Buprenorphine Treatment for Opiate Addiction-2017

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Tapering off Buprenorphine

A comprehensive guide to tapering off buprenorphine


Summary:

The purpose of a taper (instead of just stopping) is to gradually reduce tolerance, thus
distributing withdrawal symptoms over a longer period of time
minimizing the discomfort experienced on any single day.

Ending the taper at the manufacturer's lowest available dose (2mgs for Suboxone Film® and generics or 1.4mgs for Zubsolv®) can still result in significant withdrawal.1,6 Here we lay out the
rationale for tapering to much lower doses
. As the data will show
2mgs/day is closer to the midpoint of a typical taper than it is to the end
.

General rule:
Pace the taper with the body's ability to adapt
to each decrease. Dose
decreases of 25% separated by at least 10 days
has been reported to be tolerable by many.1

Buprenorphine taper schedule calculator
- create and print your own taper plan -


Are you ready to taper?

A taper should only be considered once a successful treatment period is completed.

The whole point of buprenorphine treatment is to suppress cravings and withdrawal so that you can make big changes in behavior, routine, living situation and thinking. It's these changes which, in effect, rewire the brain and reverse some of the craving-causing brain adaptations. If this is not done first the taper will likely be shortly followed by relapse.

Have you made significant changes in behavior and had a period of time to gain experience with those behaviors? Have you been able to deal with stress, anxiety and depression without craving drugs? This takes time and doesn't happen on its own, it is a deliberate effort. If you have been in stable treatment less than six months, tapering is NOT advised.

Buprenorphine is NOT a detox medication, it is a treatment medication. If you are not clear on this distinction go to the treatment page and understand it before tapering. But assuming you are ready to taper there are some things to consider.


Tapering to very low doses minimizes withdrawal

Before we continue, it should be noted that the following is a detailed explanation for those interested in the nuances of tapering and not necessary to conduct a taper. It does however help make sense of why certain protocols are likely to be more effective than others.

Cut pieces of film
Fig. 1. Suboxone Film can be cut into small pieces. Accuracy is not that important when cutting the dose. Blood levels will average out over a few days. Also, it is not a certainty that the medication is evenly distributed throughout the film or tablet, so super-precision in cutting isn't warranted.

To understand the tapering process there are a few concepts you should understand:

The Ceiling Effect of Buprenorphine:

In short, at a certain dose of buprenorphine nearly all available opioid receptors become occupied with buprenorphine.3 Each helps induce a small opioid effect.4 The cumulative effect created from all receptors is the maximum effect or the ceiling effect.4 The minimum dose to reach this point is the ceiling dose. Taking more than the ceiling dose involves so few additional opioid receptors that patients are unable to detect any additional opioid effect.4 Whether the patient's dose is at, near or above the ceiling dose, they experience virtually the same opioid effect. For this reason, tapering can be more aggressive (per mg.) at higher doses than at lower doses when more receptors are affected by dose decreases.2

PET scan
Fig. 2. PET scan showing available opiate receptors at various doses.

Fig 2 is a PET scan showing the amount of available opioid receptors at various doses.3 From this evidence it is clear that, for this particular patient, at some dose above 2 mgs. and below 16 mgs. the ceiling dose is reached, as the amount of available receptors have diminished to insignificant levels.3 If we extrapolate this admittedly very limited dataset and apply a curve shape common in biology, we can estimate approximate receptor involvement at various doses. Fig 2a illustrates this concept. It should be noted that there is great variability in reality and liberties have been taken with this particular graph, but it is meant to illustrate the point that the amount of receptors involved is not a linear relationship with dose. Therefore cutting the dose in half from 32mgs to 16mgs doesn't mean that half as many receptors are affected, in fact due to the ceiling effect there would be no discernible difference.

involved receptor graph
Fig 2a. Approximate amount of buprenorphine-occupied mu receptors/dose

If a taper should follow a steady and gradual decrease of involved opioid receptors, then 2mgs would be about the midpoint of the taper. In one of the few taper studies, both long and short tapers ending at 2mgs resulted in very low success rates.6 The researchers concluded: "For individuals terminating buprenorphine pharmacotherapy for opioid dependence, there appears to be no advantage in prolonging the duration of taper". They apparently gave no consideration to the possibility that maybe 2mgs is too high of dose to stop at. We will show it is and suggest their conclusion is wrong in that extending the taper well below 2mgs for a much longer period of time is beneficial.

