Why Buprenorphine Is No Panacea for Opioid Addiction - An Insider View

That's right - I am an insider in the current opioid epidemic.  I only treat people with addictions.  I am licensed to prescribe buprenorphine and have been for 10 years, but in my current position my role is to do independent psychiatric assessments and treat associated psychiatric comorbidity.  Opioid detox is done by addictionologists and the maintenance decision is made by a multidisciplinary committee.  In that capacity I see a wide variety of people who end up addicted to opioids and eligible for opioid maintenance treatment.  I see them in various stages of detoxification/withdrawal and maintenance.  I know what works and what does not work.  Forget what you read about from all of the politicians and administrators - buprenorphine containing products (Suboxone, Subutex, etc) are not a panacea for opioid addiction.  It takes more than a pill to stop an addiction to opioids and more importantly assist in long term recovery.  Forget what you hear about how cravings to use a substance not predicting future use.  I can predict who will be able to remain abstinent from a drug with a high degree of certainty.  Anybody who suggests that is not possible does not know what they are talking about.

What follows is a discussion of some of the factors that limit the utility of buprenorphine based products in the treatment of opioid addiction and the reasons for these limitations.  Before getting into it it I want to clarify that I do support the use of buprenorphine for the treatment of opioid addiction.  People on medication assisted treatment with buprenorphine are about twice as likely to remain off opioids as people without this treatment.  They are more likely to remain in treatment and are less likely to develop Hepatitis C seroconversion.  But there are a lot of factors that are not discussed along the way when politicians talk about widespread use of buprenorphine as the best way to address the current opioid epidemic.  I had thought about including a comprehensive table on results to look at the limitations but decided against it - due to complexity.  If you would like to see what that table looks like - let me know and I will finish it.  For now here are a few of the issues as I see it.

1.  Indefinite maintenance:  Nobody wants to be on indefinite maintenance medication - even people with known chronic medical conditions like hypertension and asthma much less opioid addiction.  The first consideration is that the person with an opioid addiction needs to view it as a chronic medical problem and most addicts do not.  That is especially true for addicts in their 20s who may have started using as early as their teenage years.  Their general attitude is that they will quit some day, but not before they have acquired enough time getting high.  That is nothing particularly unique in terms of the rationalizations that accompany addictions, but at this point in time mapped onto this demographic it may be a unique problem.  It certainly is not conducive to realizing the need to take a maintenance medication every day.  It is common in clinical practice to see a number of patients who stay on buprenorphine for a few months at a time and "go back to using heroin for a while."  The attitude about prescribing buprenorphine seems to be just to keep prescribing it and at some point a stable maintenance situation will result.  I don't think there is any evidence that will happen.  Since opioid addiction is generally a chronic condition going on and off maintenance would seem to be more likely than indefinite maintenance.  There is confusion among some prescribing physicians whether or not repeated relapses is a relative contraindication to future opioid buprenorphine use or it it means referral to a methadone maintenance clinic.  The real life problem is the patient who cannot tolerate withdrawal symptoms, may have a history of buprenorphine diversion, and has no easy access to a methadone program.    

2. Buprenorphine has definite street value:  Every opioid user knows this to be true.  Buprenorphine can generally be sold and the proceeds will result in being able to purchase 3 - 4 times the equivalent amount of heroin.  The other option is just to resume heroin and use the buprenorphine to cover heroin withdrawal when the drug is in short supply or there are not any reliable street sources.  As previously indicated this sort of diversion is a contraindication if the patient is using it as a consistent way to cover withdrawal from other opioids or to acquire other opioids. 

