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Buprenorphine the active ingredient in Suboxone
For use for long-term maintenance or as an aid to detox
Buprenorphine is an opiate medication that is widely used as an aid in stabilizing patients with opiate dependency. It can be used for detoxification, and in pain management. It is also being used as a maintenance agent, an alternative to methadone maintenance.
The drug is a schedule three opiate agonist. It used to be a schedule five medication which indicates its low abuse potential. However, when it received the indication for use in addiction, it was rescheduled for closer regulatory observation.
It has a unique profile of actions in the brain. Most importantly, it is a drug that stimulates the mu opiate receptors; but it stimulates the receptor weakly. This means that molecule for molecule; it is weaker than heroin, Vicodin etc. We refer to this property of less than maximal stimulation as a partial agonism. Since it is only a partial agonist, you get a minimal euphoric effect, so patients have less of a compulsion to misuse it. Tolerance is also less likely to develop than with full agonists. Lastly, there is a ceiling effect. After 16-20 mgs of medication/day there is no additional effects felt whether one take one extra pill or ten extra pills. For these reasons, tolerance is less with buprenorphine than with other opioids.
Buprenorphine has the one of the highest affinities for the mu receptors of any opiate medication. It will displace any abused drug or pain medication from the opioid receptor. That is why it is also said to be an opioid blocker even though it has partial stimulation effects. However, make no mistake- this is an opioid drug that results in physical dependence and withdrawal
Unfortunately, when a person has a high tolerance from using other drugs (10 bags of heroin (less if there has been fentanyl used,) >30 pills a day), withdrawal can be precipitated. That is because you are replacing a stronger drug with a weaker one. This precipitated withdrawal is relatively mild in most cases and resolves within 12-24 hours in most cases, although it occasionally last longer. Patients using lower amounts usually do not have problems. Occasionally, patients using higher amounts not have withdrawal. Whether one will have withdrawal cannot be predicted; it seems to be related to an individual’s biology.
In addition to its effect at the mu receptor, it acts as a blocker at the kappa opioid receptor, another receptor that moderates pain. Kappa receptor actions are similar to mu receptor in the periphery in that they both block pain, However, in the brain, kappa receptors stimulation cause depression and so have the opposite effect of the mu receptor which causes euphoria
Therefore, the kappa blockade caused by buprenorphine makes the situation more complex. It may reduce the overall pain relief (though it is still a good analgesic) but it will improve the sense of well being as kappa blockade relieves depression.
Buprenorphine is a long acting drug and comes out of the body slowly. This means that most people, who take the drug regularly, will not feel the drug wearing off and possibly not feel the drug when taken. If stopped, the withdrawal is less intense but significantly longer It often lasts last 5-10 days after the last day of use (but up to 3 weeks). The longer withdrawal period, combined with lower tolerance, results in a easier process and allows some to wean off.
Although, the partial opioid agonist effect is able to prevent withdrawal as well as treat chronic pain , it is not enough to cause intoxication or euphoria. Most patients will feel clean and sober on the medication. They can focus on what they need to do.. Many are able to work on the medication.
Buprenorphine makes it easier to detox but it is not a wonder drug. Adjunctive meds will be often be needed. There will still be emotional abstinence symptoms that can last a month or more. Depression can be an issue. Psychiatric medications do help. Counseling is extremely important.
Buprenorphine is widely used for maintenance as an alternative to methadone. Many stay on this drug for years and decades. Physicians, in the community, who have completed special training, can prescribe it. A list of doctors who have such training can be found at the Samsha physician locator website. However, there is wide variation in their experience and understanding in treating addiction. Each doctor will have his own rules about how often a patient is seen and whether they need to be in counseling. For most patients who require long-term maintenance, this represents an excellent treatment option
Still, I do have concerns. The highly tolerant addicts will not have their cravings controlled with this regimen. I find that about 50% really do well with long term stability and abstinence from other drugs. Others will use a variety of other controlled drugs. Many use buprenorphine intermittently and continue to use heroin or their opioid of choice.
