Feuding Ideologies, Part 3

© Navakun Phuangchan

“Dying To Be Free,” an article on the opioid addiction crisis, was well written and effectively communicated its message. That message was that abstinence-based treatment “didn’t work well for opioid addicts.” Medication-assisted treatment (MAT), especially with Suboxone, should be the standard of care. Nominated for a Pulitzer, “Dying To Be Free” was said to have influenced “a series of state and federal policy changes” away from abstinence to embrace MAT. But it has a glaring blind spot with regard to MAT, particularly Suboxone.

Pragmatically speaking, abstinent-based treatment and MAT need to learn to work together in order to effectively address the opioid addiction crisis in the U.S. “Dying To Be Free” systematically put these two approaches as being at odds with each other. It suggested we need to choose between the two, and argued that we should choose MAT. In order to support Suboxone MAT, it failed to acknowledge several serious concerns with Suboxone and other MATs. In this sense the persuasive rhetoric of the article had a blind spot.

In what follows, I hope to shine a light on what was missed with regard to Suboxone and other MATs. My intent is to bring to light the potential cons with Suboxone treatment in order to counterbalance the many pros found in “Dying To Be Free.” In order to make a truly informed addiction treatment choice both the strengths and weaknesses, the pros and cons need to be known and understood.

On September 20, 2017, Scott Gottlieb, the FDA Commissioner released a statement that said combined with counseling and behavioral therapies, MAT (medication-assisted treatment) was one of the main pillars of the federal response to the opioid epidemic. According to the Substance Abuse and Mental Health Services Administration (SAMHSA), it cuts the risk of death from all causes in half among individuals who use MAT to treat their opioid use disorder. But methadone and buprenorphine are themselves opioids and when they are combined with benzodiazepines or other central nervous system (CNS) depressants, there is a risk of serious side effects, such as difficulty breathing, coma and death.

Since the harm caused by untreated opioid addiction can outweigh these risks, the FDA advised against withholding buprenorphine or methadone-based MAT from individuals taking benzodiazepines or other CNS drugs. Nevertheless, the agency is requiring changes to the MAT drug labels to help decrease the risks of combining these drugs. Heath care professionals should educate patients about the risks of combined use, “including overdose and death.” They should taper the benzodiazepine or CNS depressant to discontinuation, if possible. They should verify the diagnosis if a patient was prescribed these drugs for anxiety or insomnia, and consider other treatment options for these conditions.

The new labeling recommends that health care providers develop a treatment plan that closely monitors any concomitant use of these drugs, and carefully taper the use of benzodiazepines, while considering other treatment options to address mental health conditions that the benzodiazepines might have been initially prescribed to address.

The FDA prescribing information for buprenorphine already notes that: “significant respiratory depression and death has occurred in association with buprenorphine,” particularly when it is used intravenously (IV) or in combination benzodiazepines or other CNS depressants, including alcohol. “Many, but not all post-marketing reports regarding coma and death associated with the concomitant use of buprenorphine and benzodiazepines involved misuse by self-injection.” Unintentional exposure of buprenorphine to children, which can cause possibly fatal respiratory depression, was warned against. It also notes the potential for dependence:

Buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. The withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset. Buprenorphine can be abused in a manner similar to other opioids. This should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion.

Buprenorphine and methadone are both opioids, with the potential for physical dependence. Therefore, they are both diverted from legitimate medical treatment for illicit use. Buprenorphine is a Schedule III controlled substance, while methadone is a Schedule II controlled substance. Buprenorphine is said to have a tolerance ceiling with respiratory depression, meaning it has a lower potential when used alone to cause respiratory depression and death. Given that buprenorphine is a partial agonist, its physical euphoria is less intense than other opioids. But tolerance to many of the effects will develop with prolonged and repeated use.

