Buprenorphine Overdose After Naltrexone Treatment

Naltrexone induces mu-receptor hypersensitivity.  Buprenorphine’s protective ‘ceiling effect’ may not prevent overdose in patients with this ‘reverse tolerance’.

A new patient described his recent history of respiratory failure several days into buprenorphine treatment.  He was told by his doctors that he experienced an allergic reaction to Suboxone. The rarity of buprenorphine or naloxone allergy led me to look deeper into his history, and my conclusion differs from what he was told by his last treatment team.
The patient, a man in his mid-50s, has a history of significant opioid use over the past 20 years.  He used a variety of opioid agonists over the past year, mostly prescription opioids, with an average daily dose greater than 200 mg of oxycodone per day.
Three months ago he went through hospitalization and detox, and after a week he was discharged on oral naltrexone.  He sought further treatment at a different institution that offered buprenorphine.  He was told to stop the naltrexone two weeks before induction with buprenorphine.
He avoided all opioids for that two weeks, and then started buprenorphine, 2 mg twice per day as directed by his physician.  The patient became progressively sleepier after each dose of buprenorphine, and after 24 hours could barely maintain wakefulness.  His complaints resulted in his admission to the hospital intensive care unit.
In the ICU he had a rocky course that included several episodes of apnea, hypoxemia and bradycardia.  The patient does not currently have the records from the hospitalization, so the course of events is based only on his recollections from several weeks ago.  He blacked out several times, and was told by doctors and nurses that his ‘heart stopped on the monitor’ during those times.  He says that his oxygen level was very low at those times according to the monitors, and according to what he was told.
After the episodes when he lost consciousness, he was told that since his heart stopped he needed emergency implantation of a pacemaker.  He said that a short time later those concerns were dropped, and no pacemaker was inserted.  He was discharged from the hospital in good condition after several days.  Follow-up with a cardiologist was not deemed necessary. He was told by his hospital physician that the episodes of lost consciousness were caused by an allergic reaction to Suboxone.  He had no rash or pruritus (itching).
I’m writing about this patient’s care in the form of a ‘case report’.  The patient does not have access to his records.  If he did, I would review them and write a formal case report for publication.  Since I’m relying on the patient’s perceptions and memories, I’ll use this blog.  I will say that I have no axe to grind, and my purpose in sharing this case is to help people avoid a similar situation.  And, of course, to keep readers of this blog entertained!
As the patient shared his story, I assumed that he had an opioid tolerance well-below the ceiling actions of buprenorphine.  When I mentioned my hypothesis, the patient smiled, and told me he had been using over 200 mg of oxycodone each day, blowing that theory to pieces.
But I returned to the same theory when he said that he followed the doctor’s orders very closely, including avoiding opioids completely for two weeks before induction.  I wondered, could a 2-week interval of abstinence lower tolerance so dramatically that buprenorphine resulted in overdose? Then the patient mentioned, in an offhanded way, that ‘he even stopped the naltrexone’.
I’ve written about the increased incidence of opioid overdose following treatment with naltrexone, a risk that is unreported and largely unknown beyond brief reports from Australia cited in the linked post.   Opioid antagonists, including naltrexone (the drug that makes up Vivitrol injections), induce ‘reverse tolerance’ in mu opioid receptors to cause a heightened response, and heightened respiratory depression, from subsequent exposure to opioid agonists.  Anyone close to the field of opioid dependence notices the increased frequency of overdose in patients newly released from confinement, whether in jail or in abstinence-based treatment.  The increased risk of death after a period of abstinence is related to the resetting of tolerance during abstinence.  A return to ‘normal’ use creates significant risk of overdose.
That risk is multiplied if the period of abstinence includes treatment with naltrexone.   Imagine a person who is using six ‘30s’ of oxycodone—180 mg—every 24 hours.  If that person waits a week and then goes on naltrexone, tolerance drops to zero and then to negative levels.  After a couple of weeks on naltrexone, a tablet of Vicodin has the potency of a tablet of Percocet.  That 180 mg of oxycodone now has the potency to cause respiratory arrest and death.
Buprenorphine is a partial agonist with a ceiling effect that prevents overdose in almost all patients who have even small degrees of opioid tolerance.   Almost all deaths from buprenorphine occur in people with limited or no tolerance to opioids.  In the presence of inverse or negative tolerance, the ceiling on buprenorphine’s opioid effect has less protective value.  Such was the case in the patient who is the subject of this discussion.
So what would have been a better plan?  Buprenorphine induction is always more dangerous in patients with low opioid tolerance, so careful patient selection will mitigate that risk.  In patients with low tolerance, reducing the starting dose buprenorphine to low-milligram levels does little to reduce the risk of respiratory depression because of the ceiling effect, which reflects the minimal difference in strength between 2 or 16 mg of buprenorphine.   Much lower doses of buprenorphine, on the order of 0.5-1 mg, are required to reduce risk of respiratory depression and overdose in patients with inverse tolerance to mu opioid agonists.
A second option would be to continue naltrexone through the induction process, and afterward gradually reduce the dose of naltrexone over a week or two.  As the block from naltrexone decreases, buprenorphine bound to mu receptors would gradually increase, allowing opioid tolerance to grow more slowly.  Precipitated withdrawal would not be a problem, as PW occurs when bound agonist is suddenly displaced by buprenorphine—  not when antagonists are displaced by agonists or partial agonists like buprenorphine.
Thankfully, the patient is now doing well, with no lingering problems caused by his course of treatment.  But the incident also relates to another common problem, i.e. the erroneous blaming of symptoms on medication ‘allergies’.  In an era of electronic medical records, that mistake often removes, permanently, a patient’s access to medication that may someday be helpful—and in the case of buprenorphine, irreplaceable.

