side effects, dosage, reviews, how to take & discontinue, uses, pros & cons, and more

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> Pristiq


US brand name: Pristiq
Generic name: desvenlafaxine

Class: Antidepressant, specifically a Serotonin and Norepinephrine Reuptake Inhibitor (SNRI)

1.  FDA-Approved Uses of Pristiq (desvenlafaxine)

  • Major Depressive Disorder (MDD) - Approved 2008

2.  Off-Label Uses of Pristiq (desvenlafaxine)

  • Hot flashes and other vasomotor symptoms of menopause. Pristiq is undergoing clinical trials for this application, as there’s more money in menopause than mental illness.
  • Pretty much everything for which Effexor is approved or used off-label:
    • General Anxiety Disorder (GAD)
    • Social Anxiety Disorder (SAnD)
    • Panic Disorder
    • Bipolar Depression
    • Fibromyalgia
    • Arthritis
    • Chronic Fatigue
    • Multiple Sclerosis
    • Lupus
    • Headaches
    • Irritable Bowel Syndrome (IBS)
    • ADD/ADHD
    • Eating Disorders

3.  Pristiq (desvenlafaxine) Pros and Cons

3.1  Pros

3.2  Cons

  • Just because some of the side effects aren’t as bad for some people doesn’t mean it’s a completely different drug than Effexor
    • Especially when it comes to the discontinuation syndrome. That may or may not suck less, but the potential of it happening is no different.
  • Weight gain is probably less likely for the same reason as Viibryd.
  • Sexual side effects are more likely for men than some SSRIs (say Prozac and Luvox).
  • Pistiq has one drug-drug interaction Effexor doesn’t: nicotine.

4.  Pristiq (desvenlafaxine) Side Effects

Like most crazy meds, Pristiq’s side effects are dosage-dependent. The more you take the more likely it is you’ll have any given side effect, and any side effect you do have is going to be worse.

4.1  Typical Side Effects of Pristiq

The usual for SNRIs: nausea, headache, nausea, dry mouth, nausea, excessive sweating, nausea, sleepiness or insomnia, nausea, diarrhea or constipation, and nausea. Those side effects typically go away in about two weeks. Weight gain is a lot less likely with Pristiq than SSRIs and Effexor, but with all the nausea and diarrhea you can expect, there may be a reason for that. Sexual side effects are less likely for women due to the effect of norepinephrine, and since Pristiq is more effective on norepinephrine than Effexor, especially at the lower dosages, that means Pristiq is less likely to cause sexual side effects in women at all dosages. It may even enhance sexual desire and response. Unfortunately extra norepinephrine can cause sexual dysfunction in men, so SNRIs like Pristiq, Effexor and Cymbalta can be as bad as, if not worse than SSRIs. While the chances of male sexual dysfunction with a pure norepinephrine-selective reuptake inhibitor (NSRI) like Strattera or reboxetine are lower than SSRIs, because the way the drugs cause the problem are different, it’s a cumulative effect.

4.2  Not So Common Side Effects of Pristiq

Urinary hesitation, high blood pressure, nose bleeds. If you get frequent nose bleeds and/or you bleed like a stuck pig during your period when you never did before, you should call your doctor1.

4.3  Pristiq (desvenlafaxine) Freaky Rare Side Effects

  • Hemophilia.
  • Dysgeusia. OK, dulling of taste isn’t particularly freaking or weird in the world of crazy meds, but the term isn’t used in PI sheets as often as the vaguer and freakier seeming “abnormal taste.” Plus I like the way dysgeusia rolls off the tongue.

5.  Interesting Stuff Your Doctor Probably Won’t Tell You about Pristiq (desvenlafaxine)

  • SSRI/SNRI discontinuation syndrome has been reported when switching from Effexor to Pristiq, so either they did something stupid, or there’s more to Effexor’s particularly hellish version of the discontinuation syndrome than serotonin.
  • While smoking has no effect on Effexor, it does affect Pristiq. If you smoke heavily you may need to take more Pristiq and take it twice a day. If you smoke less than heavily you may be hosed, because Pristiq comes in only two sizes.

