Methadone-Associated Overdose Deaths: Factors Contributing to Increased Deaths and Efforts to Prevent Them
Published: 2009-03-26T00:00:00

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Highlights:
section_title: Why GAO Did This Study
paragraphs: Prescription drug abuse is a growing public health problem. In particular, methadone-associated overdose deaths--those in which methadone may have caused or contributed to the death--have risen sharply. Before the late 1990s, methadone was used mainly to treat opioid addiction but has since been increasingly prescribed to manage pain. Taken too often, in too high a dose, or with other drugs or alcohol, methadone can cause serious side effects and death. Methadone-associated overdose deaths can occur under several different scenarios, including improper dosing levels by practitioners, misuse by patients who may combine methadone with other drugs, or abuse--using the drug for nontherapeutic purposes. This report examines the regulation of methadone, factors that have contributed to the increase in methadone-associated overdose deaths, and steps taken to prevent methadone-associated overdose deaths. GAO reviewed documents, laws and regulations, data, and research from relevant state and federal agencies, including the Drug Enforcement Administration (DEA) and the Substance Abuse and Mental Health Services Administration (SAMHSA). GAO also interviewed federal officials, officials in five selected states, officials from professional associations and advocacy groups, and experts in pain management, addiction treatment, and forensic sciences.
section_title: What GAO Found
paragraphs: Methadone is regulated as a controlled substance, under federal and state laws and regulations, when used for pain management and addiction treatment. When methadone is used for pain management, it is regulated under federal and state laws and regulations that apply to controlled substances generally and that do not impose requirements unique to methadone. For addiction treatment, however, federal and state laws and regulations impose additional requirements that are specific to the use of methadone in opioid treatment programs (OTP), which treat and rehabilitate people addicted to heroin or other opioids. GAO, however, only reviewed relevant state laws and regulations for five selected states. Although information on methadone-associated overdose deaths is limited, available data suggest that methadone's growing use for pain management has made more of the drug available, thus contributing to the rise in methadone-associated overdose deaths. Methadone prescriptions for pain management grew from about 531,000 in 1998 to about 4.1 million in 2006--nearly eightfold. Methadone has unique pharmacological properties that make it different from other opioids, and as a result, a lack of knowledge about methadone among practitioners and patients has been identified as a factor contributing to these deaths. DEA data suggest that abuse of methadone diverted from its intended purpose has also contributed to the rise in overdose deaths as the number of methadone drug items seized by law enforcement and analyzed in forensic laboratories increased 262 percent, from 2,865 in 2001 to 10,361 in 2007. Nonetheless, data and research from five states GAO reviewed suggest that the specific circumstances of these deaths are variable because of drug combinations and unknown sources of methadone. GAO identified selected efforts to prevent methadone abuse and overdose deaths that focused on education, safety, and monitoring. For example, to educate practitioners about using methadone for pain management and addiction treatment, SAMHSA is establishing a physician clinical support system for methadone. To improve safety, in 2006, the Food and Drug Administration (FDA) approved a revised label for methadone tablets that included new safety information regarding the use of methadone for pain and modified dosage instructions for those beginning pain management treatment with methadone. Additionally, to prevent diversion and abuse of controlled substances such as methadone, DEA reports that as of February 2009, 31 states have established prescription monitoring programs. Some officials and experts cautioned that any prevention efforts focused on methadone alone might unintentionally shift similar problems to a different drug. GAO received comments from the Department of Health and Human Services stating that FDA recently notified manufacturers of certain opioid drug products, such as methadone, that they must take certain steps to ensure that the benefits of these drugs continue to outweigh the risks. The Department of Justice provided GAO with technical comments.

section_title: Letter
paragraphs: Prescription drug abuse is a serious and growing public health problem.  Drug overdoses, including those from prescription drugs, are the second  leading cause of unintentional injury deaths in the United States, exceeded  only by motor vehicle fatalities, according to the Centers for Disease  Control and Prevention (CDC). Of particular concern is the sharp rise in  methadone-associated overdose deaths—in which methadone may have  caused or contributed to the death. CDC data show that from 1999 to  2005, the number of these deaths increased more than fivefold, from 786 to  4,462, a rate higher than overdose deaths associated with other  prescription narcotics, such as oxycodone, hydrocodone, and fentanyl.
Methadone has been approved by the Food and Drug Administration  (FDA) for the treatment of opioid addiction and pain, and it is relatively  inexpensive compared to other opioids. Methadone’s unique  pharmacologic properties make it different from other opioids, so it must  be carefully administered. Particular vigilance is needed when starting  treatment and increasing dosages, regardless of whether methadone is  being used for addiction treatment or pain management. FDA reports that  side effects can include slow or shallow breathing, dangerous changes in  heartbeat, and death.
Until recently, methadone was primarily used in opioid treatment  programs (OTP) to treat and rehabilitate people addicted to such opioids  as heroin or certain prescription drugs. It works as a replacement for such  drugs by preventing withdrawal symptoms. Its slow onset allows patients  to be monitored as the drug takes effect, and its 24- to 36- hour duration of  action suppresses opioid withdrawal symptoms with one daily dose. When  used for addiction treatment, methadone cannot be dispensed by a  practitioner outside of an OTP.
Since the late 1990s, methadone has been increasingly prescribed by  practitioners to treat their patients’ pain. However, while a single dose  suppresses opioid withdrawal symptoms for a day or more, it generally  relieves pain for 4 to 8 hours despite remaining in the body much longer.  Further, it may take 3 to 5 days to achieve full pain relief, so dosage  increases must be done more slowly than with other opioids. As a result,  patients may feel the need to take more methadone before the previous  dose has left the body. However, if taken too often, in too high a dose, or  with certain other medicines or supplements, it may build up in the body  to a toxic level. Variability in methadone’s absorption, metabolism, and  relative pain relief potency among patients requires a highly individualized  approach to prescribing. When used for pain management, methadone  may be prescribed by appropriately licensed and registered practitioners  and obtained through licensed and registered retail pharmacies.
Like many drugs, methadone can also be abused—that is, used for  nontherapeutic purposes or for purposes other than those for which it was  prescribed, and dangerous side effects or death can occur when  methadone is combined with other drugs or alcohol. Because of its  accepted medical use as well as its high potential for abuse and for severe  psychological or physical dependence, methadone is classified as a  Schedule II controlled substance under the Controlled Substances Act.
Questions have been raised about the regulation of methadone for both  pain management and addiction treatment, as well as the factors  contributing to the increase in methadone-associated overdose deaths.  Such deaths can occur in a number of ways, including intentional  overdoses, or suicide, and accidental overdoses due to improper dosing  levels, abuse, or patient misuse, such as by combining methadone with  other drugs. While CDC collects limited information on overdose deaths  from state death certificates, there is no standard, nationwide method to  document detailed information about each death, such as the form or  source of the drug, nor is there a standard definition for a methadone- associated overdose death, so state medical examiners and coroners  investigating these deaths may define and report them differently. Defining  methadone’s role in a death is difficult because of inconsistencies in  determining and reporting causes of death, the presence of other drugs in  the deceased person’s system, and a lack of information about the  deceased person’s level of opioid tolerance. CDC has also reported that it  has been difficult to determine the extent to which increases in  methadone-associated overdose deaths have resulted from specific  prescribing practices, misuse by patients, diversion of the drug such as by  illegal sale, or other means.
To explore these issues, you asked that we further examine methadone- associated overdose deaths. Specifically, we examined (1) the regulation  of methadone for pain management and addiction treatment, (2) the  factors contributing to the increase in methadone-associated overdose  deaths, and (3) the steps taken to prevent methadone-associated overdose  deaths.
To examine the regulation of methadone for pain management and  addiction treatment, we reviewed relevant provisions of the Controlled  Substances Act, implementing regulations, and federal case law. We  interviewed officials from the Drug Enforcement Administration (DEA)  and the Substance Abuse and Mental Health Services Administration  (SAMHSA), and we reviewed relevant agency policies. We also  interviewed officials and examined relevant codified statutes and  regulations in five selected states—Florida, Kentucky, Maine, New Mexico,  and West Virginia—to determine how these states regulate the use of  methadone for both pain management and addiction treatment. We chose  these states based on their meeting four of five criteria we selected,  including whether the state had one of the top 10 highest rates of increase  in methadone-associated overdose deaths from 1999 through 2004 and  whether there was research on methadone-associated overdose deaths in  that state. The findings from our review of these five states cannot be  generalized to any other state.
To determine the factors contributing to the increase in methadone- associated overdose deaths, we interviewed officials from CDC, DEA,  FDA, the Office of National Drug Control Policy (ONDCP), and SAMHSA.  We also interviewed officials from relevant professional associations and  experts in pain management, addiction treatment, and forensic science. In  addition, we interviewed researchers and officials in our five selected  states regarding their views on what factors were contributing to the  increases in methadone-associated overdose deaths in their states, and  reviewed state data and studies. We reviewed methadone poisoning death  data from CDC’s National Vital Statistics System and relevant DEA data,  including DEA data on methadone drug items seized by law enforcement  and analyzed in forensic laboratories. We interviewed CDC and DEA  officials to obtain information about the reliability of their data, including  quality control such as edit checks, and any limitations of these databases.  We determined that these data were sufficiently reliable for use in this  report, and identified any limitations.
