To reduce the risk of withdrawal symptoms and post-discontinuation prolonged withdrawal syndrome, as with other psychiatric drugs we recommend reducing Pristiq by 10% per month, calculated on the last dosage. (The amount of the reduction gets progressively smaller.) See Why taper by 10% of my dosage?
However, Pristiq is difficult to taper properly as it comes in only 3 dosages: low, average and excessive.
Do not alternate doses of Pristiq to taper -- this will cause the levels of this medication in your brain to go up and down and is second only to cold-turkey in causing withdrawal symptoms. AND DON'T COLD-TURKEY EITHER!!!!!!!!!
PLEASE READ THIS ENTIRE TOPIC BEFORE GOING OFF PRISTIQ.
Pristiq is a drug made of Effexor's (venlafaxine) active metabolite, O-desvenlafaxine. Pristiq is to Effexor as Lexapro is to Celexa -- a tweaked and more powerful isomer molecule. In effect, Pristiq is concentrated Effexor.
According to Pfizer http://labeling.pfiz...ing.aspx?id=497, Pristiq is available in extended-release tablets of 25mg, 50 mg, and 100 mg; the most common dosage is 50mg.
Unlike Effexor, which is metabolized primarily by liver enzyme P450 CYP2D6, Pristiq is metabolized via conjugation and liver enzyme P450 CYP3A4. It attains peak plasma concentrations in about 7.5 hours.
According to this paper, the extended-release formulation releases desvenlafaxine over 24 hours. The mean half-life of desvenlafaxine, without the extended-release monolithic matrix formulation, is around 11 hours.
The official prescribing information from the FDA contains this:
Discontinuation symptoms have been systematically and prospectively evaluated in patients treated with Pristiq during clinical studies in Major Depressive Disorder. Abrupt discontinuation or dose reduction has been associated with the appearance of new symptoms that include dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, fatigue, abnormal dreams, and hyperhidrosis. In general, discontinuation events occurred more frequently with longer duration of therapy.
During marketing of SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), and SSRIs (Selective Serotonin Reuptake Inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms.
Patients should be monitored for these symptoms when discontinuing treatment with Pristiq. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. 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..... [see Dosage and Administration (2.4) and Adverse Reactions (6.1)].
Symptoms associated with discontinuation of Pristiq, other SNRIs and SSRIs have been reported [see Warnings and Precautions (5.9)]. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. 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 is difficult to taper "at a more gradual rate." The tablets come in only 3 dosages and, officially, they should not be cut up. See http://www.primaryps...?articleid=2464
In a phone conversation with Pfizer medical information (1-800-438-1985), I learned that the extended-release characteristic is incorporated into the tablet itself (Thank you, oaklily, for this information about the matrix formulation.)
Rather than a timed-release coating, the coating on the Pristiq tablet is only protective. The extended-release mechanism is part of the tablet matrix, or the glue that holds the tablet together. This is called a monolithic matrix tablet. (If the tablet is split, the matrix is damaged and may not reliably be extended-release, depending on the size of the fragments. Larger fragments are more likely to retain some extended-release capability.
When the tablet is CRUSHED, the matrix is completely destroyed. The particles should be assumed to have NO extended-release capability.)
According to Pubmed on Desvenlafaxine: "....The extended-release tablet does not dissolve in the stomach after swallowing. It slowly releases the medicine as it passes through your digestive system. You may notice the tablet coating in the stool...."
Can the desvenlafaxine tablet be cut or crushed?
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
3. Pristiq [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc; 2008.
There is a description of the similar matrix formulation for quetiapine XR (Seroquel XR) here http://survivinganti...dpost__p__33069
PROTEST THIS DANGEROUS DRUG
- Phone Pfizer, Pristiq's manufacturer, to make a complaint: (800) 438-1985 in the US
Pfizer has not provided any specific information on how to taper from a dosage of 25mg Pristiq, the lowest available dosage.