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6.  Pristiq Dosage and How to Take Pristiq (desvenlafaxine)

As Pristiq (desvenlafaxine) comes in all of two sizes, 50mg and 100mg, I can’t really argue with Pfizer/Wyeth’s recommendations of starting with 50mg a day, taken once daily, and that’s it. See for yourself:

2.1 Initial Treatment of Major Depressive Disorder
The recommended dose for PRISTIQ is 50 mg once daily, with or without food. In clinical studies, doses of 50–400 mg/day were shown to be effective, although no additional benefit was demonstrated at doses greater than 50 mg/day and adverse events and discontinuations were more frequent at higher doses.

PRISTIQ should be taken at approximately the same time each day. Tablets must be swallowed whole with fluid and not divided, crushed, chewed, or dissolved. --Pristiq PI sheet

Since nothing above 50mg a day supposedly works, Wyeth makes a 100mg tablet for the hell of it. I’m way behind on gathering data for the efficacy of 50mg vs. 100mg vs. anything more than that. Wyeth did a lot of tests and trials at 100mg, and I suspect that was their target dosage, but the side effects at 100mg sucked too much for people in the usual 6–8 week clinical trials run to get a product approved by the FDA.

As you can see, Pristiq is currently rated safe for up to 400mg a day, just as Effexor is safe to take up to 450mg a day. However: Effexor is extensively metabolized, so the small percentage2 of people who need the high dosage of Effexor because they rapidly metabolize it would not necessarily need the corresponding dosage of Pristiq, because Pristiq is barely metabolized before you piss it out. Of course lots of people need a high dosage of Effexor because Effexor is just a weak-ass drug that, frankly, I’m astonished works at all.

7.  How Long Pristiq (desvenlafaxine) Takes to Work

Like most SSRIs and SNRIs two weeks to a month.

8.  How to Stop Taking Pristiq (desvenlafaxine)

Since the recommended dosage is 50mg a day, there isn’t a smaller pill, and Pristiq comes only in an extended release form, your only official option is to just stop taking it. Obviously that isn’t going to work if you’re taking 100mg a day, where, from the wording on the PI sheet, it reads as if Wyeth assumes you’re going to just stop taking 100mg cold turkey. Buh?

If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate. --Pristiq PI sheet

So how much more gradual can you get from 50mg? The standard protocol for withdrawing from an SSRI or SNRI if you have a history of or experience the symptoms of SSRI/SNRI discontinuation syndrome is reducing the dosage by the lowest available pill by however many days the plasma clearance is (scroll down a little if you don’t see it), or one week, whichever is shorter or easier. But what if that doesn’t work for you with Pristiq?
As with all SSRIs and SNRIs you can use Prozac (fluoxetine). Its long-ass half-life of 9.3 days makes SSRI discontinuation syndrome incredibly rare. 20mg of Prozac is approximately equivalent to 50mg of Pristiq. If that can’t happen, or doesn’t work, well, never in a million years would I thought I’d ever write this, but: try using Effexor to help mitigate the symptoms of SNRI discontinuation. If you have some 37.5mg Effexor XR capsules lying around. At least with Effexor you can lower the dosage a bit more gradually, as 75mg of Effexor = 50mg of Pristiq.

9.  How Pristiq (desvenlafaxine) Works

Based upon the monoamine hypothesis of depression (i.e. you’re messed up due to an imbalance of one or more of three of the best understood neurotransmitters: serotonin, norepinephrine, and/or dopamine), Pristiq (desvenlafaxine) attempts to balance your brain juices by inhibiting the reuptake (in English: delaying the breaking down and recycling) of serotonin and norepinephrine at their receptors in various (i.e. depending on which studies and books you’ve read and fancy brain scans you’ve looked at) locations in your brain. It may do a lot of other things that address depression, anxiety, other brain cooties and some off-label uses by encouraging the growth of new neurons, affecting hormones and CYP450 genes in your brain, and who knows what else. You also have serotonin and norepinephrine receptors throughout your body, especially in your GI and renal systems, which is why SSRIs & SNRIs are used to treat various conditions like IBS and incontinence. As Pristiq affects norepinephrine more than Effexor, it is more effective for pain and pain-related conditions like fibromyalgia, and the physical pain that accompanies some forms of depression. As Pristiq doesn’t affect norepinephrine nearly as much as Cymbalta, Savella (milnacipran), and some TCAs, it’s never going to get approved to treat pain-related conditions as they are.