To identify steps taken to prevent methadone-associated overdose deaths,  we interviewed officials from CDC, DEA, FDA, ONDCP, and SAMHSA. We  also interviewed officials from relevant professional associations and  experts in pain management, addiction treatment, and forensic science.  We reviewed relevant studies and reports about efforts to prevent  methadone and other prescription drug overdose deaths. To obtain  additional information about prescription drug monitoring initiatives, we  examined relevant codified statutes and regulations in our five selected  states. We also interviewed officials in our five selected states to learn  about initiatives in their states to prevent these deaths. However, we did  not evaluate these efforts, and our findings are not representative of all  such efforts nor can they be generalized to all states. (See app. I for a  detailed discussion of our methodology.)
We conducted our work from November 2007 through February 2009 in  accordance with all sections of GAO’s Quality Assurance Framework that  are relevant to our objectives. The framework requires that we plan and  perform the engagement to obtain sufficient and appropriate evidence to  meet our stated objectives and to discuss any limitations in our work. We  believe that the information and data obtained, and the analysis  conducted, provide a reasonable basis for any findings and conclusions.
subsections: section_title: Background
paragraphs: Methadone, a long-acting opioid medication, is available as a liquid, a solid  tablet (5 and 10 mg), a rapidly dissolving wafer or diskette (40 mg), or a  powder. Liquid methadone is most commonly used for addiction  treatment, while the 5 and 10 mg tablets are most often prescribed for pain  management. FDA considers methadone safe and effective for both pain  management and addiction treatment, although not all forms of  methadone are FDA approved for both of these purposes.
subsections: section_title: Use of Methadone for Addiction Treatment
paragraphs: OTPs offer methadone maintenance treatment, including counseling, for  people addicted to heroin and certain prescription drugs. Daily doses of  methadone help normalize the body’s neurological and hormonal  functions that have been impaired by the use of heroin or misuse or abuse  of other short-acting opioids. When starting treatment, individuals go to an  OTP daily to take their methadone dose under observation, although  patients may receive a single take-home dose for a day that the clinic is  closed for business. After a few months, they may become eligible for  unsupervised take-home doses. The National Institute on Drug Abuse  notes that 1 year is generally the minimum for methadone maintenance  treatment, and that some individuals will benefit from treatment over  several years. Buprenorphine and levomethadyl acetate (LAAM) are also  FDA-approved medications for treating opioid addiction. When used for  addiction treatment, methadone must be dispensed by an OTP that is  certified by SAMHSA and registered with DEA. As of February 2009,  about 1,200 OTPs were operating nationwide, but not all states have  OTPs. (See fig. 1.) OTPs are operated by private for-profit organizations,  private nonprofit organizations, hospitals, or government agencies.
section_title: Use of Methadone for Pain Management
paragraphs: FDA approved methadone for treating pain in 1947, but from the early  1970s until the late 1990s the drug was primarily used for treating  addiction. In the mid-1990s, various national pain-related organizations  began to issue guidelines for treating and managing pain, including using  opioids to treat both cancer and noncancer pain. For example, the practice  guidelines issued by the Agency for Health Care Policy and Research  informed physicians and other health care professionals about the  management of acute pain in 1992 and cancer pain in 1994. In 2001,  health care providers and hospitals were required to ensure that their  patients received appropriate pain treatment when the Joint Commission,  a national health care facility standards-setting and accrediting body,  implemented pain standards for hospital accreditation. At first,  methadone was prescribed more for the treatment of cancer pain, but it  has been increasingly prescribed for the treatment of chronic noncancer  pain. Methadone’s advantages include that it costs less than other opioids  used to treat pain, and it comes in multiple forms.
Unlike methadone’s use in addiction treatment where it generally must be  dispensed by OTPs, when used to treat pain methadone may be prescribed  by an appropriately licensed and registered practitioner and dispensed by  licensed and registered retail pharmacies. Licensed and registered  practitioners may also dispense methadone directly to patients for pain  management, but DEA officials said that it is not a common practice.
section_title: Relevant Federal Agencies
paragraphs: DEA, on behalf of the Attorney General of the United States, is the agency  primarily responsible for enforcing the Controlled Substances Act. Under  the act, controlled substances are classified into five schedules based on  the extent to which the drug has an accepted medical use, and its potential  for abuse and degree of psychological or physical dependence. Schedule  II controlled substances—which include opioids such as morphine,  oxycodone, and methadone—have a currently accepted medical use and a  high potential for abuse, and may lead to severe psychological or physical  dependence. DEA’s regulation of the manufacturing, distribution,  dispensing, and prescribing of controlled substances, including Schedule II  drugs, encompasses the following:    Manufacturing. DEA limits the quantity of Schedule II controlled  substances that may be produced by each manufacturer in the United  States each year. DEA determines these quotas based on a variety of  factors, including disposal and inventories. DEA also sets aggregate  production quotas that limit the production of bulk raw materials used to  manufacture Schedule II controlled substances.
Distribution. DEA regulates transactions involving the sale and  distribution of Schedule II controlled substances by manufacturers and  wholesale distributors. Manufacturers and distributors are required to  report their inventories of controlled substances to DEA, and these data  are available for monitoring the distribution of controlled substances  throughout the United States and identifying retail registrants that  received unusual quantities of controlled substances.
Dispensing and prescribing. Practitioners who dispense, administer, or  prescribe controlled substances must obtain a valid registration.
SAMHSA is the lead federal agency addressing substance abuse and  mental health services. Its mission is to build resilience and facilitate  recovery for people with or at risk for substance abuse and mental illness.  SAMHSA’s resources and programs are designed to expand service  capacity and improve service and infrastructure to address prevention and  treatment gaps. SAMHSA directly supports state and local service systems  and funds activities to improve practice through grants and contracts.  SAMHSA’s Center for Substance Abuse Treatment provides national  leadership to expand the availability of effective treatment and recovery  services for alcohol and drug problems, and to improve access, reduce  barriers, and promote high-quality, effective treatment and recovery  services for people with substance abuse problems and their families and  communities.
Under federal law and regulations, drugs must be approved by FDA before  they can be marketed in the United States. The agency reviews new drug  applications to determine whether they provide sufficient evidence that  the drug is safe and effective for the proposed use. In approving a drug,  FDA may require that the drug be dispensed only by a prescription by a  licensed practitioner. Because some risks may not become known until  after a drug’s approval and use in a wider segment of the population, FDA  has certain postmarket oversight responsibilities once a drug is approved,  such as assessing sponsors’ compliance with requirements for adverse  event reporting. The agency compiles data from sponsor reports on  adverse events, and voluntary reports submitted to its MedWatch program,  a voluntary reporting program through which health professionals and  consumers can report adverse reactions and other problems related to  FDA-approved drugs. In addition, as of 2008, if FDA identifies postmarket  safety concerns, the agency may take specific actions such as requiring  drug manufacturers to make safety-related changes to a drug’s labeling  and requiring drug manufacturers to implement a Risk Evaluation and  Mitigation Strategy when necessary to ensure that the benefits of a  particular drug outweigh the risks.
section_title: Overdose Death Investigation and Reporting
paragraphs: Death investigations in the United States are typically conducted by a  county, district, or state coroner system or a medical examiner system.  These systems investigate deaths due to external causes, such as injury or  poisoning; sudden and unexplained deaths; and deaths that occur under  medical care. Most coroners are elected, and they may not be physicians.  In contrast, medical examiners are usually appointed and are, with few  exceptions, required to be physicians and are often pathologists or  forensic pathologists.
