Enhancing The Volkow-Collins Approach To The Opioid Epidemic

Nora Volkow, MD - Director of the National Institute on Drug Abuse and Francis S. Collins, MD, PhD - Director of the National Institutes of Health co-authored a paper on the role of science in the current opioid crisis.  Full text of the article is available free online from the New England Journal of Medicine at the reference given below.  In the article the authors review the scientific interventions at three levels of care in treating opioid addiction and use, treating and preventing overdoses, and the treatment of chronic pain.  The treatment of chronic non-cancer pain (CNCP) with opioids can be realistically viewed as the precipitant of this epidemic.  The brief 4 page review is a good rapid review of the science behind these interventions.  The level of cooperation between NIDA and NIH with private industry may surprise a few people but as the authors point out -  the level of mortality with the current epidemic needs to be approached with urgency at all levels.

At the level of opioid overdose prevention and reversal - more potent and long lasting opioid antagonists are being developed to counter exposure to fentanyl and carfentanil appearing at an increasing rate on the street.  Narcan Nasal Spray is probably the most effective and practical outcome of the industry-NIDA partnership.  A wearable device that can detect signals of an impending overdose and administer a μ-opioid receptor antagonist is mentioned.  At the level of addiction treatment methadone, buprenorphine, and extended-release naltrexone are all mentioned as current treatments for opioid use disorder.  Access to providers is discussed as a limiting factor.  vaccines and novel receptor approaches are discussed as potentially new pharmacological approaches to the problem.  New approaches to chronic pain are discussed in greater detail.  Cooperation between the NIH and industry is emphasized again in terms of getting these approaches to market and clinical use.  In the concluding section - the emphasis on NIH-industry partnerships is a central theme.  The argument makes imminent sense, but after two decades of rancorous debate about the effects of pharmaceutical company pizza on prescribing - this level of access to the highest level of taxpayer funded research is somewhat stunning.

But what else might be immediately useful?  I can concentrate just on buprenorphine and come up with a couple.  Anyone working with this compound and people who are addicted to opioids routinely encounters problems with its use.  It is common to treat people who still have withdrawal symptoms and cravings on the  recommended doses and remain at high risk for relapse even after being treated with what is described as one of the best current therapies.  Taking a look at the recommended dose range from the package insert:

The upper limit of the recommended dose is 24mg/6mg buprenorphine/naloxone per day for SUBOXONE. The reported lack of significant increase in brain mu‐receptor occupancy between doses of 16 mg and 32 mg implies that there should be little difference in clinical effectiveness at doses between 16 mg and 24 mg in most patients. When a patient expresses a need for a higher dose, consider the possible causes (e.g., environmental stressors or psychosocial issues that increase cravings or possible drug interactions). Before increasing the patient’s dose, explore other alternatives. Also consider the possibility that the patient may be exaggerating symptoms to obtain additional medication for diversion. (p 34-35).

And:

The recommended target dose is 16 mg buprenorphine/4 mg naloxone per day. Clinical studies have shown that this is a clinically effective dose. Although lower doses may be effective in some patients, for most patients, a 16 mg dose should alleviate withdrawal symptoms and block or attenuate the effects of other opioid agonists for at least 24 hours. (p. 34)

In clinical practice there is a wide range of effects to buprenorphine doses.  The FDA approved considerations show the subjectivity involved in adjusting the dose.  But that is even an understatement.  There needs to be a much greater investigation of the causes of continued craving and withdrawal symptoms when the patient is taking a recommended dose of buprenorphine.  This may be a genetically determined phenomenon either at the pharmacokinetic or pharmacodynamic level.  That is only partially accounted for by drug interactions.