Methadone was first synthesized by the Nazis, who never brought it into widespread use because of side effects, which included its addictive potential. After WWII, the Americans took control of the factory where methadone, then known as dolophine or polamidon, had been invented. A 1947 study demonstrated its addictive potential, warning if the manufacture and use was not controlled, “addiction to it could become a serious health problem.” See “The Consequences of Ignoring the Past,” for more on methadone.

The addictive potential and the abuse potential for buprenorphine or methadone was not readily discussed in “Dying To Be Free.” Nor were the above-noted concerns of mixing buprenorphine and CNS depressants. The author, Jason Cherkis, did say that neither drug was a miracle cure. Suboxone blocks both the effects of heroin withdrawal and an addict’s craving and, if used properly, does it without causing intoxication.” But saying both drugs were comparable to “the insulin that a diabetic needs to live” was inaccurate and disingenuous. Chronic, long term use could lead to a lifelong dependency.

There is no getting around this. Chronic, long term use of buprenorphine and methadone produces physical dependence. A too rapid taper or an abrupt discontinuation will produce symptoms of withdrawal. Extended, chronic use over months or years could result in a lifelong reliance on the medication to avoid the discontinuation or withdrawal crisis—and the danger of returning to active illicit opioid use. In the documentary Methadonia, about methadone maintenance in New York City, one individual referred to methadone as “liquid handcuffs.”

Another disturbing blind spot in Dying To Be Free” was its discussion of a 2009 study, “Illicit Use of Buprenorphine/Naloxone Among Injecting and Noninjecting Opioid Users.” Cherkis cited it, stating the majority of addicts surveyed were buying Suboxone on the black market “in an attempt to get sober.” 74% of those surveyed said they were using Suboxone to “ease withdrawal symptoms; 64% said they were using it because they couldn’t afford drug treatment. “Even when purchased on the black market, regardless of the intentions of the user, the medication works as intended — as harm reduction.”

The study abstract contains the information Cherkis noted. But let’s take a closer look at the further results reported in the full article. First recognize the sample size was small: 51 injection opioid drug users (IDUs) and 49 noninjection opioid dug users (non-IDUs). It was also drawn from a limited area, opioid users in Providence, RI. Only 7% reported current employment and 52% reported current homelessness. The 64% who were using diverted Suboxone because they couldn’t afford treatment are easily explained by the high unemployment and homelessness figures.

In addition to the results reported by Cherkis was the following data. Among those who had used diverted buprenorphine, 60% reported using it for less than 1 week; 13% for 1 week; and 28% for more than 1 week. Of those using diverted buprenorphine less than 1 week, 32% said they only used it for one day. Fifty seven percent said they used diverted buprenorphine because they couldn’t obtain heroin; a greater percentage (68%) of IDUs than non-IDUs (41%). Forty seven percent said they used diverted buprenorphine to ‘get high’; a greater percentage of non-IDUs (69%) than IDUs (32%). Seventy six percent said it was easy or very easy to obtain Suboxone on the street.

The following quote by Tom Frieden, the former director of the Centers for Disease Control and Prevention (CDC), appeared after the selective reporting on the above study, arguing for the need of more MAT programs: “If buprenorphine is being used and being bought on the street to self-treat addiction, that’s a reflection of a need to have better medically assisted treatment programs out there.”

I don’t really think these patterns of and reasons for diverted buprenorphine use are best described as harm reduction, as Cherkis said. Technically, there are high percentages of individuals saying they used it to reduce withdrawal, and/or self-treat opioid addiction, as well to stay “clean” for some time. But most also said they used buprenorphine because they couldn’t obtain heroin. The reported time of buprenorphine use for the majority of individuals was less than a week; 32% said it was for only one day! In addition, 32% of IDUs and 69% of non-IDUs said they used it to “get high.” It seems it would be more accurate to describe this behavior as attempting a time period of controlled opioid use, rather than harm reduction.

