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David Baxter

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Gradual, 10% Dose Reductions Dramatically Reduce Antidepressant Discontinuation Symptoms
By Alison Palkhivala

MONTREAL, CANADA -- November 20, 2007 -- Ten percent weekly reductions in dose over 10 weeks can diminish discontinuation effects associated with many antidepressants of the selective serotonin reuptake inhibitor (SSRI) class. In fact, using this protocol can allow patients to discontinue SSRI therapy even if they were unable to using standard dose reduction techniques.

Data on the effectiveness of this protocol presented here in a poster here on November 16 at the 57th Annual Conference of the Canadian Psychiatric Association (CPA).

"All SSRIs product monographs as well as the literature request that doctors reduce dosage very carefully at the end of treatment," lead author Dipen Kalaria, BSc.Phm, Director of Specialty Services, Pharmacy.ca, Toronto, Ontario, Canada in an interview. "But all the monographs are silent on how this is to be done. And we know that there is a proportion of patients... who have severe discontinuation symptoms."

Pharmacy.ca is a specialty compounding pharmacy that offers its services throughout Canada. They have developed a device using a patented technique that allows them to reformulate the strength of any drug." Any pharmacy can technically do this, but the labour involved can make it quite expensive. With our patented technology, we're able to do it quite cost effectively," said Mr. Kalaria.

Using their technology, Pharmacy.ca provides patients wishing to discontinue SSRI therapy with 10% decreases in doses of the drug. Patients reduce their dose by 10% a week for 10 weeks.

To determine whether this novel titration procedure impacts on adverse effects associated with discontinuation, Mr. Kalaria and colleagues contacted 20 patients who had used this service and asked for their feedback. A total of 19 patients agreed to participate in the study, 13 of whom had tried and failed to discontinue SSRI therapy in the past using standard dose reduction techniques, consisting of dropping down to the lowest available dose of the drug and possibly breaking the tablet.

The 13 participants rated, on a scale of 0 to 3, the degree to which they suffered from any of nine side effects during their initial, failed attempt to discontinue their SSRI and their attempt using the 10-step dose reduction technique. These side effects were: irritability, dizziness, confusion, headache, nervousness, trouble sleeping, nausea, moodiness, and crying.

All 13 of the patients were able to discontinue therapy using the ten-step approach. Also, the mean scores for all nine symptoms were reduced using this approach, compared with standard tapering techniques. While all of the patients experienced symptoms using standard tapering techniques, 53% had no symptoms at all when using the ten-step approach. "It was quite dramatic in terms of the reduction [in discontinuation symptoms] and also the ability of patients to discontinue treatment," said Mr. Kalaria. "

Presentation title: A Novel Ten-Step Titration of Patients Discontinuing SSRIs Shows a Reduction in Severity and Frequency of Withdrawal Side Effects. Poster P20.
 

braveheart

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Hmmm.

Didn't really work for me and efexor. It took me several months going very very slowly, and even then it was hell. I guess it wasn't the med for me. At all.
 

Serenity

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Oh my god! How much I suffered through the years TRYING to get off of SSRI's. Each time I tried I was told that I was suffering because I really needed the drug. EVENTUALLY, I started decreasing very slowly and did it.
 

Retired

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The 10% reduction schedule over 10 weeks is an even more conservative and probably more effective schedule of withdrawing from SSRI and SNRI.

The general consensus had been to withdraw over a three to six week period, reducing in 25% steps, but when dealing with the short half life compounds such as venlafaxine (Effexor) and paroxetine (Paxil) the 10% over 10 weeks would seem to make better sense, particularly for people taking higher dosages.

The difficulty experienced is often due to inaccurate dose reduction (cutting tablets accurately) or attempting to rush the process.

Tablets contain only one score, to cut them in half making reduction to the lower end of the scale more difficult.

This is where a request to the doctor to prescribe a small number of low dose tablets and a cooperative pharmacist can help. By using a number of low dose tablets, scaled down to comply with the tapering schedule, the tablets can be accurately cut to reflect the required dose.

It should be pointed out the rationale behind tapering the dose for withdrawl is based in the pharmacology or pharmaco-dynamics of these medications.

Many of the SSRI / SNRI compounds have a short metabolic half life, and no active metabolites.

This is a good thing when treatment is initiated, because these compounds achieve a rapid steady state, meaning the amount excreted equals the amount ingested in a matter of days. Also not having active metabolites to confuse the effect of the drug, the physician and patient can determine in fairly short order how the particular compound will be tolerated.

