Lilu's research about Effexor and Pristiq tapering

[Lilu]

[Administrator's note: Our member Lilu has been researching ways to go off Pristiq and Effexor. This topic collects her very interesting findings.

 

There are many, many pages on the Web about all kinds of tapers that were successful -- every variation on dosage reduction you can think of, including cold turkey. There are at least an equal number of posts about taper failures.

 

How to reconcile the two? The fact is, tolerance for dosage reduction varies among individuals.

 

We advocate a 10% reduction method because we believe it will cause the least harm.

 

The following information has been provided by Lilu and does not reflect the recommendations of SurvivingAntidepressants.org. Those recommendations are here http://survivingantidepressants.org/index.php?/topic/876-tips-for-tapering-off-pristiq-desvenlafaxine/]

---

Ok, people, here's a very important note about using Effexor to taper from Pristiq. I just received a note from another member who is having some major side effects after switching.

Here's the important note:

50 mg of Pristiq DO NOT equal 50 mg of Effexor

50 mg Pristiq (DesVenlafaxine) = 100 mg Effexor (Venlafaxine)

The first step would be to try the switch for a week WITHOUT tapering the dose. Your body might need to adjust to having to metabolize the Venlafaxine in order to get the DesVenlafaxine.

 

1st week: switch from 1 tablet of 50mg of Pristiq to a)2 tablets of 50mg Effexor, taken in AM and PM or b)4 tablets of 25mg, taken 2 together in AM and PM.

 

2nd week: cut one of the 25 mg of Effexor in HALF (and then again in half if u want) in the PM

NOTE:depending on how slowly you want to taper, you can start cutting your 25 mg of Effexor tablets in half or even quarters. Using a pill cutter is easiest.

 

If you reduce by quarters, you'll be reducing by 6.25 mg at a time.

 

It's best to reduce your dosage in the evening if your withdrawal symptoms include drowsiness & brain-fog, as they do for me.

 

Some naturalists also recommend supplementing with Amino Acids during your taper. 1000 mg of L-Tyrosine in the morning and

100 mg of 5HTP or 500 mg of L-Tryptophan at night.

 

NOTE: I am not a physician, and my advice should not be substituted for proper medical care by a trained medical professional. I am a merely reporting my research findings here.

[Lilu]

All the information about the differences between Effexor and Pristiq are in this article from the Journal of Primary Psychiatry:

http://www.primarypsychiatry.com/aspx/articledetail.aspx?articleid=2464

Over 55% of a single dose of venlafaxine (Effexor) is eliminated in the urine as desvenlafaxine and its glucuronide conjugate.^4,9

What does this mean? It means that Effexor IS 55% Pristiq. So if you have 100 mg of Effexor, it will be processed as if you took a 55 mg tablet of Pristiq. Since there is no 55mg tablet, 50 mg of Pristiq is the closest dose to 100 mg of Effexor. That is how you convert Effexor to Pristiq. Now this applies only to an uncrushed Pristiq tablet. Once a Pristiq tablet is crushed it is no longer equivalent to 50 mg, it is now 76 mg and no longer has its extended release properties.

Desvenlafaxine is an ER formulation for once-daily administration that is designed to release desvenlafaxine over the course of the dosing interval.³Desvenlafaxine tablets contain 76 mg or 152 mg of desvenlafaxine in a matrix formulation that is designed to gradually release the equivalent of 50 mg or 100 mg of desvenlafaxine, respectively.³ To maintain the integrity of the ER formulation and prevent “dose dumping” (ie, rapid release of drug from an ER formulation), desvenlafaxine tablets should not be divided, crushed, chewed, or dissolved.³

Now, 100 mg of Effexor is only available as a tablet. But instead of trying to cut and divide a 100 mg Effexor tablet and taking it only once a day. You get a prescription for 25 mg tablets to be taken FOUR times per day. You won't really take them 4 times per day, but having 25 mg tabs is easiest for tapering purposes.

 

The other important point to take away from the excerpt below, is the possibility that the "inactive ingredients" in Effexor, about 40% that does not turn into Pristiq, that these can cause side effects. But they are just guessing. And basically what they're saying is that stoping cold-turkey was pretty bad for both drugs, but it was slightly worse with Effexor. And it may be because it has more of those "inactive" metabolites.