One of the most common situations I encounter is with people who want maintenance for a period of several months and then undergo detox. They say they want to detox slowly, The rationale is that they need time to get control of a chaotic lifestyle. They also need time for some of the drug associations they have developed (i.e. if its Friday night and my friends are partying, than I get cravings on Friday night) to weaken. These are valid arguments.
However, stabilization at a dose for more than a week or two is in effect maintenance. If your goal is to completely detoxify, I feel shorter episodes of use are more appropriate- even just a couple of days. I have found that the prolonged use of the medication leads to greater degrees of abstinence symptoms compared shorter use. This is especially true for emotional abstinence symptoms of fatigue, depression and cravings.
Early studies demonstrated that three days of buprenorphine are as effective as longer treatments. I have seen very few people who have been on the medication 4 months or more successfully complete a detox.
Buprenorphine is also useful for treating pain. It is particularly useful in persons with a history of substance misuse who need pain medications temporarily after an injury or operation. However, addiction and loss of control can and does occur. It may prove to be to weak for treatment of severe pain especially since it antagonizes the kappa receptor.
How long should we use Suboxone For?
A controversy in the field of addiction
I always tell my opiate-abusing patients that the most important decision they need to make is whether they want to detoxify off opiates or whether they want to stay on maintenance. Maintenance involves stabilization on buprenorphine for an extended or permanent period of time. A third choice that they often present to me is to stay on the drug for a few months (or perhaps a different time period) and then detox. The drug has been advised for use in all three situations and I will give my feelings about each strategy.
I want to point out that I am in the minority of physicians. Most doctors who prescribe Suboxone believe in long term use. I discuss the reasoning in a bit. I think it is important to point out that this article will contain much more of my opinions and observations and will be relative bereft of evidenced based recommendations. The main reason for this is that there are very few studies that look at various treatment protocols and their effectiveness in helping people achieve abstinence. The studies that have been done show that patients maintained on Suboxone stay in treatment longer than those who do not use it. Relapse is lower in the treated population.
There is no question that a subset of patients need to be on lifetime maintenance. There seems to be a deficiency in their ability to maintain emotional tranquility. They have chronic irritability, depression and lack of motivation without opiates. They have unmanageable drug cravings. It is unclear where the exact neurological disease exists. It might be in their opiate neurons; it might be from an imbalance in another area. However, I have no doubt that it is a biological mismatch somewhere. Replacement of opiates seems to restore optimal emotional health and many patients go on to full productive lives.
I will maintain these patients on Suboxone for now and for ever
However, I believe that most patients should be given a trial of abstinence prior to being recommended for maintenance. I do not want to commit them to a lifetime of dependency on a drug, and a dependency on a doctor to prescribe that drug.
Many doctors will take issue with me on this. Indefinite maintenance has become the standard of treatment for many. The company stresses this and many doctors assume most patients cannot achieve abstinence.
Here are my reasons for disagreement;
1-It is better no to be on a med---recently a long term patient relocated to another state. He cannot find a Suboxone doctor. With this medication- life is more complicated,
2-All opioids potentially result in neuroinflammation and cause other metabolic imbalances
3-It is easier to try for abstinence with Vivitrol first. If that fails- Suboxone could always be used. It is harder to switch to abstinence with Vivitrol after months or years on Suboxone.
4 Studies randomize patient into treatment arms without regard for motivation. My practice is not like that.
5-Most studies that show better outcome did not compare with Vivitrol
6- In the studies that used Vivitrol- outcomes were poorer; however most of the difference was due to persons being unable to start Vivitrol. Once started, those on Vivitrol did at least as well.
and last but most important: I believe that the biological abnormalities that make up the disease of addiction resolve in a good many patients. I know many who are in long term recovery. There is a lower prevalence of addiction in older adults (maybe the addicts have died early but maybe there is a change in the constituents of our motivational drive).. We will never know without attempting abstinence.
So, I will respect anyone's wishes to remain on maintenance but I would tend to want them to wean. What is the best time course for using suboxone when part of a weaning protocol?
