08/25/14

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.”

07/21/14

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.

Were the overdose deaths from methadone preventable?

Also read, “Chained to a Dragon.”