Avoiding Precipitated Withdrawal

I received the following question earlier today:
Hello Dr. Junig, I am opiate dependent or rather an opiate addict. I want to seek treatment because I can’t continue this life style. I have questions about treatment. Do I have to be in full withdrawals when I go to see a doctor? Is it true that most doctors probably won’t see me because they have too many patients already? I know Suboxone works for my withdrawals. I’ve stuck in this rollercoaster for at least four years and now I know it’s time for me to seek help.
My thoughts:
My comments, as always, are intended to increase general knowledge about buprenorphine and to promote discussion between patients and their doctors.  They are not intended to take the place of a relationship with a ‘real’ doctor!
The appropriate waiting period before starting Suboxone– ‘induction’– depends on the person’s opioid tolerance, and on the specific opioid that the person has been taking.  An opioid-free delay before induction reduces the amount of opioid agonist bound to the receptor, and lowers tolerance to some extent.  Starting Suboxone or buprenorphine is likely to cause precipitated withdrawal when either 1. There is agonist binding at the mu receptor, or 2. There is very high opioid tolerance.
It is hard to give exact guidelines, as every person reacts a bit differently.  But in general, people match up well for Suboxone induction if they are taking about 60-80 mg of oxycodone equivalents per day.  Someone on that amount of agonist, who waits over 12 hours, will generally do well at induction, unless the person has been taking methadone.  In that case, a longer waiting period is beneficial.  How long?  As long as possible, and at least a few days.  Even so, the transition from methadone to buprenorphine is difficult, often causing headaches or minor withdrawal symptoms for several days.  The best response to precipitated withdrawal is to take the prescribed dose of Suboxone/buprenorphine each day, without trying to overcome the symptoms by taking more of an agonist or extra Suboxone.  Doing so only lengthens the period of withdrawal, and considerably increases the risk of death.
If a person is taking a very low dose of an agonist, or taking a weak agonist like hydrocodone, the problem at induction isn’t withdrawal, but rather opioid intoxication, causing respiratory depression and nausea.  Nausea during induction is much more likely to signify relative overdose, NOT withdrawal.  Patients who have nausea and vomiting from buprenorphine or Suboxone should NEVER take a second respiratory depressant or sedative!  When in doubt differentiating between withdrawal and opioid intoxication, the pupils are a good guide.  Withdrawal comes with LARGE pupils.
If a person is taking a very high dose of agonist each day– over 150 mg of oxycodone or methadone, for example— that dose should be tapered down over time, to the equivalent of 40 mg of methadone per day.  Unfortunately, some people cannot carry out or tolerate such a taper.  In those cases, it may be better to have the person in a controlled environment, and wait as long as possible before induction.  Even if tolerance is very high, a person will often do well if off opioids completely for 4-5 days or more.  Of course, that’s easier said than done!
There is a cap on the number of patients that doctors can treat for addiction using buprenorphine.  Doctors can have up to 30 patients at first, and can petition the DEA to increase to 100 patients after a year.  It is frustrating to keep people who are desperate for help on a waiting list— especially when there is no limit on the number of pain patients that a doctor can treat using opioid agonists!
Suboxone relieves withdrawal symptoms when taken properly.  But the main function of buprenorphine/Suboxone is to eliminate the obsession to take opioids, and to allow patients to move forward in life without substances.  People do best if besides Suboxone, they focus on other principles of recovery, determined with their physician or with a counselor.  The point of Suboxone, in my opinion, is to learn to tolerate ‘life on life’s terms.’  That includes dosing at most twice per day, and learning to say ‘no’ to the minor cravings that most people have, even on Suboxone.
I’m glad you are looking for help– and I wish you the best!

