Saturday, April 23, 2011

White House Office of National Drug Control Policy Announces New Prescription Drug Abuse Plan

Finally, the White House Office of National Drug Control Policy is bringing some attention to the prescription drug problem and has recognized that the use of prescription drugs has far outstripped the use of any illicit substances, except marijuana.  It's great to see this issue getting some focus, and I hope, because prescription drugs are legal, it might challenge policymakers to come up with new ways of approaching drug policy.  The plan focuses on physician education and prescription monitoring, recognizing that the increase prescription drug misuse and overdoses has followed a dramatic increase in the number of narcotics being prescribed for pain in recent years.  Our drug policy has focused for so long on demonizing and punishing the relatively few users of illicit drugs, like heroin and cocaine, in ways that are highly racialized.  I am interested to see if this "new epidemic" shifts the stigma surrounding drug use and fosters a different kind of drug policy or just leads to a bifurcated system where some people get treatment and others go to prison.

Sunday, April 10, 2011

Pharmaceuticalization and Anti-addiction Medications

Another draft section from dissertation
In contrast to theories about corporate interests and profit driving medicalization and pharmaceuticalization, a landmark 1995 Institute of Medicine Report concluded: “the disincentives for the pharmaceutical industry in the development of anti-addiction medications are formidable (Fulco et al 1995: 187).”   According to Alan Leshner, former Director of NIDA, “There are virtually no market incentives for pharmaceutical companies to develop medications for drug addiction” (Leshner 1999).  Indeed, NIDA’s Medications Development Program, founded in 1990 has received substantial government funding precisely to overcome the reluctance of industry to develop addiction medications on its own.  For example, NIDA received a $500 million infusion of cash in 1996 for new medication development.  Bup received significant assistance from this program and probably would never have been brought to market without the substantial support and involvement of NIDA.  The development of bup is best understood by placing it within a broader context of the market, regulatory and cultural forces that both foster and impede the development of opioid addiction medications.
Market Forces
There are no precedents for a highly profitable addiction medication.  Pharmaceutical companies traditionally base their business models of investments in medications with large sales potential (Mark 2009).  And while some kinds of addiction appear to be quite prevalent, there is no history of an addiction medication becoming a blockbuster (Mark 2009).  Estimating the potential market for bup is difficult and clearly depends on how one defines opioid dependence as well as the recommended course of treatment.  One of the primary confounders in estimating the market for bup has to do with the recent increase in prescription drug abuse. With the possible exception of alcohol, our cultural understandings of and our policy responses to addiction have centered on illicit drugs, like heroin and cocaine.  Largely absent from our conversations about drug policy is attention to prescription drug abuse, which is far more prevalent than any other kind of substance misuse except alcohol and marijuana.  Moreover, the medical community, especially those working for the medicalization of addiction treatment, have been reluctant to address this problem probably because the vast majority of “abused” prescription drugs come from doctors.
Epidemiological studies indicate that 1.7% of people aged 19–30 have tried heroin and 18.7% have used other opioids in their lifetime (Veilleux et al 2010).  Some studies suggest that about 58% of those who currently use heroin meet the criteria for dependence (Veilleux et al 2010).  The total numbers of those dependent on heroin are actually quite small from the perspective of a pharmaceutical manufacturer looking for a market --  approximately 212,000.  From a marketing standpoint, non-medical use of prescription opioids is a more attractive market than heroin use (see Figure below) --  in 2007, an estimated 5.2 million reported using prescription pain relievers nonmedically (SAMHSA 2009).
These high rates of prescription drug abuse are not surprising when one considers that between 1991 and 2009, prescriptions for opioid analgesics increased from about 45 million to nearly 180 million, a 4-fold increase (NIDA 2010).  As the figure below indicates, prescriptions for pain relievers have sky-rocketed along with deaths caused by individuals overdosing on these medications.