3. There are a small but significant number of users who can abuse the drug:

The original buprenorphine/naloxone combination preparation was designed to prevent intravenous use of the crushed buprenorphine tablets.  Since then, there has been some evidence that the naloxone component also reduces the euphorigenic component from buprenorphine and makes increased self administration less likely (1).  Patients maintained on low dose buprenorphine alone report positive subjective ratings with both additional intravenous and intranasal buprenorphine indicating potential abuse liability (2).  The combination buprenorphine/naloxone occurred after a number of overdoses in Europe and it confers decreased intravenous abuse liability, but it does not eliminate it (3).  In an earlier high dose study of intravenous and sublingual buprenorphine doses up to 16 mg in experienced opioid users produced consistently positive but variable mood effects.   In morphine maintained heroin users intravenous buprenorphine was the only opioid not administered at levels greater than placebo compared with intravenous fentanyl, oxycodone, or heroin (4).  That is an expected effect due to the partial antagonist effect of buprenorphine.  The authors comment that in research setting buprenorphine inconsistently precipitates withdrawal in opioid dependent subject in research settings.  For example moderate to severe withdrawal occurs in subjects taking 60 mg/day of methadone but no to mild withdrawal (from 2 and 8 mg buprenorphine doses) in subjects taking 25-30 mg/day of methadone.  Other studies  looking at rapid dose induction in heroin dependent men resulted positive ratings and experiencing the buprenorphine as an opioid agonist rather than an antagonist.  This same variability is noted clinical, largely by patient history and there seem to be a small number of patients who can escalate the dose beyond the theoretical ceiling due to opioid antagonism.  There is limited information on escalating the oral dose of buprenorphine or buprenorphine/naloxone.  In one study (5), 19 subject were maintained on 4 mg/day of buprenorphine alone and then were given 2 mg increments at 2 hour intervals for a total of three doses of buprenorphine alone.  In this study the authors thought that abuse liability based on subjective ratings was low.   All of this variability can be observed at the clinical level and it is very important that the prescribing clinicians know the individual and their response patterns very well.  

4. The existential condition of 20 year olds:    

One of the unique aspects of the current opioid epidemic is the number of young people that it affects.  Unused medicine cabinet opioids have been identified by the CDC as an important gateway drug to heroin use.  Using prescription opioids increased the likelihood of heroin use 55 times.  This same cohort is caught in a culture that is swinging toward increased permissiveness of substance use with broadened legalization of cannabis and excessive stimulant prescriptions for attention deficit~hyperactivity disorder and a subculture of performance enhancement in colleges and universities.  One of the logical extensions of these cultural currents is to see drugs as a solution to a problem and opioids are viewed as being no different.  A unique aspect of alcohol and drug taking in American culture has been that the early twenties is a time to do it and get it out of your system.  A large number of young opioid addicts who continue to use and routinely go off and on buprenorphine maintenance will say that they felt like they were too young to stop using.  They wanted to keep on going for a while before they stopped.  Most 20 year olds have a sense of invulnerability and that also plays a role in the use of dangerous drugs and alcohol.              

5.  Inadequate dosing

One of the main lessons that an addiction psychiatrist learns early on is that opioid use and withdrawal is a great mimic of psychiatric conditions specifically insomnia, anxiety and depression.  Practically everyone in withdrawal experiences these syndromes at one point or another.  There is a natural tendency during a psychiatric interview to describe practically all of the recent history as being dominated by the withdrawal symptoms.  Conversely, when the correct dose of buprenorphine is prescribed all of the insomnia, depression, and anxiety clears and it clears completely.  There are no associated psychiatric problems and the patients does not need any additional pharmacological therapies.  This cannot be emphasized enough because opioid users will naturally end up on benzodiazepines and z-drugs for sleep and anxiety and both are contraindicated with opioids.  Even antidepressants are a potential problem due to case reports of buprenorphine based products and antidepressants causing serotonin syndrome.  That is an admittedly rare syndrome, but potentially very serious if it occurs.        

The second issue is dose adequacy in terms of cravings about opioids.  By definition cravings are an intense urge to use opioids.  At the height of opioid withdrawal they occur with the withdrawal symptoms.  As buprenorphine maintenance is established they may occur at times during the day when there are breakthrough withdrawal symptoms.  Eventually even when the acute withdrawal symptoms are treated cravings can persist.  The ideal response is that cravings to use are eliminated as well as any thoughts about using or acquiring opioids.  This is possible during treatment but results vary from person to person especially as the physician attempts to establish the proper maintenance dose of buprenorphine.  In my experience cravings and intense thoughts about using are poor prognostic factors due to heightened relapse potential.    

