by Steven Scanlan, M.D.

Palm Beach Outpatient Detox

Boca Raton, FL

www.pbod.org

(561) 901-0040

This discussion is addressed to providers as well as their patients who have become dependent on Suboxone (buprenorphine plus naloxone) or Subutex (buprenorphine alone) and who are seeking knowledge and hopefully wisdom about its use and abuse. Knowledge allows us to know, but wisdom gives us the power to act. The reader needs to be extremely inquisitive. Prescribers may initially be put on the defensive, but I ask that you be patient and take the time to hear me out. We all have the same goal, that of helping patients. I will outline here my method of detoxing patients off Suboxone in an outpatient setting.

Patients, the first question you need to ask your current Suboxone doctor is whether he has ever taken anyone completely off Suboxone or Subutex. If he says that he just tapers a patient down after they have been on it long-term and they are fine, then he is disingenuous or at least ill-informed. If he tells you that he is going to put you on 16mg sublingually for six months while your brain stabilizes and heals and then taper you off it he is purposely or unknowingly misleading you. How can your brain heal if you are still taking an extremely potent opioid that is classified as a pain medication and approved by the FDA as a medication to treat severe pain? On the other hand, if he tells you about the symptoms I discuss below and has previously helped people get off Suboxone when they are ready, then stick with this doctor and do what he says. When I detox patients off Suboxone I follow them for approximately 5 or 6 months and see them once a week during that time. I make sure to follow them for at least two months after we stop the Subutex. I do not use Suboxone, only Subutex, and I will explain why not.

You may wonder what my background and credentials are that qualify me to be discussing this topic. I am board-certified in Psychiatry and have two board certifications in Addiction Medicine. I have spent more than 10,000 hours performing inpatient and outpatient detoxes and have performed many types of detox with patients who have a wide variety of co-morbid medical and psychiatric conditions in addition to their drug and/or alcohol dependency. I have successfully detoxed a large number of patients off Suboxone. Finally and quite significantly, I am an addict myself and realized I had a problem during my residency training in anesthesiology. I feel that this gives me a special perspective on these topics. I am able to empathize with patients and understand the unpleasantness of detoxification because I have undergone the process myself.

The problem I am finding in America is that doctors know how to get patients on Suboxone, but no one knows how to get them off it. At least in Europe the manufacturers have come out with a 0.3mg tablet that makes the process of weaning someone off Suboxone much easier than trying to cut an 8mg tablet or a 2mg tablet if it is available. The company that created Suboxone (Reckitt Benckiser), instead of making a 0.3mg tablet available in this country, when Suboxone became generic, they came out with a Suboxone film instead. Naturally, they recommend that the film not be cut into smaller pieces as it cannot be guaranteed that the medication will be uniformly distributed throughout the film. Do you wonder why we do not have a 0.3mg tablet in America? I believe it has a lot to do with money. As for the medical literature, I feel that no one in the medical community should be allowed to prescribe a drug unless they know not only how to get a patient stabilized on that medication but also how to take them off it after acute, sub-acute, and chronic use when the conditions are appropriate to discontinue it.

What kinds of doctors prescribe Suboxone? Before you go any further, I suggest that you look up the federal regulations for a patient to receive methadone maintenance at the following website: http://methadone.org/namadocuments/es10new_federal_regulations.html). Those requirements are more stringent than for prescribing Suboxone. ANY physician who takes an eight-hour course ONLINE can obtain authorization to prescribe Suboxone. Unfortunately, a large percentage of doctors who have received this online training know very little about addiction. It is far out of the scope of their practice. As a psychiatrist, you won’t see me prescribing Accutane for acne as it is out of the scope of my practice. Nevertheless, in America the large majority of physicians prescribing Suboxone have no training in addiction medicine. Here in Florida we have a lot of non-psychiatrists prescribing Suboxone. Furthermore, we have a lot of psychiatrists without addiction medicine training prescribing Suboxone. Most of the doctors prescribing Suboxone are not providing any addiction support other than a five-minute appointment and a prescription. It is a rather lucrative business for them. A physician can make good money prescribing it with little effort being expended and can feel good about it as the individual in the throes of addiction can have his life stabilized and made more manageable. Yet this stabilization with Suboxone without addiction treatment being given is just a giant Band-Aid, and if you go to a doctor who just keeps you on 16-24mg a day with no plan of decreasing your dose, then you will inevitably have major problems down the road. Before Suboxone, doctors referred opiate dependent patients to addiction medicine centers where detox and treatment were provided or to methadone clinics that have very strict guidelines and provide access to addiction counseling. That crucial component that is being skipped is that nowadays the majority of people being prescribed Suboxone are not being given addiction treatment. Simply stated, one drug is being traded for another and no psychic change is being encouraged in the addict. Do you want it sort of fixed right now or do you want it fixed right?

I am also discouraged by the fact that there exists little or no information or any studies from the medical community about the long-term effects of being on Suboxone or how to get a patient safely off it. There is a lot of information about how amazing Suboxone is and how many lives it saves, how safe it is, and how Suboxone cannot be abused. I remain more than a little skeptical about some of these claims. While performing detoxes over the last five years I have learned that most of the information in the medical literature is incomplete. Worst of all, the information found on the internet is extremely polarized; either Suboxone is depicted as a miracle drug or it is condemned as the devil incarnate and a scourge. It is disheartening to me to look at the blogs about Suboxone and see that a lot of people are suffering and attempting to get off Suboxone without professional help. As their Suboxone providers cannot give them answers as to how to get off the Suboxone, people are turning to blogs to find guidance. People are self-experimenting with hordes of narcotic and non-narcotic drugs to try to take themselves off Suboxone and then sharing their experiences. Furthermore, a blog may have nine posts telling how hard and terrifying it is to come off chronic Suboxone use, and then a post will be written about how easy it is to do so. As I know how difficult it is to come off, I wonder if there is some type of corporate social media manipulation going on when a blog post states that a chronic user can easily come off Suboxone. Are favorable comments being planted by those who may profit financially from them? I can sympathize with the fear people who are trying to come off Suboxone must experience when they cannot find any definitive answers. I will try in this discussion to provide these answers, because there IS a safe way to come off Suboxone.