The registration of deaths varies by state. Death certificates can be  completed by funeral directors, attending physicians, medical examiners,  or coroners and contain such information as the deceased person’s age,  sex, and race; the circumstances and cause of death; and the signature of  the physician, medical examiner, or coroner. Each disease, abnormality,  injury, or poisoning that the medical examiner or coroner believes  contributed to the death generally is reported. The original records are  filed in state registration offices. Statistical information is compiled in a  national database through the National Vital Statistics System by CDC’s  National Center for Health Statistics. From these data, monthly, annual,  and special statistical reports are prepared for the United States and for  cities, counties, states, and regions by various characteristics, such as sex,  race, and cause of death. However, statistical data derived from death  certificates can be no more accurate than the information provided on the  certificate. For example, causes of death on the death certificate reflect a  medical opinion that might vary among the individuals completing the  certificates.
section_title: Methadone Is Regulated as a Controlled Substance and Subject to Additional Requirements When Used for Addiction Treatment
paragraphs: Methadone is regulated as a controlled substance, under federal and state  laws and regulations, when used for pain management and addiction  treatment. When methadone is used for pain management, it is regulated  under federal and state laws and regulations that apply to controlled  substances generally and that do not impose requirements unique to  methadone. For addiction treatment, however, federal and state laws and  regulations impose additional requirements that are specific to the use of  methadone.
subsections: section_title: When Used for Pain Management, Methadone Is Regulated as a Controlled Substance under Federal and State Laws and Regulations
paragraphs: The use of methadone for pain management is regulated under federal and  state laws and regulations that apply to controlled substances generally  and that do not impose requirements unique to methadone. DEA has  certain authorities, under the Controlled Substances Act, to regulate the  use of methadone for pain management, as part of its oversight for  controlled substances. For example, practitioners must register with DEA  in order to dispense, administer, or prescribe Schedule II through V  controlled substances. The Controlled Substances Act and  implementing regulations also require that Schedule II controlled  substances, including methadone, only be dispensed by pharmacists upon  a written prescription, which must be issued for a legitimate medical  purpose by registered practitioners acting in the usual course of  professional practice. In addition, DEA uses its data on the distribution of  methadone and other controlled substances to identify retail-level  registrants, such as pharmacies, that receive and dispense unusual  quantities of these drugs. Under these authorities, DEA may take action  against practitioners that fail to prescribe or dispense controlled  substances, including methadone, for legitimate medical purposes, one  sanction of which is suspension or revocation of DEA registration.
The use of methadone for pain management is also regulated under state  law and regulations that apply to controlled substances generally. In the  states we reviewed, some of these requirements were similar to provisions  of the federal Controlled Substances Act. For example, these states  require, in general, that Schedule II controlled substances may only be  dispensed by pharmacists upon a written prescription of a practitioner.  States also may impose requirements beyond what is required under the  federal Controlled Substances Act. For example, officials in Maine said  that they require the use of tamperproof prescription notepads when  writing prescriptions for Schedule II drugs. However, none of the laws and  regulations in the five states we reviewed had any provisions specific to  methadone when used for pain management other than provisions that  generally apply to all Schedule II controlled substances.
Because states regulate the practice of medicine and pharmacy, controlled  substances that are prescribed, administered, or dispensed by state- licensed practitioners are also generally regulated under these state laws  and regulations. For example, in the states we reviewed, physicians must  be licensed by their state boards of medicine in order to engage in the  practice of medicine, which includes the prescribing of drugs. Similarly,  pharmacists must be licensed by their state boards of pharmacy in order to  engage in the practice of pharmacy, which includes the dispensing of  prescription drugs. Under this authority, the state medical boards and  state boards of pharmacy oversee the regulation of the practice of  medicine and pharmacy, respectively. As part of this oversight, these  boards or other related state agencies may investigate complaints about  practitioners, discipline practitioners that violate applicable laws or  regulations, and facilitate rehabilitation of practitioners when appropriate.
States and professional licensing boards may further regulate the  prescribing or dispensing of controlled substances for the treatment of  pain. According to the Federation of State Medical Boards, a number of  states have implemented standards for the use of controlled substances  for pain, including the five states we reviewed. Some of these states have  based these standards on the model policy for use of controlled  substances for the treatment of pain published by the Federation of State  Medical Boards. For example, Florida law expressly provides that  physicians may prescribe or administer controlled substances for the  treatment of intractable pain. Under its regulations, Florida’s Board of  Medicine and Board of Osteopathic Medicine also impose standards that  include steps physicians must take prior to prescribing controlled  substances for pain.
section_title: When Used for Addiction Treatment, Methadone Is Subject to Additional Requirements under Federal and State Laws and Regulations
paragraphs: Although methadone is subject to federal and state requirements that  apply to controlled substances, there are additional requirements specific  to methadone when used for addiction treatment. For example, as part  of its enforcement responsibilities under the Controlled Substances Act,  DEA has the authority to regulate the use of methadone for addiction  treatment. Under the act, OTPs must register with DEA in order to  dispense or administer methadone for addiction treatment, and there are  three conditions for this registration. Under the first condition of this  registration, DEA must determine that the OTPs will appropriately secure  stocks of methadone and maintain appropriate records. DEA officials  informed us that they also inspect OTPs in order to ensure that OTPs are  maintaining proper security, safety, and storage of methadone and other  narcotic drugs used for addiction treatment. DEA officials said that  inspections are conducted every 3 years, and there are a series of  graduated penalties if OTPs are not in compliance, including suspension or  revocation of OTP registration. If DEA suspends or revokes a registration,  that OTP would be unable to purchase, administer, or dispense methadone  to OTP patients for addiction treatment.
As a second condition of DEA registration for OTPs, SAMHSA must  determine that OTPs are qualified to engage in methadone maintenance  treatment for addiction. Federal opioid treatment regulations define  SAMHSA’s standards for determining whether OTPs are qualified.  Specifically, such standards include requiring OTPs to obtain a current,  valid certification from SAMHSA to dispense methadone for addiction  treatment. To obtain certification, an OTP must have a current, valid  accreditation by an accreditation body, such as the Joint Commission or  other entity designated by SAMHSA. An OTP also must comply with a  number of other requirements for certification established by SAMHSA.  These other requirements include maintaining a diversion control plan that  contains specific measures to reduce the possibility of diversion of  methadone from legitimate treatment to illicit use and ensuring that all  licensed professional care providers comply with the credentialing  requirements of their respective professions.
The third condition of DEA registration for OTPs requires SAMHSA to  determine that OTPs will comply with standards regarding unsupervised  take-home doses of methadone. SAMHSA has established specific criteria  for unsupervised take-home doses of methadone under federal regulations  for OTPs. (See table 1.) These criteria were established to limit the  potential for diversion of methadone to illicit uses. OTPs are also required  to maintain procedures for take-home doses of methadone that will allow  identification of the theft or diversion of these doses, such as by labeling  containers with the OTP’s name, address, and telephone number. For  additional information on select aspects of the federal regulations relating  to OTPs, see appendix II.
States may also regulate the use of methadone for opioid addiction  treatment under state laws and regulations, which may be equal to or  stricter than federal standards. For example, while federal regulations do  not specify the days or hours that OTPs must be open, regulations in three  of the states we reviewed—Kentucky, Maine, and West Virginia—require  that OTPs be open 7 days a week. Further, states may implement drug  testing requirements that are stricter than the federal standard of at least  eight random drug abuse tests per year for each patient in maintenance  treatment. For example, in Maine, drug tests on OTP patients must be  conducted at least every 30 days unless the individual treatment plan  indicates that drug testing should be done more frequently. Appendix II  compares OTP regulations in the five states we reviewed.
Each state with OTPs also has a state agency or official designated to  oversee opioid treatment in that state. Each of the five states we reviewed  had an official designated as the state methadone authority or state opioid  treatment authority, although responsibilities for this position varied and  these officials had other duties in addition to responsibilities in overseeing  the state’s OTPs. For example, a state official told us that the primary  responsibilities of the State Methadone Authority in West Virginia were to  approve or disapprove OTP patients’ requests for exceptions to  methadone take-home policies and to receive and refer patient appeals  and grievances to the designated state oversight agency. In contrast, in  addition to approving or disapproving take-home exception requests, a  state official explained that the State Opioid Treatment Authority in New  Mexico has initiated activities such as site audits of the eight existing  OTPs in the state to ensure compliance with state regulations. These  officials also have quarterly conference calls with SAMHSA and their  counterparts from other states to discuss issues regarding OTPs and best  practices.
section_title: Increased Availability Combined with Lack of Knowledge and Abuse of Diverted Methadone Have Contributed to Increasing Methadone- Associated Overdose Deaths
paragraphs: Although information on methadone-associated overdose deaths is  limited, available data suggest that methadone’s growing use for pain  management has increased availability of the drug, therefore contributing  to the rise in methadone-associated overdose deaths. Lack of knowledge  about the drug’s unique pharmacological properties among practitioners  and patients as well as abuse of diverted methadone also appear to have  contributed to these deaths. State data and research support the idea that  lack of knowledge and abuse of diverted methadone contributed to deaths,  but also suggest that the specific circumstances of these deaths are  variable.
subsections: section_title: Methadone’s Growing Use for Pain Management Has Increased the Drug’s Availability, Contributing to an Increase in Overdose Deaths
paragraphs: The growing availability of methadone through its increased use for pain  management is a contributing factor to the rise in methadone-associated  overdose deaths. DEA data show that from 2002 to 2007, distribution of  methadone to business types associated with pain management— pharmacies and practitioners—almost tripled, rising from about   2.3 millions grams to about 6.5 million grams. In contrast, distribution to  OTPs increased more slowly, from about 5.3 million grams to about   6.5 million grams. See table 2 for the numbers for methadone distribution  to four business types from 2002 through 2007. Similarly, data from IMS  Health, a private company that tracks prescription drug trends, showed  that from 1998 through 2006 the number of annual prescriptions of  methadone for pain increased by about 700 percent, from about 531,000 in  1998 to about 4.1 million in 2006.