The subpopulation of people addicted to opioids from chronic pain treatment can generally benefit from seeing physicians with expertise in pain management with buprenorphine preparations.  It may require split dosing and other adjustments.

6.  The lack of appropriate prescribing 

This can occur in several ways.  There can be a lack of physicians who are licensed to prescribe buprenorphine.  There can also be physicians available to prescribe it who are not able to maintain patients on the drug.  Finally there are physicians who are overcharging for the services they provide and that leads to patient dissatisfaction and discontinuing the buprenorphine strictly on that basis.

All of these problems can be addressed.  They can be addressed by providing good medical care.  They can also be addressed by addressing the 30 year old problem of rationing services for addiction and mental health services.  Any person going in to be seen by a physician for opioid use problems needs to feel like they are understood.  They have to be able to communicate with that physician about their addiction.  They have to know that their physician understands addiction and is not just there to provide prescriptions.

Treating opioid addiction is more than prescribing a medication.  It requires a relationship  with a competent physician.  That competent physician needs to be technically competent to prescribe the drug and discuss all of the above issues with every patient with an opioid addiction and every one of those patients who will take buprenorphine.

That is the same as the general plan for just about any complex medical problem.      

George Dawson, MD, DFAPA

References:

1: Jones JD, Sullivan MA, Vosburg SK, Manubay JM, Mogali S, Metz V, Comer SD. Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in buprenorphine-maintained heroin users. Addict Biol. 2015 Jul;20(4):784-98. doi: 10.1111/adb.12163. PubMed PMID: 25060839.

2:  Jones JD, Madera G, Comer SD. The reinforcing and subjective effects ofintravenous and intranasal buprenorphine in heroin users. Pharmacol Biochem Behav. 2014 Jul;122:299-306. doi: 10.1016/j.pbb.2014.04.012. PubMed PMID: 24793093; PubMed Central PMCID: PMC4094364.

3: Comer SD, Sullivan MA, Vosburg SK, Manubay J, Amass L, Cooper ZD, Saccone P,Kleber HD. Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers. Addiction. 2010 Apr;105(4):709-18. doi: 10.1111/j.1360-0443.2009.02843.x. Erratum in: Addiction. 2010 Jul;105(7):1332. PubMed PMID: 20403021.

4: Comer SD, Sullivan MA, Whittington RA, Vosburg SK, Kowalczyk WJ. Abuse liability of prescription opioids compared to heroin in morphine-maintained heroin abusers. Neuropsychopharmacology. 2008 Apr;33(5):1179-91. PubMed PMID: 17581533.

5: Singhal A, Tripathi BM, Pal HR, Jena R, Jain R. Subjective effects ofadditional doses of buprenorphine in patients on buprenorphine maintenance. Addict Behav. 2007 Feb;32(2):320-31. PubMed PMID: 16814937.

6: Umbricht A, Huestis MA, Cone EJ, Preston KL. Effects of high-dose intravenous buprenorphine in experienced opioid abusers. J Clin Psychopharmacol. 2004 Oct;24(5):479-87. PubMed PMID: 15349002.

The Reality Of Burprenorphine Therapy

It is increasingly popular for politicians and healthcare businesses to discuss their ideas about how to end the opioid epidemic that they started.  One of the common themes is widespread availability of both buprenorphine maintenance therapy and naloxone opioid antagonist therapy for acute overdoses.  I am certainly not opposed to either and in fact work in an addiction treatment environment where these are two of several medication assisted therapies used to treat addictive disorders.  I am skeptical of the idea that broad prescribing of these therapies in either primary care clinics or some treatment settings will ever occur.  Naloxone will be more readily available because there is a movement to create easy access without a prescription.  That will never happen with buprenorphine.  Last week - an article in JAMA backs up my skepticism (1).