Tough Choice

I have been struggling with part II, primarily because there are no easy answers to the situation. I realize that I could easily criticize whichever path a doctor suggests for our imaginary patient.
As an aside, I believe that a major reason for the lack of sufficient prescribers of buprenorphine in some parts of the country is the ‘damned if I do, or damned if I don’t’ scenario. All docs are aware of the current epidemic of opioid overdose deaths, and I think most doctors assume that tighter regulations on opioids are appropriate, and are just around the corner. Some addiction physicians and some pain physicians, particularly those who prescribe opioids, fear being grouped by the media, DEA, or a licensing board as part of the problem, rather than as part of the solution. I recently read of a doctor charged with manslaughter for being one of several prescribers for a person who died from opioid overdose. He prescribed meperidine—and outdated and toxic medication—which likely contributed to the charges… but the story creates a chilling atmosphere, regardless. Suboxone and buprenorphine are much safer medications, but when the target population consists of people with addictions to opioids, there will always be some people who use the medication inappropriately— some with disastrous results.
For those late to the party, we are discussing the best treatment approach for someone who cannot control using opioids, but who for now, at least, has a low opioid tolerance. Starting buprenorphine in such a patient will cause opioid side effects, as described in an email that I received from a woman who was addicted to hydrocodone for four years, who stopped taking hydrocodone for 7 days before induction with buprenorphine.
She wrote:
This Suboxone is making me feel like crap. He has me on 8mg/2mg sublingual 2/day. It’s awful…
She had been taking 20-30 mg of hydrocodone up to 5 times per day, stopping them a week before induction. She continued:
Have had a headache in the base of my skull since starting Sub 4 days ago, nausea, vomiting, sweating a lot, face feels like it’s on fire, can’t taste anything, throat hurts, can’t sleep because my face & eyes itch so bad that I’ve rubbed them raw.
These are classic side-effects of over-narcotization from buprenorphine. A person in this position typically feels better holding the buprenorphine, and when the nausea is eventually gone, taking a greatly reduced dose of the medication. The problem is that if the dose is too low, there is no advantage to buprenorphine over other opioids. The whole point of taking Suboxone is to stay on a blood level HIGHER than the ceiling effect, as that essentially tricks the brain, since the opioid effect stays constant even as the blood level falls.
In a few days, the writer’s tolerance will increase to a level where she can take an entire dose of Suboxone without nausea. And by that time, the medication will greatly reduce the desire to take opioids.
Will she be better off on buprenorphine or Suboxone than she was on hydrocodone? Her tolerance will be higher—meaning greater physical withdrawal if she stops the buprenorphine, than she would have had stopping the hydrocodone.
But on the other hand, she tried to stop taking hydrocodone for several years, and couldn’t. She was taking over 4 grams of acetaminophen per day— the other medication present in Norco besides hydrocodone— which is enough to cause death through liver toxicity. And the ups and downs of hydrocodone addiction create a living Hell that eventually demoralizes the person.
I hear from writers who are angry at their physician for getting them ‘stuck on Suboxone’, saying they should have simply tapered off the hydrocodone instead. My answer is that it is easier to SAY ‘I would have tapered of hydrocodone’ than it is to actually taper and stay off hydrocodone!
A doctor seeing the patient I wrote about in part one, or the person above, would face two options:
1. Cause an incidental ‘high’ by administering buprenorphine, and titrating the dose up to a level that eliminates cravings, or:
2. Use an alternate treatment strategy.
Some doctors would opt for the latter, saying they are not comfortable with deliberately intoxicating patients with opioids—something that is unavoidable when starting a low-tolerance patient on buprenorphine (or Suboxone; note that the naloxone component of the medication is irrelevant to this discussion, as it has no action unless injected).
In such cases people are often referred to step-based or other residential treatment centers. I’ve written some pessimistic opinions about those places, but I’m just trying to be accurate. I realize that there are many people dedicating their lives to treating people with addictions in such places—ranging from free, community-supported programs to $80,000 per month luxury rehabs. As dedicated as those people are, the success rate of such programs remains low, and the risk of fatal overdose is present upon discharge. Most people who have gone through residential treatment relapse. And many people have been through rehab multiple times, yet continue to struggle.
Vivitrol, a monthly, injectable form of naltrexone, has been marketed to fill in this space, as a protection against relapse after residential treatment or after several weeks of detox. But for whatever reason, most people opt to forgo that medication, instead placing misguided faith in their own ability to stay clean. So what usually happens is that people with a lower tolerance to opioids repeatedly go through detox, or repeatedly pay for residential treatment, only to return to using opioids. Tolerance increases over time and eventually they present with a tolerance level where Suboxone seems more appropriate.
Assuming, of course, they live that long.

Do You Prescribe Buprenorphine?

I’m not sure about the make-up of readers of this blog.  I know that there are about 20,000 page views each month, but I don’t know how many are by people addicted to opioids, people taking buprenorphine, family members of addicts, or physicians who prescribe buprenorphine.  If you fall into that latter category– i.e. if you prescribe buprenorphine, or if you prescribe other medications to treat opioid dependence such as Vivitrol or methadone– consider joining the group at linkedin.com called ‘Buprenorphine and other medication-assisted treatment of opiate dependence.’  If you already belong to LinkedIn, you can simply follow this link to join: http://www.linkedin.com/groupRegistration?gid=2710529
I have always resisted separating those who prescribe buprenorphine from those who are prescribed the medication.  I have avoided, for example, placing a ‘doctors’ section’ at SuboxForum, as I don’t want there to be two separate discussions.  Clearly, each group would benefit from the wisdom of the other.  But there are some physicians who want to discuss prescribing habits, techniques, and science with other docs, who are not comfortable discussing some topics in the ‘presence’ of their patients.
Non-docs, please don’t flame me for this decision;  I’ve wrestled with it, and have made this decision, at least for now.   Frankly, the discussions at SuboxForum are far more interesting than anything that has come up so far at the linked in site!    But some docs who prescribe buprenorphine are isolated out there, perhaps even looked down on by their peers for working with addiction– and that is a crying shame.    I want to get those docs some support.  My goal ultimately is to bring the two sides together, so that docs can talk to addicts and realize that they are the same species as the rest of their patients!
Thanks all,
JJ

Sick from naloxone, maybe?