I feel that fear is caused by a lack of knowledge, so I will share what I know. Again, I believe that wisdom consists of acquiring knowledge and then taking the proper action. As I explain later, in certain circumstances it may well be better for some patients just to stay on Suboxone maintenance. The type of detox I propose is only right for those who are willing to take all the necessary steps to change their lives. This detox is only for someone who is capable of rigorous honesty. Trying to come off Suboxone on one’s own is a tragically flawed idea.

I do agree that Suboxone is the most powerful detox tool ever created. It helped get me detoxed off my own addiction. At the time I begged my doctor to let me stay on it, but he told me that I could live without narcotics if I was willing to work a program of recovery. He also told me if I took it too long I would have a very hard time coming off Suboxone. Furthermore, he explained to me that if I wanted to practice medicine again I had to be off all narcotics, reminding me that Suboxone is a very potent narcotic. He told me that doctors who agree to dedicate themselves to a twelve-step program, go to a weekly support group for doctors with a psychologist, and agree to urine monitoring have a 91% success rate at the five-year mark in Florida. He explained to me that the disease of addiction does not discriminate and that the procedure for doctors is the same as for everyone else. I asked him again why doctors could not just do opiate replacement with Suboxone. Again he stressed how hard it is to come off after taking it chronically and that we do not know the effects of taking it for a prolonged period. At that time, in 2003, the longest it had been studied with someone taking it was six weeks. Unfortunately, not much has changed in the meantime, since there are no studies looking at the risks of taking Suboxone long-term. Nor are there studies on how to detox an individual off Suboxone who has taken it chronically. I will outline below my experience with detoxing patients off traditional opiates (e.g. oxycodone) with Subutex. I will then discuss how I detox patients who have been taking Suboxone chronically.

I have detoxed thousands of addicts off traditional opiates with Subutex, but I will never use it for longer than six weeks and always try to use it for a maximum of a month. Why do I say this? Almost 95% of what is written will say that this is the miracle drug for addicts and should be used for replacement therapy. I do recognize the fact that violent crime has decreased greatly since this has become an opiate-maintenance drug. I do acknowledge that HIV and hepatitis C infection has decreased because of Suboxone being used as a maintenance drug. I know that people in the throes of addiction who were robbing, stealing, and losing their employment, friends, and family are often able to rebuild their lives through Suboxone maintenance.

In view of all these benefits, why do I even agree to attempt to detox someone off Suboxone? The answer is complicated, but I came up with my reasons after talking to hundreds of patients who were on maintenance therapy. They started telling me about the side effects they were having from long-term use. Patients said they felt dead to the world and without feelings. They started exhibiting elevated cortisol levels, thyroid problems, low testosterone, hair loss, decreased libido, and immune function problems. As a doctor, I was alarmed by these physical symptoms, but I knew that Suboxone has never been proven as the cause. What really moved me was the explanation of the emotional state – the complete lack of feelings and anhedonia (the inability to experience pleasure from activities usually found enjoyable). Patients also reported their poor response to stress when they did not take enough Suboxone. In addition, loved ones reported to me that they felt like they were living with a stranger, although a stranger whose life was more manageable than before.

While I was trying to figure out exactly how to plan detox off Suboxone I met a man (not in my office) who had been arrested while on Suboxone (but not because of it, of course). He had been on 32mg of Suboxone sublingually a day for three years when he went to jail for nine months. He said he was not detoxed in jail and was only given clonidine (a blood pressure medication that helps with flu-like symptoms of opiate withdrawal) for a week while incarcerated. He told me he was “very sick” for 63 days and then he realized he was going to make it. He started going to 12-step meetings in jail, and when he got out after nine months he continued to do so. He has been sober for five years and has not relapsed. I decided that if a person on 32mg a day could make it, then many others could too. However, could it be done in an outpatient setting? Since no inpatient detox facilities were offering real Suboxone detox and were just tapering patients off Suboxone in a week and then discharging them to home or a rehab facility where they were certain to experience intense withdrawal symptoms, I thought I would attempt to institute a complete and thorough detox off Suboxone.

When I made the decision three years ago that I would begin offering Suboxone detoxes at my office, the first step was deciding that I had to be very selective in deciding who I would take. Since I was not yet entirely sure how to properly perform the detox and since there were no studies or research on the subject, I wanted only highly motivated individuals. I would take only patients who had already cut down to 4mg sublingually a day. This eliminated a lot of potential patients, as most Suboxone providers keep their patients on 16-24mg a day. This amount taken chronically I consider overkill, as the half-life of Suboxone is somewhere between 20 and 80 hours, such that the serum load of Suboxone is increasing daily in these patients. In my opinion, any patient who has been on Suboxone for a year should be on 4mg or less, then 2mg or less at two years, and finally 1mg or less after three years. You would be amazed at the amount of buprenorphine and norbuprenorphine (the primary active metabolite of buprenorphine) that is in the urine I send to the labs for quantification for someone who has been on Suboxone chronically versus acutely.