I am aware of only two studies that address an optimal time course for detoxification . One, from the early 1990's showed a 3 day detox was as successful as a 30 day. A more recent study showed a ten day detox was as successful as one that took 40 days. In neither case, did the groups follow up with vivitrol as Vivitrol was not an option at the time
When I did my first detoxes, I took a few weeks with some success. Later on, I used the drug for 2-4 days with an increase in the number of patients who became opiate free.
More recently a study was published showing a single day n of suboxone vs 7 days. They wanted to know which was more successful in getting onto Vivitrol. The 1 day protocol was 50% more successful
Nowadays, many doctors now do Suboxone; many patients have come to my office with the expectation that longer time is needed for treatment. If I try to shorten their treatment, they get upset and either relapse or find another doctor. Therefore, I am back to doing detoxes that last a few weeks; however, I have never obtained the same results that I did when I used a shorter protocol.
Many patients do not want long-term maintenance but do not want to detox either. They have decided they should be on buprenorphine for some period of time like 2 months or 6 months or a year and than detox. The reasoning behind this makes a lot of sense. “If I stay on the drug for a while,” they reason, “ I get to stabilize my life, learn to do things without drugs. Once things are better, I will be able to get off the drug” Many doctors also recommend this course.
The only problem is that, in my experience, this strategy does not work. The patient stays well for a while than relapses when their buprenorphine dose drops below some critical level.
In fact, I have seen patients who had undergone a relatively short-term detox with me (less than a week) who stayed clean for several months or longer. They subsequently relapsed and went to another physician. This physician maintained them for months. They were unable to get opioid free.
I find if I treat a person for more than a month, the chances that they will achieve abstinence goes down significantly. Most patients stay on Suboxone or return to their drug of choice. It seems that the Suboxone causes a physical dependency that is different from that of other opioids. I have spoken with other addiction physicians and they too have noticed it is harder to come off of the drug after 4-8 weeks
My default approach to any patient is to try to wean them within a week
My greatest concern is that the relatively easy access to buprenorphine is going to create an entire class of chronically opioid dependent people, a great many of whom might have been opiate-free if they had just tried to tolerate a little more.
I do not always recommend abstinence first line.
For young adults who have a career of drug use spanning many years I recommend longer term treatment. Their histories usually include multiple treatments and,or no time clean. There are usually co-existing psychiatric problems or a poor home life. It would be impossible to expect them to stay clean. Nevertheless, I am always torn because I know they will have a harder time stopping with this strategy. Recently, I was asked to put a 16 year-old kid on maintenance that had such a story (use since age 13 and failed treatments). Yet, I wondered how angry that person might be when at 25 he realizes he is on a medication for life. Is that good care?
Another type of person who I would consider long-term use is a person with very significant psychiatric problems since withdrawal can be expected to exacerbate this. Nevertheless, when they are more stable, I would try to wean them off.
If some one is in a exceptionally turbulent period in their life, I recommend stabilization for a short time until things have stabilized. Often, however, I found these patients go from turbulence to turbulence.
Despite my recommendations for quick detox, I will treat anyone who wants a longer treatment. If they do not believe they can accomplish abstinence, they will find some reason to relapse. I do not want to force them back to their drug of choice. Hopefully, at some later date, they will detox even if it is more difficult.
Naltrexone
Could it be a cure for addiction
There is a medication called naltrexone that that I feel is extremely important to optimize chances for long-term abstinence. There is no question in my mind that this is the most underused intervention in the field of addiction medicine.
So what does it do? The medication had traditionally been considered only an opioid blocker. It was designed to prevent someone addicted to heroin or pain medication from getting high. The medication would presumably sit in mu opioid receptor without stimulating it. However, it does not let heroin and/or pain medication from interacting with the receptor. This creates a chemical wall between the bloodstream and the brain. Therefore, the addict would not feel anything even if they used their drugs. The clinical result would be that their drug use would go down.