A person wrote about feeling sick after taking Suboxone, thinking that naloxone is to blame and frustrated that her physician would not prescribe Subutex:
I first read your blog last week as I was going through the despair and misery of withdrawal from Percocet, and considered suicide. I didn’t want to die, or create anymore suffering for my family; I just didn’t see any options or hope. Your well written words (I thank you deeply) about the hell of withdrawal got my attention & brought me to tears. I continued to read, found out about Suboxone, which led me to message boards from others like me. For the first time I felt hopeful. I found a doctor and made an appt, and after the initial, office administered dose I found myself feeling the best I had in years– no withdrawal and no physical pain – wow! At the 2hr follow-up I told (the doctor) that my pain was completely gone, which she disputed, saying it’s not prescribed for pain. What I know now is that she had given me Subutex in the office, and a Suboxone prescription to take home!!I filled the prescription, took the ½ pill dose, and within minutes my stomach hurt/gnawed, and I developed a very strange headache and mild to moderate chest pain. By the evening I’d vomited and the headache worsened. By next morning I had the worst headache ever and started vomiting large amounts of bile, all of which continued throughout the day. My doc insisted I show up for the follow up appt. that day, even though I was too sick to hold my head up. She insisted I was sick from withdrawal

Image result for chemical structure of naloxone 3d
Naloxone, a mu-opioid receptor antagonist

To date I’m taking 3 Excedrin for migraine within an hour of every Suboxone dose as I get a bad headache every time.  I also wake up with a moderate headache every day. The last few days I’ve noticed I don’t feel emotions, joy, or happiness. I feel depressed & don’t care about things that would typically give me happy goose bumps – my grandkids, my dogs, sunsets.

I asked the sub doc to put me on Subutex which she refused to do. I explained that if someone was this ill from BP or diabetes meds, and there were other options, it would be unethical to not help the patient. I spend $180 for medication that makes me ill- every day.
I’ve spent the day trying to find a doc who will prescribe Subutex, with no success. Ironically, a few years ago my own doc recommended this drug for my back/leg pain.  I don’t know what to do.  I can’t stay on Suboxone or go off. Do you have any suggestions? 
 My answer:
I hope that your weekend is going OK.  I have a few thoughts about your situation, but I don’t know how much help they will be, as ultimately you are dependent on the prescribing doc.  But maybe we will find something that will help.
It sounds like you have a pretty good understanding about buprenorphine and Suboxone, but there are a couple areas that need clarification.  For most people- more than 95% of people in my estimation—there is no difference in the subjective experience from taking Suboxone vs. Subutex.  The active drug, buprenorphine, is present in both, and the naloxone that is present in Suboxone has no significant effect.  The ceiling effect of Suboxone is due to buprenorphine;  naloxone plays no role in that effect.  Both Suboxone and Subutex can be used for pain, and both can be used for ‘induction.’  There are some misguided physicians out there who think that Subutex is a better choice for induction, thinking that naloxone will cause withdrawal during the induction process—but those doctors are wrong.  Both Suboxone and Subutex cause precipitated withdrawal, which comes from buprenorphine, not naloxone.  Naloxone does not pass through the mucous membranes lining the oral cavity, and instead ends up being swallowed, and taken up into the portal vein from the proximal small intestine.  In MOST people, naloxone is then rapidly destroyed by the liver before getting into the systemic circulation.  In a FEW people, though, naloxone causes side effects.  Side effects are of two basic types.  The first type is an allergic reaction to naloxone, causing flushing, wheezing, and perhaps nausea, vomiting, and/or rash.  Allergic reactions can occur from very small amounts of a substance, and so people can have allergic reactions to naloxone even when the drug is essentially cleared by the liver and too little remains to cause symptoms of withdrawal.
A second type of reaction is more common in my experience, and that is where the naloxone is not destroyed well be the liver and instead gets into the systemic circulation and then to the brain and spinal cord, where it blocks the opiate effects of buprenorphine.  In this case the person would have typical symptoms of withdrawal, including headache, depression, anxiety, restlessness, pain, diarrhea, and nausea.  Naloxone is not a long-lasting medication, so I would expect the withdrawal-type symptoms to last only for several hours.
As I mentioned, naloxone is usually destroyed very efficiently by the liver before reaching the systemic circulation, a process called ‘first pass metabolism.’.  There are many medications that interfere with liver enzymes, although I do not know of specific inhibitors of the enzymes that destroy naloxone.  In other cases, people have a genetic background that results in reduced metabolism of certain substances including naloxone.  Your symptoms occur shortly after each dose, which is what we would expect in a person who is not fully metabolizing naloxone.
I do not know why your physician is refusing to prescribe Subutex, but it sounds as if she is concerned about diversion.  In my opinion, concern in this instance is misguided.  Yes, there is a diversion problem with buprenorphine, but there is not a difference between Suboxone and Subutex in this regard—i.e. BOTH are diverted.  Studies suggest that buprenorphine is not generally diverted for the purpose of ‘partying’ or getting high, but rather is taken by addicts who are trying to treat themselves to get off opiates, or who need something to carry them over when heroin or oxycodone are not around.  In either case, the presence of naloxone does nothing to reduce diversion.  As you likely know, naloxone only prevents against intravenous use of Suboxone—a type of diversion that accounts for a very small percentage of cases.
You are welcome to share this with your physician.  Unfortunately there are some thin-skinned doctors out there though, so be careful that you do not get yourself kicked out of treatment!  I have a couple other suggestions that might be safer.  First, you are welcome to send me a list of medications you are taking, and I will check to see if any of them are inhibitors of the liver enzymes that metabolize naloxone.  Prozac, for example, is a potent inhibitor of one group of enzymes, and therefore can affect the half-life of a number of medications.
A second thing you can do has been described in earlier posts.  The idea is to absorb the buprenorphine without absorbing the naloxone.  Since naloxone is taken up only at the intestine, the key is to avoid swallowing the naloxone.  Start with a dry mouth.  Put the tablet in your mouth and bite it into pieces to get it dissolved in a small volume of saliva.  Then use your tongue like a paint brush, and spread the concentrated saliva over the mucous membranes in your mouth for about 10 minutes.   After ten minutes spit out the saliva, which contains the bulk of the naloxone.  Be sure to avoid eating or drinking for about 10 more minutes, as you don’t want to rinse away the buprenorphine that is attached to the surfaces in your mouth.   This method of dosing seems to be more efficient than placing a tablet under the tongue, and allows more control over the absorption of naloxone.   I’ve had a number of patients who initially felt that their dose of buprenorphine was too low, who then felt better dosing this way.  And I have had a few patients who believed they were getting headaches from naloxone, who had fewer headaches after dosing this way and spitting out the naloxone.
One final thought.  I did not address your comments about joy, happiness, passion, or depression because it is usually not a good idea for us addicts to focus on whether we are adequately ‘feeling’ those things.  Opiate addicts tend to spend too much time looking ‘inward,’ thinking about how they feel.  One goal with treatment is to get them thinking about things OUT THERE in the world, rather than about how they are feeling ‘inside’  (Don’t confuse this point, though, with ‘feelings work.’  Addicts tend to have a hard time identifying feelings and recognizing the nuances between one feeling and the next, and there is much to be gained in working on identifying and recognizing feelings during group or one on one psychotherapy.  This work is to be distinguished from the self-obsessed search for happiness that many of us addicts get wrapped up in from time to time).  Once a person decides he/she is not feeling ‘passion,’ the absence of passion becomes a self-fulfilling prophecy.  The same holds for feeling sad, lonely, or depressed.  I do not have an explanation for why Suboxone vs. Subutex would result in a lack of happiness or passion, except perhaps by causing low level withdrawal symptoms that affect mood.  I SUSPECT that those feelings are more ‘psychological’ than anything else.   I also do not know why your symptoms on Suboxone last all day long, although I suppose it is possible that for some reason your body metabolizes naloxone extremely poorly, causing it to sicken you for the entire period of time between doses.
If the ‘spitting technique’ works, that is one more bit of data that you can take to your physician.  Hopefully, if that is the case, she will have a change of heart.