Buprenorphine Half-life:

Buprenorphine doesn't completely metabolize between doses. It typically takes between 24-42 hours to metabolize half of it, but could range as much as 20-70 hours.9,10,11 We use 37 hours as an average in our calculations, but be aware of the range if your results don't meet expectations. Therefore, after the first 37 hours, only about ½ of the buprenorphine has been metabolized, while half remains to continue to elicit an effect. After another 37 hours half of that remains and so on. At typical maintenance doses, previous doses can contribute to the overall blood levels for 5-12 days (depending on actual metabolic elimination rate). At very low doses, by day three the amount of buprenorphine still un-metabolized is so small its effects are negligible.

half-life graph
Although this graph starts at 16mgs., the curve would be the same for any dose.

Buprenorphine Blood Level Buildup, Stabilization

As patients take subsequent doses of buprenorphine before the prior dose has completely metabolized, a buildup occurs in blood levels. (Fig 3) The buildup continues for approximately 5-12 days at which time the dose taken 5-12 days prior has nearly fully metabolized. This is the stabilization period. When dose is decreased the effects of this build up should be considered before the effects of the new lower dose can be evaluated.

11 day half-life graph
Fig. 3. Blood levels build up until stabilization

Putting It All Together

We now know that doses at or above the ceiling dose can be decreased more aggressively than lower doses. We know that 2mgs/day is not the end of the taper but closer to the midpoint. We know that due to the half-life, buprenorphine builds up in the blood and may still produce effects 5-12 days later, particularly at higher doses. Armed with these considerations we can construct a taper plan which will minimize discomfort.

Buprenorphine Taper Plan

By coupling what we learned above with anecdotal taper testament found online, we can estimate that dose decreases of 25% with 10 days between drops should be tolerable.1 Furthermore, if our initial dose is at, near, or above our estimated ceiling dose we can taper more aggressive initially, maybe as much as 50% drops. As we approach 2mgs and below, we should expect more noticeable differences between each dose decrease and may need to slow down the pace. Once at a very low dose (less than 0.5mgs) we can speed up the pace once again as the buprenorphine is metabolized down to insignificant levels in just a few days.

Emergency Buprenorphine Taper

If you find yourself in a situation where you must taper off immediately for some reason and don't have the time or enough buprenorphine for a planned taper, you can try an emergency taper. With the emergency taper you stop all buprenorphine until the onset of withdrawal. At that time you take small doses (<= 1mg) every hour until withdrawal is tolerable. Then, take buprenorphine only when symptoms become intolerable and only enough to stop the withdrawal. Although this method minimizes withdrawal intensity for a given amount of available buprenorphine, there could still be considerable withdrawal depending on tolerance and the amount of buprenorphine available.

Which brand of buprenorphine to use

As of late 2016 there are 3 name brand and at least 4 generic buprenorphine products to choose from. For ongoing treatment something can be said for the newer brands; with their better bioavailability side effects may be fewer and some dose and copay card combinations make it the least expensive option (including generics). (see cost page) But when tapering, particularly at doses below 2mgs, Suboxone Film (as pictured above) offers the advantage of being larger thus easier to cut into the fractional doses necessary for the taper. Pieces of film left over between doses should be stored in a childproof pharmacy bottle with a silica gel pack to absorb humidity and prevent the opened film from becoming sticky. (see storage section)

