Advert
Advertisements help to support the work of this non-profit organisation. To go ad-free join as a Member.

#8 John250

  • Guest
  • 1,451 posts
  • 109
  • Location:Temecula
  • NO

Posted 16 October 2018 - 09:40 PM

Agomelatine

https://www.ncbi.nlm...les/PMC3213641/




0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users