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Hi, well now i'm switching from Celexa to Pristiq. Technically, i have taken Effexor in the past and it was alright but from my understanding Pristiq is actually a stronger NRI than Effexor because even at 50 mg, the starting dose it inhibits both Serotonin and Norepinephrine reuptake. 

I'm hoping the norrpinephrine enhances my motivation some. I basically found Wellbutrin like taking nothing.

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On 11/12/2020 at 11:04 AM, OCDme said:

Hi, well now i'm switching from Celexa to Pristiq. Technically, i have taken Effexor in the past and it was alright but from my understanding Pristiq is actually a stronger NRI than Effexor because even at 50 mg, the starting dose it inhibits both Serotonin and Norepinephrine reuptake. 

I'm hoping the norrpinephrine enhances my motivation some. I basically found Wellbutrin like taking nothing.

If you took Effexor XR at 150mg then you have a fairly good idea what Pristiq 50mg feels like already except now you'll theoretically have fewer side effects. However, despite Pristiq's improved tolerability, it shouldn't necessarily be misconstrued as a more powerful antidepressant as well. In fact, it's generally regarded that slightly reduced efficacy with Pristiq in some patients is the tradeoff for getting improved tolerability. Like they now want to try you on Pristiq first because it is an SNRI and inherently stronger in some ways than an SSRI, but if you tolerate it and need more oomph after 100mg then they just cut you over to Effexor and titrate you up to 300mg from there. But 300mg of Effexor is generally stronger than 100mg of Pristiq despite the theoretical equivalency of 100mg desvenlafaxine being produced in the human body from 300mg of venlafaxine.

I hope Pristiq does well for you. I'm on Trintellix now for depression, but if I had to pick a generic antidepressant that I would go back to if this was no longer covered, Pristiq would be it. I absolutely loved it. Only reason I stopped taking it at the time was because it was still brand-only and I was switching to a new insurance that wouldn't cover it. So I had to go to Effexor 150mg because that was covered. Worked well but kinda pooped out, at which point I went to Cymbalta 60mg until I started seeing a new pdoc and was properly rediagnosed.

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Effexor is the most effect I've gotten from an antidepressant but Pristiq did nothing for me. But that's probably because very few antidepressants have an effect on me *sigh*

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update

i've currently had my celexa lowered again and now am on day 2 on Pristiq 100 mg.  In two weeks my celexa will be lowered once again and i will take 150 mg Pristiq.

Im hoping on this 100 mg, I start to notice some norepinephrine action. My doctor seems pretty sure an SNRI will give me a better effect than a plain SSRI.

In theory the extra norepinephrine might give a kick to the ability to feel positive emotions over time. 

 

To give a comparison of SERT affinity to Norepinephrine NET ratio

Effexor is 30 to 1

While Pristiq is 14 to 1

 

Giving pristiq more norepinephrine activity than its parent drug

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54 minutes ago, OCDme said:

update

i've currently had my celexa lowered again and now am on day 2 on Pristiq 100 mg.  In two weeks my celexa will be lowered once again and i will take 150 mg Pristiq.

Im hoping on this 100 mg, I start to notice some norepinephrine action. My doctor seems pretty sure an SNRI will give me a better effect than a plain SSRI.

In theory the extra norepinephrine might give a kick to the ability to feel positive emotions over time. 

 

To give a comparison of SERT affinity to Norepinephrine NET ratio

Effexor is 30 to 1

While Pristiq is 14 to 1

 

Giving pristiq more norepinephrine activity than its parent drug

Affinity isn't everything. The effect at a given concentration also matters. Something can bind but have little effect or have no effect.

As indicated before, someone who takes 150mg of venlafaxine daily will have, at steady state, concentrations of O-desmethylvenlafaxine that are equivalent to concentrations seen on 50mg of desvenlafaxine daily. Venlafaxine has an affinity for the norepinephrine transporter of 2480 nM (nanomoles). However, its IC50 (half-maximal concentration) is 535 nM. This would suggest that while its affinity is low, it is able to elicit an inhibitory effect on the transporter at a range of doses. And at 150mg, it is likely that venlafaxine's inhibitory effect on the norepinephrine transporter is minimal and that the majority of inhibitory effect on NET at that dose is mediated by the metabolite, O-desmethylvenlafaxine.

With the above in mind, one would then expect that 300mg of venlafaxine would yield concentrations of O-desmethylvenlafaxine at steady state reflecting a daily dosage of desvenlafaxine around 100mg. This is true. However, O-desmethylvenlafaxine's pharmacology is different. While it does have a greater affinity for the NET at 558.4nM, its IC50 is 531nM, indicating that its affinity for the receptor and its half-maximal concentration are similar and a range of doses may not yield a differential effect. So going from 50mg to 100mg on Pristiq may bring NET inhibition to more of a maximum, going to 150mg may not make a whole lot of sense, hence why they never made a 150mg tablet.

Therefore, one can expect that at 300mg of venlafaxine, you would have more of a therapeutic effect (and more side effects) than 100mg of desvenlafaxine. Additionally, you can go to 450mg on venlafaxine and treat some really severe depression where desvenlafaxine generally has no added effect. Additionally, where venlafaxine has an affinity for the dopamine transporter at high doses, desvenlafaxine is devoid of activity. Venlafaxine also can have effects on pain via the opioid system due to its structural similarity to tramadol. Evidence supporting desvenlafaxine's ability in pain does exist, but it's far more sparse. That's not to say that desvenlafaxine isn't a strong antidepressant, because it is. It's an SNRI for starters, and it's starting to be recognized like citalopram as a medication that some people are just ultra-compatible with.

BUT, if you're on 100mg of Pristiq and still feel like you need more, then go to 150mg of Pristiq and aren't impressed, don't be surprised. But it may be worth switching over to 300mg of Effexor XR or higher instead if your doctor is open to it.

Edited by browri
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Thank you so much for your input Browri. That was very informative and I really appreciate it. Time will tell how I do but i'm staying optimistic about the Pristiq.

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6 minutes ago, OCDme said:

Thank you so much for your input Browri. That was very informative and I really appreciate it. Time will tell how I do but i'm staying optimistic about the Pristiq.

I would too. Like I said earlier, I think that if I couldn't take Trintellix anymore due to an insurance coverage issue, I would go to generic desvenlafaxine in a heartbeat over most others except maybe duloxetine (Cymbalta).

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