I also accepted only patients who were willing to give up all drugs and alcohol and to start attending twelve-step meetings and to getting a sponsor. “But I never had a problem with alcohol or marijuana, and I don’t like meetings,” some would say. I would politely tell them to go find another doctor. I also required 20 minutes of cardiovascular exercise a day to target cortisol (a stress hormone). I also required a urine specimen at every visit and sent it to a lab for qualitative and quantitative analysis. The urine tests served to keep patients accountable and to give me data about the pharmacokinetics of the Suboxone and other detox drugs I would use. Also, when the prospective patient got into my office I asked them if they were willing to go to any length to get sober. I expected an immediate affirmative reply. Finally, I discussed how detoxing off Suboxone will be a long process but I told them that I knew it could be done. I also informed them that if they ever decided that they could not continue to come to me and told me that they needed to get back on Suboxone rather than going back to using illicit drugs, I would not prevent them from taking that step. This would be preferable to the potential loss of job and family, incarceration, or death.

I realized then that I had to learn everything about buprenorphine pharmacology with a focus on elimination time of buprenorphine and more importantly receptor pharmacology at the mu and kappa receptors. Remember, Suboxone is buprenorphine plus naloxone, while Subutex is buprenorphine alone. My initial focus was on the long half-life of buprenorphine, but I realized this was only partially responsible for the prolonged, unique withdrawal period when a patient stopped taking Suboxone.

Over the next three years while working daily with patients to get them off Suboxone many other questions arose, and I will review them and attempt to answer them below. I will describe the symptoms of Suboxone withdrawal and explain how I have noted that it has two distinct phases: mu (part I) and kappa (part II). I will explain my concerns about buprenorphine’s long-term blockade of the kappa and mu receptors. I will briefly discuss the delta and OR-1opiate receptors. I will also discuss the phenomenon of how in short-term use norbuprenorphine (the metabolite of buprenorphine) is eliminated faster than buprenorphine, whereas in long-term use it builds up and takes longer to be eliminated than buprenorphine when detoxing off Suboxone. Norbuprenorphine acts completely the opposite at the kappa and delta opiate receptors than buprenorphine does. I will also talk about cortisol function and its role in this detoxification. I will also talk about some of the medications I use, but will not report the specific dosage. This type of detox should only be done under the care of a qualified physician. I feel that fear is caused by a lack of knowledge so I will share what I have learned. Again, I believe that wisdom consists of acquiring knowledge and then taking the proper action.

Pharmacodynamics

I must first say that the next portion of this paper is very technical and “dry” and is more oriented to the health-care practioner or the very interested reader and one may wish to skip down to the section labeled “the jump”. Also, one must understand that some of the concepts I am explaining are theoretical and have not been proven in a laboratory. Unfortunately there is so much we do not understand on how the brain works and how specific psychiatric medications work. For example, the model for how anti-depressants work, especially the selective serotonin reuptake inhibitors (SSRIs), is still only theoretical and has not been proven. Psychopharmacology has always been a passion of mine, but you must understand that the knowledge it has given me just gives me a better idea of how a medication may work for someone. The more educated I become the less I see psychiatry as an art and more as a process of trial and error.

When opioids bind to a receptor in the brain they have significant effects on the dopamine and norepinephrine neurotransmitter levels in the body. Opioids facilitate pain relief and also activate pleasure centers in the brain that signal reward (increased dopamine). The addictive rewarding properties of opioids are thought to be mediated through activation of the ventral tegmental area dopamine neurons that protect the cerebral cortex and most importantly, the limbic system.

Tolerance and dependence will develop in anyone who takes opiates for longer than a few weeks. When a patient truly has a pain disorder they will develop dependence on opiates and over time will need more and more medication to manage the pain. When a person takes their medication as prescribed and does not abuse it they would be defined as opiate dependent. I use the word dependent in the case of someone taking opiates every day for 2-3 weeks, in which case their body will become dependent on them. If opiates are stopped suddenly, then there will be withdrawal symptoms. When a person takes opiates to abuse them and to “get high” or takes more than they are prescribed for pain control, then they would be classified as an opiate abuser or an opiate addict.

Approximately 90% of the patients treated in my office are addicts, and the other 10% are opiate-dependent. The opiate-dependent patients are most likely to find pain relief by means of one or more of the following during detox: rest, physical therapy, non-opiate pain management, non-invasive procedures, or surgery. Opiate-dependent patients have a comparatively easy time getting off opiates at my office, except those patients who are on chronic Suboxone maintenance for pain management. Opiate addicts, on the other hand, encounter more difficulty because they must now take responsibility for their disease of addiction, and this involves a person first admitting that they do have a problem and are willing to make permanent changes in their lives after the detox is complete. The common analogy that is often proposed is that Suboxone is to an addict as insulin is to a diabetic. This analogy is a great sales pitch for Suboxone, but it is not valid. We need to separate facts from myths. If a type 1 diabetic does not take insulin he will die. If an addict stops taking Suboxone after making a number of changes to his emotional and spiritual outlook and attitude and has a recovery program in place, then he has a good chance of being extremely healthy, happy, and productive. If an addict stops taking Suboxone and does not follow a recovery program, then there are only four likely outcomes: resuming opiate addiction, life behind bars, a ruined life, or death.