 

How do discontinuation symptoms for desvenlafaxine compare with venlafaxine ER?Direct head-to-head comparative studies of desvenlafaxine and venlafaxine ER to evaluate discontinuation symptoms have not been conducted. In the absence of data from prospectively conducted studies, the relative rates of discontinuation symptoms are not known. However, it may be possible to speculate that a lower rate of discontinuation symptoms could occur with desvenlafaxine, because it has fewer metabolites that do not have antidepressant pharmacological activity (but that may have pharmacological activity potentially associated with AEs), compared with venlafaxine ER, which has additional metabolites (eg, N-desmethylvenlafaxine) that may contribute to AEs, including discontinuation symptoms. Data from the venlafaxine ER and desvenlafaxine clinical trial programs indicate that abrupt discontinuation of both drugs was associated with dizziness, nausea, headache, insomnia, diarrhea, anxiety, fatigue, abnormal dreams/nightmares, and sweating. In addition, following abrupt discontinuation of venlafaxine ER, agitation, anorexia, confusion, impaired coordination and balance, dry mouth, dysphoric mood, fasciculation, flu-like symptoms, hypomania, nervousness, sensory disturbances (including shock-like electrical sensations), somnolence, tremor, vertigo, and vomiting were noted.^3,13

But it still seems like tapering slowly using Effexor tablets is still the best way to go. I personally was not able to cut Pristiq tablets evenly no matter how I tried. And a compounding pharmacist did assure me that "your body does not know the difference between Desvenlafaxine and venlafaxine".

 

[Altostrata]

There is absolutely no question that desvenlafaxine (Pristiq) is a metabolite of venlafaxine, or Effexor.

 

The volume of an excreted metabolite does not necessarily indicate an equivalency of dosage. I'm not an expert on metabolites but from what I've read, sometimes the volume of a metabolite is even greater than the original drug.

 

Once a Pristiq tablet is crushed it is no longer equivalent to 50 mg, it is now 76 mg and no longer has its extended release properties.

It no longer has extended-release properties. I do NOT believe the active ingredient content increases from 50mg to 76mg.

 

Unless we have a pharmacology expert interpret that article from the Journal of Primary Psychiatry, I don't feel comfortable drawing dosage conclusions from it.

[Lilu]

For those who choose to switch from Pristiq to Effexor, in order to taper slowly, here's a website that was put together specifically to help people withdraw from Effexor (Venlafaxine). There is a detailed reduction schedule and information about what symptoms to expect.

 

Information starts here: http://www.clinical-depression.co.uk/anti-depressants-withdrawal/

 

 

Dose reduction schedule: http://www.clinical-depression.co.uk/anti-depressants-withdrawal/dosages/

Instead of using 25 mg tablets, they use 75 mg capsules and 37.5 mg tablets. In either case, the reduction is done very slowly, according to their program. Reducing only by 1/4 mg once every 3 days.

[Lilu]

There is absolutely no question that desvenlafaxine (Pristiq) is a metabolite of venlafaxine, or Effexor.

 

The volume of an excreted metabolite does not necessarily indicate an equivalency of dosage. I'm not an expert on metabolites but from what I've read, sometimes the volume of a metabolite is even greater than the original drug.

 

Once a Pristiq tablet is crushed it is no longer equivalent to 50 mg, it is now 76 mg and no longer has its extended release properties.

It no longer has extended-release properties. I do NOT believe the active ingredient content increases from 50mg to 76mg.

 

Unless we have a pharmacology expert interpret that article from the Journal of Primary Psychiatry, I don't feel comfortable drawing dosage conclusions from it.

 

I based my conclusions by looking at the diagrams that show how Venlafaxine is converted into Desvenlafaxine. http://www.primaryps...en_figure1a.jpg It shows that 56% of Venlafaxine is converted into Desvenlafaxine.

 

Also, both the compounding Pharmacist that suggested that I use Effexor and my doctor told me that the equivalent dose of a 50 mg tablet of Pristiq is 100 mg of Effexor tablets taken twice a day divided at 50 mg per dose.

 

Also the article clearly states:

Desvenlafaxine tablets contain 76 mg or 152 mg of desvenlafaxine in a matrix formulation that is designed to gradually release the equivalent of 50 mg or 100 mg of desvenlafaxine, respectively.³ To maintain the integrity of the ER formulation and prevent “dose dumping”

 

To me that means that a 50 mg tablet actually contains 76 mg. Because that's what it says it contains. But really this is irrelevant. You would still be ingesting less than a whole tablet, and thus reducing if you decided to cut the Pristiq tablets.

[Lilu]

Venlafaxine Dose Reduction Schedule: http://www.clinical-depression.co.uk/anti-depressants-withdrawal/dosages/

 

Resource: http://www.clinical-depression.co.uk/anti-depressants-withdrawal/

 

You can print out and give this to your doctor.