Most officials from federal and state agencies, as well as experts in  addiction treatment and pain management that we spoke with, cited the  increased availability of methadone due to its use for pain management as  a key factor in the rise in deaths, while some added that addiction  treatment in OTPs was not related to increased deaths. Federal officials  and experts in epidemiology, pain management, and addiction treatment at  SAMHSA’s National Assessment of Methadone-Associated Mortality in  2003 also acknowledged a correlation between the increased distribution  of methadone through pharmacies for pain management with the increase  in methadone-associated overdose deaths and reached consensus that the  increase in these deaths was not associated with addiction treatment in  OTPs. Additionally, in 2006 CDC researchers suggested that the increase in  deaths involving methadone was related to physicians increasingly  prescribing the drug for pain. The researchers reported that the increase in  deaths tracked the increase in methadone used for pain management  rather than its use in OTPs.
To explain the increasing prescribing of methadone for pain management,  many officials and experts we spoke with mentioned the publicity  surrounding the increased abuse and diversion of the drug OxyContin in  the early 2000s as a reason for the increased prescribing of methadone for  pain. A November 2007 report by the National Drug Intelligence Center  (NDIC) also noted that following increases in OxyContin addiction and  death rates, many practitioners began using methadone instead to manage  pain.
section_title: Lack of Knowledge about Methadone by Practitioners and Patients Has Also Contributed to Methadone-Associated Overdose Deaths
paragraphs: Lack of knowledge about the unique pharmacological properties of  methadone by both practitioners and patients has also been identified as a  factor contributing to methadone-associated overdose deaths. Background  information prepared for SAMHSA’s 2007 Methadone Mortality  Reassessment meeting noted that physicians need to understand  methadone’s pharmacology as well as specific indications and cautions  before using it to treat pain or addiction. FDA has issued similar  statements, adding that practitioners should closely monitor patients when  starting treatment with methadone or converting patients to methadone  from other opioids. Some experts we spoke with advocated a “start low  and go slow” approach with methadone. Additionally, some pain  management specialists we interviewed warned that practitioners  following conversion tables, which are commonly used to switch patients  to methadone from other drugs, may start some patients on too high a  dose. The specialists explained that using these conversion tables for  patients who have already developed a tolerance for other opioids may be  lethal, because tolerance for other opioids is not equivalent to tolerance  for methadone.
Several sources have also cited inadequate training among some  practitioners. NDIC reported in 2007 that some general practitioners and  novice pain management specialists may lack the training to adequately  monitor patients to whom they prescribe methadone. A 2005 survey by the  National Center on Addiction and Substance Abuse found less than half of  surveyed physicians (48 percent) received instruction in pain management  while in medical school. DEA also noted that several of the top prescribers  of methadone have been practitioners with specialties not generally  associated with extensive training in pain management. Reports based on  SAMHSA’s 2003 National Assessment of Methadone-Associated Mortality  and 2007 Reassessment recommended that practitioners needed better  training in how to manage pain and addiction. Many experts,  representatives of national associations, and state officials we spoke with  agreed that more training in both pain and addiction treatment and about  methadone’s unique properties is needed for medical professionals.  However, opinions varied about whether such training should be optional  (e.g., offered for continuing education credit) or mandatory (e.g., required  for license renewal).
Insufficient patient education has also been cited as contributing to  methadone-associated overdose deaths. Patients may not understand how  methadone works, including that it can stay in the body long after the pain  returns. As a result, these patients might take methadone more frequently  than prescribed to manage their recurring pain, risking overdose as the  drug builds to toxic levels in their bodies. Unaware of potentially lethal  drug combinations, patients might also take methadone with other drugs,  including antianxiety drugs and other opioids, or alcohol.
section_title: Abuse of Diverted Methadone Is an Additional Contributing Factor to Methadone- Associated Overdose Deaths
paragraphs: Data suggest that abuse of diverted methadone is also contributing to the  rise in methadone-associated overdose deaths. Increased thefts as well as  seizures of methadone by law enforcement indicate that more diverted  methadone is available for potential abuse. DEA tracks drug abuse,  including the diversion of legally manufactured drugs such as methadone  into the illegal market, through its National Forensic Laboratory  Information System, which collects the results of state and local forensic  laboratories’ analyses of drugs seized as evidence by law enforcement  agencies. The DEA data on national estimates of the most frequently  analyzed drugs seized by law enforcement from 2001 through 2007 showed  that the number of methadone drug items analyzed by state and local labs  increased 262 percent, though the estimated number was smaller than that  of some of the other drugs (see table 3). In 2007, DEA reported that per  prescription, methadone was more likely to be diverted and abused than  either hydrocodone or oxycodone based on its analysis of data from the  National Forensic Laboratory Information System and IMS Health.
Likewise, DEA data on drug theft and loss showed that methadone thefts  nationwide more than doubled, from 176 in 2000 to 393 in 2007. For the  five states we reviewed, the data showed that most thefts were reported  from pharmacies, while no thefts were reported from OTPs in four of  these states during the same time period.
Federal and state officials told us that abuse of prescription drugs,  including methadone, has become more of a problem in recent years than  abuse of illicit drugs, such as heroin or cocaine. Officials from ONDCP  said that overall opioid drugs are being increasingly diverted and abused,  while abuse of illicit drugs is decreasing. SAMHSA’s National Survey on  Drug Use and Health provides some additional information about where  those who are abusing prescription pain relievers, such as methadone,  obtain their drugs. According to the 2007 survey, among the estimated 5.2  million persons aged 12 or older who reported using prescription pain  relievers nonmedically in the past 12 months, 56.5 percent said they got  the drugs from a friend or relative, another 18.1 percent reported that they  got the drug from just one doctor, 4.1 percent reported that they got the  pain relievers from a drug dealer or other stranger, and 0.5 percent  reported buying the drug on the Internet.
section_title: State Data and Research Support That Lack of Knowledge and Abuse of Diverted Methadone Contribute to Deaths, but Death Circumstances Are Variable
paragraphs: Data and research regarding methadone-associated overdose deaths in the  five states we reviewed support the idea that lack of knowledge and abuse  of diverted methadone contributed to deaths, but also suggest that the  circumstances under which people are dying are variable. Specifically,  state data and research show that death circumstances, such as the source  of the drug and the most commonly detected other drugs, may vary by  state. Furthermore, participants at SAMHSA’s 2007 Methadone-Associated  Mortality Reassessment concurred that the circumstances of methadone- associated overdose deaths vary by state. While research suggests that the  source of methadone for those who die from overdose deaths is often  unknown, available information indicates that there are three distinct  populations who are dying: individuals with a prescription for methadone;  individuals undergoing methadone maintenance treatment in OTPs; and  individuals who obtained methadone from some other source, such as  diversion. However, generally more of those who died had a prescription  for methadone or obtained it through diversion rather than receiving  methadone for addiction treatment in an OTP. For example, a Kentucky  study of deaths from 2000 to 2004 found that of the 95 deaths for which  coroners documented methadone use, 48 percent of those who died had a  physician’s prescription for methadone, 20 percent obtained methadone  through illicit means, 22 percent obtained methadone through unknown  means, and 10 percent had received treatment in OTPs. Coroners’  investigations also documented that one-third of the victims had been  undergoing pain management. A New Mexico study of unintentional  methadone-associated overdose deaths from 1998 to 2002 found that  although a much larger percentage of deaths were related to methadone  maintenance treatment than in the other states we reviewed, more deaths  overall were linked with prescriptions for methadone. Specifically, of the  79 methadone-associated overdose deaths for which a source of  methadone was available, 39 percent had methadone because they were  undergoing methadone maintenance treatment, while 47 percent had a  prescription for methadone. See appendix III for a summary of the  findings of research studies in the five states we reviewed.
