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SSRI (Escitalopram) OR SNRI (Venlafaxine): which goes best with a stimulant?

12K views 51 replies 7 participants last post by  jim_morrison 
#1 ·
when the goal is to let the stimulant do it's dopaminergic job the best. (NA, not so important for me)

There's some knowledgeable people here (or were at least), so I'd appreciate anyone who shares his/her informed opinion.

If you know someone with the necessary psychopharmaceutical knowledge, please also ask him/her and share his/her wisdom right here.

I've heard more than my share of conflicting opinions, so why not add some more and maybe even end up with a clear winner ;)

I need to make this decision by Monday morning so I'd like to be as informed as possible ;)
 
#2 ·
I'm only theorizing here, but since serotonin is on a seesaw like mechanism with dopamine (for the most part) then something like an SSRI would be notorious at blunting the dopaminergic action of a stimulant.

Since Effexor has a greater affinity for serotonin than say, Cymbalta, I hypothesis that Cymbalta (with a more balanced ratio of Sert to NA reuptake would allow amphetamines to work better.

From what i understand, Effexor is strongest on Sert followed by NA and then at higher dosages DA.

So therefore, trying an SNRI that has a better ratio of Sert to NA may allow DA to work better...

However, i could see Effexor at the 300+ mark being more synergistic with amphetamine, due to the induction of its effects on DA. But, im guessing this would put quite a strain on the cardiovascular system and BP monitoring would be recommended.
 
#6 ·
Thanks for the info mate!

Effexor/Venlafaxine becomes an SNDRI at doses from 375 mg and higher. BUT, it BLOCKS DA, for the MPH (also a DRI) this would make no difference but would the Dexamphetamine not be limited more compared to Escitalopram?

So the options are:

1) Escitalopram 20 mg + 20 mg long acting MPH + 3x20 mg Dexamph

2) Venlafaxine (Effexor) dose is going to be either 375, 450 or 600 mg/day + 20 mg long acting MPH + 3x20 mg Dexamph

3) Variants with any of these 4

You'd go for option 2 metha?
 
#4 ·
I stopped Escitalopram few days ago, 10mg dose which is low but it still make feel more apathy than usual. I have not taken more "hard" drug such as amphetamine but i still consume caffeine which is also a stimulant and the caffeine is good enough to fight apathy and make me feel more motivated.

I'm assuming you are taking stimulant for motivation and attention issue. So i think that taking SNRI, which increase heart rate since it inhibit norepinephrine and taking stimulant together might be too much on your heart.
 
#5 ·
I've tried them all together it was pretty much overload with adderall and effexor. Dexedrine and effexor caused anger. Ritalin you couldn't feel or notice it working. I was developing veriscose veins from to much NE. But then again I was probably also smoking and drinking on them as well. Give it a shot it may work for you.

Effexor also pretty much stop the the crash. I think NE is protective against the comedown maybe even neuroprotective against high DA. High NE seems to reduce depression thur modivation and staying busy. Where high DA can make you relaxed and lazy. Try it out.
 
#7 ·
I would use escitalopram. Most stims. are competitive NE inhibitors at NET and the amps. will also effect VMAT inside the neuron. I wouldn't want to add an allosteric NE inhibitor, like an SNRI to that. The stimulant will basically nullify any actions of the NE reuptake inhibitor.
 
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#13 ·
So, methylphenidate primarily acts as a norepinephrine-dopamine reuptake inhibitor. Methylphenidate is most active at modulating levels of dopamine and to a lesser extent norepinephrine. It also binds to and blocks dopamine transporters and norepinephrine transporters.

So, it would be overkill IMO, to use 2 psycho stims that are both binders to DAT and NET. The only difference being that Dexamp. actually is transported into the cell. Where it also acts as a competitive inhibitor at the VMAT transporter. That is the key difference between a stim. like Ritalin and a true amp., like Dexedrine.

So, one or the other my man, Dexedrine does not have as much peripheral stimulation as Ritalin, IMO. It helps more with concentration. That is what I have noticed from trying the two. Plus, the lowest dose you can get away with therapeutically, the better.
http://stahlonline.cambridge.org/pr...utics&name=Amphetamine (d)&title=Therapeutics

http://stahlonline.cambridge.org/pr...s&name=Methylphenidate (d)&title=Therapeutics
 
#15 ·
Dexedrine effects NE more than Ritalin but keep the dose as low as possible. I do well on 7.5-10mg a day. Anything higher can cause anti-social symptoms with me and as always talk to your pdoc about all of these possibilities.
 
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#17 ·
Just read some stuff about Mirtazapine (a med I hated when I took it as a stand alone med):

"Main Thesis: SWIM believes that taking Mirtazapine (brand name Remeron) has increased his sensitivity to stimulants, Dextroamphetamine in particular, and believes that a number of pharmacological actions, described below, facilitate this phenomenon."

and bla bla bla

What interests me is that it apparently potentiates stimulants and reduces SSRI sexual dysfunction.

Escitalopram 30 mg + Dextramphetamine 20 mg x3 + Mirtazapine 15 mg

Would adding 15 mg Mirtazapine do all of it's tricks? Or is there a specific minimum dose needed?
 
#21 ·
They say that mirtazapine's affects on sleep are paradoxical. Do you find that to be true?
 