[Altostrata]

The information oaklily pointed to at http://www.clinical-depression.co.uk/anti-depressants-withdrawal/reduction-instructions/ is a complicated way to cross-taper from Effexor XL to regular Effexor, incorporating a step down from 75mg Effexor XL to 37.5mg Effexor in about 5 days, and includes skipping doses. In about 2 weeks (???), it reduces the dosage to zero.

 

The authors' other instructions, Antidepressants - Venlafaxine Withdrawal at http://www.clinical-depression.co.uk/anti-depressants-withdrawal/dosages/ , conflict with the above.

 

These other instructions drop from a combination of 75mg Effexor XR capsules and 75mg regular Effexor tablets (150mg total) to 75mg total in 46 days by quartering the tablets.

 

(The authors, who are unaware of the uses of liquid Effexor, appear to be therapists utilizing hypnosis http://www.clinical-depression.co.uk/about/ They are also selling a program http://www.clinical-depression.co.uk/depression-recovery-program/ )

 

A second phase of the schedule drops from 75mg Effexor XR capsules to zero mg Effexor in another 59 days by cross-tapering to substitute 37.5mg regular Effexor tablets for the Effexor XR and quartering the 37.5mg tablets for the capsules.

 

From day 19 to day 59, it weirdly and unnecesssarily alternates dosages.

 

While any kind of dosage reduction schedule is better than cold turkey or a two-week taper -- and I credit the authors with providing a 2-month alternative -- these procedures seem unnecessarily difficult to follow. While cross-tapering is a good idea in switching drugs, I absolutely disagree with alternating dosages. The dosage reduction schedule is never any less than 9.375mg per day (a quarter of a 37.5mg tablet).

 

I would not recommend the above procedures for anyone who's been on Effexor, Effexor XR, Pristiq, or a combination of any of these for more than a month, or who might be sensitive to dosage reductions.

[Altostrata]

For those who choose to switch from Pristiq to Effexor, in order to taper slowly, here's a website that was put together specifically to help people withdraw from Effexor (Venlafaxine). There is a detailed reduction schedule and information about what symptoms to expect.

 

Information starts here: http://www.clinical-depression.co.uk/anti-depressants-withdrawal/

 

 

Dose reduction schedule: http://www.clinical-depression.co.uk/anti-depressants-withdrawal/dosages/

Instead of using 25 mg tablets, they use 75 mg capsules and 37.5 mg tablets. In either case, the reduction is done very slowly, according to their program. Reducing only by 1/4 mg once every 3 days.

 

I have serious reservations about these methods, see my comments above.

 

I would not recommend these procedures for anyone who's been on Effexor, Effexor XR, Pristiq, or a combination of any of these for more than a month, or who might be sensitive to dosage reductions.

[Lilu]

Yeah, that is strange to alternate dosages that way from am to pm. But it is designed to minimize withdrawal symptoms completely. Here the authors explain why they use a combination of capsules and tablets and how they calculate the dosages: http://www.clinical-depression.co.uk/anti-depressants-withdrawal/avoiding-withdrawal-symptoms/

Edited February 4, 2013 by Altostrata
corrected link

[Skyler]

Hi Oaklily.. I realize you are coming from a good place, but I would rather stick to information about Alto's methods. There are many protocols available on the web. People who post them have varying degrees of understanding.. usually from none to not so much. Refuting them individually is time consuming at best, just way too much effort. Perhaps you could post to that site itself if you are interested.

 

This forum is a safe haven, an away place from the uninformed, and others who would unwittingly cause us harm. Specific taper information is best left to Alto, in whom we can safely place our trust. I'm sure you want to be protected as well.

 

Thanks for understanding,

Skyler

 

Edited 3:55 PM

[Lilu]

Hi Oaklily.. I understand you are coming from a good place, but I would rather stick to Alto's methods. There are many protocols available on the web. People who post them have varying degrees of understanding.. usually from none to not so much.

 

This forum is a safe haven from the uninformed, and others who would unwittingly cause us harm. Specific taper information is best left to Alto, in whom we can safely place our trust. I'm sure you want to be protected as well.

 

Thanks for understanding,

Skyler

 

Actually, I have been doing medical research, specifically on Depression, neurotransmitters, psychopharmocology, Effexor, and Pristiq, for the last 8 years. I was on Effexor for 3.5 years, from which I withdrew on my own using only capsules. I am quite familiar with all the different aspects of this drug., as well as it's metabolite, Pristiq, which I have studied and been on as well.