In addition, data and research from the five states we reviewed show that  methadone is often found in combination with other drugs or alcohol,  suggesting a lack of knowledge about the dangers of combining  methadone with other drugs or that people are abusing methadone. In  Florida, for example, of the 1,095 methadone-associated overdose deaths  in 2007, 124 deaths were caused by methadone alone, while 971 deaths, or  about 89 percent, were caused by methadone in combination with other  drugs. The Kentucky study found that only 6 percent of the 176  methadone-associated overdose deaths were caused by methadone alone;  other frequently detected drugs included antidepressants,  benzodiazepines, and other opioids. The New Mexico study showed  somewhat different results, and found that of the 143 methadone- associated overdose deaths, 22 percent were due to methadone alone,   24 percent were due to methadone and prescription drugs (no illicit  drugs), 50 percent were due to methadone and illicit drugs, and 4 percent  were due to methadone and alcohol.
section_title: Education, Safety, and Monitoring Efforts to Prevent Methadone- Associated Overdose Deaths Have Been Implemented by Government Agencies and Other Organizations
paragraphs: Education, safety, and monitoring efforts have been implemented to  prevent methadone abuse and methadone-associated overdose deaths— either specifically or as part of broader efforts to prevent prescription drug  abuse and deaths—by various federal agencies, states, and other  organizations. Educational efforts include physician training on the  appropriate use of methadone to treat pain and opioid addiction, and  public education campaigns about the dangers of methadone and other  prescription drugs. Steps taken to improve the safety of using methadone  include limiting the distribution of a high-dosage methadone tablet  intended only for use in addiction treatment. In addition, states may  monitor prescriptions of controlled substances as well as OTP patient  enrollment through statewide registries.
subsections: section_title: Efforts to Educate Practitioners and the Public about Methadone and Other Prescription Drugs Have Been Initiated by Federal Agencies, States, and Other Organizations
paragraphs: Because lack of knowledge of methadone’s unique properties has  contributed to overdose deaths, federal and state officials and other  experts agreed that more education is needed for practitioners and the  public about how to safely use methadone and avoid its potential dangers.  A number of efforts to educate practitioners and the public about how to  use methadone and other prescription drugs safely have been initiated by  federal agencies, states, and other organizations. Some of these efforts  target methadone specifically while others are more broadly focused on  using opioids to treat pain and preventing prescription drug abuse. Some  officials and experts we spoke with cautioned that methadone is part of a  larger problem of prescription drug abuse, and that prevention efforts  focused on methadone alone might have the unintended consequence of  shifting similar problems to a different drug—much like what occurred  with methadone following reports of abuse and diversion of OxyContin.
subsections: section_title: Educational Efforts Targeted at Methadone
paragraphs: In August 2008, SAMHSA announced a 3-year grant of $1.5 million to the  American Society of Addiction Medicine to educate physicians and other  practitioners on the appropriate use of methadone to treat pain and opioid  addiction. The grant is to establish the Physician Clinical Support System  for methadone, offering free support to prescribing physicians and other  practitioners. SAMHSA reported that this system would include mentoring  support, observation of practice, and consultative services by phone and e- mail. The system would also inform prospective practitioners through a  Web site and published resources about science-based best practice  guidelines for treating opioid addiction. According to SAMHSA, this  initiative would aim to address the rise in methadone-associated overdose  deaths spurred by misuse and abuse.
SAMHSA also has several current or planned educational initiatives  focusing on OTPs. A risk management course for practitioners will focus  on the safe use of methadone in OTPs, with a special emphasis on the  beginning of treatment. The course will also educate OTP practitioners  about using other drugs in conjunction with methadone, including  benzodiazepines. In addition, SAMHSA is working with two work groups  that include experts from academia, medical associations, medical  researchers, and other federal agencies, such as FDA, to develop  additional methadone-specific guidelines. One work group is reviewing  available information to develop best practices on methadone and cardiac  issues. The guidance will help practitioners identify patients at risk for  cardiac arrhythmias that may be exacerbated by methadone, and provide  information on how to monitor those patients for ongoing risks. Another  work group is reviewing methadone interactions with other common  drugs, including HIV drugs. The ensuing guidelines will help practitioners  safely treat patients who may be receiving several drugs simultaneously.
SAMHSA is also collaborating with FDA on a consumer education  campaign designed to increase awareness of the potential for serious, life- threatening side effects in patients taking methadone for pain management  or addiction treatment. FDA reports that the multimedia educational  campaign would target OTPs and patients, pharmacies dispensing  methadone, practitioners, and the public. According to FDA, materials  developed for the campaign would include a brochure or flyer, fact sheets,  podcasts, and online information. SAMHSA reported that the materials  were scheduled to be finished by April 2009.
section_title: Educational Efforts Targeted at Opioids and Other Prescription Drugs
paragraphs: SAMHSA, along with the American Academy of Pain Medicine, the  American Academy of Family Practitioners, and other medical  organizations, has developed a continuing medical education course on  how to safely use prescription pain relievers to treat pain. As of February  2009, 20 courses had been taught in 16 states. SAMHSA reported that 12  courses would be taught in 2009 and that priority would be given to states  or regions with high per capita rates of opioid-associated overdoses and  deaths. A brief Web-based version of the course has been developed in  collaboration with MedScape, an online medical education company.  Further, a five-module online version of the course will be posted on  SAMHSA’s Web site and disseminated through medical organizations and  medical schools that offer continuing education credits.
The Federation of State Medical Boards developed a book, Responsible  Opioid Prescribing: A Physician’s Guide, in collaboration with a national  pain expert. The book includes strategies for treating chronic pain and  reducing the risk of addiction, abuse, and diversion. The federation  intends to distribute the book through state medical boards, and reports  that medical boards can customize the book to include state-specific  statutes, regulations, and guidelines. The federation reported that more  than 60,000 copies of the book had been distributed in 13 states as of  October 2008, and it intends to expand distribution in 2009 as more funds  are raised.
Officials in the five states we reviewed told us about their states’ efforts to  educate practitioners and the public about controlled substances and drug  abuse. For example, Kentucky’s Operation UNITE (Unlawful Narcotics  Investigations, Treatment, and Education) works to rid communities of  illegal drug use, coordinate treatment and support for substance abusers,  and educate the public on the dangers of drug use. New Mexico’s Board of  Pharmacy participates in the New Mexico Pain Policy Initiative, which  educates practitioners on requirements for prescribing controlled  substances and for New Mexico’s Prescription Drug Monitoring Program.  In West Virginia, law enforcement officials, physicians, and others have  formed a controlled substance advisory board to address prescription drug  abuse. One of its projects is to educate patients on the dangers of  diversion by providing them with information when they pick up their  prescriptions from pharmacies and to educate physicians about how to  reduce doctor shopping. In addition to the five states we reviewed, Utah  has also experienced rising prescription drug overdose deaths and has  implemented two notable campaigns intended to reduce deaths and other  harm from prescription drugs. The Use Only as Directed campaign  educates the public about protecting themselves from unintentional  overdose deaths. The Zero Unintentional Deaths campaign educates  physicians, chronic pain sufferers, and communities about unintentional  overdose deaths from prescription drugs.
Federal agencies have also begun educating the public about prescription  drug abuse. For example, in January 2008, the ONDCP through its National  Youth Anti-Drug Media Campaign launched a national television, print, and  online advertising campaign to educate parents about teen prescription  drug abuse. The campaign includes tips for preventing teen prescription  drug abuse, such as safeguarding all drugs at home, monitoring drug  quantities, and properly concealing and disposing of old or unused  medicines in the trash. SAMHSA also piloted a public education program  called SMART Rx in which participating pharmacies inform customers  about controlled substances when they fill prescriptions. The information  provided covers the risks and dangers associated with the opioid or  benzodiazepine medication, steps to keep the medication from  adolescents, and safe disposal of unused medications. SAMHSA reported  that evaluations suggested that consumers found the content useful and  kept the information for future reference or shared it with someone else.
section_title: DEA and FDA Have Taken Steps to Improve the Safety of Using Methadone
paragraphs: Both DEA and FDA have taken steps to improve the safety of using  methadone. DEA officials told us that the agency formed a methadone  mortality working group in 2006 to review information related to the  increases in methadone-associated overdose deaths, including DEA  methadone distribution data and data from other federal agencies, such as  FDA and CDC. The data showed that methadone 40 mg diskettes had been  increasingly prescribed for pain, despite only being FDA approved for  addiction treatment in OTPs—a practice described as off-label  prescribing. Some experts said that if prescribed for pain to a person  without a tolerance to opioid drugs, an initial dose of 40 mg could  potentially be deadly. DEA data show that distribution of the methadone  40 mg diskettes to retail pharmacies increased almost sixfold from about  350,000 grams in 2002 to about 2 million grams in 2007. At the same time,  distribution to OTPs fell slightly from about 1.4 million grams to 1.2 million  grams. Following their review, DEA officials told us that they became  concerned about the diskette’s increased use for pain management. DEA  then worked with methadone manufacturers, which agreed to voluntarily  restrict distribution of the diskettes to only OTPs and hospitals. Because  the restriction began January 1, 2008, it is too soon to determine any effect  on methadone-associated overdose deaths. DEA reported that it would  continue monitoring methadone distribution and prescription data to  evaluate the impact of the initiative.
In November 2006, FDA approved a revised label for methadone 5 mg and  10 mg tablets that included new safety information regarding using  methadone for pain, such as warnings about life-threatening adverse  events and modified dosage instructions. The revised label states that  methadone can cause slow or shallow breathing and dangerous changes in  heartbeat that may not be felt by the patient. The new dosage instructions  for methadone prescribed for pain state that the usual initial dose should  be 2.5 mg to 10 mg taken every 8 to 12 hours, or a maximum daily dose of  30 mg, slowly adjusted for effect. The previous instructions allowed initial  total daily doses up to 80 mg a day, which several experts said could be  hazardous or even deadly. As FDA approved the revised methadone label,  it also issued a public health advisory for health care professionals and  patients, stating that prescribing methadone is complex and that it should  only be prescribed for patients with moderate to severe pain when their  pain is not improved with other non-narcotic pain relievers. The advisory  noted that FDA had received reports of life-threatening side effects and  death in patients taking methadone, both those newly starting methadone  for pain control and those who have switched to methadone after being  treated for pain with other strong narcotic pain relievers.
