Discontinuing Effexor XR
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Q:  Discontinuing Effexor XR

Greetings Dr. Phelps!

I have been reading that antidepressants can cause rapid cycling in bipolar patients and additionally, that the medication Effexor XR has a difficult withdrawal effect upon its discontinuation.  My question therefore is:  What is the most best method of Effexor XR withdrawl and what is the most successful treatment program you have seen for those who suffer from BP II disorder?
Thank you

Dear Jonathon -- 
Effexor XR has definitely been the one that my patients seem to have the hardest time stopping.  It's almost as though their degree of bipolarity predicts how much trouble they're going to have, and women with bad mixed states and rapid cycling seem to have the most trouble. Looks like you have one thing going for you in that respect so far, if I'm right about any of that (i.e. being male). 

You may have heard or read about the so-called "Prozac bridging" strategy.  As I recall this is described in some detail in Joseph Glenmullen's book, Prozac Backlash (lots of accurate stuff in there, and lot's of overstating too, in my opinion). I think he has nearly a whole chapter on it, by the title of "Held Hostage", one of his frequent phrases therein. Here's a short version of this strategy (somewhat to my surprise, I cannot find a good link on this; there probably is one out there somewhere). But I've wanted to write this down where I can get at it, so here goes....

Serotonergic antidepressants all have been shown to have this problem of "withdrawal". To my knowledge, there is no well-researched explanation for it (plenty of guesses and hand-waving explanations regarding serotonin receptors). People get all sorts of strange symptoms, usually within 24-48 hours without a dose of one of these antidepressants.  Dizziness is one of the most common; others include pins-and-needles sensations in hands and arms; "electric shock" sensations (Glenmullen describes one patient who was convinced a loose wire had fallen into the swimming pool where she was working out, and yelled at everyone to get out quick!); flu-like symptoms such as nausea, headache, weakness, low energy, even runny nose; and emotionality, including easy tearfulness, depression, anxiety, and irritability; and sleep disturbance with unusual dreams. 

Most antidepressants, like most medications have "short half-lives".  This is the official term to describe how fast a medication leaves your bloodstream after you stop taking any further doses..  The time it takes for your blood level to drop by half is "one half-life". For example, consider a medication with a half-life of 24 hours (rather long; many are a little shorter, closer to 10 hours). If take your last dose Monday morning, by Tuesday morning your blood level is now half of what it was (say, measured at noon on each day).  Ah, but watch closely now, here's the important point:  each day after this, your blood level falls to 1/2 of what it was the previous day.  So, in this example, by Wednesday at noon you've dropped to half of Tuesday noon's level.  Note that you're now at 1/8th of where you started. Keep going with this math, and you can see that on Thursday you're at a sixteenth of your original dose, on Friday 1/32nd, and so forth. 

In general, we figure about "five half lives" and there will be so little left, we can call it zero. Why all this fuss about half-lives? Because it leads us to Prozac as a solution to "withdrawal" problems:  Prozac has a half-life of a week! (I'll be using the term Prozac here, because if you write it 20 times it sure is easier than "fluoxetine", the real name, that is, the generic name and the name under which you can get it mighty cheap, compared to brand name Prozac).  It is removed from the bloodstream very slowly -- so slowly, it takes a week to get rid of half of it!  Then, by using our "five half lives" rule, we can figure that Prozac will take over a month to go slowly away (5 weeks to get to 1/64th of the original). 

Thus, Prozac is generally assumed to "self-taper": it does not require careful dose reduction as we would do for Effexor, where I'll often take a month or often more to come down by 37.5 mg steps (the smallest practical step possible). So, the trick is to put these two strategies together. We lower Effexor to the point where one is taking only a single 37.5 mg XR pill per day.  From there, it's that last jump that usually causes all the trouble for people (if one goes slowly enough, getting down to that point is usually not too much trouble, although often people start to notice each step down once they get below 150 mg per day; those that do are more likely to have trouble when they make the last jump to zero). 

Instead of shaving some of those little beads out of the capsule and then trying to reassemble it; or dumping all but a small portion of it on applesauce and consuming them thus, which are alternative strategies for gradually lowering the dose from 37.5 mg and which have not generally worked very well for my patients (I'm not clear on whether that's because it's too much fuss, doing this over weeks; or because they get tired of it and jump to zero and end up getting the symptoms they were trying to avoid), we use the "Prozac Bridge" to zero. After at least a week on 37.5, longer if it's been rough getting there (and if the reason we're trying to take it out isn't too horrendous to force the whole thing to go faster), one stops the Effexor entirely and substitutes in its place one dose of Prozac at 20 mg. (Some doctors use two doses of 10 mg, one each day for two days; or two days of 20 mg for people who have had a lot of trouble and might need a longer bridge.) After that, no more antidepressant, and we just wait for the Prozac to gradually go away over the next several weeks. Since the "pile" of Prozac we built up in the bloodstream is much smaller than the levels one gets to after a month or more of 20 mg daily, this whole thing really does not take the 5 weeks to get to very low blood levels. You probably get there in a week or two, but some will still be lingering for weeks, just a tiny amount. 

Many of the folks I've tried this with (about 20 times total, I'd guess, over the last 5 years or more) have still had withdrawal effects but they were much milder than they had when they tried to jump to zero without the bridge. Two or 3 people have had such severe withdrawal symptoms, despite the bridge, that we ended up using 10 mg of Prozac every day for a few weeks. The, again using that long half-life to advantage, they gradually lowered it from there, by taking out one pill per week: first take it every day but Sunday; next week every day but Sunday and Wednesday; next week only Monday, Thursday and Saturday, and so forth each week until only taking it one day a week -- and then finally stop.  Everyone has been able to get off that way without too much struggle with withdrawal symptoms. 

There: that's the very long answer to your question.  Remember, don't try to do this on your own without your doctor knowing what's going on. I wrote this all out so that you'd know what the strategy looks like, not so you can do it yourself.  To do this on your own will seriously undermine your treatment, as your doctor will no longer be able to interpret your symptoms or give you proper guidance. And besides, she'd hate me.  So, please do not use this information to go around your doctor's intentions.  You'll be better off in the long run being up front with your plan, even if she doesn't agree with it: "I'm going to stop this stuff..."  Then she gets a chance to participate in the decision-making, which is both fair given the energy she is putting in to this, however minimal it may be if she is as busy as some doc's can get; and also a good way to get a good outcome in the long run, better than trying to run the show by yourself.  End of that little sermon.  

Good luck with your next step, Jonathan. (As for "treatment program", you'll see my general outline/recommendations on the Treatment page which you reach by starting  from here.). 

Dr. Phelps 

Published September, 2005


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