According to SAMHSA, in 2004 approximately 1.4 million people were dependent on or abused prescription pain medications.  Unfortunately, SAMHSA does not separate out dependence from abuse (misuse that does not rise to the level of dependence) (SAMHSA 2009).  Whether or not those who abuse, but are not dependent on opioids, would receive bup is unresolved.  According to the CSAT National Advisory Committee considering the regulation of bup:  “eligible patients should include vulnerable people who are using heroin often despite experiencing adverse effects on their lives, even is they are not physically dependent” (1999:18).   If the market for bup extends to both prescription opioids and heroin and to those who are “dependent” and “abuse” these substances, the number of potential customers reaches several million.
The potential market for bup is also affected by the course of treatment -- how long people should be prescribed bup.  The length of treatment is affected by two factors – the physical dependence of those taking bup on the medication and the social construction of opioid dependence.  There is little debate over the fact that bup, like any opioid is physically addicting and, therefore, it will be difficult for people to stop taking it.  Some scholars suggest that “people will substitute affordable treatment for drug use if it is accessible” (Charles 2003: 6).  That is, bup can be seen as essentially a substitution for heroin or other prescription opioids, but one that is legal, more economical, and easier to obtain from the user’s standpoint.  From a macro-economic standpoint, shifting people’s dependence to bup moves the profit from the sale of the addictive substance to the pharmaceutical manufacturer (and the healthcare system) away from the illicit drug trade.  This is not to deny that personal and societal benefits may result from this shift, but from the standpoint of who profits --  it is the healthcare and pharmaceutical industry.  Moreover, to the extent that the addiction being treated is caused by legally prescribed pharmaceuticals, the healthcare and pharmaceutical industry is profiting on both ends – from the original prescription of the addictive opioids (i.e., pain medications) to the prescription of the addictive treatment (i.e., buprenorphine).  Bup “treats” the harm caused by iatrogenic medicine while the pharmaceutical industry profits.
Another potential source of profit stems from the social construction of bup as a chronic, relapsing disease.  The chronic, relapsing disease model has become ascendant is recent years.   This particular construction of addiction means that individuals being prescribed bup will be taking it “for long periods of time, or perhaps even indefinitely in some cases” (CSAT NAC 1999).  Like insulin for diabetics, if opioid dependence is a chronic disease, then bup will be needed, if not forever, then for months or years.  In addition, acceptance of relapse as part of the “disease” means that, rather than being seen as a failure of the medication, relapse presents another opportunity to re-engage the patient/customer in a new course of treatment. The chronic, relapsing disease frame works to the benefit of the manufacturer by developing a customer base that will be advised by professionals to take their medication indefinitely and, if they should relapse and stop taking the medication, they will be encouraged to resume taking the medication as soon as possible. 
Despite the potential market for bup, realizing this market faces a number of barriers.  Addiction medications are competing with a very well established behavioral drug treatment industry as well as criminal justice responses to addiction.  Moreover, treatment for addiction is often not covered or has limited coverage by insurers (Finkelstein, Netherland et al 2011).  Both the delivery and payment of addiction treatment has historically been separate from medical care, which poses a number of financing barriers (Finkelstein, Netherland et al 2011).  Bup treatment, being one of the first and only medications for addiction treatment delivered in medical care settings poses unique financing challenges.  For instance, it is often not clear which payer is responsible for covering the cost of medication and which, if any, is responsible for the cost of visit, particularly if it involves counseling.  And because bup is considered novel (as one of the only addiction medications that can be prescribed in a physician”s office), many insurers, hospitals, and pharmacists do not cover it at all (Finkelstein, Netherland et al 2011).

The regulatory barriers to developing an addiction medication are clear --  if such medications can only be dispensed through the highly regulated and intensely stigmatized methadone clinic system, they will reach relatively few people.  In 2000, Joe Biden, then a Senator, lamented the ways in which the regulation of addiction treatment stifled the pharmaceutical industry’s involvement:
The difficulty of distributing treatment medications to addicts not only hurts those who are not getting the treatment they need, but also stifles private research.  I have often bemoaned the fact that private industry has not aggressively developed pharmacotherapies.  As we increase access to these drugs, we increase incentives for private investment in this valuable research (CR, 11/22/100, p. S9115).