The JAMA article looks at 3234 buprenorphine prescribers in the 7 states with the most buprenorphine prescribers.  In their introduction the authors talk about the policy initiatives to increase the maximum patients per prescriber from 30 to 100 patients after a year.  The average monthly patient census per month varied from 7 - 22 patients and a median monthly patient census of 13 patients.  The duration of treatment episode was 53 days.  This illustrates that the monthly census was well below the allowed limits and the duration of treatment was well below the recommended maintenance guideline of 12 months.  They cite evidence that novice prescribers wanted more access to substance use counselors or other prescribers with more experience as potential limiting factors.

The authors of this article do not offer other explanations for the low rate of buprenorphine prescribing.  I have a few.  I really do not like stigma arguments.  To me stigma seems like an excuse for not being able to overcome societal biases toward a particular problem.  I don't see how you can train to be a physician and not have most of these biases wrung out of you.  With addictions and mental illnesses there may be a stronger bias based on personal experience.  Some physicians may have come from a family where the the father was an alcoholic or a heroin addict living homeless on the street and everybody was used to that idea.  Some physicians may have come from families where the father was still drinking and dying of cirrhosis and the familiy opinion was that he "has a right to drink himself to death" rather than get treatment that he did not want in order to stop drinking.  Other physicians may have come from families where father and his father both had severe alcoholism.  Grandfather drank himself to death by the time he was 50.  Father got treatment for his alcohol problem and was in stable recovery for years.  All of these personal experiences and the reactions to them will affect how a physician approaches alcoholism and addiction.

Those biases are all part the the inevitable decision-making process that leads physicians down specific career paths.  I have lost count of the number of times that another specialist told me that they really liked psychiatry and were considering the residency except for certain features of the field.  A couple of examples include needing to try to predict suicide and aggression and live with the consequences or dealing with a certain diagnostic group like patients with severe personality disorders.  People are less specific about addictions, probably because as medical students and interns we all see the severe effects.  Most of the acute care hospitals where physicians train have 30-50% of their admissions based on the acute effects of alcohol or drug use.  That includes many admissions for acute hepatitis, hepatic encephalopathy from cirrhosis, acute alcohol poisoning, acute overdoses on addictive drugs, and various psychiatric morbidities like delirium and psychosis from the acute effects of addictive drugs.  It is less obvious but addictive drugs and alcohol are also overrepresented as reasons for admission to surgical trauma units and burn units.  Most interns and residents see these effects first hand and develop both short term and long term perspectives on these problems.

This seems like another case of managers and politicians not appreciating the intense interpersonal aspects of medicine.  Physicians are all not foot soldiers just waiting for the next assignment from a policy maker.  Physicians have probably carefully selected the type of practice they want to be in and there are more than the technical aspects of the speciality that were considered.  It takes a unique skill set to treat people with addictions.  Treating and maintaining an opioid addict in treatment long enough with buprenorphine maintenance for them to realize any benefit is a very unique skill.  Being affiliated with other buprenorphine prescribers is also a necessity to provide cross coverage for patients.  Speciality care centers for addiction seem like an idea to me that does not get a lot of consideration.  Trying to run a buprenorphine maintenance program in a practice environment that is rationed to the degree it currently is does not seem feasible to me.  Adding buprenorphine maintenance as just another task for a busy primary care physician practicing primary care medicine is not likely to work.  It should be obvious that these physicians have  more than enough to do right now.

There is a lot more to it than increasing the maximum numbers of opioid addicted patients on buprenorphine maintenance and trying to treat as many people as possible.  The data from this paper illustrates that.  There is also the issue of the preventing the pool of opioid users from increasing while trying to treat those who are currently dependent on these drugs.  That seems like the best long term option to me.

Addressing this complicated problem takes more than a licensed buprenorphine prescribing physician sitting behind a desk who is willing to prescribe it.  It takes better infrastructure including managers who are enlightened enough to get that physician the kind of resources they need to do the work.  I never hear politicians or policymakers talking about that.


George Dawson, MD, DFAPA


Reference:

1: Stein BD, Sorbero M, Dick AW, Pacula RL, Burns RM, Gordon AJ. Physician Capacity to Treat Opioid Use Disorder With Buprenorphine-Assisted Treatment. JAMA. 2016 Sep 20;316(11):1211-1212. doi: 10.1001/jama.2016.10542. PubMed PMID: 27654608.