About fourteen months before “Dying To Be Free” was published, “Addiction Treatment With A Dark Side” appeared in The New York Times. It too looked at Suboxone treatment, but presented a different, more nuanced side to Suboxone treatment. Cherkis selected out one aspect of the article, that it “linked hundreds of deaths in the U.S. to buprenorphine and Suboxone.” He focused in on the phrase used to say buprenorphine was a “primary suspect” as a cause of death in CDC data analyzed by the NYT. He then noted there should be caution used before attributing a “primary suspect” drug as a cause of death, which he neglected to show is exactly what the NYT article did do.

The NYT article said the 420 deaths with buprenorphine as a “primary suspect” paled in comparison to those reported to the FDA from methadone for the same time period. It also said “The F.D.A. information, which is spare, does show that more than half of the American buprenorphine deaths involved other substances and that only two of 224 cases specifying ‘route of administration’ indicated injection — the primary concern of regulators.” Fifty deaths were noted as suicides, 69 as unintentional overdoses from drug abuse, and 30 were fetal or infant deaths after exposure in the womb.

The NYT claimed some experts believe buprenorphine is not being monitored systematically enough to gauge the full scope of its misuse. The CDC does not track buprenorphine deaths. Most medical examiners, emergency rooms, prisons, jail and drug courts don’t routinely test for it. The director of the Center for Substance Abuse Research at the University of Maryland said: “I’ve been studying the emergence of potential drug problems in this country for over 30 years. . . . This is the first drug that nobody seems to want to know about as a potential problem.”

Then “Addiction Treatment With A Dark Side” had a section noting some of the aggressive actions taken by Reckitt Benckiser, the company that brought Suboxone to market, “to protect its lucrative franchise.” I’ve noted these and similar actions by Reckitt Benckiser in previous articles: “A Double-Edged Drug,” “The Seduction of Opioid Substitution” and “The Opioid Buzzard.” The Times article documented the widespread association between Reckitt Benckiser and the federal government in bringing Suboxone to market, and in providing a place for lucrative employment when government officials left public service for employment in the private sector.

At one point in “Dying To Be Free,” Cherkis said the “squeeze of regulation” was responsible for opportunistic forces, such as “cash only Suboxone clinics and shady doctors,” as well as the “vibrant black market for illicit buprenorphine. Read the section, “Troubled Histories” in the NYT article and the follow up NYT article, “At Clinics, Tumultuous Lives and Turbulent Care” to get a clearer, more accurate picture of the problems with some of the existing Suboxone treatment centers and providers.

You also find a lengthy section describing the benefits of Suboxone treatment. Cherkis did say in “Dying to Be Free” that the NYT article did not question the efficacy of Suboxone when it was used properly. But why didn’t he discuss or cite some of the concerns? I think it was because “Dying To Be Free” was intended to be a persuasive piece of rhetoric to promote the widespread use of buprenorphine in MAT.

Undoubtedly, “Dying To Be Free” has had a significant influence on opioid treatment. But it seems that it did not present a well-rounded picture of both the problems and the benefits with MAT, specifically Suboxone. It seems to have a biomedical bias with regard to conceiving and treating opioid addiction. In Part 1 of “Feuding Ideologies,” I indicated how its rhetoric was a straw man attack on abstinent-based treatment while it extolled MAT. In Part 2, I showed how it misrepresented the recovery philosophy of Alcoholics Anonymous. Here in Part 3, I looked at how its biomedical bias seemed to dismiss or ignore many of the problems with Suboxone as a MAT for opioid addiction.


Chained to a Dragon

By the time Stephanie (not her real name) had been seen for her first “counseling” appointment, she had already been activated as a client at the methadone clinic. She met the required criteria: 18 or over (she was 18); previous failed drug treatment (as an adolescent who smoked pot she had failed to complete an outpatient drug treatment program); she reported using heroin for a year (with her older boyfriend); she was eligible for Medicaid. Heroin addiction is considered a “life threatening medical condition” for which a doctor had already signed and completed the necessary paperwork for the clinic to get paid; and Stephanie to receive additional medical care. She didn’t realize she has just chained herself to a dragon.