Opiate withdrawal: hell beyond words– does your doctor care?

I am often told by opiate addicts that they would kill themselves rather than go through withdrawal again.  I assume  that the comments are  exaggerations to make a point.   But a recent nightmare helped me realize that the comments are not hyperbole– but rather are serious attempts by addicts to describe just how horrible their experiences were.  I remember my own detox only when I force myself to remember it (0r after the occasional bad dream);  I have a tendency to repress the memory, perhaps as people do with traumatic memories.  But when I really think about my experience during those 5-7 days at the end of that horrible hall in that horrible ward, I cannot imagine going through the experience again, for any reason.  I hate to say it as a psychiatrist who knows the damage done to the survivors of suicide, but I understand the logic of choosing death instead. 

The loneliness is the worst part

When I discuss addiction and detox with other doctors, one frustration is that there are no words to express the horror of severe withdrawal.  (The other frustration, by the way, is that few doctors seem interested in knowing about the experience– but I’m not going to fix that problem with my blog!)  Opiate withdrawal is not a matter of physical pain, although physical pain is surely a part of the experience.  The term  ‘depression’ likewise do not capture the experience.  Nobody has the energy or wherewithall to write during the experience, and so it is unlikely that we will read a great description recorded in ‘real time’.  But when I meditate on the experience in order to improve my memory, I am struck by the utter despair, the self loathing, the hopelessness, and the complete isolation that I felt during detox.  I remember thoughts of being ‘cursed’, or of being possessed by demons of death– I felt as if the world I had known was long gone, and I was left alone with demons.  I had no vision of hope for the future.  I remember trying to take my mind off of the horrible thoughts by directing my attention on the clock, which seemed to move backwards, it was going so slow.
I am writing this somewhat self-effacing description of the experience because of a thread in SuboxForum earlier today, from a woman who was trying to make it through 24 hours in order to get induced with buprenorphine.  She was asking whether she could use anything to help her make it, such as tylenol, ibuprofen, or the Xanax that she has been prescribed for the past year.  For the record, yes– you CAN take all of those things.  In fact, ideally a person going through the 24 hours of hell will be given sedatives, clonidine, anti-emetics, and anti-diarrheals to make the process a little more bearable. 
For any doctors who are reading this and thinking that doing so is a waste of time, or who takes refuge in saying ‘I don’t know the person well enough to prescribe those things,’ shame on you– because withdrawal really, really stinks.   To the writer on the forum this morning, I hope you made it.  If not, don’t give up.  It is hard to see in the middle of all that horror, but it will be worth it.