The long-term use of opioids results in changes in the number and sensitivity of opioid receptors. Understanding receptor pharmacology is important in determining how a patient is to be safely and comfortably detoxed off opiates. Patients often want to be educated about the pharmacology of buprenorphine and the receptors they bind to. As we know, buprenorphine is found in pure form in Subutex and is combined with naloxone in Suboxone. The naloxone serves no purpose other than to be the most incredible marketing tool for the makers of Suboxone. Consumers are told that if an individual takes the Suboxone anyway but sublingually, such as by snorting it or shooting it up intravenously they will cause themselves to go into precipitated withdrawal. The ratio of buprenorphine to naloxone is 4:1 in the Suboxone pill or film. Unfortunately, buprenorphine’s affinity for the opiate receptor is too great for this small amount of naloxone to have any effect on the opiate receptor. If someone does have precipitated withdrawal from taking Suboxone the cause would be from the buprenorphine rather than the naloxone. There must be enough open opiate receptors for the buprenorphine to bind to, and thus enough time must have passed for the opiate being replaced to have been excreted and fall off the opiate receptor.

During detox from traditional opiates (e.g. oxycodone) with the use of Subutex, a good physical indication that it is safe to begin taking Subutex (buprenorphine) is moderate to severe withdrawal from the opiate that the patient has been using. At that point an indispensable asset is a doctor who has a good knowledge of pharmacokinetics and can state exactly how many hours one has to wait to start buprenorphine. Some individuals are ready in 6-8 hours based on the type of opiate they use, the duration, the amount, and the half-life of the opiate. Other patients have to wait up to 36-48 hours. When I detox someone off a high dose of methadone I often have to switch to a short-acting opiate for 4-10 days and then can start the buprenorphine 10-12 hours after discontinuing the short-acting opiate. Because buprenorphine is a partial agonist at the mu receptor (which will be discussed below) and has a higher affinity than any street opiate, other than fentanyl, it will kick off any other opiate off the receptor. Buprenorphine will win the pharmacological game of “king of the hill.” Because buprenorphine is a partial mu agonist and not a full agonist, if it displaces enough of a full agonist opiate off the opiate receptors it will cause precipitated (sudden) withdrawal. It is an intense shock to the body to go from full agonism at the opiate receptor to suddenly only partial agonism. Imagine running through a very bright, enormous room lit by overhead halogens and then suddenly the room being lit only by two candles. You are going to crash into a chair, a desk, or even a wall!

The central nervous system (brain and spinal cord) is comprised of four main opioid receptors (mu, kappa, delta, and nociceptin). Opioid receptors are proteins that are found mainly in the brain, spinal cord, and the gastrointestinal tract. The mu receptors are involved in the regulation and mediation of analgesia (pain-relief), physical dependence, and euphoria. It has long been shown that kappa receptors can play a role in spinal analgesia, diuresis (increased urine excretion), sedation/activation, and anxiety/depression. It has also been speculated that an agonist at the kappa opiate receptor is protective of addiction. The delta receptor is involved with pain relief and physical dependence. The nociceptin receptor has been found to deal with anxiety, depression, appetite, and regulation of tolerance at the mu receptor. We know little in medicine about the delta and nociceptin receptors, while the mu and kappa receptors have been better studied. Buprenorphine is a partial mu and OR-1 agonist and a full antagonist at the kappa and delta receptor. The metabolite of buprenorphine, norbuprenorphine, is a partial mu and kappa opioid agonist and a delta opioid antagonist. Buprenorphine is a novel agent in that it is one of the only opioids that interact with all four opiate receptors in a unique partial agonist and full antagonist combination at each receptor. Buprenorphine is the only common opiate prescribed that antagonizes both the kappa and delta receptor. Of course, naltrexone (not to be confused with naloxone), the famous opiate blocker, is a competitive antagonist at the mu and kappa opioid receptors, and to a lesser extent at delta-opioid receptors, but I have never met a patient who took it longer than six months, and naltrexone’s elimination half-life is short.

Buprenorphine has been found to have a much less potent effect at the delta and OR-1 receptors than the mu and kappa receptors. In a study of rhesus monkeys, the kappa agonist buprenorphine was approximately 30-fold less potent as a delta antagonist than as a kappa antagonist. Buprenorphine’s affinity for the OR-1 receptor has been found to be two orders of magnitude lower than the affinity for the mu and kappa opiate receptors. Thus, in this article I will only be discussing how I find that chronic buprenorphine use affects the mu and kappa opiate receptors and how I go about detoxing a patient based on this knowledge. I will explain my opinion that the detox from buprenorphine is bi-phasic, as certain withdrawal symptoms are mu-related and others are kappa-related.

To start the detox off Suboxone, the first step is to get a patient switched from Suboxone to Subutex. I have found that this transition is relatively easy since the conversion in milligrams is identical. Approximately 90% of patients report that they notice no change in how they feel switching from Suboxone to Subutex. Approximately 10% of patients say that they immediately feel better after switching over. I believe that these patients could be hyper-absorbers of the naloxone in Suboxone and are getting an amount of naloxone in their serum that is causing mild negative side effects. Unfortunately, with the half-life of naloxone in Suboxone only being one hour this would be a difficult theory to prove.

Once the plan for switching the patient from Suboxone to Subutex is in place, I take a thorough medical history (just as I do with a detox off traditional opiates). If a patient has a history of serious medical problems such as stroke, heart attack, arrhythmias, or organ failure it is not safe to perform this type of detox in an outpatient setting or possibly even attempt to get off the Suboxone at all. Also, if a patient has severe chronic pain that will not remit with non-narcotic treatment then it is probably best to stay on the minimum effective amount of Suboxone maintenance rather than try to come off it. Buprenorphine has recently been approved by the FDA to treat chronic pain. Fortunately, in my time in south Florida I have met a group of doctors who specialize in non-narcotic pain management. I have referred patients with chronic pain who want to be detoxed off Suboxone to this group of doctors (www.ommdoc.com). These doctors have been able to manage the pain to a point where I could then detox these patients whose detox I would not have attempted otherwise. The first appointment at their office lasts three hours, and the doctors there take the time to call me and discuss strategy and the feasibility of a patient’s quality of life becoming narcotic-free. They also fax me an eight-page report that I can use to help understand if my patient’s pain is neuropathic, nociceptive, visceral, and somatic or a combination of two or more types.