They may suggest alternating dosages to taper Pristiq. Don't do this -- it's like playing ping-pong with your brain.
File a complaint about the difficulty of tapering off Pristiq -- the range of dosages is inadequate.
- Also complain to the FDA 1-800-FDA-1088 Mon–Fri between 8:00 a.m. and 4:30 p.m. EST.
OPTIONS FOR TAPERING PRISTIQ
Since medicine knows nothing about tapering Pristiq, the following are all informal suggestions. Try any of them at your own risk. Please let us know how you do by posting in this topic.
Cut up Pristiq tablets
Despite the warnings not to cut it up, patients have cut up Pristiq tablets to taper.
Now that the 25mg tablet is available, cutting it into quarters gives you the option to taper by 6.25mg per step.
If you are taking 100mg Pristiq or 50mg Pristiq, you may wish to request part of your prescription be written for 25mg tablets. (For insurance coverage of multiple dosages, your doctor most likely will have to specify taking Pristiq in "divided doses.")
Rather than a timed-release coating, the coating on the Pristiq tablet is only protective. The extended-release mechanism is part of the tablet matrix, or the glue that holds the tablet together. If the tablet is split, the matrix is damaged and may not reliably be extended-release, depending on the size of the fragments. Larger fragments are more likely to retain some extended-release capability.
If the matrix is sufficiently broken, a Pristiq fragment becomes desvenlafaxine, with an 11-hour half life. If you cut up the tablet, you might take smaller divided doses of Pristiq, more than once a day, like immediate-release Effexor, to mimic an extended-release dose.
From reports on the Web, cutting up tablets does seem to work for some but it makes others ill, possibly because of "dose dumping" (because the matrix is destroyed) when the entire dose is released at once, instead of being gradually released through the matrix formulation.
It seems to sometimes cause stomach upset, which may be reduced by taking it with food.
You may find you need a precise way to measure your tablet fragments. See Using a digital scale to measure doses
As you get down to a low dose, you may wish to switch to Effexor to more precisely control dosage decreases, see below.
Crush Pristiq tablets, weigh powder with a digital scale
This is similar to cutting up tablets -- Pristiq is a "do not crush" medication, as it is a time-release drug.
Conceivably, dividing the dose and taking a measured amount of powder more than once a day, like regular Effexor, may make this method feasible.
Crushing the tablet and making sure the shell fragments are evenly distributed in the powder would be a more precise way of tapering than cutting up tablets.
As Pristiq's extended-release mechanism is part of the tablet matrix, or the glue that holds the tablet together, when the tablet is crushed, the matrix is completely destroyed. The particles should be assumed to have NO extended-release capability.
The Pristiq powder becomes desvenlafaxine, with an 11-hour half life. If you pulverize the tablet, you might take smaller divided doses of Pristiq, more than once a day, like immediate-release Effexor, to mimic an extended-release dose.
Peer discussion of this method starts here http://survivinganti...dpost__p__27417
Reducing from 100mg Pristiq to 50mg Pristiq
Drug switches incur additional risk. Before trying a switch to Effexor or Prozac (fluoxetine) from 100mg Pristiq, it's probably wise to go down to 50mg Pristiq first, if possible.
- You might use a 50mg tablet plus a 25mg tablet plus 3/4 of a 25mg tablet (18.75mg) to make the first reduction to 93.75mg
- 2nd reduction: a 50mg tablet plus a 25mg tablet plus 2/4 of a 25mg tablet (12.5mg) to go to 87.5mg
- 3rd reduction: a 50mg tablet plus a 25mg tablet plus 1/4 of a 25mg tablet (6.25mg) to go to 81.25mg
- 4th reduction: a 50mg tablet plus a 25mg tablet to go to 75mg
- 5th reduction: a 50mg tablet plus 3/4 of a 25mg tablet (18.75mg) to go to 68.75mg
- 6th reduction: a 50mg tablet plus 2/4 of a 25mg tablet (12.5mg) to go to 62.5mg
- 7th reduction: a 50mg tablet plus 1/4 of a 25mg tablet (6.25mg) to go to 56.25mg
- 8th reduction: a 50mg tablet
If withdrawal symptoms occur, some people have found taking an additional fragment of a tablet can smooth the transition from one dosage to another.