 

I also would not post links to any sites that I didn't feel contribute greatly to this discussion or that have a lot to offer. I believe that the site referenced above has a lot to offer, whether or not you choose to follow their specific reduction schedule. The reduction schedule was posted as a guide. Specifically to show that a taper should be done very slowly, especially if you are sensitive. And can be done as slowly as 1/4 mg tablet per day or every 3 days, as shown on this schedule.

 

But there are things I would do differently then indicated on this reduction schedule. From personal experience, I would not alternate taking a capsule in the morning and then at night. That resulted in unpleasant side-effects, such as brain fog.

[Lilu]

Helpful Effexor taper reduction schedule from someone's personal experience. It is interesting to note that he maintains each new dose for a month before reducing any further.

 

http://www.drugs.com/forum/featured-drugs/tapering-how-effexor-method-1-a-32337.html

[Altostrata]

There are any number of variations on tapering schedules. We're not trying to show them all here.

 

A quarter of a tablet every few days, even a quarter of a 25mg tablet, is a precipitous taper. We absolutely do not recommend it. There's a good reason we talk about a 10% taper per month; it has to do with the slope of the decrease over time, which I'm sure you can visualize, oaklily.

 

Given that some people can quit cold turkey and not feel it, ANY taper might work for some. But we're trying to communicate a methodology that might be safe for almost everyone: Start slow and speed up if you can tolerate it.

 

Those tapers are too fast, excessively complicated and, by the way, conflict with each other. Even the authors couldn't keep them straight.

 

I give them points for trying, but I don't agree with their over-intellectualized half-life rationale. Withdrawal symptoms are related to rate of taper (see above), not half-life, and steady-state blood level can be achieved with immediate-release Effexor as well as extended-release.

[Altostrata]

Yeah, that is strange to alternate dosages that way from am to pm. But it is designed to minimize withdrawal symptoms completely. Here the authors explain why they use a combination of capsules and tablets and how they calculate the dosages: http://www.clinical-depression.co.uk/anti-depressants-withdrawal/avoiding-withdrawal-symptoms/

 

Please allow me to point out that although the authors did a lot of work intellectualizing half-life as a basis for tapering, they did not apply it, as they recommend skipping doses and moving them around by 12 hours at a time.

[Lilu]

I've sent out a bunch of e-mails to psychiatrists requesting their estimates of Pristiq-Effexor equivalency.

I found an article that addresses the very question of dose equivalency between Venlafaxine & Desvenlafaxine

Metabolites: novel therapeutics or “me-too” drugs? Using desvenlafaxine as an example

byThomas L. Schwartz

Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York, USA

"That brings us back to dose equivalencies in venlafaxine/desvenlafaxine dyad. The minimum therapeutic dose of venlafaxine ER is 75 mg/d, whereas that of desvenlafaxine is 50 mg/d. Of note, all therapeutic doses ever studied of the latter (50–400 mg/d) have been statistically efficacious. There has not been a minimum therapeutic dose discovered for desvenlafaxine. The first interpretation should clinically state that 75 mg must equal 50 mg based upon regulatory trials and FDA benchmarks. A pharmacodynamic interpretation would differ in that 75 mg of venlafaxine ER is likely a pure serotonin reuptake inhibitor (SRI) with little norepinephrine reuptake inhibitor (NRI) properties.¹³ Both antidepressants have different neurochemistry ratios at their starting doses and cannot be seen as equivalent. Using this extrapolative method, perhaps equivalent doses are 150 mg and 50 mg, respectively, because venlafaxine ER's NRI potential becomes noticeable at 150 mg/d, likely comparable to desvenlafaxine's 50 mg starting dose.

 

Pharmacokinetically, we should again cite the work of Nichols etal.,^4,8 and observe the ratios of desvenlafaxine to venlafaxine after metabolism (DES/VEN ratio). Efficient metabolizers taking 75 mg of venlafaxine developed a DES/VEN ratio of 6.2, where poor metabolizers were approximately 50% less with a 3.3 ratio. Therefore, in some efficient metabolizing patients, 75 mg of parent venlafaxine ER drug may convert to a 300 mg equivalent of desvenlafaxine. As a result, the jury is out, in that 50 mg of desvenlafaxine metabolite antidepressant might equal 75 mg, 150 mg, or 18.75 mg of the parent drug."

 

source:

http://journals.camb...8e851f47f408cbf

 

[Lilu]

In determining the equivalent dose of Effexor in relation to Pristiq, I would still go by this diagram, which shows that 56% of Venlafaxine (Effexor) is converted into Desvenlafaxine (Pristiq)

 

http://www.primaryps...en_figure1a.jpg

 

Also in Stahl's Essential Psychopharmocology, it states that pristiq is about half of effexor. But like in my previous post, he points out that this is true unless you are a poor metabolizer.

http://books.google....afaxine&f=false

[Skyler]

Thanks for all the info., which I'm working my way through. Just wondered if you knew the link to the .pdf article does not work?