Here, Biden recognizes that the longstanding prohibition on physicians prescribing medications to treat addiction creates a disincentive to industry to invest in the research and development needed to bring new medications to market.  Government regulation of addiction treatment --  which is, in fact, quite different from that governing any other “disease” -- suppresses the profit motive.  If addiction is to become like other diseases, then regulations must change so that industry forces can drive medication development. 
For bup to succeed economically, RB had to overcome the legal restriction preventing doctors prescribing medications for addiction treatment. RB clearly understood that trying to market bup through the existing methadone clinic system was unlikely to be profitable:
…from a corporate perspective it seemed unlikely that a drug confined to a limited number of clinics that were already comfortable using generic methadone would be used enough to justify the investment involved in taking buprenorphine through the regulatory process…  [T]o recover any significant portion of corporate expenditures… buprenorphine would need to reach the mainstream practice of medicine…[and] a period of market exclusivity would be needed to protect the product (Jaffe and O'Keeffe 2003)(p.S7-8). [emphasis added]

RB was unwilling to invest in bup without some prospect that it could be marketed outside of the methadone clinic system to the medical mainstream even though they recognized that this required a significant legislative change.  Moreover, they required a period of exclusivity to insure that they could recoup some of their investment without competition from a generic brand.  Reckitt Benckiser succeeded in achieving both of these aims.  Through the passage of DATA 2000, they expanded “access to treatment” (in the parlance of policymakers) and created a huge potential market for themselves. They also succeeded in insuring a period of exclusivity by getting bup protected by the orphan drug law.  Periods of market exclusivity are routinely granted to incentivize the development of new medications, so it is perhaps not surprising that RB obtained a 7 year orphan drug status that expired in 2009. 

In addition to regulatory disincentives, the stigma surrounding addiction and its treatment for both “patients” and physicians has been cited as impeding the development of anti-addiction medications (Fulco 1995; Leshner 1999).  The stigma surrounding drug addiction as well as the ambivalence around its status as a disease may also be the reason why there are few, if any, established patient advocacy groups calling for the expansion of medication treatments for addiction.[1]  And despite the high prevalence of people thought to have opioid dependence, stigma is widely perceived as keeping them from seeking treatment
Perhaps even more daunting for industry than patient stigma is the stigma surrounding physicians who treat addiction (see previous Chapter).  The restriction on physicians prescribing medication to treat addiction, which dates back to the court decisions following the Harrison Act, stemmed directly from the perception that much of the blame for addiction fell upon the physicians and pharmacists who manufactured and sold addictive medications (e.g., tonics containing opiates or cocaine) (Weinberg 2005).  Moreover, many of the early medical cures for addiction soon became seen as addictive agents themselves. This is especially true with opiate dependence, where synthetic (and legal) opiates have long been touted by medical experts as the solution to addiction.  Bup is just the latest in a long line of such “medications.”  For example, morphine was once used to treat addiction to opium; heroin to treat morphine addiction; and methadone to treat heroin addiction.  This historical cycle of addiction medications prescribed by physicians becoming the cause of addiction has contributed to the stigma surrounding addiction medicine (Weinberg 2005).  The recent rise in and attention to addiction to prescription drugs has re-raised the specter of the drug-peddling doctor.
The ways in which pharmaceutical companies and doctors were implicated in causing addiction historically have continued to impact addiction treatment today.  Some scholars believe that medical professionals have actively abjured their role in the treatment of addiction and have thus discouraged the development of pharmaceutical treatments (Weinberg 2000).  Since doctors got out of the business of addiction treatment following the passage of the Harrison Act, medical education has largely excluded any attention to addiction or to treatment.  On average, medical students receive 12 hours of education on addiction (Miller et al 2001), and only 8% of medical school curricula require a course on addiction (Physician Leadership on National Drug Policy 2000).  Even if one overcomes the regulatory barriers to physicians’ treating addiction as NIDA and RB did, one must still overcome the reluctance of physicians to treat addiction and to be tainted by accusations that bup is just another addictive drug.