Sick When Starting Suboxone: Abres Los Ojos!

An interesting case from a reader:
Thanks Doc for your efforts. I appreciate you.
I am a four year hydrocodone addict 55 years old. I became addicted when I used the drug for an injured cervical disc.
A couple of years ago I found out about suboxone and got in touch with a Dr. in Tulsa who prescribed it for me. I waited until I thought I was in withdrawl..about twenty hours and took my first dose. I became dizzy, nausiated, numb and all I could do was make it to the bedroom where my nausea eased a bit…I never vomited. I lay there for ten hours in a numbed state half in and out of sleep. The next day I was fine.
The Dr. said I took it too early. So, I waited a week without any hydros and took another pill and got the same results. The Dr. said to flush them and I did.

Two years later I am still an addict. Do you think I should try again? Could I take small slivers of the pill without the negative effects? What do you think?
I am desperate to get clean.
I have also heard about subutex but have never tried it. Could it be that subutex is what I should try for?
Respectfully,
John in Oklahoma
My Response:

High on opiates
High on opiates

How much hydrocodone were you taking in the days leading up to taking Suboxone? Your reaction sound more like a person overdosing on buprenorphine than precipitated withdrawal– do you remember, at the time you were nauseated, were your pupils very large, or very small? If you were in withdrawal your pupils would be huge; if you were overdosing they would be ‘pinpoint’, and if you were having an allergic reaction of some type, they would be about normal.
20 hours should be plenty long for hydrocodone, and your second attempt could not have been precipitated withdrawal, providing you weren’t on some other opiate. Nausea and vomiting are not the main features of withdrawal; more typical would be lower abdominal cramps and diarrhea. Nausea is a big part of overdose, on the other hand. The potency of Suboxone (any dose above 4 mg) is equal to about 30 mg of methadone, or about 60 mg of oxycodone, or about 100 mg of hydrocodone… if you were taking the 5 mg tabs, that would mean that a tablet of Suboxone would equal the potency of about 20 tablets of vicodin. Since vicodin lasts only a few hours, to have an equal tolerance you would need to be taking about 20 times 6 = 120 tabs of vicodin per day. That is a lot of vicodin– enough to kill you by destroying your liver, so you were probably taking significantly less.
Out of junk
Out of junk

I think the Suboxone was just too strong. Yes, you could try working your way up with tiny pieces, but it is
hard to titrate at the low doses because of the unusual dose/response curve. I think a better way, if you are not on a huge dose of vicodin, would be to use clonidine, immodium, and maybe some other things to help with the withdrawal, and use the steps to stay clean… otherwise you will be moving up the tolerance ladder.
Subutex would be another option if I am wrong with my assumptions about your dosing– some rare people do have bad reactions to the naloxone, even though little gets into the system. One other hypothesis… if you were taking tons of vicodin, and your liver was in bad shape, your liver might not have been able to destroy the naloxone (first pass metabolism at the liver is what keeps the naloxone in Suboxone from working), and so the naloxone in Suboxone precipitated withdrawal.
Good luck!
John Writes Back:
Yes, Dr. you may be right. My dose was relatively low, I was taking at or about four or five lortab 10 tablets a day.
I wasn’t aware of the potency of the suboxone. I seem to remember I took the four or five mg. tabs, the small orange hex shaped one.
I did not check my pupils, but if I take it again I will be sure to do that.
I know my dosage is not that of others and that Vicodin addiction is not that of Oxycontin or heroin. That said, I still feel hoplessly addicted to them and have tried the twelve steps twice. That is why I am interested in the suboxone, but like you say it would be stepping up the tolerance ladder, I suppose. Since my willpower is nonexistant at this point, I think I am going to give the suboxone one more try the way I suggested and I will let you know how it works.
Half-wasted?
Half-wasted?

Thanks for your timely reply, and I think you hit the nail on the head.
God bless you
John in Oklahoma
And Me Again:
You might want try a bit of a medication called ‘hydroxyzine’, which is used to reduce nausea from opiates– although it also can be quite sedating, so don’t drive on the combination. A non-sedating alternative would be odantreson (zofran), which is what is given post-op for nausea. In fact, forget the hydroxyzine– premedicate yourself with a dose of zofran, about 4 hours before the induction, and you should do much better.

Precipitated Withdrawal– Now What?