The reality is that naltrexone does so much more than that. In addition to having a blocking effect, the medication seems to have other effects that reduce craving for opioids. This reduction in cravings is the main reason I use it. The mechanisms for accomplishing the reduction is not 100% agreed upon but I believe I have several insights into what they might be.
At the simplest level, the knowledge that the person can't get high may reduce craving. Why use if you can't get high? Maybe this is the only reason it works but I believe there is much more to it.
Naltrexone clearly affects the time course of the post-acute withdrawal syndrome. Post-acute withdrawal syndrome consists of long term irritability, cravings, depression and insomnia. It likely represents low-grade withdrawal and it is probably contributed to by persistent physiologic imbalances that make the brain less sensitive to its own endorphins. This can take from several months to up to a year to resolve. The use of naltrexone accelerates the resolution of these imbalances and people feel better within a week or two.
A large part of this syndrome is due to over activity of the endorphin receptors in the prefrontal cortex or executive part of the brain. It has been shown that small amounts of opioids added here induce addictive behavior.
Naltrexone has classically been considered just a blocker so it has been difficult to understand what it's direct effects on the brain might be. However, recent research over the past few years show the drug works as an INVERSE AGONIST. In order to understand this means, one must first understand that the opioid receptors have a baseline activity even when not stimulated. It is as if there is an idling speed (which is significantly increased during early withdrawal) and will be active even when not filled with either a drug or a natural endorphin neurotransmitter. The naltrexone reduces this activity.
By reducing the activity of the opioid receptors, the prefrontal cortex activity is normalized and cravings are reduced.
Some patients voice a concern that naltrexone would reduce pleasure by blocking natural endorphins; however, clinical experience shows this does not happen. Its' action as an inverse agonist explains how naltrexone can work without having to block the endorphins. While it is possible that these are partially blocked, millions of years of evolution have resulted in a high degree of attraction between the natural endorphins and the receptor; They are not easily blocked- even by naltrexone. Therefore, people do not have to fear the loss of pleasure from losing their own endorphins.
Another effect of Naltrexone is to block kappa receptors in the brain. This will relieve anxiety and irritability. Kappa receptors are a sub-class of opiate receptors. Unlike mu receptors, which when stimulated result in euphoria and pain relief, kappa receptor stimulation will cause psychological distress. In animal studies, when kappa receptors are blocked, there is evidence of an improved psychological state. Naltrexone blocks kappa receptors and will therefore improve mood and reduce cravings. In fact, this may indicate a need to continue naltrexone for several months or longer to keep cravings under control.
There is also evidence that naltrexone's effect on blocking opioid receptors in the hypothalamus will reduce appetite. Perhaps, the anti-craving effect of naltrexone is also related to a generalized anti-appetite effect.
Whatever the mechanisms are, patients on naltrexone clearly crave opiates less and feel better. The effects on some patients have been striking and have mimicked the reduction of cravings seen with high doses of Suboxone. However, with naltrexone, there is no physical dependence and the drug can be stopped at any time. The worst problem I see with stopping the drug before 3-4 months of therapy is a reemergence of cravings- there is no physical withdrawal. I have not see cravings emerge after 6 months of use.
I believe that every one should go on the medication for at least several months. They should use it even longer if they have problems with impulse control or if they are surrounded by triggers.
It is also beneficial for alcoholics. Their cravings are reduced and they will reduce or stop alcohol when on it
Naltrexone is currently available as a pill and is used at doses that range between 50 and 100 mgs. Although it has been usually prescribed as a once a day pill, I find it works much better at twice daily dosing.
September of 2010 saw the injectable form of naltrexone, VIVITROL made by Alkermes, receive an indication for use in opioid dependence. This has been had an astounding benefit for those using it. It is expensive- $800-900/month for self pay. Most insurance companies cover it, charging a typical brand name copay which Alkermes will forgo (if you have a coupon). It is safer, easier, and more effective than the pills, but the pills are cheaper ($30-100/month)
There are also non-FDA approved implants which are used but data on their effectiveness is limited.
Chart showing reduction of craving in persons on vivitrol vs those receiving placebo