Additionally, in February 2009, FDA sent letters to manufacturers of  certain opioid drugs, including methadone, indicating that these drugs will  be required to have a Risk Evaluation and Mitigation Strategy to ensure  that the benefits of the drugs continue to outweigh the risks. In the first of  a series of meetings, FDA invited those companies that market the  affected opioid drugs to a meeting with the agency in March to discuss  strategy development. Additional steps will include discussions with other  federal agencies, patient and consumer advocates, representatives of the  pain and addiction treatment communities, health care professionals, and  other interested parties. FDA is planning a public meeting in late spring or  early summer to allow for broader public input and participation in this  process.
section_title: States May Monitor Prescriptions for Controlled Substances and OTP Patient Enrollment to Prevent Abuse and Diversion
paragraphs: States may monitor prescriptions for controlled substances and OTP  patient enrollment to prevent abuse and diversion. Prescription drug  monitoring programs facilitate the collection, analysis, and reporting of  information about the prescribing, dispensing, and use of controlled  substances such as methadone. DEA reported that as of February 2009, 31  states had operational prescription drug monitoring programs to help  prevent abuse and diversion of controlled substances, including  methadone, and 4 of the 5 states we reviewed had operational programs.  These programs may provide information to practitioners on patients and  to other entities, such as licensing boards, on prescribing and dispensing  practices of practitioners, or state law enforcement and regulatory  agencies, to assist in identifying and investigating activities potentially  related to the illegal prescribing, dispensing, and procuring of controlled  substances. According to the Alliance of States with Prescription  Monitoring Programs, states have found that these programs are among  the most effective tools to identify and prevent drug diversion at the  practitioner, pharmacy, and patient levels. CDC officials told us that they  have a study under way to evaluate the impact of state prescription drug  monitoring programs on drug overdose deaths.
Prescription drug monitoring programs may vary in ways such as what  data must be submitted and who has access to the information. For  example, with respect to access to prescription monitoring data, West  Virginia allows authorized agents of the state police and federal law  enforcement agencies to have access to prescription monitoring data. In  contrast, in Maine, access by law enforcement is more limited as law  enforcement officials can access prescription monitoring data only by  grand jury subpoena for cases they are currently investigating. See  appendix IV for a comparison of some of the characteristics of the four  prescription drug monitoring programs we reviewed.
However, prescription drug monitoring programs have limitations. Their  usefulness depends on practitioners using the programs, and in the four  states we reviewed with prescription drug monitoring programs,  practitioners’ use was not widespread, according to state officials. In  addition, not every state has a prescription drug monitoring program, and  state officials we spoke with said that people would sometimes cross state  borders to obtain prescription drugs in a state without a program.  Furthermore, while DEA reports that several states’ programs have the  capability of generating reports on out-of-state prescribers or patients,  they do not routinely disseminate this information to other states.  Another limitation of prescription drug monitoring programs mentioned  by state officials was the lack of patient data on methadone dispensed in  OTPs and from federal facilities such as Department of Veterans Affairs’  hospitals or Indian Health Service facilities. Therefore, in the four states  we reviewed with a prescription drug monitoring program, data on any  prescription drugs received by patients at these types of facilities would  not be captured by the program.
States may also create systems to monitor the population of patients  enrolled in OTPs. To monitor their patients, OTPs in Florida created a  central registry designed to ensure that patients do not enroll in multiple  OTPs within the state, thus preventing patients from receiving unsafe  levels of methadone or additional methadone that could be diverted.  Officials said that each OTP patient is given a unique identifier and a  picture is taken and entered into the registry. All Florida OTPs, both  nonprofit and for-profit, use the registry, according to state officials.
section_title: Agency Comments
paragraphs: We provided a draft of this report to HHS and the Department of Justice  for their review. We received general comments from HHS. (See   app. V.) HHS provided clarification that in 1947 when federal law only  required that new drugs be shown to be safe, FDA approved methadone as  safe for pain management. When the law was amended in 1962 to impose  additional requirements for the approval of new drugs, FDA  retrospectively reviewed the efficacy of methadone for the treatment of  pain. In addition, HHS stated that an attempt by FDA to restrict the  distribution of methadone for pain was struck down by a court in the  1970s. HHS also reiterated that FDA recently sent letters to the  manufacturers of certain opioid drug products, including methadone,  indicating that these drugs will be required to have a Risk Evaluation and  Mitigation Strategy to ensure that the benefits of the drug continue to  outweigh the risks. Both HHS and the Department of Justice provided  technical comments on a draft of this report, which we incorporated as  appropriate.
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If you or your staffs have any questions about this report, please contact  me at (202) 512-7114 or kingk@gao.gov. Contact points for our Offices of  Congressional Relations and Public Affairs may be found on the last page  of this report. GAO staff who made major contributions to this report are  listed in appendix VI.
section_title: Appendix I: Scope and Methodology
paragraphs: To examine the regulation of methadone for pain management and  addiction treatment, we reviewed relevant codified federal statutes and  regulations pertaining to the prescribing, administering, or dispensing of  methadone for pain management and addiction treatment. Our review was  limited to relevant provisions of the Controlled Substances Act and  implementing regulations, including Department of Justice, Drug  Enforcement Administration (DEA), and Substance Abuse and Mental  Health Services Administration (SAMHSA) regulations. We also examined  federal case law and relevant federal agency policies, including DEA’s  policy statement on dispensing controlled substances for the treatment of  pain. We interviewed officials at relevant federal agencies, including  SAMHSA and DEA. We also interviewed officials and reviewed  information from relevant national associations, including the Federation  of State Medical Boards.
In addition, we interviewed officials and examined relevant codified  statutes and regulations in five selected states. The states we reviewed  were Florida, Kentucky, Maine, New Mexico, and West Virginia. Each of  the states met four or more of the following criteria:    a top 10 rate of increase in methadone-associated overdose deaths from    a top 10 number of methadone-associated overdose deaths per 1,000,000    a state or district medical examiner system,    an operational prescription drug monitoring program, and    state-focused, methadone-specific research.
We examined how the prescribing, administering, or dispensing of  methadone for pain management and addiction treatment were regulated  in our five selected states. We only examined codified state statutes and  regulations containing requirements relating to the administering or  dispensing of methadone in opioid treatment programs (OTP) and the  prescribing, administering, or dispensing of controlled substances to  individuals for medical purposes, including pain management. In each  state we interviewed officials from the state agency with oversight of  OTPs, state boards of medicine and pharmacy, and law enforcement  officials. The findings from our review of these five states cannot be  generalized to all states.
To determine the factors contributing to the increase in methadone- associated overdose deaths in recent years, we interviewed officials from  the Centers for Disease Control and Prevention (CDC), DEA, the Food and  Drug Administration (FDA), the National Drug Intelligence Center (NDIC),  the National Institutes of Health, the Office of National Drug Control  Policy (ONDCP), and SAMHSA. We also interviewed professional  association officials from the American Association for the Treatment of  Opioid Dependence, the Federation of State Medical Boards, HARMD  (Helping America Reduce Methadone Deaths), the National Alliance of  Methadone Advocates, the National Association of Boards of Pharmacy,  the National Association of Medical Examiners, the National Association  of State Alcohol and Drug Abuse Directors, and the National Association  of State Controlled Substances Authorities. In addition, we interviewed  pain management, addiction treatment, and forensic science experts.
We reviewed national reports, including reports based on the 2003  SAMHSA Methadone Mortality Assessment and 2007 Reassessment and a  November 2007 NDIC report on methadone mortality. We reviewed CDC  methadone poisoning death data from the National Vital Statistics System,  which tabulates information reported on death certificates. We  interviewed CDC officials to obtain information about the reliability of  their methadone mortality data, including how CDC ensures the quality of  the data and any data limitations. In addition, we interviewed officials in  our five selected states’ medical examiners’ offices about the factors  contributing to the increase in methadone-associated overdose deaths in  their states. We also reviewed state data and studies from our five selected  states and interviewed researchers about their efforts to investigate  methadone-associated overdose deaths in their states. However, because  there is no standard definition for what constitutes a methadone- associated overdose death, there may be some variation in how states  define this term and how they report these numbers. For example, data  from Florida distinguish whether methadone was simply present or was  the cause of death, but not all states make this distinction. Defining  methadone’s role in a death can also be complicated by inconsistencies in  determining and reporting causes of death, by the presence of other drugs,  and by the absence of information about the source of methadone and the  deceased person’s level of opioid tolerance. Results from these five state  studies cannot be generalized to other states.