I saw this question on another board– I didn’t want to add my reply to the other five answers already listed, so I’ll put it here for hopefully the next unfortunate person in ‘precipitated withdrawal’ to find.
For those who don’t know, precipitated withdrawal occurs when a person’s level of opiate stimulation is suddenly reduced by another medication blocking the receptor site.  This occurs when an overdose patient is given an opiate antagonist such as IV naloxone.  As soon as the naloxone hits the receptors in the brain, the oxycodone, methadone, heroin, or other agonist is ‘displaced’ and the receptor is ‘blocked’ by the naloxone.  I actually did this to myself on several occasions back in my using days; once by out of desperation and stupidity using an unmarked syringe that contained naloxone, and two other times by ingesting naltrexone, an orally-active opiate blocker, in attempts to make myself ‘get clean’.  Those experiences lead to my first comment about precipitated withdrawal:  you won’t die… but you will wish that you did!
The active ingredient in Suboxone, buprenorphine, will cause withdrawal if a couple things are present: first if the person has taken an opiate agonist recently enough so that there is still agonist drug bound to the receptors, and second if the person’s tolerance is greater than that associated with about 30 mg of methadone– equal to the opiate-stimulating activity of Suboxone. If a person just took his first 20 mg of oxycodone, I wouldn’t expect the buprenorphine in Suboxone to induce withdrawal because at his tolerance level, his receptors will see buprenorphine only as an agonist– not as an antagonist. The rules are not ‘hard and fast’, but depend in a complex manner on the interaction between recent use, half-life of the recently-used drugs, and the person’s tolerance. For example, if a person is used to 600 mg of oxycodone per day, but hasn’t used for 24 hours—long enough to get most of the oxycodone out of the system—I would still expect the person to have precipitated withdrawal– because even after 24 hours without using, the person’s tolerance level will still be quite a bit higher than the ’30 mg of methadone’ level of stimulation caused by buprenorphine. There is a bit of an art to avoiding the withdrawal, but sometimes it can’t be avoided. For example, in the 600 mg oxycodone case, I could tell the patient to go without using for three days;  that would be enough time for their tolerance level to drop closer to the ’30 mg methadone’ mark… but the person will feel utterly horrible during that time, and sometimes it is obvious that there is NO chance the patient will stay clean that long. So there are two choices; schedule an induction in three days and then cancel when the person breaks down and uses something the night before the induction, or shoot for 24 hours of clean time and let the patient know that he/she is going to be a bit sick at the induction.
I should mention that the ‘proper way’ to manage the patient taking 600 mg of oxy per day is to taper the person down to the equivalent of 30 of methadone per day.  This never works;  first of all, it is illegal for any doc to taper opiates for the purpose of treating opiate addiction, unless the doc is part of a registered methadone center– and methadone centers, in my experience, are not interested in doing the work of tapering people off opiates.  They tend to do what they want, and that is to increase the dose of methadone– not decrease it.  But even if the patient found a doc willing to break the law and schedule a taper, the tapering schedule cannot be followed by the addict.  I suddenly think of the old joke…’if I could walk THAT way, I wouldn’t need the talcum powder!’…  as I think in a similar vein, ‘if I could do a taper, I wouldn’t need an addictionologist!!’

The good news is that precipitated withdrawal is much shorter than real withdrawal.IF you have precipitated withdrawal, all is not lost—providing you do the right things.First, understand that you are going to be sick for about 24-48 hours no matter what you do.Your choice, at this point, is: after you get better, will you be on Suboxone, or will you be using?

If you have PW (I’m sick of writing out Precipitated Withdrawal), the most important thing is to FINISH THE INDUCTION! Complete the dosing of Suboxone, as quickly as possible—take the full 8 or 16 mg. If you stop the induction early, after only 4 mg, you will likely end up using later in the day to try to overcome the block.  That gets real dangerous, and only prolongs the misery– and in a few days when you finally have the Suboxone out of your body you will still be using. On the other hand, if you complete the dosing of Suboxone– take the full induction dose of 8 to 16 mg– you will be at a place where no amount of using will overcome the block (so don’t even try!).  Try to deal with the withdrawal in the usual manner (clonidine, immodium, warm bath) and the next morning take another 16 mg dose of Suboxone. Keep dosing each morning—DON’T mess with multiple daily doses as they won’t help and they can potentially make it worse (if you take very large doses of Suboxone it becomes a pure antagonist). If you just keep dosing 16 mg per day each morning, by day two you will be much better, by day three you will be 90% better, and by day 4 you will be out of withdrawal. It’s fast—unless you play with it.

By day 4, you’re done with the misery and on Suboxone. Your addiction will be in remission, provided you do the other things required to get better—things which are usually fairly easy to accomplish if you have some level of desire for the sober life. And it is wonderful to have the chains removed! Once you are at this point, KEEP TAKING THE SUBOXONE! I read the comments at some sites about ‘coming off sub’—it is important that you understand that virtually ALL of those people—the ones who go on Suboxone, get their lives back, but then believe some idiot ranting that ‘they aren’t really sober’ and go off Suboxone— will only be using again, probably in a matter of weeks. It is so unfortunate… people go to these message boards and read ‘support’ and ‘encouragement’ to ‘get off Suboxone’, usually doing the taper wrong, suffering through unnecessary withdrawal, and blaming their misery on the Suboxone…  Then they write with excitement how they are now ‘really clean’… But in a week they are gone from the message board, too busy to write, scrounging up money to buy dope—or more likely, selling their computer for the money for dope. It doesn’t work, people.

Is it ever possible to get off Suboxone?  Yes– if you are willing to treat your addiction with something else, usually twelve-step-oriented recovery.  Suboxone alone is not a cure– it is a means to induce remission of opiate addiction.  For someone who got clean ‘the old fashioned way’, the glass is half full!