When to take your taper dose

Taking your buprenorphine first thing in the morning is best. There is good reason for this. By taking your dose in the morning, buprenorphine blood levels are lowest while you are asleep. Therefore, when the buprenorphine is providing the lowest level of craving and withdrawal suppression you are asleep and aren't dealing with it. Another reason is, you want to avoid anticipation of taking the dose, because this is the type of brain activity you want to eliminate. Anticipating the dose then receiving the reward of the dose, may be reinforcing the behavioral patterns you have worked so hard to eliminate. By taking it early in the morning, there is no need to think about it for the rest of the day. Exception: If insomnia becomes acute, you may benifit from taking your daily dose at night.

Take your full day's dose all at once

Don't split up the day's taper dose. As mentioned above, taking it early prevents you from thinking about and anticipating your dose. Also, once you finally stop, it is an easier transition from taking something once a day to zero times a day, than it is from taking something 2-4 times a day, to zero times a day. Also avoid complicated rituals like dissolving the medication in water and metering out portions for the taper. Simply cutting the film or tablet is all you need to do. Exception: Again, if insomnia becomes acute, splitting the dose up by taking some in the morning and some at night might help.

Buprenorphine Taper Schedule Calculator

The taper calculator below accounts for the information presented above. Because everyone is different this should only serve as a suggestion and might need to be tweaked for individuals. One convenient feature is it estimates the total time and total amount of buprenorphine required to conduct the taper. The taper schedule can be edited and printed out as well.





Create a customized taper schedule.5

* If your dose has varied over the past 10 days use the form below to calculate your starting dose.


Enter your daily buprenorphine dose for the past 10 days
starting with yesterday















Remember, the taper schedule is not etched in stone. Individuals will respond differently to the same taper schedule. It is meant as a rough guide which must be tailored to match an individual's body and circumstance. The main concept is to pace taper rate with the individual's ability to adjust to each decrease. However it can be helpful to have a guide to loosely follow and to estimate about how long it will take and how much buprenorphine will be required.

Buprenorphine and Pain

Buprenorphine is a painkiller. A return of minor aches and pains is to be expected when you stop taking a painkiller. This is not withdrawal, it's the pain the painkiller was killing but isn't killing anymore. Aleve® or some other OTC painkiller, might help but only when and if you need it. Hyland's® Restful legs tablets have also been reported to be effective especially, at night. For sleep, patients have suggested Valerian root and Melatonin. Maintaining good overall nutrition and keeping well hydrated is also important. But maybe the most important thing is to keep busy, preferably away from home. Sitting home waiting for symptoms to appear is a sure way to fail.

Pain is progress

The discomfort you feel while tapering can be thought of as an indication of your tolerance diminishing. The necessary discomfort stimulates the body to produce endorphins. If you can possibly motivate yourself to exercise, even brisk walking, the pain will be less noticeable and you benefit form the exercise. It might also help you sleep better.

Depression and Tapering

Along with being a painkiller, buprenorphine has been recognized as an anti-depressant.7,8 Just as when you stop taking a painkiller, pain comes back, when you stop an anti-depressant, depression may come back too. The severity of the depression could determine the success or failure of the taper. Be prepared to deal with the reemergence of depression, particularly if you suffered from it before starting buprenorphine treatment. This might entail working with a psychiatrist and having antidepressant medication on the ready, before concluding the taper.

Pausing the Taper

If you hit a dose level which produces unacceptable levels of withdrawal discomfort, it is acceptable to go back up in dose, one step, for a few more days. Alternatively, you can hold at that dose for a longer period of time than indicated on the taper schedule. Since everyone’s body and brain is unique, the generic taper schedule may need to be tweaked slightly. Once your body adjusts to the dose level the taper can be resumed.