The Regulation of Addiction Treatment

Another piece from my dissertation.  Very much a work in progresss.

History of Addiction Treatment Regulation in the US
The distinction between legal medicines and illicit drugs is relatively recent and changes over time. Indeed, the history of opiates is one of new formulations brought to market to treat addiction to older formulations.  Substances that start out as therapeutic medicines become drugs of abuse. How these distinctions between medicines and drug are made, maintained and challenged has everything to do with the prevailing logic about addiction as well as the professional, political and economic forces of a given era.  And while these distinctions are largely historical and artificial (heroin has been both a medicine and a drug), they become enormously significant because of the social, cultural and legal meanings and actualities we attached to them.
In the 1800’s, any adult could by any medicinal products made by any manufacturer for any reason (Parrish 2003).  Our current system of regulating, prescribing, and controlling medication evolved in the early 1900’s beginning with the passage of the Harrison Narcotics Act in 1914.  Designed in part to raise revenue and in part in response to efforts to professionalize medical practice, the Harrison Act required the registration and licensing of pharmacists, physicians and manufacturers; levied taxes on the sale of medicines; and restricted the sale and use of narcotics to those prescribed by a physician for a medical reason (Parrish 2003).  For the first time, narcotic use was divided into legal use for a medical purpose and criminal use. 
Having restricted the sale of opiates to medical use, the Harrison Act created a controversy over whether using opium or morphine to maintain an “addict’s” supply was a legitimate medical reason (Weinberg 2005).  It raised the question that remains in play today -- is addiction a medical condition that should be ‘treated’ by prescribing either the substance to which the person is addicted or a substitute/treatment medication?  Are ‘substitution’ therapies a legitimate treatment for a medical disorder or is it just another way of dealing drugs?  The Treasury Department,[1] then charged with the enforcement of the Harrison Act, argued that prescribing opiates to addicts did not constitute medical treatment and that doctors who made such prescriptions could be arrested for narcotics trafficking.  In 1919, just months before alcohol prohibition took effect, the U.S. Supreme court concurred with the Treasury Department, and in 1920, the American Medical Association condemned the prescribing of opiates to addicts (Jaffe 2003).  Physicians could then, as now, prescribe narcotics for medical reasons other than treating addiction, and the prescription of opiates for pain remains a widespread practice.  Heroin, for example, though it could not be legally manufactured in the U.S. after 1924 (DeGrandpre 2006), could still be legally prescribed for conditions other than addiction until the Narcotic Control Act of 1956 (Carnwath and Smith 2002).  Even today, opiates like methadone, can be prescribed by a physician for pain but not to treat addiction (unless through the highly regulated methadone clinic system). With these regulatory changes and without the support of the American Medical Association, physicians quickly withdrew from having any formal role in addiction treatment.  Rather than being seen as a medical condition that could be treated by doctors using prescribed narcotics, overcoming addiction came to be seen largely as a matter of transforming people’s will and behavior (Carnwith and Smith 2002; White 1998).
Following the passage of the Harrison Act, U.S. drug policies generally became more punitive and oriented towards criminal justice rather than a medical approach.  In the 1950’s, minimum mandatory sentences were imposed for selling opium, coca, cannabis and their derivatives.  And in 1970, the Comprehensive Drug Abuse Prevention and Control Act (also known as the Controlled Substances Act) established a 5-tier scheduling of drugs by the Drug Enforcement Agency purportedly based on the substance’s potential for abuse, accepted medical use, and accepted safety under medical supervision.   For example, heroin is classified as a schedule I substance because it is seen as having a high abuse potential and no legitimate medical use.  Methadone, in contrast, is a schedule II narcotic because, although it is seen as having a high abuse potential, it also has purported medical value (both for the treatment of opioid dependence and pain).  As a schedule II substance, it is highly regulated.  See figure below for examples of narcotic scheduling. 