I also take a comprehensive psychiatric history, as I do with all patients. Almost every patient I see for possible Suboxone detox has at some time in their life been diagnosed with a psychiatric illness and prescribed psychotropic medication. Fortunately, just because a patient has been told they have a psychiatric illness does not mean they truly have one. I have found for every six patients I see who have been told they have bipolar disorder, only one of them truly meets the DSM-V (Diagnostic and Statistical Manual of Mental Disorders, Volume Five) criteria. Many patients have been diagnosed while they were using alcohol or narcotics, so what appears to be an organic psychiatric illness could actually be substance-induced. I question patients about periods of their lives when they were free of drugs or alcohol for a prolonged length of time and ask if they had psychiatric symptoms then. I need to know if a patient had psychiatric symptoms before they started using drugs and alcohol. With some patients being diagnosed with ADHD (attention deficit hyperactivity disorder) and started on amphetamines by age seven or starting to experiment with drugs and alcohol by early adolescence the picture is often clouded. I also ask them if, from the time when they started using drugs and alcohol, they ever had a prolonged period when they were completely abstinent. I also ask if during this time of abstinence they suffered from psychiatric symptoms. Almost every patient I have helped achieve sobriety struggles with some anxiety or depression in the first six months, but these conditions then will dissipate if the patient does not have organic psychiatric illness. If a patient does have a history of organic psychiatric illness and is not on medication, I will discuss treatment strategies. If the patient is already symptomatic I will most likely offer to start medication. If a patient does not have symptoms but I feel they have truly met criteria for a psychiatric diagnosis in the past, we discuss possibly starting medication prophylactically or waiting to see how they feel as the detox progresses. I perform the Suboxone detox slowly, so there is definitely time to wait and see. On the other hand, the non-narcotic medication I prefer to treat anxiety or depression usually takes a month to start working and helping.

Finally, a number of patients who come to me are already on medication and state they feel stable on their medication and would like to continue on it. That is a good strategy unless the patient is on a psychiatric medication that increases norepinephrine. A number of opiate withdrawal symptoms are caused by the body’s sympathetic nervous system releasing norepinephrine, especially the flu-like symptoms. This is why the medication clonidine, which attenuates the sympathetic nervous system, is such an effective medication to treat withdrawal symptoms. I have found that if a patient is on Wellbutrin or Effexor at a dose of 150mg or above, Cymbalta, Strattera, or ADHD medications, then the Suboxone detox will be more difficult since these medications can worsen opiate withdrawal symptoms. I try to switch patients to medications other than the above to treat their psychiatric illness before starting to taper them off Suboxone. Furthermore, I also encourage my patients who use caffeine to start cutting down because caffeine also worsens opiate withdrawal symptoms. I always know when a patient is through the worst of their opiate detox when they ask for coffee!

Another dilemma to take into account in choosing the treatment strategy is the fact that buprenorphine can actually lessen depression. The partial mu agonism at the opiate receptor helps with depressive symptoms, and the kappa antagonism gives the patient with depression more energy and also lessens vegetative symptoms of depression. I have found that people with organic depression are usually keeping themselves on high doses of Suboxone (16mg or higher) and when they try to decrease that dose they experience rebound depressive symptoms, especially when they get down to doses of 8mg or less. Patients with anxiety present much differently. The partial mu agonism at the opiate receptor helps with anxiety, but too much buprenorphine at the kappa receptor causes too much stimulation and worsens the anxiety. Most patients with a history of anxiety have already weaned themselves down to 6mg of Suboxone or less, since any higher dose makes them hyper-stimulated and anxious in chronic use. Unfortunately, many Suboxone providers do not realize that continued high dose Suboxone maintenance in a patient with anxiety will worsen their anxiety. Some of these patients are then put on other addictive medications such as benzodiazepines (e.g. Xanax/Klonopin) to treat the anxiety, thus complicating the picture by getting the patient dependent on two different classes of narcotics. I have mostly been successful detoxing patients off Suboxone who have no psychiatric illness or patients with a history of anxiety. I have had a few patients with an anxiety history who have been dependent on benzodiazepines and Suboxone. In these cases I will first detox them off the benzodiazepine and then off the Suboxone.

Once I have gotten the patient stabilized on Subutex, have obtained their biological, psychological, sociological, and spiritual makeup, and have identified all psycho-social stressors, we are ready to start the detox off buprenorphine. I prefer to bring the patient down off the Subutex very slowly. When a patient is on 6mg or less we go down 0.5mg a week. When we get to 2mg a day we decrease by 0.25mg a week. Patients come into see me weekly. At every appointment I obtain a urine drug screen. The urine drug screen is both qualitative and quantitative for all narcotics and a metabolite of alcohol (ethyl-glucunoride) that can be detected for up to a week after drinking. A qualitative urine result for a drug just tells me if the urine shows a presence of the drug. The quantitative urine result tells me the amount of the drug in nanograms per milliliter of urine. The drug screens are important because they help keep my patients accountable and also tell me if they have deviated from the treatment plan. Also, with knowledge of the quantitative amounts of Subutex in their urine compared to the concentration of their urine (specific gravity), I can make sure the patient is not taking more Subutex than they are supposed to.