Investigation of withdrawal symptoms and continued craving is more than just a passing concern.  It potentially determines who will be able to remain on maintenance therapy and stay off of heroin.  It is important because a significant number of these patients are being actively treated for psychiatric disorders with antidepressants, anxiolytics, atypical  antipsychotics and mood stabilizers.  How much of that medication use is due to inadequate treatment with buprenorphine and the common symptoms of insomnia, anxiety, and depression associated with opioid withdrawal.  These are all very complex clinical situations.  Many of these patients have a life long history of stress intolerance and there can be a reluctance on the part of clinicians especially if they have no mental health training to explore and treat those problems.  Once the patient has been indoctrinated into the idea that a maintenance medication is going to help them stay off heroin - it is a difficult transition to now say that all of these other factors are now important and need to be addressed.  That is especially true when some of the existing buprenorphine studies minimize counseling or are publicly presented as "counseling adds nothing to the results obtained with buprenorphine."  Finally, there is a large social media movement of people who want to stop buprenorphine and are warning others about it.  What is behind this widespread dissatisfaction and what needs to be done to resolve it?  The overall impression that all of the issues in this paragraph leaves is that buprenorphine is another heavily hyped medication that does not live up to the claims.  All of these areas could use much clearer input from NIDA through additional scientific investigation.

Additional studies on drug interactions with buprenorphine are critically needed.  I use a standard commercially available drug interaction software package.  Any time I enter a psychiatric medication I get a warning to consider to modify therapy and a list of 230 potential drug-drug pharmacodynamic interactions at the CNS level.  Since there is a high prevalence of patients on maintenance psychiatric medications this represents a deterrent to some physicians, especially if they are not psychiatrists and they are in a state with an unfavorable malpractice environment.

The next issue is determining who is susceptible to opioid overuse and dependence.  In my mind the phenotype is very clear.  The person who takes the first opioid tells me that they either "fall in love with it" or they experienced an intense euphoric and almost hypomanic effect.  They felt transformed by the medication into a person that they had always wanted to be.  Side effects are modestly effective deterrents, but I have been told that side effects and a complete lack of analgesia are acceptable in order to get the intense, euphoric high.  How can these people be identified?  The authors discuss biomarkers for pain and pain relief - but the single-most important biomarker would identify this high risk group of patients for addiction.  There are currently commercial databases out there that poll their members on various traits and symptoms.  Can NIH or NIDA design the polling questions and look for markers in these existing databases?

Even before that marker is identified, is there a simple strategy that could be used in clinical practice? Could a clinician tell a patient to self monitor for the intense euphoria and report back to the physician as soon as possible if it occurs?  Could the patient be told to just dispose of the pills by bringing them in to the pharmacy if euphoria and thoughts of dose escalation occur?

These are some thoughts that come to mind that might be immediately useful.  They would address both the limitations of medication assisted treatment and identifying the at-risk population for primary prevention of opioid use problems.                
    

     
George Dawson, MD, DFAPA

1: Volkow ND, Collins FS. The Role of Science in Addressing the Opioid Crisis. N Engl J Med. 2017 May 31. doi: 10.1056/NEJMsr1706626. [Epub ahead of print] PubMed PMID: 28564549.

Clinical Care - The Hype Versus the Reality

As noted in recent posts, I was a participant in a conference that focused on the clinical care of patients with addictions.  The intended audience was primary care physicians.  One of the advantages of a course like this is that there is a lot of cross talk between the presenters and those attending the conference.  After a three hour segment about the treatment of opioid addiction and chronic pain, I was approached by a physician who updated me on the state of treatment of addictive disorders and psychiatric disorders in primary care.  One of the recommendations by our speakers was to suggest that drug and alcohol counselors in their own clinics might provide very useful approaches to treatment that could not be provided by the primary care physicians.  It is difficult to see how busy primary care physicians could suddenly take an hour or two to do group therapy for patients addicted to opioids or benzodiazepines.  Taking breaks from the productivity based schedule to do indicated psychotherapy for patients with histories of trauma is even less likely.  After all, isn't this the medical home model?