 

source:

http://journals.camb...8e851f47f408cbf

[Altostrata]

As a result, the jury is out, in that 50 mg of desvenlafaxine metabolite antidepressant might equal 75 mg, 150 mg, or 18.75 mg of the parent drug.

The action of desvenlafaxine is STRONGER (isomer effect) milligram per milligram than venlafaxine, not only because of varying serotonin-norepinephrine conversion but because the MOLECULE itself (isomer) interacts differently with the receptor.

 

This confounds even this very informed attempt to establish an absolute equivalency between Pristiq and Effexor dosages.

 

http://drugtopics.modernmedicine.com/news/pristiq-has-been-approved-fda-treat-major-depressive-disorder

Breden wonders if the benefit of desvenlafaxine over venlafaxine is similar to the perceived benefit of escitalopram over citalopram, where escitalopram may offer better antidepressant activity based on the fact that it contains only the pharmacologically active S-isomer of the drug. Citalopram itself is a mix of both the S- and R-isomers, the latter of which has little to no antidepressant effect and may theoretically dilute the action of citalopram or contribute to side effects.

http://www.ama-assn.org/ama/pub/physician-resources/medical-science/united-states-adopted-names-council/naming-guidelines/geometric-isomerism-chirality-the-usan-perspective.page

Because the presence of a second enantiomer in racemic mixtures is associated with a potential for drug-drug interactions, severe adverse reactions, and market withdrawals, the use of stereochemically pure drugs is thought to offer advantages and was recommended by the FDA in its 1992 guidelines. Chiral switches may have an improved therapeutic index through increased potency and selectivity, decreased side effects, an improved onset and duration of effect, and decreased drug-drug interactions.

[Altostrata]

See this demonstration (PDF) from Lilly http://adurs.com/Websites/adursdemo/Images/isomers%20and%20Metabolites%20-James%20L%20Roerig.pdf.

 

The desvenlafaxine part starts on slide 59.

 

See the venlafaxine vs desvenlafaxine curves on slide 65 and 66 (very similar).

 

Drug Reference for FDA Approved Psychiatric Drugs

http://www.neurotransmitter.net/drug_reference.html

Possible Mechanisms of Action:

Desvenlafaxine inhibits the reuptake of serotonin and norepinephrine (154). It has a greater affinity for the serotonin transporter (154).

....

154. Deecher DC, Beyer CE, Johnston G, Bray J, Shah S, Abou-Gharbia M, Andree TH.

Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor.

J Pharmacol Exp Ther. 2006 Aug;318(2):657-65. Epub 2006 May 4. [Full Text]

From Deecher, 2006

Studies comparing the receptor and transporter binding profile of several SSRIs and SNRIs have illustrated that these drugs and their metabolites each have unique functional activity ratios (Owens et al., 1997; Bymaster et al., 2001). However, in vitro assays may not accurately depict in vivo activity because of factors such as pharmacokinetics, blood/brain permeability, protein binding, and clearance of compound. In addition, the amino acid binding sites for specific drugs versus different radioligands can influence apparent in vitro affinities.

Desvenlafaxine binds differently to serotonin transporters than venlafaxine. This is also true of escilatopram (Lexapro) vs citalopram (Celexa). Escilatopram is an isomer of citalopram.

[Lilu]

Thanks for all the info., which I'm working my way through. Just wondered if you knew the link to the .pdf article does not work?

 

source:

http://journals.camb...8e851f47f408cbf

 

No, I didn't realize the link doesn't work. The system didn't give me the option to edit my post.

Here's the link to the abstract where you can click on pdf or html to view. It's free.

http://journals.camb...ine&aid=8685315

[Altostrata]

Primary Psychiatry. 2009;16(12):1-8

Desvenlafaxine: Frequently Asked Questions

 

http://www.primarypsychiatry.com/aspx/articledetail.aspx?articleid=2464

Desvenlafaxine is an SNRI that is a more selective inhibitor of 5-HT reuptake than NE reuptake.1 Desvenlafaxine does not have significant affinity for cholinergic, histaminergic, dopaminergic, or α-adrenergic receptors.1 Membrane radioligand binding bioassays determine the Ki value, which is a measure of binding affinity; lower Ki values indicate more selective binding.1 In vitro studies demonstrate that the Ki values for desvenlafaxine are 40.2 nM for the human serotonin transporter (hSERT) and 558.4 nM for the human norepinephrine transporter (hNET), for a ratio of 14.1

 

In contrast, the Ki values for venlafaxine are 82 nM for hSERT and 2480 for hNET, indicating a ratio of 30.14

 

....

as mentioned above, venlafaxine and desvenlafaxine differ in the relative degree of 5-HT and NE reuptake inhibition1,14; these differences may lead to differences in relative efficacy or tolerability, or both, for some patients, although conclusions are limited in the absence of data from head-to-head clinical trials.