With patients who take buprenorphine only for a short time, the buprenorphine level is higher than the norbuprenorphine level. For patients who have been taking buprenorphine for a long time, however, the norbuprenorphine level is significantly higher than the buprenorphine level. As long as buprenorphine is present in the serum the norbuprenorphine is unable to have an effect and is essentially “cancelled out”. When a long-term user of buprenorphine finally stops taking the drug it will take approximately 7-10 days for it to be completely eliminated from the body and a few days longer for the norbuprenorphine to be completely eliminated. As we perform a buprenorphine detox, the key is to decrease the serum level of buprenorphine very slowly so the patient does not feel post-acute withdrawal symptoms (PAWS) that strongly. PAWS are caused by the body not getting an opiate saturation at the receptor that is high enough for the body to avoid going into a state of panic. The body starts releasing excess norepinephrine (adrenaline) from the brainstem, cortisol releasing factor (CRH) from the hypothalamus, and cortisol from the adrenal system. The norepinephrine increase causes increased anxiety, hot/cold sweats, restless legs, heart palpitations, and irritability. The increase in CRH and cortisol leads to colds, infections, muscle pains, constant fatigue, poor appetite, and loss of libido. It is impossible to perform a buprenorphine detox without the patient feeling PAWS. The watershed amount of buprenorphine at which most patients start experiencing discomfort (PAWS) is an amount less than 2mg sublingually a day. I warn patients again that there is no such thing as a painless detox. The “tox” in detox does not stand for “feeling awesome.” With the use of clonidine to attenuate the body’s release of norepinephrine and daily exercise to help decrease the body’s release of cortisol (stress response) the patient can function adequately. Furthermore, as morning cortisol levels tend to be the highest of the day, I recommend that patients exercise in the first two hours after awakening. I also recommend supplements that have been shown to help decrease cortisol levels. Some possible supplements are the following: ashwagandha, Vitamin C, Vitamin B6, phosphatidylserine, theanine, and Omega 3’s. Cortisol levels can also be improved with meditation, twelve-step meetings, and spiritual endeavors. Furthermore, there has been a lot of research recently discussing how the medication gabapentin (Neurontin) has helped with the negative symptoms the patient experiences from the increase in CRH and cortisol.

As the buprenorphine detox progresses the speed at which the buprenorphine can be reduced greatly declines. Once the 2mg mark is reached a small fraction of buprenorphine is removed weekly. I always recommend that the patient take their dose of buprenorphine in two divided doses, usually one in the morning before they exercise and the other one about 2:00 p.m. If the patient has any PAWS between doses or after the second dose they can use a small amount of clonidine to help battle the PAWS or take some in the evening to help with symptoms at night. The patient has to understand that when they start coming down from less than 2mg of buprenorphine they are going to have only about ten productive hours a day and will have to rest the other fourteen hours of the day. When the patient gets down to less than 1mg the productive hours slide down to about six or eight hours a day. Often a patient will feel PAWS, but if they take a small amount of clonidine and rest for 20-30 minutes they will feel well enough to carry on with their daily duties. Often when we get to 2mg or less of buprenorphine, the patient is going to experience insomnia. A larger dose of clonidine at bedtime can be very helpful with the insomnia and can help target restless leg syndrome. I also often prescribe one or more non-narcotic medications to target insomnia if needed. These medications interact with the brain’s histamine or melatonin receptors in order to promote sleep.

There is not a set amount of buprenorphine that a patient has to be on when we decide to discontinue the buprenorphine entirely. Every patient is different, and I have found that I can use the buprenorphine and norbuprenorphine quantification in relation to urine specific gravity as a good gauge for discontinuation. Simply stated, some patients metabolize buprenorphine and norbuprenorphine faster than others so are ready to “jump” (stop buprenorphine) from a higher dose. Obviously I will try to get a patient to the lowest amount of buprenorphine possible before discontinuing. Often when a patient has little productivity during the day while still on buprenorphine and I am not able to maximize productivity with other medication we often plan to “jump” as soon as possible. Everyone has a different “tipping point,” and with experience I have become more adept at determining when to have the patient “jump”. I have found that patients who exercise almost daily, maintain a good diet, find an hour to rest during the afternoon, and attend twelve-step meetings they can get down to extremely low doses of buprenorphine. Also, it is important that patients maximize their efficiency with performing daily life tasks during the hours when they feel well and are not experiencing PAWS.

The Jump (Discontinuing Buprenorphine)

It is imperative for the healthcare provider to understand that there is not a set quantity of buprenorphine that a patient should be on when they will be able to finally stop buprenorphine. I have had a number of patients discontinue buprenorphine at amounts up to 2mg with success. The typical range that my patients “jump off” from is usually between 0.25mg and 1mg sublingually a day. Each individual is unique; consequently I analyze a number of variables to help determine when I feel it is possible to discontinue buprenorphine altogether:

Weight of patient Age of patient Body fat content of patient/volume of distribution Urine concentration of buprenorphine and especially norbuprenorphine in ratio to specific gravity of urine sample. This can also give an idea of how well the body is metabolizing the buprenorphine and the long half-life norbuprenorphine. Psychiatric history (more difficult to jump from low amount of buprenorphine with history of depression, especially melancholic/vegetative type). History of buprenorphine use (quantity/duration)

Obviously the lowest possible amount of daily buprenorphine intake that a patient can get down to before the jump is always the best. The biggest problem usually is that the patients who come to me in the outpatient setting have many outside work and family responsibilities. During the Subutex taper at every decrease in daily amount the patient usually struggles some during hours 48-96 after the decrease and then stabilizes again. When a patient gets down to an amount at which they are not able to stabilize again, then it may be time to jump if I cannot determine a course of action other than increasing the Subutex again.