Once at 50mg, stabilize for a month at least and consider your plan for the next stage of tapering.
Use a combination of Pristiq tablets and Effexor liquid
Pristiq cannot be made into a liquid, but its close relative immediate-release Effexor (not Effexor XR) can.
You may be able to go off Pristiq by taking part of your dose in lower-dose tablets and part in liquid Effexor, gradually converting to all-liquid Effexor as you get to lower dosages. This may offer a convenient and gradual path off Pristiq.
Only regular immediate-release Effexor can be made into a liquid (see Tips for tapering off Effexor (venlafaxine) ). As immediate-release Effexor has a short half-life and is usually dosed twice a day, you may wish to take the liquid portion of your dosage later in the day.
For example, if you are taking 100mg Pristiq, you may wish to take your daily dose as one 50mg tablet and the rest in a liquid made from immediate-release Effexor. You can titrate the liquid by 10% of your daily dosage to taper until you get to 50mg. Then you can take a 25mg Pristiq tablet with the rest in a liquid made from immediate-release Effexor. When you get to 25mg Pristiq, you might switch to splitting the tablet and taking the rest in Effexor liquid and so on until you are taking only liquid Effexor.
You will have to request a prescription for Effexor tablets as well as Pristiq from your doctor.
Have Pristiq made into smaller dosage capsules by a compounding pharmacy
Compounding pharmacies can crush the tablets and put the powder into smaller capsules by weight. Like cutting up tablets or crushing, this destroys the time-release quality, but the compounded method is much more exact.
(According to my compounding pharmacy, they can put in a slow-release additive distributing absorption over 8-10 hours. This is not as long as the Pristiq time-release coating, but at least it's something. Check with your compounding pharmacy about this.)
In your body, crushed Pristiq is similar to regular immediate-release Effexor, with an 11-hour half-life.
You may wish to have your dose compounded to take twice a day. If you are taking 50mg Pristiq, for example, you would have 60 capsules compounded per month. Each capsule would be 1/2 of 45mg (a 10% reduction of 50mg) or 22.5mg. You would take two capsules per day, once in the morning, and once in the evening.
The next month, you would have 60 capsules compounded, each capsule being 1/2 of 40.5mg (a 10% reduction of 45mg) or 20.25mg. And so forth, for each reduction.
If this does not work, you may wish to switch to Effexor XR and use the bead-counting method. Regular Effexor probably wouldn't be an advantage over Pristiq compounded to custom dosages.
Switch to Effexor or Effexor XR
Note: If you've had an adverse reaction to Effexor before, do NOT switch from Pristiq to Effexor.
"Desvenlafaxine (O-desmethylvenlafaxine) is the major active metabolite of venlafaxine."
Since the relationship is so close, switching to regular Effexor tablets, which you can cut up or make into a liquid, this may be the best way to taper off Pristiq. Because it has a mean half-life of 5 hours, you'd have to take regular Effexor twice a day.
According to FDA Prescribing Information for venlafaxine (Effexor), the usual dose of Effexor is 150mg per day.
Like Pristiq, Effexor XR is released gradually and needs to be taken only once a day.
Since 150mg Effexor and 50mg Pristiq are both "normal" dosages of their respective drugs, they may be roughly equivalent. (See discussion of Effexor and Pristiq dosage equivalency starting http://survivinganti...dpost__p__42249 )
You'd have the difficulty of tapering off Effexor or Effexor XR -- themselves notorious for withdrawal difficulties -- but at least you can do that gradually. See Tips for tapering off Effexor and Effexor XR (venlafaxine).
