A Case for Increased Regulation

It is a generally accepted fact that we (US & Canada) are experiencing an “Opioid Epidemic.” The President of the United States, Donald Trump, recently declared this epidemic a National Health Emergency and signed an Executive Order to provide authority to various government departments regarding a rapid response plan. The Center for Disease Control and Prevention reports that around 1,000 people a day need to be treated in relation to the effects of opioid use and 33,000 people died during the year of the study (CDC, 2015). Worse still is a death rate of 52,000 during the following year as reported by Attorney General Jeff Sessions. The situation continues to deteriorate due to the illegal market using additives such a carfentanil to increase the effect of street Heroin while lowering the cost. This synthetic opioid is so powerful that two crystals similar in size to salt is lethal. Clandestine manufacturers do not have the pharmaceutical expertise to transform the crystalline substance to powder and blend it with the Heroin in consistent measured doses, making it inevitable that the strength varies significantly even within small quantities such as 1 gram. Accidental lethal doses are now becoming common, increasing the already disastrous mortality rate.ODMedical prescribers are also a huge part of this complicated problem. In the 15 years preceding the report of opioid deaths, prescriptions for opioids quadrupled but there was no change in the amount of pain reported, and significantly, the number of deaths involving prescription opioid overdoses also quadrupled (CDC, 2016). The role of pharmaceutical companies is also significant as their sales reps are the primary source of information for a lot of woefully under trained doctors.

The amount of overdose events is so prolific that it is common for fire and police departments to administer a revival drug (opioid antagonist) called naloxone (Narcan) in addition to paramedics. This requires additional training and accountability depending on the route of administration. There is a nasal mist, an intermuscular injection device similar to an epi-pen and intravenous injection.

What we have here is a situation that is out of control and growing worse over time. Doctors, feeling societal pressure, have drastically reduced their prescribing of opioids but unfortunately this has had the effect of legitimate pain management patients to be undertreated and often being forced to turn to the illegal market for relief; compounding the problem.

This is an instance that calls for more government regulation. Doctors should be certified before prescribing opioids and the training must be consistent and meet specific  national and eventually international standards. First responders also need standardized training, not only on administering revival medication but on the nature of addiction and the need to stop seeing addiction as a crime in and of itself. Addicts will commit crimes to pay for their drugs but an education is desperately needed to combat current biases and treat addicts as people in need of assistance instead of prison. Then we have the problem of the criminal element that manufactures, imports and distributes opioids. In addition to narcotic interdiction and more security at our borders, a change in criminal enforcement policy as well as drug classification changes need to be addressed if we are to eliminate the illegal drug trade and the criminality associated with it. This can only be accomplished through government regulation which will, in some cases, result in less criminal sanctions and more evidence based treatment programs as well as substance use education. Indeed, more regulation will lead to less criminal enforcement but it is only through regulation that standards can be set for a transfer of responsibility from law enforcement to health care. Opioids are a particular class of narcotics that have far reaching effects when a human becomes physically dependent. When the drug dose is reduced or stopped, the physical and mental distress of the patient is extreme. The abstinence syndrome or “withdrawal” period can last for weeks or months. The ordeal is so onerous that 30-91% of those opioid dependent persons attempting a detoxification program give up and drop out (Singh and Basu, 2004) only to return to opioid use and the risk of adverse consequences up to and including death by overdose. The trauma this causes families, loved ones and colleagues cannot be measured accurately. A government’s first responsibility is to the safety of its citizens. The Opioid Epidemic is most emphatically a Public Safety issue and it is the responsibility of the government to serve its citizens and put regulations in place.opioid injection

I am suggesting a 7 point strategy:

  • Treatment: Treat the physical dependence and provide psychological counselling to the patients.
  • Education: Initiate an education program that begins at an early age all the way through high school in an effort to prevent this from reoccurring. Prevention is preferable to treatment after the fact.
  • Decriminalization: Initiate Drug Courts to refer drug related cases to treatment programs without the stigma of a criminal record that could adversely affect the citizen for life. [This will meet with public resistance and may take time to develop an ethical coercion campaign to educate them on the benefits]
  • Regulation: Pharmaceutical companies need to be regulated and held accountable for both their production and marketing of opioid medications.
  • Certification: Doctors need to be trained and certified in pain management and treatment requiring recertification to ensure best practices and avoid undertreating legitimate pain patients.
  • Interdiction: Increase interdiction of illegal narcotics domestically while securing international borders.
  • Legislation: Introduce legislation making it legal and safe for Certified Doctors to prescribe pharmaceutical Heroin (diamorphine) to those patients who can forensically be verified as being physically dependent on illegal street Heroin. Diamorphine has been a pharmaceutical product in Britain since the 1920s and many European countries for decades. Switzerland has conducted many large scale studies showing the efficacy of the treatment which eventually convinced Germany to follow suit. This will eliminate the underground criminal market and will ensure that the citizen who is diagnosed with Opioid Use Disorder has a safe and consistent dose of the drug with the agreement that a conversation begin. In order to get a week’s supply of Heroin prescribed, the patient would need to give up one hour of his time a week to chat with a drug counsellor. There is no end date but the objective would be to have the patient detoxify if possible but other managed options should also be available such as replacing the heroin injections with a long acting oral opioid like Methadone or Buprenorphine. It has to be the patient’s decision to seek treatment since the patient’s participation is absolutely required for success. Should the patient be unable to bear the distress of a lengthy withdrawal, they should be allowed to demand an exit from the program and return to their current prescription opioid. They may try as often as they are willing, with no penalty if unsuccessful. Relapse is part of the journey to recovery. There is a third option for intervening in this Epidemic/National Health Emergency which brings us back to strategy point one; treatment.