10.  Pristiq’s Half-Life & Average Time to Clear Out of Your System

Pristiq (desvenlafaxine) has a half-life of 11 hours. It takes about three days to clear out of your system. That’s plasma clearance.

Half-life is the average time it takes for you to process half of the drug’s active ingredient. If a drug has a half-life of around 24 hours and you take a dose of 100mg, you’ll have roughly the equivalent a 50mg dose after one day, a 25mg dose after two days, and so on. The rule of thumb is: multiply the half-life by five and you get how long it is for the dose you took to be cleared from your bloodstream3, so there’s nothing swimming around to attach itself to your brain and start doing stuff. That’s called “plasma clearance.” Complete clearance is a complex equation based on a lot of factors which may or may not: be published in the PI sheet, include personal data like your weight, or even completely figured out by corporate and independent researchers. It usually winds up being 2–5 days after plasma clearance no matter what4, but can take weeks.

 Sometimes a drug will clear from your brain and other organs before it clears from your blood. 

11.  Days to Reach a Steady State

Steady state is usually reached in four to five days.

Steady state is the flipside of half-life. This is when you can expect to get over side effects caused by fluctuating amounts of a medication in your bloodstream. Often, but not always the same amount of time as the plasma clearance above.

12.  Comments

I initially thought Pristiq was a patent-extender of Effexor (venlafaxine), much in the same way that Invega (paliperidone) is a patent-extender of Risperdal (risperidone). I was wrong. Sort of. Pharmacologically they are quite different. Desvenlafaxine succinate (the active ingredient of Pristiq) is similar, but not identical to o-desmethylvenlafaxine (the active metabolite of venlafaxine hydrochloride, the active ingredient of Effexor). Plus venlafaxine HCl does stuff, and isn’t just something you take that needs to be converted by your liver into something useful, like Risperdal and Trileptal are. So Pristiq is a different drug than Effexor (venlafaxine); Pristiq is even more different from Effexor than Lexapro (escitalopram) is different from Celexa (citalopram).

But in many ways they are the same drug. Their effect on norepinephrine doesn’t come close to that of Cymbalta, Savella, or several TCAs. They have similar side effects. They are less likely to poop out, and more likely to be effective than an SSRI. Because Effexor is, in a way, two drugs while Pristiq is essentially one, Effexor might be more effective for more people, albeit with a harsher side effect profile and more drug-drug interactions.

I’m reserving my judgment until I do more research. As it is now Pristiq is looking like a failed attempt at being a patent-extender for Effexor, and Pfizer is going to push it as a menopause med, probably with a new name, once they get approval.


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13.  Pristiq Ratings, Reviews, & Other Sites of Interest

Pristiq Ratings & Reviews Page.

13.1  Rate Pristiq

Give your overall impression of Pristiq on a scale of 0 to 5. Detailed ratings and reviews are available on the Pristiq Ratings & Reviews Page.

Get all critical about Pristiq

3.5 stars Rating 3.3 out of 5 from 132 criticisms.
Vote Distribution: 15 – 10 – 10 – 15 – 44 – 38


13.2  Rate this article

If you’re still feeling judgmental as well as just mental5, please boost or destroy my self-confidence by honestly (and anonymously) rating this article on a scale of 0 to 5. The more value-judgments the better, even if you can criticize my work only once.

Get all judgmental about the Pristiq (desvenlafaxine) Synopsis

4.5 stars Rates 4.1 out of 5 from 80 value judgments.
Vote Distribution: 0 – 2 – 1 – 6 – 40 – 31



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13.3  Full US PI sheet, Global SPCs & PILs, Other Consumer Review & Rating Sites, check for drug-drug interactions

Drugs.com’s drug-drug and drug-food interaction checker

It’s always a good idea to check for drug-drug interactions yourself. Just because most people in the crazy meds business know about really important interactions (e.g. MAOIs and a lot of stuff, warfarin and everything on the planet) doesn’t mean the person who prescribed your meds told you about them, or the pharmacist has all the meds you take at their fingertips like they’re supposed to. Or they have the time to do their jobs properly when not dealing with complete idiots or playing Angry Farmers on the Faecesbooks.



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13.5  Discussion board

If you have any questions not answered here, please see the Crazymeds Pristiq discussion board.