 

....

Desvenlafaxine is an ER formulation for once-daily administration that is designed to release desvenlafaxine over the course of the dosing interval.3 Desvenlafaxine tablets contain 76 mg or 152 mg of desvenlafaxine in a matrix formulation that is designed to gradually release the equivalent of 50 mg or 100 mg of desvenlafaxine, respectively.3 To maintain the integrity of the ER formulation and prevent “dose dumping” (ie, rapid release of drug from an ER formulation), desvenlafaxine tablets should not be divided, crushed, chewed, or dissolved.3

 

....

How should treatment with desvenlafaxine be discontinued?

 

The abrupt cessation of SSRI and SNRI treatment in some patients has been associated with the emergence of a constellation of symptoms referred to as the discontinuation syndrome. Symptoms associated with the discontinuation syndrome vary in type and severity from one patient to another, emerge within 2–5 days after the antidepressant is abruptly stopped, and resolve within 1–2 weeks.22 In those patients who do experience symptoms upon abrupt discontinuation of antidepressants, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (eg, paresthesia, such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and tinnitus are among the symptoms that have been reported.22 Gradual tapering of the dose of antidepressants, either by decreasing the daily dose or by lengthening the dosing interval is recommended to minimize discontinuation symptoms.23

 

Symptoms associated with discontinuation of desvenlafaxine treatment for depression were assessed in two short-term studies (8 weeks in duration) of 50 and 100 mg/day. Upon completion of the studies, treatment was discontinued without an intermediate dose for patients randomized to the 50-mg groups, and for patients in the 100-mg groups, the dose was reduced to 50 mg for 1 week and discontinued thereafter.17,24 Although the rate of discontinuation symptoms was significantly higher in the 50-mg groups during the first week (or in the second week for patients being tapered from the 100-mg dose), neither the group of patients whose desvenlafaxine therapy was tapered nor those who were discontinued from the 50-mg dose had a mean score on the 43-item Discontinuation-Emergent Signs and Symptoms checklist25 that fulfilled criteria for “discontinuation syndrome.”17,24 Nonetheless, patients should be advised that discontinuation symptoms should be anticipated, though the severity is not predictable. Some patients who experience discontinuation symptoms following cessation of the 50-mg/day dose may benefit from a more gradual dose reduction; because the lowest available dosage form of desvenlafaxine is a 50-mg tablet that may not be broken or crushed, tapering may be achieved by increasing the dosing interval (ie, desvenlafaxine 50 mg every other day). However, it should be noted that this tapering strategy has not been specifically evaluated in clinical studies.

 

How do discontinuation symptoms for desvenlafaxine compare with venlafaxine ER?

 

Direct head-to-head comparative studies of desvenlafaxine and venlafaxine ER to evaluate discontinuation symptoms have not been conducted. In the absence of data from prospectively conducted studies, the relative rates of discontinuation symptoms are not known. However, it may be possible to speculate that a lower rate of discontinuation symptoms could occur with desvenlafaxine, because it has fewer metabolites that do not have antidepressant pharmacological activity (but that may have pharmacological activity potentially associated with AEs), compared with venlafaxine ER, which has additional metabolites (eg, N-desmethylvenlafaxine) that may contribute to AEs, including discontinuation symptoms. Data from the venlafaxine ER and desvenlafaxine clinical trial programs indicate that abrupt discontinuation of both drugs was associated with dizziness, nausea, headache, insomnia, diarrhea, anxiety, fatigue, abnormal dreams/nightmares, and sweating. In addition, following abrupt discontinuation of venlafaxine ER, agitation, anorexia, confusion, impaired coordination and balance, dry mouth, dysphoric mood, fasciculation, flu-like symptoms, hypomania, nervousness, sensory disturbances (including shock-like electrical sensations), somnolence, tremor, vertigo, and vomiting were noted.3,13

[Lilu]

The action of desvenlafaxine is STRONGER (isomer effect) milligram per milligram than venlafaxine. This confounds even this very informed attempt to establish an absolute equivalency between Pristiq and Effexor dosages.