We reviewed relevant DEA data, including Automation of Reports and  Consolidated Orders System (ARCOS) data, DEA National Forensic  Laboratory Information System (NFLIS) data, and DEA Theft and Loss  data.
ARCOS is an automated drug reporting system that monitors the flow of  DEA controlled substances from the point of manufacture through  commercial distribution channels to the point of retail sale or distribution,  including hospitals, retail pharmacies, practitioners, midlevel  practitioners, and teaching institutions. ARCOS summarizes these  transactions into reports, which give federal and state government  investigators information that can then be used to identify the diversion of  controlled substances into illicit channels of distribution.
NFLIS systematically collects results from solid dosage drug analyses  conducted by state and local forensic labs across the country. NFLIS  provides information for monitoring and understanding drug abuse and  trafficking involving both controlled and noncontrolled substances in the  United States, including the diversion of legally manufactured drugs into  illegal markets. As of March 2007, 44 state lab systems and 94 local lab  systems, comprising 274 individual labs, were participating. Because  NFLIS is a voluntary reporting system and the number of participating  state and local laboratories has changed over time, DEA officials  recommended that we report the NFLIS national estimates of analyzed  drug items, instead of the actual numbers, to show trends over time, which  they said would not be affected by the number of labs participating each  year. DEA’s national estimates are calculated every year based on a  national sample model of state and local laboratories. DEA officials told us  they began producing national estimates in 2001.
DEA’s Theft and Loss database collects data on theft and loss of controlled  substances by number of thefts; drug and dosage forms; business type,  including pharmacies, hospitals, and manufacturers; and type of theft,  such as night break-in or armed robbery. DEA registrants are required to  report theft and loss of controlled substances to DEA. Although the  database contains information on the forms of controlled substances lost  or stolen, DEA officials told us there is no standard liquid dosage unit that  would allow us to provide the total volume of liquid methadone stolen;  therefore, we did not report thefts by form of methadone.
We interviewed DEA officials to learn about data collection; quality  control, such as edit checks; and any limitations of these databases. We  determined that these three sources of data were sufficiently reliable for  use in this report, and included any limitations identified.
To determine steps taken to prevent methadone-associated overdose  deaths, we interviewed officials at relevant federal agencies, including  CDC, DEA, FDA, ONDCP, and SAMHSA. We also interviewed officials  from relevant national associations, including the Federation of State  Medical Boards, National Association of Medical Examiners, and National  Association of State Controlled Substances Authorities, and experts in  pain management, addiction treatment, and forensic science. In addition,  we reviewed relevant studies and reports about efforts to prevent  methadone and other prescription drug overdose deaths and interviewed  officials in our five selected states to learn about initiatives in their states.  To obtain additional information about prescription drug monitoring  initiatives, we examined relevant codified statutes and regulations in our  five selected states. We only reviewed codified state statutes or  regulations relating to systems that monitor the prescribing of controlled  substances. The findings from our review of these five states cannot be  generalized to all states.
Because many efforts under way to prevent methadone-associated  overdose deaths are new, their effectiveness has not yet been evaluated.  Also, because we interviewed experts, officials from select organizations,  and state officials, our findings do not represent all efforts to prevent these  deaths. Finally, because methadone is part of a larger problem of  prescription drug abuse and overdose deaths, many of the efforts are not  focused on methadone alone.
We conducted our work from November 2007 through February 2009 in  accordance with all sections of GAO’s Quality Assurance Framework that  are relevant to our objectives. The framework requires that we plan and  perform the engagement to obtain sufficient and appropriate evidence to  meet our stated objectives and to discuss any limitations in our work. We  believe that the information and data obtained, and the analysis  conducted, provide a reasonable basis for any findings and conclusions.
section_title: Appendix II: Comparison of Federal and Selected States’ OTP Regulations
paragraphs: The following table describes selected requirements of the federal OTP  regulations, as well as selected requirements of the OTP regulations in  Florida, Kentucky, Maine, New Mexico, and West Virginia.
Before a client  receives an initial  dose of  methadone or  other medication,  physician must  document current  physiological  addiction, history  of addiction and  exemptions from  criteria for  admission. (§ 65D- 30.014(4)(e)(1)) -Dose means a  1-day quantity of  an approved  controlled  substance,  administered on  site, in not less  than 1 fluid  ounce of an oral  solution,  formulated to  minimize misuse  by injection.  (1:340.1(7))
Initial doses of  methadone  must not  exceed 30 mg  unless the  physician  documents the  need for a  higher dose.  (§ 19.8.6.5) -Initial dose must  not exceed   30 mg.  -If 30 mg does not  reduce withdrawal  symptoms, may  provide additional  10 mg only if  documented. -The initial full- day dose of  medication shall  be based on the  physician’s  evaluation of the  history and  condition of the  patient. -If 40 mg does not  reduce withdrawal  symptoms, may  provide additional  dose only if  documented. -Usual initial dose  of methadone  should be 20 to  30 mg. Reasons  for exceeding an  initial dose of   30 mg must be  documented. -Proposed  programs must  include in their  applications  initial and daily  dosage levels  and daily dosage  levels.  (1:340.4(3)(x),  (y)) -Subsequent  doses are based  on the patient’s  needs.  (§ 7.32.8.21(D)) -Medical record  must indicate  reason for dose  changes and  must be signed  by the medical  director or  program  physician.  (1:340.6(5)) -Initial dose  should not  exceed 40 mg  unless physician  or prescribing  professional  documents that  symptoms were  not suppressed  after a 3-hour  period of  observation.  -Justification for  daily doses  above 100 mg  must be  documented.  (§ 64-90-35)
Must consider the  following criteria  in determining  patient eligibility:  -Phase 1: No  program  infractions for 90  consecutive  days. -No evidence of  recent drug abuse. -Absence of  recent drug  abuse, including  alcohol abuse. -Cessation of  illicit drug use. -Phase 2: No  program  -Results of drug  tests must be  reviewed and  considered as  part of the  treatment  planning  process and  decisions for  take-home  -Regularity of  program  attendance. -Regular  attendance at  OTP. dosing.  (§ 19.8.6.6) -No serious  behavioral  problems at the  OTP. -Length of time in  comprehensive  maintenance  treatment. -No recent criminal  activity.  -Stable home  environment and  social  relationships. infractions for  180 consecutive  days; pursuing  one of the  following: gainful  employment,  vocational  training, higher  education,  volunteer  opportunities, or  parenting  classes if a stay- at-home parent. -All decisions  regarding take- home privileges  shall be  documented in  the client record  and shall  comply with the  requirements  cited in 42  C.F.R. pt. 8.  (§ 19.8.10.1) -Length of time  and level of  treatment in  medication  therapy (ability to  self-medicate). -Absence of  known criminal  activity. -Absence of  recent criminal  activity. -Sufficient length  of time in  treatment. -Absence of  serious  behavioral  problems at the  program. -Absence of  serious  behavioral  problems. -Assurances that  take-home  medication can be  stored safely. -Phase 3: No  program  infractions for  270 consecutive  days; same entry  requirements as  for phase 2. -Special needs  such as physical  health needs. -Absence of  abuse of drugs,  including  excessive use of  alcohol. -Assurance that  medication can  be safely stored  in patient’s home. -Satisfactory  progress in  treatment to  warrant  decreasing the  frequency of  attendance. -Stability of  patient’s home  environment and  social  relationships. -Other special  needs of the  patient, such as  split dosing,  physical health  needs, pain  treatment, etc.  -Capacity to  safely store take- home medication. -Verifiable source  of legitimate  income.  (§ 65D- 30.014(5)(d)) -Phase 4:  Successful  completion of  phase 3 and  adhered to  program  requirements for  2 consecutive  years.  (1:340.11) -Patient’s work,  school, and daily  activity schedule.  -Hardship  traveling to and  from the program. -Stability of the  home  environment and  social  relationships. -Rehabilitative  benefit outweighs  the potential risk  of diversion.  (§ 7.32.8.23(B)) -Patient’s work,  school, or other  daily life activity  schedule.  -Hardship in  traveling to and  from the program.