This physician was very aware of those constraints.  He had tried to implement these modalities in his clinic, but they were rejected outright by administrators.  We discussed some of my experiences in managed care settings as a consultant to internists in managed care settings.  I had an internist call me and say that he had a patient who was addicted to opioids and needed detox prior to surgery.  I called my boss about the resources available for that.  He told me that we did not have the time available to do detox from high dose opioids.  That problem has continued to worsen.  This physician was also not having any luck with getting detox for pre-op patients.  The opinion at the conference by speakers was that slow and gradual detoxification from opioids and benzodiazepines was the exception rather than the rule.  It is theoretically possible in highly motivated individuals with a relatively unlimited time frame.  The best approach seems to be fairly rapid detox with adequate protection (in the case of benzodiazepines and alcohol) against seizures.  Attempts at "outpatient detox" range from handing the patient a bottle of benzodiazepines in the emergency department to "social detox" in holding areas that monitor people and send them back to the emergency department if it looks like they are going into worsening withdrawal.  There are no acknowledged standards in the area.  Nobody complains about this inadequate care for addiction most likely due to the stigma of addiction and the general plan of many places to "get rid of" addicts rather than providing them with any kind of treatment that might be useful.

The evidence-based psychosocial treatments discussed at the conference highlight further deficiencies in the system of care.  The National Institute of Drug Abuse and their Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition) was referenced.  Even a cursory look at these guidelines shows that there is probably no managed care system in the country that adheres to these guidelines.  A couple of examples:

"Research indicates that most addicted individuals need at least 3 months in treatment to significantly reduce or stop their drug use and that the best outcomes occur with longer durations of treatment."  (Principle number 5).

There are certainly plans that offer no coverage for addiction at the extreme end.  Many plans that do, follow utilization review protocols that frequently review the treatment being provided with an eye toward providing the least expensive care.  In some cases people with severe problems and no significant withdrawal or medical problems are discharged.  The default position is that the patient must fail, in many cases several times before treatment is funded.  In many cases there is a focus on whether the addiction or the psychiatric disorder is "primary" in order to shuffle the patient from one pool of money to another (addiction <-> psychiatry).  All of this financial gaming leaves the addicted patient out in the cold.  That starts with inadequate to nonexistent detox to treatment that lacks the necessary intensity to be successful.  It can also create a very negative and counterproductive attitude by the system of care to the patient with the problem.

"Sanctions or enticements from family, employment settings, and/or the criminal justice system can significantly increase treatment entry, retention rates, and the ultimate success of drug treatment interventions." (Principle number 11).

When insured patients are incarcerated or committed for problems associated with an addiction there is usually a strong push to get the patient into public systems of care.  That includes state hospitals, public clinics, and public mental health problems.  The strategy is clear - shift the cost of treating addiction and mental health problems to government run systems.  Most states have taken a page out of managed care and responded by decreasing available treatment centers and hospitals.

All of these business manipulations do not bode well for people who need care for even moderately complex problems.  Certainly the detoxification and treatment of an otherwise healthy 25 year old is much different from a 60 year old with cirrhosis and diabetes.  But the system of care is currently not set up to provide necessary care for the least complex patient.  At a policy conference in Hawaii in 2011, I asked the policy wonks who were there to tell us how the "medical home" would revolutionize care for addictions: "What would keep a managed care company from doing a screening exam and leaving it at that."  His response was: "nothing".  It appears that I am able to predict the behavior of managed care systems much better than the policy wonks.

What would help?

The same thing that many professional organizations have failed to do over the past three decades.  Physician organizations like the American Society of Addiction Medicine (ASAM) need to promote adequate treatment guideline, make them publicly available, and embarrass these companies into using them.  ASAM currently has a complex matrix that is supposed to correspond with levels of care.  They are largely ignored by managed care companies.   ASAM should talk about the heavy drinker coming into the emergency department and walking out with a bottle of lorazepam.  It is rather ironic that NIDA does not step up and say what standards should apply, but any regulation needs to consider the Congressional sausage factory and their negative impact on quality care.

The negative impact of business on quality care is most obvious in the areas of psychiatric services and addiction.  Following the status quo and even going as far as endorsing managed care tactics is good for business, but not for people trying to recover from addiction.  From a policy standpoint, this is a much bigger problem than any issue with pharmaceutical companies, conflict of interest, or even perceived problems with psychiatry.  Denying that basic truth may be the result of three decades of ignoring this problem, but complaining about less important issues will not change the skewed health care landscape or get necessary treatment for people with psychiatric and addictive disorders.

George Dawson, MD, DFAPA