What I take away from this research study, is NOT that Pristiq is stronger than Effexor, but that without Genetic Typing, it is impossible to find out what type of metabolizer a person is. It is impossible to know what percentage of Venlafaxine/Effexor, the parent drug, can be converted into its active metabolite, Desvenlafaxine/Pristiq. And therefore difficult to determine if using Effexor to taper Pristiq will work for you.

 

"Patients with normal concentrations of CYP450 2D6 hepatic enzymes have no difficulty converting venlafaxine into desvenlafaxine, both of whose levels may be easily measured. Ultimately these efficient, normal patients will show very high levels of desvenlafaxine and minimal to no venlafaxine parent drug after absorption through the gut." "Those who are CYP450 2D6-deficient genetically will have ratios less than one, as they cannot easily convert venlafaxine to desvenlafaxine."

http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8685315

 

What does this mean to those who want to stop using Pristiq? Here's how I see it:

 

Scenario 1. If a person has ever been on Venlafaxine/Effexor, and it was effective, that means that their body was able to convert it to Desvenlafaxine/Pristiq. People in this category should easily be able to use Effexor to taper and get off of Pristiq.

 

Scenario 2. If a person has never taken Effexor, but Pristiq was effective for them, there is no way to know if using Effexor in order to taper Pristiq will work for them. Since it is possible that their body may not be able to convert one drug into the other. Effexor may work or it may not. In this case, it may be better to switch to an SSRI like Prozac and then taper that.

 

Scenario 3. If a person has never taken Effexor, and Pristiq was not effective for them, it still may be possible to use Effexor to taper down in order to stop. Just because Pristiq was not effective does not mean that it was not active in the body. But really there is no way to know if this will work. Switching to an SSRI may also be a better option for these patients. Again, Effexor may work or it may not.

 

In conclusion: If you have used Effexor before, with some sort of reasonable outcome, you should be able to easily switch back to Effexor after using Pristiq, in order to taper easily. There may be additional side effects, since Effexor does cause more side effects than Pristiq. However, in my experience, with each "installment" of using Effexor, there were significantly less side effects with each use.

 

BUT if you have never used Effexor, regardless of whether Pristiq was or was not effective for you, switching to Effexor to taper Pristiq might not work for you. It might still work, but you won't know without trying. If you don't want to go thru the trial and error process with Effexor, you are looking at all the other options discussed in this topic.

 

Here's a brief summary (for those for whom switching to Effexor is not an option):

 

a. Cut the Pristiq tablets yourself. Some of you are doing this. But I have not been able to get a straight cut on the Pristiq tablets.

 

b. Switching to Prozac or some other SSRI

 

c. Have a compounding pharmacy crush the Pristiq tablets & put into capsules. The compounding pharmacy I talked to doesn't make tablets and you would need varying doses of the capsules. This requires a detailed prescription from your doctor. It may be covered by your insurance, otherwise it is expensive. A liquid suspension might be possible. Last I spoke with the Pharmacist, he said he would have to do further research into this drug, to determine what can be done with it. But recommended switching to Effexor.

[Altostrata]

oaklily, I disagree with all of your scenarios.

 

To understand that paper, you need to have a deeper knowledge of hepatic metabolism (P450 cytochromes). I suggest you read the work of Sheldon Preskorn.

 

(By the way, Pristiq is not metabolized hepatically. It bypasses the P450 cytochrome system entirely.)

 

The term "effective," as you use it, is vague and not in any way indicative of one's P450 cytochrome status. One may find Effexor "effective" for any number of reasons, including the placebo effect.

 

You also need to take into account the different binding properties, mentioned elsewhere, of the two molecules.

 

There are so many factors involved, precise equivalence of Pristiq and Effexor dosages cannot be calculated.

 

Readers of this topic: Please see the first post in this topic for a summary of tips for coming off Pristiq http://survivingantidepressants.org/index.php?/topic/876-tips-for-tapering-off-pristiq-desvenlafaxine/page__view__findpost__p__7507

 

In my opinion as a layperson, switching from Pristiq to closely related Effexor is a much more reliable way to go off Pristiq than switching to Prozac.

 

(Please don't cross-post the same post in the Tips for Tapering Pristiq topic.)

[Lilu]

As a layperson, with no background in pharmaceuticals, I think you're making this too technical. I really have no interest in delving into this deeper than I already have. I am just simply using my intelligence to understand these drugs, and make it undrstandable to other lay people like myself. I really have no training in science or math beyond high school. ( I have a college degree, but in the arts.)