The Case for Ultra-Rapid Opioid Detoxification as an Intervention Strategy for the Global Community

Earlier I described the horrific suffering involved with withdrawal from a strong opioid and the understandably high dropout rate from this natural detoxification process. Although the withdrawal is not fatal, the distress can be so bad that patients at times may find death preferable to another day of this intense mental and physical trauma. The symptoms of withdrawal include acute diarrhea, vomiting, intense sweating, goosebumps, extreme depression, flu-like malaise, cramping, skin nerve reactions that feel like bugs crawling on or under the skin. Suffice it to say that it’s an ordeal for the patient. Many describe it as the sickest they’ve felt in their life.

Ultra-Rapid Opioid Detoxification (UROD) is a medical procedure whereby the opioid dependent patient is put to sleep under anesthesia and given a drug called Naltrexone which blocks the opioid receptor in the brain, almost instantly starving the brain of the opioid and causing an acute abstinence syndrome or accelerated withdrawal. The patient is not conscious and is unaware of the traumatic withdrawal symptoms. During this time the vital signs are closely monitored as well as the signs of the intensity of the withdrawal. When the withdrawal has subsided to a tolerable level, the patient is relieved of the anesthetic and is heavily sedated. Other drugs are given to offset the residual withdrawal symptoms and the patient is kept sedated and comfortable. After 48 hours, the patient is given some prescriptions to take for the next week or so and can be released into the care of family or a home care worker to recover from the procedure. While the patient is under anesthesia, a slow release pellet of the drug Naltrexone that was used to induce withdrawal is inserted in the fatty layer under the skin in the lower abdomen and will continue to block the opioid receptors for up to 6 months so that the cravings stop and even if they relapsed and used an opioid again, they wouldn’t get high because the neurotransmitter is blocked. To illustrate the strength of Naltrexone, consider Heroin to be masking tape in terms of its “stickiness” and think of Naltrexone as Velcro. The Heroin doesn’t have the binding ability to overpower the Naltrexone. Detoxification will be 100% complete and Behavioral Therapy (Cognitive or Dialectical) can move forward.

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Because this procedure needs to take place in a fully functioning medical environment for anesthesia, the cost is high and it wouldn’t make sense to build these clinics in smaller communities. Since the expertise is very limited it would make more sense to build treatment centers in larger metropolitan cities in each state or province and have the patients travel to the center for the treatment. By centralizing specialists in large clinics, it could also function as a center for natural detoxification and psychological counselling. Each Center could be a teaching hospital so that others could get certified.

There have been problems in the past with this procedure because it was unregulated. The level of care was inconsistent and some people died needlessly. But peer reviewed articles have shown the procedure to be both safe and effective (Salimi Al, Safari F, Mohajerani SA, Hashemian M, Kolahi AA, Mottaghi K, 2014). Traditional methods such as weaning or titrating, even when substituting Methadone, are usually unsuccessful. Also, because the experience causes such distress, it deters people from attempting it (Kaye, et al. 2003). There are detractors who say that there is no benefit to using the procedure; that the risks of anesthesia are high and will not recommend it ( Gowing L, Ali R, White JM, 2010). If the procedure was regulated, a standard of care could be maintained and as was shown earlier, the benefits are very evident both to society (legal, medical costs and crime rates) and the patient (stable, crime free life) who is suffering with the disorder.