But a compound that achieves rapid steady state needs to be tapered on withdrawl, because just as blood levels reached their max in the onset, they reach their minimum just as quickly on withdrawl....unless they are tapered to allow the brain chemistry to acclimate to the change.

Long acting SSRI's such as Prozac (fluoxetine) do not usually cause withdrawl symptoms on discontinuation, but physicians might still taper out of caution.
 

AndPao

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Hi - out of interest, would this be an appropriate method for cutting back on Mirtazapine?

With thanks and best wishes.
 

David Baxter

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As Steve says above, the suggestion of 10% over 10 weeks is a very conservative procedure that most patients will probably not require.

However, the recommendation to taper off gradually should work for any of the newer SSRI or SNRI antidepressants. I don't see any reason why that would not be good advice for mirtazapine as well.
 

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The elimination half-life of mirtazapine ranges from 20 to 40 hours, which is in agreement with the time to reach steady state (4 to 6 days).

Although I cannot substantiate this information from what I consider to be an undisputable source, the figures quoted agree on several resouce sites.

Assuming the half life is 20 to 40 hours for mirtazapine, then this compound would fall into the category of short acting medications, thereby requiring tapering on discontinuation.

When one SSRI /SNRI is substituted for another, the substitution usually takes place without any tapering or "wash-out" required.

However the prescribing physician's instructions should always be followed because there may be other extenuating factors affecting one's medication profile.
 
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thanks for this thread, it is valuable information. i hope when the time comes for me to come off my medication that it will go ok.

what is the standard dosage amounts available for any given drug? i find it hard to imagine each anti-depressant out there would have a dose in multiples of 10% available.
 

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There is no standardization in dosage structure, since each compound is different and clinical trials contribute to the manufacturer deciding on the tablet dosages that will make prescribing simpler.

So the tapering can be calculated on an approximate basis, starting off with the maintenance dose currently being taken and calculate the number fo steps for decrease and the percentage to decrease in each step.

This is where your pharmacist can help in providing lowerdose tablets toward the end of the tapering schedule to allow easier dividing of the tablets.

Your pharmacist will likely require a revised prescription from your doctor to authorize the change in tablet dose and qualtity of tablets due to the laws that govern how pharmacists are permitted to dispense.

To ensure there are no unexpected adverse effects during this process, if you have been taking brand name meds, stick with the brand name med; if you have been taking a generic, stick with the same generic manufacturer for the tapering. There may be differences in the way the med is absorbed, so it's better to lessen the chances of any surprises.
 

David Baxter

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It's also a function of the half-life of a particular medication and the probability of troubling discontinuation effects - some (notably Paxil and to a lesser extent Effexor) are much more likely than others among the SSRI/SNRI family.

For example, another strategy for some medications is to taper down to a lower dose or the lowest manufactured dose and then continue tapering by goping to every second day, then every third day, etc. But this is something that should definitely be discussed with your doctor, who knows you and your medical history.
 

braveheart

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to taper down to a lower dose or the lowest manufactured dose and then continue tapering by going to every second day, then every third day, etc.

That's more or less what I did with efexor.
 

AndPao

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Hi David, hi Steve,

Thank you for your comments. Of course, I wouldn't make any changes without first talking to my doctor, but it's always interesting to learn more about how these things work.

All the best.
 

Peanut

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Hi - out of interest, would this be an appropriate method for cutting back on Mirtazapine?

With thanks and best wishes.

I just asked my doctor that today and she said: out of a 45 mg dose to take 3 15mg pills and split them in half and reduce by half every four days.

This is not advice, just FYI since I just asked her that exact question today.
 

Peanut

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I had to come back to this thread and add that I decided not to taper, just to stop cold turkey, and although there had not been anything really bad, there was a little anxiety surge for 2 days a couple days afterward and now, about a week later I am having some stomach discomfort. So, on one hand it's nice to get it over with, but in retrospect I can see where tapering may have been good. I'm not sure I would have done it differently (this is the third time I've done it this way) but I could see the other side of it.
 

David Baxter

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I decided not to taper, just to stop cold turkey

That's all well and good, but what about a little more focus on stopping cold humans? It hasn't made it above about -4 Celsius in several days around these here parts. :panic:
 

Peanut

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LOL Thanks that helped my sore tummy! Those are cold humans! It's been windy turkeys around here, so windy schools have been closing and trees have been breaking!
 

lallieth

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When I went off celexa last year it took me 3 months to taper it,while that may seem like a long time, I am glad I did.My dr and I came up with a tapering schedule,which made it alot easier
 

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