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14.  References

Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (Essential Psychopharmacology Series) Third edition by Stephen M. Stahl © 2008 Published by Cambridge University Press.

Primer of Drug Action 12th edition by Robert M. Julien Ph.D., Claire D. Advokat, Joseph Comaty © 2011 Published by Worth Publishers.

The Prescriber’s Guide (Essential Psychopharmacology Series) Third edition by Stephen Stahl © 2009 Published by Cambridge University Press.

Clinical Handbook of Psychotropic Drugs 18th edition Adil S. Virani, K. Bezchlibnyk-Butler, J. Jeffries © 2009 Published by Hogrefe & Huber Publishers.

PDR: Physicians’ Desk Reference 2010 64th edition back through to 53rd edition of 1999. Old copies of the PDR come in handy for PI sheets that are no longer available and difficult to find, as well as to track the changes in both indications and adverse effects.

Full US PI sheet for Pristiq


1 Especially any of you guys who are bleeding like stuck pigs during your periods. You should have called your doctors last week. Along with lawyers, publicists, and maybe a priest.

2 The current estimates of people who rapidly metabolize - i.e. quickly clear Effexor out of their system and need to take a high dosage of Effexor XR and other once-a-day meds twice a day, is 1-2% of the population. My guess is around 5-7% of the readers of Crazymeds.

3 Based on Julien's calculations from A Primer of Drug Action, the half-life multiplied by five is the generally accepted estimate of how long it takes a single dose of any given drug to be eliminated from the blood stream/plasma of someone with a normal metabolism. That's also the rough estimate for steady stage if they can't get, or won't provide a number for that.

4 For crazy meds. I have no idea what the average complete clearance is for other types of medications. For all I know there are drugs that utterly vanish from your system in under five passes, and others that won't let go of your squishy bits for years after you stop taking them.

5 Thank you! I'll be here all weak. Be sure to tip your content provider. And don't try the veal, it's cruelicious!


If you have any questions not answered here, please see the Crazymeds Pristiq discussion board. We welcome criticisms of the articles, notifications of bad links, site problems, consumer experiences with medications, etc. I’m not always able to write back. Hence I never answer questions about meds via e-mail that are answered by this or other articles. Especially if they have been repeatedly asked on the forum. That’s why we write these damn things. Questions about which meds are best for your condition should also be asked on the forum; because this is a free site, so the price of admission is making things easier for somebody else searching for the same answer. We don’t deal with children on the forum or in private because after doing this for ten years I don’t have the emotional stamina to deal with kids who have brain cooties. How to contact Crazymeds. — Jerod Poore, CME, Publisher crazymeds.us


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Pristiq, and all other drug names on this page and used throughout the site, are a trademark of someone else.

will probably have the name of the manufacturer and trademark owner (they’re not always the same company) at or near the very bottom. Or ask Google who the owner is. The way pharmaceutical companies buy each other and swap products like Monopoly™ real estate, the ownership of the trademark may have changed without my noticing. It may of changed hands by the time you finished reading this article.




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All rights reserved. No warranty is expressed or implied in this information. Consult one or more doctors and/or pharmacists before taking, or changing how you take any neurological and/or psychiatric medication. Your mileage may vary. What happened to us won’t necessarily happen to you. If you still have questions about a medication or condition that were not answered on any of the pages you read, please ask them on Crazy Talk: the Crazymeds Forum.
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1 While there are plenty of books to help you with hypochondria, for some reason there’s not much in the way of websites. Then again, staying off of the Internet is a large part of curing/managing the disorder.

2 Remember kids, Microsloth operating systems are like TOS Star Trek movies with in that every other one sucks way, way more. With TOS Star Trek movies you don’t want to bother watching the odd-numbered ones. With Microsloth OS you don’t want to buy and install the even-numbered ones. Anyone who remembers ME and Vista knows what I mean.

3 Have I mentioned how open source operating systems for commercial applications is one of the dumbest ideas in the history of dumb ideas? I don’t even need my big-ass rant any more. Heartbleed has made my case for me. And that’s just the one that got all the media attention. The very nature of an open source operating system makes security as much of an illusion of anonymity. Before you flip out too much: the domain Crazymeds is hosted on uses a version of SSL that is not affected by the Heartbleed bug. That’s one of the many reasons why I pay a lot of money and keep this site on Lunarpages.

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