Another potential roadblock to wide acceptance of UROD is the entrenched bias of addiction clinic medical doctors who make a living prescribing Methadone and Buprenorphine substitution medications. These patients represent regular customers for life. The pharmaceutical companies who manufacture and sell these long acting substitution opioids are also potential lobbyists against the treatment because as noted earlier, this would be a lifelong treatment and represents significant profits. The only way to counter the propaganda of the pharmaceutical companies targeting public opinion would be a social media campaign. Ten years ago it would not have been possible to compete with television advertising but with the spread of social media it is now possible, especially with an issue that has the spotlight on it like the Opioid Epidemic does. People on substitution medications are still Opioid dependent; one opioid was simply switched for another one. There are health benefits compared to using street drugs, to be sure. Substitution is not a treatment for addiction. If pharmaceutical Heroin was available, the harm reduction delivered by the substitution drug is less, due to the decreased risk of a pharmaceutically manufactured drug. Also it is much more difficult to detox from the long acting opioids because of their extended half life. Detoxification completely eliminates the opioids from the body. Naltrexone stops the cravings and blocks the actions of future opioid use. A person free from the dependence can focus on behavioral therapy (CBT or DBT) to deal with the absence of the drug and the potential significant positive changes in their lives, including their family and colleagues.

Peter MacNeil

Opioid Treatment Paradigms

There are two accepted paradigms for opioid addiction; abstinence and replacement therapy. Replacement regimes typically substitute acute acting opioids such as Heroin, Morphine, Oxycodone, etc. with long acting drugs such as Methadone or Buprenorphine. Abstinence protocols require a complete detoxification from the drug as an initial step before psychological treatments can proceed. The detoxification process induces an abstinence syndrome commonly referred to as “withdrawal” and usually includes flu-like symptoms such as emesis (vomiting), diarrhea, hyperhidrosis (sweating heavily), as well as, other feelings of discomfort, including but not limited to hyperalgesia (sensitivity to pain) and negative mood changes. Natural detoxification can last several weeks or months and due to the subjective distress involved, 30-91% of participants may drop out (Singh and Basu, 2004). It should be noted that this sample, while significant, is of people who voluntarily entered the detoxification program. The failure rate among those forced into a program or unethically coerced by threat is far more disappointing and of great concern. Ultra-Rapid Opioid Detoxification (UROD) significantly compresses the time frame as well as the discomfort level experienced and since the subject is under anesthesia, the detoxification rate is 100% as they are unaware of the progress of the procedure and in any event, cannot escape.

Introduction

Western society is currently in the unenviable position of dealing with an old enemy that has returned with increased strength. While opioid abuse and subsequent addiction and dependence is not a new phenomenon, the current manifestation is unprecedented. Due to pharmaceutical refinement of natural opioids and the introduction of even more powerful synthetic opioids, there is great cause for concern. While it is difficult to assess illicit drug use statistics due to human beings being deceptive about illegal activity, there are two consequences of opioid abuse that cannot be hidden from the view of authorities; overdoses resulting in emergency room treatment and unfortunately, death. Death cannot hide behind the cloak of deception.

According to the Center for Disease Control and Prevention, more than 1,000 people are treated every day for opioid abuse (CDC, 2016). More concerning from this same report is that 33,000 people died from an opioid overdose in the US during the year 2015. The incidence of opioid overdose continues to rise at an alarming rate. At a House Intelligence Committee hearing on June 13, 2017, Attorney General Jeff Sessions testified under oath that in 2016 there were 52,000 opioid overdose deaths. Consider these statistics from the above CDC report:

“The majority of drug overdose deaths (more than six out of ten) involve an opioid. Since 1999, the number of overdose deaths involving opioids (including prescription opioids and heroin) quadrupled. From 2000 to 2015 more than half a million people died from drug overdoses. Ninety-one Americans die every day from an opioid overdose.

We now know that overdoses from prescription opioids are a driving factor in the 15-year increase in opioid overdose deaths. Since 1999, the amount of prescription opioids sold in the U.S. nearly quadrupled, yet there has not been an overall change in the amount of pain that Americans report. Deaths from prescription opioids—drugs like oxycodone, hydrocodone, and methadone—have more than quadrupled since 1999.” (CDC, 2016)

In light of this phenomenon which has been named a “crisis” and an “epidemic” by clinicians and governments alike, every intervention strategy should be considered seriously by governments as Public Safety is the primary responsibility of government and in this case Public Health has been demonstrably shown to be overlapping with Public Safety, not unlike other mortal threats of the past.

The Controversy

In order to assess the viability of UROD as an intervention strategy, there are two issues to sort out; efficacy and ethics. Does the research indicate that this procedure works? The short answer is yes. The detoxification process is complete. However, this is only the first step in the overall treatment of addiction. In order to justify the significant cost, as well as the risks associated not only with anesthesia, but the sudden detoxification process itself, can it be shown that it leads to long term abstinence compared to other interventions? As noted earlier, there are certain and specific risks to the patient as well as costs to society if this procedure is to be subsidized by taxpayer dollars. We will examine an overview of the procedure and issues that have arisen regarding both the efficacy of the procedure, as well as the ethical issues involved.