 

I think my reasoning here makes good common sense and is a reasonable guideline to follow. I don't need to get any more technical about Effexor and the word "effective". I think the average user will know what I mean. Obviously those, who had a bad reaction and couldn't tolerate Effexor, would not consider using it to switch from Pristiq. And those who've been on Effexor before, and found that it helped them somewhat, with tolerable side effects, but with some improvement in their depression or whatever it was prescribed for, then they know that it would be safe to go back to Effexor.

 

Also, many doctors do use Prozac as a bridge, even though its an SSRI. Pristiq's function as an SNRI is not that strong. It's a 14:1 ratio of Serotonin to Norepinephrine. Supplementing with L-Tyrosine which the body converts to Norepinephrine might be good when switching to Prozac. It might be a better option for some people than going on Effexor either because they had a bad reaction to it in the first place or don't really know how they will react.

 

Unfortunately, it seems with any of the options, it is impossible to escape some side effects. Ultimately, using your gut feeling about what is the best option for you, knowing your body, and hopefully working with a knowledgeable doctor will help. Sadly, most of us wind up playing guinea pigs with our own bodies, and suffering as a result.

 

Good luck to you all and wishing you successful tapers and freedom from pharmaceuticals!

[Altostrata]

oaklily, you have to be technical to understand what these sentences in these papers mean. That's why they provide their citations -- so you can get up to speed on the concepts they're working with.

[SourCherry]

I have tried Effexor and it makes me vomit, even with food. Is there something else?

[Altostrata]

Do you mean taking Effexor to go off Pristiq?

[Lilu]

I have tried Effexor and it makes me vomit, even with food. Is there something else?

Hi,

Did  you taper in any way or switch to another medication?  How was your withdrawal?

[Lilu]

It's been many months since I've posted here. In looking for the best way to get off of Pristiq, I have tried many things. In the past I have tapered Effexor xr, got off it completely for 4 months, and then reinstated. I've switched to Pristiq from Effexor, and then years later bridged with Lexapro.  After trying to taper Pristiq, I quit cold turkey while on Lexapro. I have now started a liquid taper of Lexapro.

 

This is what I learned from my experience:

 

Cutting Pristiq tablets:

Cutting Pristiq tablets caused extreme mood and energy swings.  I tried taking a portion of the Pristiq tablet both in the morning and at night, and I just couldn't maintain or establish any kind of stable mood or energy level.  It was a constant roller coaster. Extreme fatigue and drowsiness upon waking. Then feeling more alert and energized about 2 hours after taking a dose of Pristiq. Then experiencing a  crash of energy after 4 or 5 hours. The same thing with then next dose. Up and down. So after 2 1/2 weeks of this, I just stopped taking it. I was already a month into Lexapro, and it helped buffer the Pristiq withdrawal, which amounted to a week of flu-like symptoms.

 

Switching to Effexor:

Although Pristiq is a metabolite of Effexor, Effexor has quite a few other metabolites that can cause a lot of unpleasant side effects. Effexor is by far the worst drug I have been on in terms of the quantity and intensity of side effects.  Since Effexor is not available in liquid form, and is almost as difficult to taper as Pristiq, I don't recomment this as an option, especially if you've never been on Effexor.

 

Bridging: Switching from Pristiq OR Effexor to another antidepressant.

Choose a drug that also comes in liquid form. Preferably one that has the longest half-life.  I would have chosen Prozac, but since I gained a lot of weight on Prozac in the past, I opted for a drug I had not tried before - Lexapro.  I'm not sure if Lexapro is the best option, but I like the fact that it's lowest dose is 5 mg.  Even at 5 mg, at 10% taper will still take at least 6 months to a year, depending on how long your "holds" are. Going from 75 mgs of Effexor would take at least 2 ears! Don't worry about Effexor being an SNRI and Prozac or Lexapro an SSRI, Effexor only affects Norepinephrine at doses starting at 150 mgs.

 

Quitting cold turkey

This is not an option for those of us who have been on psych meds for a long time. I found that out the hard way. Do it, and get ready to meet your evil twin!   For some of us, withdrawal syndrome happens even after a short period on psych meds, as I've read about from members on this forum. I guess the only way to find out, is to see if you have any severe symptoms within 2 weeks.  I'd say if you start having symptoms that weren't there before, reinstate right away, and accept the fact that you'll have to taper slowly. Sigh.....I know, it's a pain having to deal with oral syringes and calculators, and sticky messes...but aren't we all in a "sticky mess" already?

[Altostrata]

Thanks for this, Lilu. Great info.

[Lilu]

Thanks for this, Lilu. Great info.

 

Oh thanks! I'm so glad you approve!