Waiting for Suboxone after Heroin

How long do you have to wait before taking Suboxone, if one had been using heroin for almost a year? What can one take to ease the withdrawal symptoms in the meantime while waiting? Are treatment centers effective places to go to as a start or just start out with a qualified Suboxone doctor? Any feedback would be great! Thank You.
Hi, and thanks for writing.  Once a person has been on something for a couple months it doesn’t matter if it is three months or three years– the tolerance and risk of precipitated withdrawal are more a function of dose and type of drug than of time.  For example, methadone and high-dose fentanyl have long elimination half-lives and therefore take longer to leave the body before starting Suboxone, whereas low-dose fentanyl or crushed oxycodone have short half-lives and leave more quickly.  Heroin is somewhere in between, longer acting than oxycodone but shorter than methadone.
As soon as you start withdrawing, your tolerance will start to fall.  It falls the fastest initially and then slows down a bit after the first couple days.  For heroin, people who go three days without using will do great– that is more than enough time.  If your daily dose is on the low side 24 hours is sufficient to avoid precipitated withdrawal;  if your dose is real high you might want to try to go a bit longer, say 36-48 hours or so. Treat withdrawal symptoms by treating the individual symptoms.  First, take clonidine– that will reduce all of the symptoms by about half.  It requires a prescription but most docs will prescribe it, as it is pretty safe.  You can take the skin patch, but i prefer the pills because they can be controlled more easily to increase or decrease the dose.  I give 0.1-0.3 mg every six hours or so; stop it if you get light-headed when standing up quickly.  It is a $4 med at Wal-Mart. For the diarrhea and cramps, take immodium, sold over the counter.  For body aches take ibuprofen and tylenol (both if your liver and stomach are in good shape– avoid the tylenol if you have hep C).  A small dose of ativan or valium goes a long way in the evening;  the clonidine helps with sleep as well.  If you don’t have either you can take some benadryl– it will make you sleepy and might reduce your anxiety a bit.  Keep warm by soaking in a hot bath as much as possible– that will also relax your muscles.
Some detox centers use Suboxone, but some don’t– be sure to check.  Likewise different providers have different styles.  The local hospital by me makes Suboxone patients spend the night before induction!  Not sure how the insurance companies let them get away with that.  But some docs around here make people wait longer before starting Suboxone– I have heard some descriptions of other places that sound a bit silly, like ‘just don’t take anything for a week’.  Hmmm. Reminds me of that old joke where the guy goes into the pharmacy and asks for talcum powder and the woman says ‘sure– walk this way’.  As she walks away the guy says ‘if I could walk like that I wouldn’t need the talcum powder!’   (sorry– working on a Sunday does that to me…)
SD

Precipitated Withdrawal

thank you anyway for replying.. So when i do get into seeing a doctor, i must be in withdrawal? I am so confused on this issue.  I am taking suboxone, but most likely have to take the lortab when it is out of my system because of the pain i do have. The lortabs are a prescription that i have been on for over a year.  I just know that i can’t stop taking them on my own, thats why i tried the suboxone.  I researched how to take it and it works wonders for me.
My Answer:
The primary issue with precipitated withdrawal isn’t so much being in withdrawal, but instead has to do with your level of tolerance.  Tolerance goes up with every dose of an agonist, and plummets when a person is in withdrawal.  In predicting precipitated withdrawal one looks at whether a person’s tolerance is higher or lower than it would be taking 30 mg of methadone per day.  A person taking 100 mg of methadone per day who didn’t start withdrawal will have severe withdrawal during Suboxone induction;  A person taking 10 mg of methadone per day who didn’t start withdrawal may actually get a mild ‘high’ during methadone induction.  Lortab includes hydrocodone, the active ingredient in Vicodin.  Hydrocodone is metabolized to a more potent drug—hydromorphone or Dilaudid—to varying degrees in different people (I am about to post something about that), so it is hard to predict the tolerance level in a person on hydrocodone.  The tolerance depends on how their genetics make them metabolize the drug.  For that reason one cannot simply say that 50 mg of vicodin per day won’t result in precipitated withdrawal.  These metabolic relationships occur with other opiates as well and explain why some people say they have never had precipitated withdrawal, and other people do have it, despite taking the same doses of the same opiate.


It is impossible to guarantee that precipitated withdrawal won’t occur, but one can make it exceedingly unlikely by reducing their use of opiates a bit as the induction approaches and then getting good and miserable before starting the induction by discontinuing use for 24 hours or so.  People on super-high doses of a drug like methadone (which tends to stay around in the body for awhile) have the highest risk for precipitated withdrawal, but can make it unlikely by stopping use for 3-4 days, as tolerance drops the fastest in a person who completely stops using.  For what it’s worth, I had precipitated withdrawal myself back in my using days on at least 3 occasions;  twice, in desperation, I took oral naltrexone (an opiate blocker) thinking it would help me stop using;  a third time I injected IV narcan by accident.  The naltrexone incidents were the worst, as that drug lasts for 24 hours or so.  It was pretty horrible, but I did live through it, and the experiences certainly gave me a stronger desire to stay clean!
SD
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