Program  physician may  approve  temporary  unsupervised  take-home doses  for documented  emergencies or  other exceptional  circumstances.  (§ 64-90-41) -Days 1-90: No  take-home  doses. -Must be available  to all methadone  clients during  holidays, but only  if clinically  advisable.  (§ 65D- 30.014(4)(g)) -Phase 1: One  take-home dose  per week.  -Phase 2 and 3:  Up to two take- home doses per  week. -Take-home  methadone  shall be  dispensed in  liquid form only  in single dose  containers, or in  dry form only in  multiple dose  containers. -A patient in  comprehensive  maintenance  treatment may  receive a single  dose of take- home medication  for each day that  a provider is  closed. -For the first   90 days of  treatment: A  single take-home  dose for the week  of each holiday  that the clinic is  closed. -Phase 4: Up to  three take-home  doses per week. -No take-home  doses permitted  during the first   30 days in  treatment unless  approved by the  state authority. -No take-home  privileges  during the first  90 continuous  days of  treatment. -During the first  90 days, One  take-home dose  per week  maximum. -First 30 days of  treatment: No  take-home doses  except the  holiday dose. -Clients in  continuous  treatment may  qualify with  negative drug  screens as  follows:  -91-180 days:  One take-home  dose per week. -91-180 days:  Two take-home  doses per week  maximum. -31-90 days: One  take-home dose  per week plus the  holiday dose.  -91-180 days:  Two take-home  doses per week. -181-270 days:  Two take-home  doses per  week. -181-270 days:  Three take-home  doses per week  maximum. -Phase I: Days 31- 90 – one take- home dose per  week. -181-270 days:  Three take-home  doses per week.  -Remainder of  the first year:  Maximum 6-day  supply. -Phase II: Days  91-180 – two take- home doses per  week. -Second year of  treatment:  Maximum 13-day  supply. -Phase III: Days  181-1 year – three  take-home doses  per week with no  more than a 2-day  supply at any one  time. -Under  emergency  conditions, a  program may  issue 14  consecutive  days of take- home doses  without  notification of  Center for  Substance  Abuse  Treatment  (CSAT); must  notify state  narcotic authority  and request an  exception to  dosing  procedures. -271-360 days:  Three take- home doses per  week.  -361 days  onward: Six  take-home  doses per  week.  (§ 19.8.10) -For the  remaining months  of the year,   6 days of  medication  maximum per  week. -Certain  exceptions for  emergencies.  (§ 19.8.12) -After 1 year of  continuous  treatment,  maximum 2-week  take-home  supply. -After 2 years of  continuous  treatment:  Maximum   1-month supply  with monthly  visits. -Phase IV: After   1 year – four take- home doses per  week with no more  than a 2-day  supply at a time. -After 2 years,  maximum of   1-month take- home supply, but  must make  monthly visits. -Phase V: After   2 years – five  take-home doses  per week with no  more than a 3-day  supply at a time. -Medical director  or program  physician may  grant an  exception,  subject to written  approval from  state narcotic  authority for  clients with  serious physical  disabilities or  subject to  exceptional  hardship. -Exceptions made  only as provided  by federal OTP  regulations and  as approved by  the state  methadone  -State authority  may approve  exceptional  unsupervised  doses on a case- by-case basis if  the program  physician applies. (§ 64-90-41.6,  41.7) -Phase VI: After   3 years in  treatment – six  take-home doses  per week.  (§ 65D- 30.014(5)(e)) -State narcotic  authority may  grant additional  exceptions for  medical  emergency or  natural disaster. (1:340.11,  1:340.16) authority.  (§ 7.32.8.23(C),  (D)) -Must be open  Monday through  Saturday.
Must be open   7 days a week  with the optional  exception of nine  specified  holidays.  (1:340.6(16))
Must be open   7 days weekly,  including all  holidays.  (§ 19.8.4.2) -Must have  medicating hours  and counseling  hours that  accommodate  clients, including   2 hours of  medicating time  daily outside of  9:00 a.m. to   5:00 p.m.
Must be open  every day of the  week except for  federal and state  holidays, and  Sundays, and be  closed only as  allowed in  advance in writing  by CSAT and the  state methadone  authority.  (§ 7.32.8.18(C)) -Must provide   24-hour, 7-day a  week access to  designated  program staff so  that patient  emergencies may  be addressed  and dosage  levels verified.  (§ 64-90-20.1.c) -Must medicate on  Sundays  according to client  needs. -Must be open   7 days per week,  but may close for  eight holidays  and two training  days per year.  (§ 64-90-41.6.a) -Must give a  minimum of a   7-day notice for  observed holidays. -No two holidays  can occur in  immediate  succession unless  provider is granted  an exemption by  the federal  authority.  -On days when  provider is closed,  services must be  accessible to  clients for whom  take-out  methadone is not  clinically  advisable. (§ 65D- 30.014(4)(g))  -Must participate  in regional registry  activities for the  purpose of sharing  client identifying  information with  other providers  located within a  100-mile radius, to  prevent the  multiple enrollment  of clients at more  than one provider.
Proposed  programs must  include in their  applications a  system to  prevent client’s  multiple program  registration.  (1:340.4(3)(k)) -Must make and  document good  faith efforts to  determine that a  patient seeking  admission is not  receiving opioid  dependency  treatment  medication from  any other source,  within the bounds  of all applicable  patient  confidentiality  laws and  regulations. -Must have a  procedure for  ensuring that  patients are not  enrolled in more  than one OTP.
Prior to  admitting a  client, must  confirm using  the Office of  Substance  Abuse’s system  that client is not  currently  enrolled in  another OTP. If  system is  unavailable,  must check with  all OTPs within  3 calendar days  of admission.  (§ 19.8.4.4-5) -When  practicable, must  obtain a release  of information  from the patient  in order to check  the records by  telephone or fax  of every OTP  within 100 miles  to ensure that the  patient is not  currently enrolled  in other  programs. -A record of  violations by  individual clients  shall become part  of the record  maintained in an  automated system  that may be  accessed by all  participating  providers.  (§ 65D- 30.014(4)(f)(1),  (7)) -The release  must state that  only prior  admissions may  be the subject of  inquiry, not  contacts without  admission. -Must confirm that  the patient is not  receiving  treatment from  any other OTP,  except under  exceptional  circumstances,  within a 50-mile  radius of its  location, by  contacting any  such program or  by using the  central registry,  when established. -Results of the  check must be  placed in the  clinical record. -The Department  of Health may  establish an  Internet-based  registry of all  current patients of  a New Mexico  OTP for the  purpose of  creating a system  that prevents  patients from  receiving  medication from  more than one  OTP. Each OTP  as a condition of   -The check shall  be duplicated if  the patient is  discharged and  readmitted at any  time.  (§ 64-90-30) approval to  operate shall  participate in the  central registry as  directed by the  Department of  Health.  (§ 7.32.8.19(F),  (G))   in its entirety by reference and provides that to the extent  there is a conflict between federal regulations or standards and the standards set forth in this rule, the  more stringent standard applies. W. Va. Code St. R. § 64-90-2..
Dosing refers to standards for doses of methadone.
section_title: Appendix III: Data and Research regarding Methadone-Associated Overdose Deaths in Five States
paragraphs: The following information on methadone-associated overdose deaths in  Florida, Kentucky, Maine, New Mexico, and West Virginia was taken from  data and research in these states.
History of substance abuse:  78%  Used diverted  pharmaceuticals: 63%  Doctor shopped (Five or  more prescribing clinicians  in the year before death):  21%  Florida Department of Law Enforcement, Medical Examiners Commission, Drugs Identified in  Deceased Persons by Florida Medical Examiners: 2007 Report (June 200).  5 cases.
L.B.E. Shields et al., “Methadone Toxicity Fatalities: A Review of Medical Examiner Cases in a Large  Metropolitan Area,” Journal of Forensic Sciences, vol. 52, no. 6 (2007).
Marcella H. Sorg and Margaret Greenwald, Maine Drug-Related Mortality Patterns: 1997-2002, a  special report prepared in cooperation with the Maine Office of the Attorney General and Maine Office  of Substance Abuse, December 2002.
N. Shah, S. L. Lathrop, and M. G. Landen, “Unintentional Methadone-Related Overdose Death in  New Mexico (USA) and Implications for Surveillance, 199–2002,” Addiction, vol. 100, no. 2 (2005).
A. J. Hall et al., “Patterns of Abuse Among Unintentional Pharmaceutical Overdose Fatalities,” JAMA,  vol. 00, no. 22 (200).
section_title: Appendix IV: Comparison of Prescription Drug Monitoring Programs in Four Selected States
subsections: section_title: Kentucky All-Schedule Prescription Electronic Reporting System (KASPER)
paragraphs: This references the effective year of the state law or regulation that provided the authority to  establish the state’s prescription drug monitoring program.    hours of treatment.  -CA-000027-OA, 200 WL 2671 (Ky. Ct. App. June 1, 200). A Kentucky court also  recently determined that a criminal defendant had the right to obtain KASPER data for discovery  purposes during a criminal proceeding. The court found that the defendant’s right to due and  compulsory process took precedence over any limitations in access authority under state law. See  Commonwealth, Cabinet for Health & Family Services v. Bartlett, No. 200-CA-000046-OA, 200 WL  2690 (Ky. Ct. App. June 1, 200).
section_title: Appendix V: Comments from the Department of Health and Human Services
section_title: Appendix VI: GAO Contact and Staff Acknowledgments
subsections: section_title: Acknowledgments
paragraphs: In addition to the contact named above, key contributors to this report  were Bonnie Anderson, Assistant Director; Lisa A. Lusk; Lisa Motley;  Christina Ritchie; Hemi Tewarson; and Timothy Walker.