Examples of Narcotic Scheduling Under the Controlled Substances Act
Most restrictive
Least restrictive
Schedule I
Schedule II
Schedule III
Schedule IV
Schedule V
Low dose formulations of codeine
Cough suppressants with codeine

Buprenorphine with naloxone

Hydrocodone (Vicodin)

Low doses of codeine

Oxycodone (Percoset)

Codeine (certain formulations)

NOTE: Scheduling based on purported abuse potential and currently accepted medical uses

The Controlled Substances Act (CSA), which plays a central role in the social construction of bup, was considered an unhappy compromise even when it was passed because it embodied all of the tensions and ambivalence in our relationships to substances and to drug policy more generally.  Courtwright (2004:11-12) argues that the CSA framework was intentionally flexible to “give experts the authority and the resources to continuously fine-tune the nation’s medico-legal response to the drug problem.”    As I discuss is more detail below, in the case of bup, the CSA meant both that bup proponents had to win over DEA officials and that the DEA had to so some creative interpretation of the science behind bup to justify reclassifying it as schedule III narcotic. 
Following the CSA, the trend in drug policy was towards increasingly harsher and more punitive laws to lock up those who either possessed or sold drugs.  Beginning with New York’s Rockefeller Drug Laws passed in 1973,[2] both states and the federal government established an increasingly draconian set of penalties for drug possession and use that resulted in the mass incarceration of those who used or sold drugs, particularly in among people of color.  Incarceration rates have sky-rocketed (see Figure below), largely as a result of increasingly punitive drug laws (Shiraldi and Ziedenberg 2000).

Figure XX:  Trends in Incarceration Rates (per 100,000)
(in thousands)