The Procedure

An accurate medical history is required to screen for contraindications. A full blood panel, as well as an EKG and lung X-ray to screen for irregularities are also requirements.

Medications to soften the withdrawal symptoms as well as an antiemetic are given pre-anesthesia. Anesthesia is induced using Propofol, a non-opioid drug that is short acting and easily titrated. This drug also has such an effect on memory that it has the nickname “milk of amnesia” which blunts the traumatic memories associated with surgery and is helpful with sudden withdrawal as well. Midazolam is added to the Propofol infusion to induce deeper sedation. Once sedated, a strong opioid antagonist called Naltrexone is slowly introduced and withdrawal signs are monitored along with vital signs associated with anesthesia. During the anesthesia, a naltrexone pellet can be inserted in the fat tissue of the lower abdomen (more about this later). When acute withdrawal signs subside, the patient is released from anesthesia and sedated with benzodiazepines for a suitable period. During the next 48 hours, careful monitoring is required and the patient is treated with medications to offset residual withdrawal systems and to remain sedated. Once stable, the patient can be released into the care of family or a home caregiver.

The Issues:

Efficacy

UROD has been shown to be both safe and effective as a means of detoxification when standard procedures are followed (Salimi A1, Safari F, Mohajerani SA, Hashemian M, Kolahi AA, Mottaghi K, 2014). Studies have shown that cardiac complications and gastrointestinal ulcerations have occurred but may be accounted for by deviating from standard anesthetic protocols and poor prescreening (EKG, etc.). However, it must be mentioned that some researchers analyzing data have found that there is no benefit to detoxification under sedation and the risks of anesthesia are high. This, combined with the costs and allocation of scarce resources are significant enough not to recommend the treatment ( Gowing L, Ali R, White JM, 2010). This is contradicted by the other studies cited. For example (Kaye, et al. 2003) suggests that traditional methods of detoxification such as weaning, even with substitution of Methadone is usually unsuccessful. The team also concludes that since the withdrawal process is extremely distressing, it deters people from attempting it. Others terminate the process and return to opioid use (Basu, 2004). Since this procedure is successful for these two groups of people, how can it be said that there are no benefits?

Ethics

Commercial practitioners have advertised this procedure as a “miracle cure” without true informed consent being sought. Obviously, the dangers, as well as the benefits need to be disclosed before obtaining consent and a full explanation of the residual symptoms in the days and weeks following the procedure given. Long term treatment should also be discussed. Detoxification is a first step.

There remains a public health debate regarding the allocation of scarce resources for this procedure which are properly the domain of government agencies. However, if the patient is willing to pay for services rendered, is it ethical for a government to outlaw a procedure that a patient may require for various reasons and agrees to assume the risks by giving consent after full disclosure?

Long Term Abstinence Success Rates

Detoxification is a distinct process from relapse prevention. (Diaper AM, Law FD, Melichar JK, 2014) The discontinuation of the drug is the goal of detoxification and using the tools mentioned, abstinence can be aided by pharmacological means.

The surgical insertion of the opioid antagonist Naltrexone blocks the opioid receptors and assists with the long term goal of abstinence (Singh and Basu, 2004). In a study of 424 patients taking oral Naltrexone over a two year period, 75.75% were successfully abstinent while all of those in the failure group had stopped taking Naltrexone (Salimi, et al., 2014). The subcutaneous pellet relieves the voluntary discontinuation during the critical period.

Conclusion

Ultra-Rapid Opioid Detoxification is both an effective and safe procedure for detoxification. The additional benefits of the insertion of a long term pellet helps maintain abstinence and is an aid to those in long term psychosocial addiction programs. The cost and expertise needed remain an issue for government but should not prevent others from having access to the procedure if they are willing to assume the risks and costs.

Peter MacNeil

References

Diaper AM, Law FD, Melichar JK. Pharmacological strategies for detoxification Br J Clin Pharmacol. 2014 Feb;77(2):302-14.

Kaye AD, Gevirtz C, Bosscher HA, Duke JB, Frost EA, Richards TA, Fields AM. Ultrarapid opiate detoxification: a review Can J Anaesth. 2003 Aug-Sep;50(7):663-71.

Gowing L1, Ali R, White JM. (2010) Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal Cochrane Database Syst Rev.

Salimi A, Safari F, Mohajerani SA, Hashemian M, Kolahi AA, Mottaghi K (2014) Long-term relapse of ultra-rapid opioid detoxification J Addict Dis.;33(1):33-40.

Singh J, Basu D. (2004) Ultra-rapid opioid detoxification: current status and controversies – Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh – 160012, India