Methadone maintenance is considered by many to be the “gold standard” for opiate/opioid use disorders. And leaving methadone treatment is seen as ill advised in the literature. “Methadone Maintenance Treatment: (MMT)” by Herman, Stancliffe and Langrod, said that: “Methadone maintenance reduces and/or eliminates the use of heroin, reduces the death rates and criminality associated with heroin use, and allows patients to improve their health and social productivity.” Leaving Methadone Treatment” by Magura and Rosenblum, cautioned that: “The detrimental consequences of leaving methadone treatment are dramatically indicated by greatly increased death following discharge.”

But let’s flip this gold standard over and look at the other side. A 2005 review of the MMT literature, “Eyes Wide Shut?” suggested that rigorous evaluation of MMT programs is rare. The evidence for the effectiveness of MMT is mixed; and largely partial and only over the short term. “The quality of existing MMT research, and evidence for its general effectiveness are limited.”

An HBO documentary, “Methadonia,” painted a bleak picture of the life of several MMT patients in NYC. Steve, one of the persons followed in the film, who was trying to get off of methadone, said: “Once they get you hooked, you’re nothing but a junkie. Come get your fix in the morning.” You can view “Methadonia” online for free here and here. It is also available through Netflix. At one point in the film, Steve nods out repeatedly in the middle of speaking to the camera.

A recovering heroin addict I know told me about a classroom discussion he participated in about the pros and cons of methadone maintenance. My friend was for abstinence-based recovery; a classmate who was in a MMT program was pro medication-assisted recovery. In the middle of a statement on the benefits of MMT, the classmate nodded out for several seconds, picked right back up where he’d stopped speaking and finished his statement. My friend’s comment was: “I rest my case.”

According to Magura and Rosenblum, a large percentage of those who attempt to taper off of methadone will either resume active heroin use or resume MMT. They pointed to the considerable evidence that individuals who left methadone treatment had a high rate of relapse to opiate use. “Until we learn more through research, it is unwise to structure methadone programs … to discourage or impede long-term maintenance, and at the same time to pressure patients overtly to accept abstinence.” Herman et al. said: “It may be necessary for patients to remain in treatment for indefinite periods of time, possibly for the duration of their lives.”

A recent article in the New England Medical Journal strongly advocated for expanded access to medication-assisted therapies (MAT) like methadone maintenance, saying: “Expanding access to MATs is a crucial component of the effort to help patients recover.” But the authors fail to clearly distinguish between opioid MATs like methadone and buprenorphine and non-opioid naltrexone.

Further, while the “abuse liability” of buprenorphine is acknowledged by the authors as a disadvantage, the “abuse potential” of methadone is not! The opioid addicts I’ve known with experience using or abusing methadone and buprenorphine have always testified of the exponentially greater difficulty they have withdrawing or tapering off of methadone and “bupe” than they have with heroin.

Steely Dan, in their classic song “Time Out of Mind”, sung about “chasing the dragon.” This was a reference to the technique of using a straw or tube to inhale the vapor from heroin that had been placed on a piece of tinfoil and heated. The metaphor is an allusion to the hope that the next dose of heroin will return the user to the nirvana of their first high. But continued use never quite lives up to the promise. Each use leads to diminishing positive effects, leading to a fruitless chasing of the dragon to recapture the initial high. That is what the promise of methadone maintenance is like—chasing a chained dragon. To learn more, see my paper “Chasing a Chained Dragon: Methadone Abuse and Misuse.”

Do you see any value to expanding access to methadone maintenance treatment programs?

Also read, “The Consequences of Ignoring the Past.”