I let everyone know that they will need to arrange to have between 10 and 14 days off, free of all responsibilities, when the jump is finally instituted. I have noticed that the withdrawal symptoms coming off the buprenorphine are often split into two phases (mu and kappa). The first phase (mu) usually lasts approximately ten days. These symptoms are synonymous with typical withdrawal symptoms that occur when the mu-opiate receptor is not being activated. The patient will need around-the-clock use of clonidine for the first ten days and will most likely be taking the clonidine every four hours. The clonidine will help ease the flu-like symptoms seen and will help some with anxiety. The patient will most likely require a larger dose of clonidine at bedtime to help with insomnia and to target restless legs syndrome (RLS). The clonidine use will make a person feel tired, but it will help greatly with easing discomfort.

I also start the use of a medication called chlorodiazepoxide when the Subutex is stopped. It is a very long-acting benzodiazepine of limited potency. In all my years of practicing addiction medicine I have never heard or seen someone abusing or addicted to chlorodiazepoxide. Chlorodiazepoxide does not seem to have the reward to the brain that other benzodiazepines such as Xanax, Klonopin, Ativan, or Valium seem to provide. Chlorodiazepoxide is effective at targeting the anxiety that accompanies the withdrawal off the Subutex and along with clonidine at bedtime is extremely helpful in combating insomnia. I have found that patients do not abuse the chlorodiazepoxide since it is not rewarding and if they take too much they feel very sluggish and tired. The first ten days off the Subutex the patient is taking a small amount of chlorodiazepoxide twice during the day and a large dose an hour before bedtime along with the clonidine. After ten days off the Subutex the patient stops taking chlorodiazepoxide during the day but still takes a large dose at night. The evening dose of chlorodiazepoxide is decreased slowly over the next thirty days. Chlorodiazepoxide has an extremely long half-life, so when it is time to start decreasing the dose, the patient continues to feel stable. As the chlorodiazepoxide is lessened the patient will need a non-narcotic medication to be added to also help with sleep. The intent is to target the histamine receptor with something such as trazodone, or diphenhydramine and/or to target the melatonin receptor with something like porcine melatonin or Rozerem. Sometimes the sleep disturbance is so bad that I may have to prescribe Seroquel to take off-label to target insomnia.

Approximately ten days after jumping from the optimally low dose of buprenorphine, the first phase of withdrawal symptoms seem to pass. Those withdrawal symptoms are mainly the muscle pain, headache, poor appetite, moderate weakness, lower back pain, and temperature dysregulation. During this time the patient is not working and is resting most of the day. Some of my patients try to get out of the house once a day to try to get to a twelve-step meeting. Patients at this time are on clonidine around the clock, a muscle relaxant, and chlorodiazepoxide. Sleeping will not be efficient, as the patient’s sleep architecture is severely disrupted. Sleep will come in periods of two to three hours at best, and the patient will be cold when they fall asleep and hot and covered in perspiration when they wake up. The patient will have to get out of bed to stretch their legs and probably take a shower to help get back to sleep. It is important to take time to go through a full-body stretch multiple times a day during the first ten days off Subutex.

Usually somewhere during days 8 to10 off Subutex the patient starts to feel better, as the major mu-opiate receptor withdrawal symptoms have lessened. The patient is still going to continue to have problems with hot-cold sensations. There is about a two or three day “honeymoon” period during which the patient feels pretty good. Unfortunately, this does not last, because the second phase of the detox then begins. The second phase of the detox is, I believe, related to buprenorphine’s effect on the kappa-opiate receptor. Remember, buprenorphine acts as an antagonist on the kappa-opiate receptor. This antagonistic effect on the kappa receptor lessens depression, increases energy, and can decrease anxiety at the lower doses. Thus, when buprenorphine is stopped it is realistic to expect that a patient will have more depression, greater fatigue, along with heightened anxiety and fear. I have noticed this second phase of the detox (kappa) usually lasts from days 10 to 28 approximately. The patient will at times be in a dark place in their mind and will be easily overwhelmed psychologically. This is why it is so vital to have a good support system and be involved in a twelve-step program.

It is at this point that I am glad I have taken plenty of time to determine if a patient has a true history of pathological anxiety or depression. If they do have a history of primary anxiety or depression, I try to have them on the right anti-depressant or anti-anxiety agent before this phase of the detox. Another big problem is the intense fatigue that patients feel coming off the Subutex during the second phase of the detox. Patients who had been exercising daily before the jump are glad they had built their stamina up before they got off the buprenorphine to help them get through this period of increased fatigue. It is also essential at this time to cut down on the amount of clonidine and chlorodiazepoxide because those medications will intensify the fatigue. The non-narcotic muscle relaxant will be stopped at this point as well since it will also contribute to fatigue. The patient will tolerate only small doses of clonidine during the day and a higher dose at bedtime during the second phase of the detox. These amounts will be decreased daily in small increments. The patient will only be on chlorodiazepoxide at night during the second phase, and we will be tapering that down.

I have heard of some clinicians prescribing amphetamines such as Adderall or Ritalin during this second phase of the detox to battle fatigue, but I am not an advocate of this treatment for two reasons. The first reason is that the amphetamines are rewarding, and the addict limbic system will not tolerate their taking the amphetamine as prescribed. Remember that amphetamines are schedule 2 narcotics, whereas buprenorphine is a schedule 3 drug and therefore has a lower dependency potential. Amphetamines are addictive, and I believe they are not appropriate to use even in the short term. The second reason that I would not recommend amphetamines is that as the patient reaches about days 16 to18 off buprenorphine, I have noticed another phenomenon. At this time, the patient is starting to physically feel better and has more energy, but I have noticed a significant emotional state at this point in the detox. The patients tend to present with a hyper-awareness of their surroundings and mild paranoia and delusional thinking at times, and I believe amphetamines could make these feelings become pathological. I notice patients becoming more zealous about conflicts in society, and they often speak about what I could best describe as “crusades of righteousness.” I have never had a patient disturbed enough that I felt they needed treatment with anti-psychotic medication, but I make sure to educate patients about this emotional state. On the other hand, I also start to hear about the positive aspects of the detox as the patient is starting to “feel” and experience significant emotions again. I love hearing the stories from the patients about their rediscovering music and literature and crying easily after meaningful conversations or dramatic movies. Medically speaking, I surmise that the mix of intense feelings that are arising signal the beginning of healing of the limbic system in the brain.