#24 ·
Hey man, I was on Celexa a year ago which is the ****ty version of Lexapro. It worked ok for a month, then it made my SA so much worse. It's logical to think "I don't need NA". I used to think that too. But I'm trying Effexor out now, lowest dose though so it probably doesn't come near norepephrine. It does have an indirect impact on the opioid mu and delta receptors, and the alpha 2 adrenergic receptor. Let me tell you, I notice a huge difference between this feeling and Celexa. Way better for SA.
 
#25 ·
No I'm really having too much of it, increased HR and BP, tremor, anxiety, ...

Lowering the dose of the Dextroamphetamine would help, but that would also lead to less Dopamine, which is the opposite of what I'd want.

I want to block some of the Noradrenaline effects of the Dextroamphetamine.

Apparently, the NRI Reboxetine blocks the stimulating effect of amphetamines (stimulating effect meaning NA effects) so Venlafaxine/Effexor also being an NRI should also do it? While leaving the Dopamine effects like they are now on Escitalopram?
 
#26 ·
Apparently, the NRI Reboxetine blocks the stimulating effect of amphetamines (stimulating effect meaning NA effects) so Venlafaxine/Effexor also being an NRI should also do it? While leaving the Dopamine effects like they are now on Escitalopram?
You could say that. NRIs kinda balances out your systems norepephrine. Dexamphetamine and Effexor is very likely to be a winner for you man. Remember with amphetamines, tolerance is a *****, long term amphetamines will make you have less overall dopamine. So use breaks often.
 
#34 ·
Also not available here.

But I assume mine and Thethinker's reasoning is correct jim? Venlafaxine should act on the NA part of Dextroamphetamine just as an SRI acts on the SERT part of XTC, that being causing a ceiling effect on it. (XTC/MDMA I know from personal experience is basically robbed of it's Serotonin boosting effect when on an SRI)

It would be great if I (and others) could use Dextroamphetamine or MPH with an AD, while being able to dose the stimulant as high as I need it to be for the Dopamine, while not being overloaded with too much Noradrenaline.

I need that Dopamine since Serotonin alone obviously isn't doing what it used to do, but being a "tweaker" is not fun neither, not to mention very unhealthy :b
 
#38 ·
Yes sleep aids are really bad for depression.

I'm not a fan of Remeron neither as you know (to put it lightly), and Zolpidem is absolutely terrible as well.

My depression got a lot better once I finally stopped using it. (I only used it periodically).

A lot of times you are indeed better off not sleeping, I have the same experience.

You could use Lyrica for the insomnia, short half life (about 6 hours) and it improves REM sleep without the nightmares a lot of other meds cause. It does work for this purpose, doesn't give a "kick" but it's certainly helpful.
 
#42 ·
Yes, there's no doubt whatsoever about that.

If I were you, I'd ditch the sleep meds and try to get Lyrica. 150 Mg per night should be enough to get you a good night's rest without all of the issues you'd have with Z-drugs, Remeron, etc...

My sleep has been a lot better since I added the Lyrica.

I'm thinking of trying the Lyrica with Dextroamphetamine (and a few days trial of Methylphenidate just to know how both combine) without Effexor or any other AD.

There's no discussion that both stims worked better without the Escitalopram and I assume that goes for any other AD as well.

The 4 best meds for my depression I've taken up until now (and I've taken many lol) are Lyrica, Dextroamphetamine, Ritalin and Xanax, as weird as that may sound since none of them actually is an antidepressant.

Dextroamphetamine +- 60 mg/day + Lyrica 600 mg/day (or 3*300 if my psychiatrist agrees) + Xanax xr 0.5 mg 2x/day

is what I'm going to suggest to my psychiatrist tomorrow. I've never had much of a problem quitting addictive meds (I've gone cold turkey each time and I managed) so why not give the meds that worked best for me a try in a combination of them?

There's also a Glutamate-GABA theory of depression I've recently read about in a nice pdf file, so I even have theory to back it up.
 
#43 ·
Or would Clonazepam be "less depressing" as claimed in Stahl's Prescriber Guide?

I only have experience with Xanax and I recall Xanax is the only benzodiazepine that is actually used for depression but Stahl seems to think Clonazepam is the best benzodiazepine for depression for some reason?
 
#44 ·
I'll ask about Lyrica next time I see my doc. Lamictal certainly works fine with Dexedrine for me.

It's true as far as I know that Xanax is regarded as the benzodiazepine with the most antidepressant effect. Stahl also claims that Xanax-XR has a longer biological duration of action than Clonazepam. I think the notion that they can worsen depression is a bit overstated.
 
#46 ·
I'll ask about Lyrica next time I see my doc. Lamictal certainly works fine with Dexedrine for me.

It's true as far as I know that Xanax is regarded as the benzodiazepine with the most antidepressant effect. Stahl also claims that Xanax-XR has a longer biological duration of action than Clonazepam. I think the notion that they can worsen depression is a bit overstated.
Yes, it also depends on the benzodiazepine and the dosage.

I know from experience that the lowest possible dosage of Xanax xr has an antidepressive effect (for me at least), while for instance Clorazepate or Diazepam have a depressive effect.

It's my experience that the more sedating the benzodiazepine is, the more depression it causes (or can cause). Clorazepate and Diazepam are significantly more sedating than Alprazolam and thus result in more depression. It's common sense when you think about it. Sedation rarely works for depression.
 
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