The Consequences of Ignoring the Past

In 1964, Drs. Marie Nyswander and Vincent Dole read about methadone in the drug literature, thought it could be useful in treating heroin addicts, and methadone maintenance treatment was born. For the next three decades, methadone was primarily used in opioid maintenance treatment. Then in the mid-1990s methadone began to be used as an alternative medication for chronic pain. But there were problems when methadone was used for pain relief—people began dying from accidental overdoses.

Methadone has some advantages as a pain reliever. Its longer duration of action meant it could be taken only 2 or 3 times a day rather than 4 to 6 times a day. It is also lower in cost than other prescription painkillers. Insurance plans see methadone as a cheaper, generic alternative to other long-lasting painkillers like OxyContin. A Consumer Reports comparison of the estimated costs for long-acting opioids indicated that the average monthly cost for 5 mg methadone pills was about $17. The monthly cost for 10 mg sustained-release OxyContin was $164. Fentanyl extended-release 25 mg was $303.

By 2009, methadone accounted for almost 1 in 3 prescription painkiller deaths. More people overdosed on methadone than heroin. SIX TIMES as many people died from methadone overdoses in 2009 than in 1999. See the following chart taken from the CDC “Morbidity and Mortality Weekly Report” for July 6, 2012.

methadoneOne of the issues was that the FDA-approved package insert for methadone recommended high initial doses of up to 80 mg per day. As reported in the NYT article, “Methadone Rises as a Painkiller With Big Risks,” Dr. Robert Newman, an expert on addiction said: “This could unequivocally cause death in patients who have not recently been using narcotics.” In November of 2006, after overdose deaths from methadone became more widely known, the FDA decreased the recommended starting limit to no more than 30 mg per day.

However, it has been reported that lethal respiratory problems can still occur with doses as low as 30 mg daily with some individuals. The problem is that methadone can take as long as two weeks to be converted into inactive metabolites with methadone-naïve patients. So the accumulation of methadone, especially with methadone-naïve individuals, can lead to “sedation, respiratory depression respiratory arrest and even death.” These same effects can occur with someone who is tolerant of opioids, but generally takes higher doses.

The respiratory depressant effect from methadone typically peaks later and lasts longer than its analgesic effect. In other words, someone taking methadone for pain will have relief for about 4 to 8 hours. But the methadone is still pharmacologically active. Taking more methadone for pain relief could mean greater toxicity and the danger of respiratory problems, since the recent dose for pain relief combines with the still-not-fully metabolized methadone of the first dose.

Sadly, if the history of methadone had been taken to heart, perhaps some of these problems could have been avoided. Maybe some of the accidental overdoses could have been prevented.

Methadone was first synthesized in the mid-1930s as an alternative painkiller to morphine, which the Germans anticipated the Allies would not be willing to share with them once war was declared. Known at the time as polamidon, it was never brought into commercial use. An American doctor, who did a good bit of the early clinical research with it after the war, said a former employee of the German company that invented polamidon (methadone) told him they had discounted its usefulness because of the side effects.

The factory where polamidon was invented came under the control of the Americans after the war. All German patents, including those for polamidon, were requisitioned as spoils of war. Eli-Lilly and other pharmaceutical companies began clinical trials on what was thought to be a revolutionary new painkiller, now with the name of dolophine—combining the Latin word dolor (pain) and the French word fin (end).

A 1947 study by Isbell et al. noted that volunteer subjects had problems with rapidly developing tolerance and euphoria. There were also signs of toxicity, inflammation of the skin, deep narcosis (unconsciousness) and a general appearance of illness with high doses. They also observed that: “morphine addicts responded very positively” to dolophine. They concluded that dolophine could be highly addictive: “We believe that unless the manufacture and use of methadon [methadone] are controlled addiction to it will become a serious health problem.”

The philosopher George Santayna said: “Those who cannot remember the past are condemned to repeat it.” In the case of methadone, it seems that those who don’t remember the past are condemned to suffer the consequences.

Also read, “Chained to a Dragon.”