During the second phase of buprenorphine detox, if the medications are “dialed in” correctly the patient will start to thrive. The patient will still have to battle feelings of fatigue, temperature regulation, and anxiety, but with support they will continue to improve physically and psychologically. Sleep will slowly get better. They will begin to experience the full gamut of feelings. There will be periods every day of profound happiness, yet other moments plagued with restlessness, irritability, and discontent. The patient’s ability to deal with stress will be diminished, so it is important that during the first thirty days after discontinuing buprenorphine they have the first two weeks off from work and then make sure not to engage in too much overwhelming activity for the next two weeks after that. After thirty days off buprenorphine the patient is usually doing very well. The fear is gone, and the patient usually has a profound sense of gratitude and an appreciation for life. A plan is by then in place for finishing the taper off any clonidine or chlordiazepoxide. Most of my patients by this time have thoroughly become dedicated to a twelve-step program and are augmenting their recovery with individual therapy and an exercise regimen. By three months the patients who have stayed sober describe how they are finally experiencing a sense of well-being and feel comfortable in their own skin. Of all the patients I have detoxed, the ones who were detoxed off Suboxone have the highest success in maintaining their sobriety at one year. I believe the journey to sobriety for them was so perilous that they are extremely vigilant in their recovery program and seem to maintain a healthy fear of ever consuming alcohol or any drugs again.

In conclusion, my hope is that this discussion will help anyone on Suboxone to become more knowledgeable by my sharing my clinical and personal experiences. It is also my hope that this review will stimulate discussion among prescribers as well. This is not a “how-to” guide, and, I repeat, I absolutely do not recommend that anyone attempt to detox off Suboxone or Subutex without the help of medical professionals. Some people are doing quite well on Suboxone maintenance and are experiencing no overwhelming side effects. I am not against any individual’s choice of maintenance when appropriate, and I know it has helped thousands of patients improve their quality of life. The majority of health care professionals do endorse maintenance treatment. There is a very well-written blog (suboxonetalkzone.com) by Jeffrey Junig, M.D, who is very supportive of maintenance treatment. A popular blog that discusses some of the negative experiences people have had with Suboxone and provides support for those trying to decrease or stop Suboxone can be found at the website subsux.com (#Ratch).

Anyone who is questioning Suboxone maintenance should do as much research as possible. If you are having some of the physical, emotional, or spiritual side effects from buprenorphine that I talk about here, then it may be time to look at other options. I wrote an article for Addiction Professional magazine in 2010 that has resulted in more than one thousand emails from readers having questions and asking for help. I hope this present discussion can provide answers to all who took the time to write me.

When I wrote the article in 2010, I was vehemently against Suboxone maintenance. Since then I have modified my opinion to a certain extent, and I now no longer see the argument as so “black and white”. When my mentor, Dr. Jason Jerry, M.D., at the Cleveland Clinic, read my article in 2010 (“Suboxone: Concerns Behind the Miracle” AddictionMedicine (November/December 2010, pp.28-29, which is available on my website), he told me that the biggest problem with the Suboxone debate is the polarization of opinion with there being little gray area in the argument. He stated that some patients where he practices do not have all the recovery resources available to them that I had when I got into recovery. Some people cannot afford to go to treatment or there is only one 12-step meeting a week in their area. Suboxone maintenance may be the only option available to avoid actively using narcotics. I realize Dr. Jerry was right and that I had become a zealot. I now believe that Suboxone maintenance IS the right path for some patients. I nonetheless do continue to feel that it is the responsibility of the providers of medication containing buprenorphine to educate their patients about the pros and the cons of buprenorphine maintenance. Often patients do not find how hard it is to come off buprenorphine until they have been on it for a prolonged period. Simply stated, anyone taking buprenorphine for longer than six weeks is going to have a quite difficult time coming off of it. I encourage all providers and patients involved with buprenorphine to make well-informed decisions. If you have made the decision to attempt to detox off buprenorphine, then you no longer have to be fearful, but you do need to be patient and knowledgeable.

I hope this discussion will help patients to achieve their goals. Feel free to contact me with comments or questions at Palm Beach Outpatient Detox (www.pbod.org). I only work individually with a maximum of six patients at a time who want to be detoxed off a buprenorphine product as the detoxes are very time-consuming and difficult. I only work with patients who live nearby and can come to see me weekly. I do not accept patients who do not live in South Florida. I am excited to recently hear that a new inpatient detox and rehab is opening in southern Florida that will offer a more prolonged detox and treatment for patients who want to be detoxed off Suboxone or Subutex who do not live near my office in Boca Raton, FL. There is also another outpatient detox in Miami called Miami Outpatient Detox (www.outpatientdetoxinc.com) whose physician, Juan Oms, M.D., I personally trained in my methods. He is my closest colleague. I am hopeful that more inpatient and outpatient detoxes will follow suit and offer specialty detoxes for individuals who are interested in being detoxed off of Suboxone or Subutex.