Mid-taper Breaks

It's okay to take a break from the taper if you need to, as long as it is minimal and infrequent. An example would be if you have been at 0.5mgs/ day for a week and still feel withdrawal discomfort, taking up to 1-2mgs one day will remove all withdrawal symptoms for that day and possibly the next, giving you time to refocus, get things done, and prepare for the final leg of the taper. One day at a higher dose will not increase your tolerance, thus reversing your progress, as long as you limit such higher doses to once or twice during the taper. If you can, try and not take any the following day. This may not be that difficult since about half will still be present the next day. Then resume the taper schedule.

Optional Ending Kicker Dose

Once you fill out the form above and create the taper schedule, you'll notice that on the last day of the taper is a higher dose than recent previous doses. The idea is to take advantage of the half-life property and extend the taper a few days more. The higher dose raises blood levels, without raising tolerance, and as this final dose metabolizes blood levels slowly decrease until reaching zero, thus extending the taper. That's the theory, but we know of no studies that have looked at this, only doctors who employ this in their taper plans.1 It's up to you whether or not to include it. Good luck.


References:
  1. Anecdotal evidence compiled from several social media sites over a period of several years
  2. National Alliance of Advocates for Buprenorphine Treatment- www.NAABT.org
  3. PET scans- mu receptors- Effects of Buprenorphine Maintenance Dose on mu-Opioid Receptor Availability, Plasma Concentrations, and Antagonist Blockade in Heroin-Dependent Volunteers - 2003 - www.nature.com
  4. TIP-40, buprenorphine treatment clinical guidance - government document 2004
  5. Results produced by the NAABT.org taper engine (beta)
  6. Buprenorphine tapering schedule and illicit opioid use- Clinicaltrials.gov, Identifier: NCT00078117 -Ling - study
  7. Buprenorphine treatment of refractory depression, Bodkin [study]
  8. The Buprenorphine Effect on Depression, Richard Gracer, MD [article PDF]
  9. Zubsolv full prescribing information submitted to the FDA - Zubsolv PI
  10. Bunavail full prescribing information submitted to the FDA - Bunavail PI
  11. Suboxone Film full prescribing information submitted to the FDA - Suboxone Film PI

Notes:

  1. Brand names for buprenorphine/naloxone (bup/nx)

    combination products in the US:
    Suboxone Film
    ,
    Zubsolv
    ,
    Bunavail
    , and generic equivalents of the discontinued Suboxone Sublingual Tablets.
  2. Buprenorphine products in the US WITHOUT the added naloxone

    safeguard:
    1. Subutex Tablets
      (
      discontinued in 2009
      ) but the
      generic equivalents remain available
      .
    2. Buprenex®
      is an injectable,
      FDA approved for pain
      NOT addiction -
      illegal to prescribe for opioid addiction
      .
    3. Butrans®
      Patch, also
      FDA approved for pain
      and NOT addiction -
      illegal to prescribe for opioid addiction
      .
    4. Pharmacy-compounded bup or bup/nx
      preparations - NOT FDA approved for addiction -
      illegal to prescribe for opioid addiction
      .
  3. Probuphine®
    is an insertable
    buprenorphine rod
    which goes under the skin and releases bup over the course of 6 months. It
    was FDA approved in May of 2016
    , and is for the treatment of addiction.
  4. Belbuca™
    is a
    buprenorphine film
    which goes on the inside of the cheak. It
    was FDA approved in October of 2015
    , and is for the treatment of pain - NOT FDA approved for addiction -
    illegal to prescribe for opioid addiction
    .
  5. Download Adobe Reader to view PDF files

Disclaimer:

  1. Nothing on this site should be confused for medical advice. The information provided here should only serve to inspire you to find out more from credible sources. We hope to help you understand the disease better so that you know what questions to ask your doctor. Never take any online medical advice over that of a healthcare professional, assume it's all made up. Despite the links to peer reviewed studies all interpretations of said studies may be opinion, unreliable or erroneous. If some patients found something beneficial to them it's not an indication that it will be beneficial to you, on the contrary, it may be dangerous. You, not us, are responsible for what you do with the information you get from this site or any site.

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