While the general trend after the 1900’s was to treat the non-medical use of narcotics as a crime, there was always some recognition that addiction might be more amenable to treatment than incarceration.  In 1919, in what Conrad (2002) has called the “swan song of the medical era” for addiction, 40 carefully regulated narcotic clinics were opened in the U.S. with the goal of providing morphine to opiate addicts until they could be “cured.”  However, by 1923 these clinics were closed, in part due to the urging of the American Medical Association (AMA) which was trying to distance the medical profession from having any role in supporting or fostering addiction (Conrad 2002).   According to White (1998: 119), “[i]t was universally understood that physicians had a played a significant role in the development of this problem through their excessive administration of narcotics to their patients.”  Ever since this strategic move by the AMA, the role of physicians in the treatment of addiction has been minimal --  that is, until the Drug Addiction Treatment Act of 2000 and the FDA approval of bup in 2002.
Following the passage of the Harrison Act and the subsequent court decision barring physician treatment of addiction through prescription medications, addicts were either locked up or sent to ‘narcotic farms’ where they were ‘rehabilitated’ through behavioral therapies, isolated to prevent the spread of addiction, and removed from the temptations thought to encourage their drug use (White 1998).  During this same period, individuals who classified themselves as “addicts” developed Alcoholics Anonymous and the 12-step method of treatment, which favored ‘self-help’ over professional interventions.  For the next several decades, addiction treatment relied on a variety of self-help or behavioral models, all of which held abstinence from all drugs (and many medications) as their ultimate goal (White 1998).  These kinds of treatments reinforced the notion that changes in environment or behavior could overcome addiction, a failure of will or morality (White 1998).
The return to using a drug/medication substitute to address the problem of addiction did not re-occur until the advent of methadone in early 1970’s.  Methadone marked a profound shift in U.S. drug policy but also revealed the deep ambivalence of policymakers and the public over drugs and drug treatment.  Indeed, methadone was not originally billed so much as a medical treatment but as a solution to the problem of urban crime (White 1998).  Early research on methadone showed that methadone reduced crime and the consumption of heroin while allowing individuals to return to “productive citizenship” (Jaffe and O’Keefe 2003).  The first studies focused on, not only how methadone reduced heroin use, but how it increased people’s ability to get and hold a job and reduced their need to obtain money for heroin through illegal activities (Nelkin 1973).  The Nixon Administration, elected on a law-and-order platform, faced enormous pressure to solve the ‘drug problem’ and rising rates of urban crime and became champions of methadone treatment.  Drawing on a small group of pioneering scholars who lobbied for a medical approach to addiction, Nixon create a national network of methadone programs that was serving 80,000 by 1973 (White 1998).
However, many people viewed methadone treatment as simply substituting one drug for another (White 1998), and the regulatory apparatus that grew around it reflects methadone’s ambivalent status as both a legitimate medication and a drug of abuse.  As methadone treatment became institutionalization in the 1970s, it became mired in a maze of bureaucratic and regulatory restrictions.  The Department of Justice and Treasury opposed methadone, and in the early 1970’s, the FDA imposed strict rules on how it was to be dispensed essentially creating a special, closed system for methadone treatment (Jaffe and O’Keefe 2003).   Rather than being distributed like other medications, methadone was (and still is) dispensed through a highly regulated system of clinics. Daily attendance is generally required, and patients must consume their doses on site in front of staff.  The amount of the dose is also carefully regulated, and unlike other medications, methadone cannot be taken home or self-administered without special permission and privileges.  Even the form of the medication – a thick syrup --  is designed to guard against the diversion of the drug and to insure that it can not be illegally injected.  In short, from a regulatory point of view, methadone (when prescribed for addiction treatment) is like no other medication in the U.S.   As Jaffe (2003: 55) puts it, methadone represents a “substantial departure from the usual practice of allowing licensed physicians to use their own professional judgment, guided by the drug’s labeling to determine how to prescribe a medication.”  Because of their historical role in fostering narcotic addiction, the general prohibition on prescribing narcotics for treating addiction, and methadone’s excessive regulation, very few physicians are involved in methadone treatment.  Rather, methadone clinics generally have a medical director who oversee the prescriptions but are largely staffed by counselors and other mental health professionals.
This ambivalence over using medications to treat addiction was codified in 1974 through the Narcotic Addict Treatment Act.  The Act gave the newly created Drug Enforcement Agency (DEA) control over the storage and security of drugs used in the treatment of addiction and required the DEA registration of practitioners, but it gave the Department of Health and Human Services responsibility over setting treatment standards (Jaffe 2003).  While there was some limited success in the 1990’s to ease methadone regulations, the dual system of oversight that includes both the criminal justice (in the form of the DEA) and the medical (in the form of Health & Human Services) approach to dealing with addiction medications remains in place.  It is into this confusing and contradictory regulatory world that bup entered.

[1] Early efforts to control substances focused on taxation strategies.  Therefore, the regulation of narcotics began as a function of the Treasury Department.  The Federal Bureau of Narcotics was created in 1930 but still operated under the Treasury Department. As drug control efforts focused more on law enforcement strategies, new administrative structures were created at the federal level, including the U.S. Interdepartmental Committee on Narcotics in 1954 and the Drug Enforcement Agency in 1973.
[2] The Rockefeller Drug Laws were toughest drug possession and sales laws in the country, establishing mandatory minimum sentences for relatively low-level offenses and greatly curtailing the discretion of judges to offer alternative penalties or sentences.  Despite the fact that these laws were criticized for treating non-violent offenses as harshly as violent ones, they quickly become the model for other drug laws across the country. In 2009, more then 35 years after their passage, some of these laws were reformed to curtail the use of mandatory sentencing and restore judicial discretion over many drug offenses.