The psychiatrist who writes the 1boringoldman.com blog reports success in switching one patient from Pristiq to Effexor, then tapering Effexor, here (see comments)
I had a lady who could not tolerate coming down on the dose for the reason you mentioned. So we moved to Effexor which went fine and then after two weeks, came down successfully.
Another psychiatrist said when he tried this, the switch from Pristiq to Effexor was "seamless."
Dr. Stuart Shipko posts here:
Given the lack of research on the topic, my opinions are necessarily anecdotal, and YMMV. Despite the Effexor XR supposedly having problems with bead tapering because not all beads contain active ingredients, I have had consistently good results bead tapering Effexor XR. My approach is to change Pristiq to Effexor XR. For 50 of Pristiq I make an immediate substitution of 150 of the Efxr and after a few days the Efxr is decreased to 100 mg and kept stable for a week before tapering from the Efxr.
Advice from a psychiatric pharmacist
I have been corresponding with a professor at a prominent US university pharmacy department. Here is his best guess at how to taper Pristiq (he does not want his name published):
One may want to consider the following options:
- Always taper to lowest available strength (ie – 50mg) before attempting to discontinue
- Switch to venlafaxine IR [regular Effexor immediate-release] product (a non-coated tablet which is splittable) and taper further. [See above.] Although there is no absolute dosing equivalence between the two products, a reasonable assumption might be that 50mg of desvenlafaxine is roughly equivalent to 100-150mg of venlafaxine.
- OR Switch to low-dose fluoxetine (eg – 10mg) [See below.]
Then taper off fluoxetine (Prozac). See Tips for Tapering Prozac
Advice from Dr. Stephen Stahl, author of the manual Essential Psychopharmacology
In his widely read psychopharmacology manual, eminent psychopharmacologist Stephen Stahl advises titration by crushing the tablets and mixing in fruit juice, see http://survivinganti...dpost__p__14799
According to our member oaklily, Stahl is wrong. Making a liquid from Pristiq does not work, see http://survivinganti...dpost__p__24822
Dr. Stahl intends to correct his book, according to this correspondence 09/15-9/16/13 with him:
....I am most appreciative of your input. It is only by thoughtful suggestions like yours, and colleagues who take the time to email me, that I am able to incorporate the best possible information. Many, many thanks.
In answer to your question about comparing the doses of venlafaxine to desvenlafaxine, there are three articles attached, published in the journal I edit, CNS Spectrums which may be of use to you. Generally, my thinking is that 50 mg desven may be close to 75 mg venlafaxine, and so on up the titration scale....
In the absence of cutting pills or diluting, the best way to come off these agents is to start fluoxetine and then try to taper Pristiq, every other day or every third day, maintaining Prozac which has a very long half life. Then after a few weeks you can stop fluoxetine.
Of course, even taking a drug once a day has fluctuations, but there is less fluctuation if one half life is skipped than if it is stopped. A masochist could take each pill one hour later, at 25, then 26, then 27 hours until you get to 48 hours but problems doing this at night. If unable to tolerate every other day fluctuations, have to cross titrate to a long acting substitute such as fluoxetine.
"Bridging" with Prozac or another antidepressant
Any drug change incurs additional risk. A switch to Prozac from Pristiq may not work -- they are very different drugs -- or you might have adverse reactions to Prozac.
Prozac is regularly used to "bridge" off Effexor. Given that Pristiq is a cousin of Effexor and Effexor XR, it is possible that one can, similarly, use Prozac to withdraw from Pristiq.
Attributed to Joseph Glenmullen, the "bridging" technique is described by a doctor here http://www.bipolarwo...2005/ph1354.htm
Read this entire topic before attempting a switch to Prozac: The Prozac switch or "bridging" with Prozac
Later, taper off Prozac. At least Prozac comes in a liquid.
To do this, consult a doctor knowledgeable about this technique.
Edited by Altostrata, 22 October 2016 - 03:09 PM.