2 replies to this topic

[Heinsbeans]

It has come to my realisation that 5-HT3 antagonists can reduce extracellular dopamine in the nucleus accumbens: https://www.reddit.c...in_the/dtkun7k/

 

Does this mean that 5-HT3 antagonists such as Trintellix can nullify some of the cognitive enhancing, wakefulness increasing and motivation inducing effects of modafinil? Even though I only take 5mg Trintellix every night, it has a 66hr half-life so my 5-HT3 receptors are probably permanently antagonised. Is that going to make modafinil work less effectively? I've always thought that it was a good thing to antagonise 5-HT3 receptors seen as it's one of the pro-cognitive mechanism of vortioxetine: https://www.scienced...8390816301630. 

 

Is it better to upregulate or downregulate your 5-HT3 receptors for depression, ADHD and cognitive enhancement? Seen as Trintellix is both a SRI (downregulates) and 5-HT3 antagonist (upregulates), does it eventually upregulate or downregulate your 5-HT3 receptors?

 

Would it be a better for me to switch to 5mg Lexapro if I want to have a better synergy with modafinil? 

 

I've discussed this briefly with someone else but we never got very far on it: https://www.reddit.c...h_your/dr9vzpa/

 

Here's what I've found about the modafinil's effect on 5-HT3 receptors so far:

 

The vigilance promoting drug modafinil decreases GABA release in the medial preoptic area and in the posterior hypothalamus of the awake rat: possible involvement of the serotonergic 5-HT3 receptor

 

Summary of the study: 

• Modafinil decreases GABA release in the medial preoptic area and posterior hypothalamus possibly via 5HT3 agonism
• It is known that a 5-HT3 agonist, given i.c.v., produces wakefulness ^[14]
• In agreement, the 5-HT3 receptor agonist m-chlorophenylbiguanide after intracerebroventricular injection increases wakefulness, an effect which is blocked by the 5-HT3 antagonist MDL 72222 ^[14]
• The present results demonstrate that modafinil decreases MPA and PH GABA release in the awake rat in part by local 5-HT3 receptor activation

^{[14] Ponzoni, A., Jaime, M.M. and Jantos, H., The effects of selective activation of the 5-HT3 receptor with m-chlorophenylbiguanide on sleep and wakefulness in the rat, Eur. J. Pharmacol., 249 (1993) 259-264.}

 

Sounds to me like modafinil is activating the 5-HT3 receptor in order to reduce GABA. Not sure if that can cause a conflict with Trintellix which I take at night?

[Heinsbeans]

A little more background about myself:

 

I'm actually thinking about completely coming off SSRIs very soon as it is of little help. But I'm waiting for my 23andMe result to come back so that I can check to see if I have any ADHD gene or problem with dopamine synthesis.

 

From my experience, I had no luck in getting anything prescribed from a public or private psychiatrist besides SSRIs, SNRIs or antipsychotics such as Risperdal. And they pretty much assume everyone that comes into their office have depression and turns their back to adult ADHD. So I am going to start self-medicating by ordering Strattera or Reboxetine online and see how I respond to it.

 

What led to me wanting to try them was my partial success to 120mg Cymbalta which was the most life changing medication I've ever been on as it increased my motivation and energy to the point that it allowed me to find employment and work full-time for the first time in my adult life. But I decided to get off of it due to overpowering sexual side effects and emotional blunting.

 

So in the meantime, I just need to know which SSRIs synergises the most with modafinil.

 

Currently, I'm leaning towards switching to either 5mg escitalopram or citalopram. They will probably be less 'pro-cognitive' on paper and has a statistically higher likelihood of coming with more sexual side effects. But I'm only going to be on 5mg and since it's pure SSRIs, it might be easier to completely taper off using escitalopram. Not to mention I no longer want to waste $62 per month on something that's barely helping me.

 

Another consideration is switching to Prozac which has a very long half-life and comes in capsule beads which in practice might be even more easier to taper off than escitalopram. But it's less widely used than citalopram, I don't know what to expect as I've never taken it before and I also don't know the equivalent dosage to 5mg Trintellix.

[justmodz]

I dont think it is a case of which SSRI synergises the most with modafinil as there are no studies to show one is any better than the other, however, it is more likely which SSRI suits you better nothing more.  The addition of modafinil when using SSRIs may alleviate some of the depression experienced studies ahve shown

 

http://www.cam.ac.uk...rity-when-taken

 

https://www.news-med...ffectively.aspx