Substance Abuse Treatment 

ADVISORY

News for the Treatment Field 

Spring 2009 

Volume 8 

Issue 1 

continued on reverse... U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Substance Abuse and Mental Health Services Administration 

Center for Substance Abuse Treatment 

www.samhsa.gov 

Emerging Issues in the 

Use of Methadone
 

This Advisory presents information on the increase 

in deaths related to methadone, particularly in 

combination with other drugs or substances, but 

stresses that methadone is effective and safe in 

the treatment of opioid addiction and chronic pain 

when it is used appropriately. In light of the rise 

in fatalities associated with the use of methadone, 

it is important to explore the extent of the problem 

and the risks associated with methadone use and 

to identify potential dangers and take action to 

prevent harm to patients who use methadone for 

addiction treatment and in managing chronic pain.1 

The Substance Abuse and Mental Health Services 

Administration (SAMHSA) convened a national 

assessment conference in 2003 to examine factors 

behind the increase in methadone-related deaths. A 

reassessment meeting was convened in July 2007.2 

The meeting reports, background papers, and other 

information are available at http://www.dpt.samhsa. 

gov/medications/methadone.aspx. 

Use of Methadone 

Increasing 

Methadone, a synthetic, long-acting opioid, 

has been used for more than 40 years in the 

treatment of opioid addiction. During the 

past 10 years, its use for treating chronic 

pain has increased. Methadone has been 

available as an approved narcotic painkiller 

for more than 50 years. It is available as a 

liquid, tablet, or dispersible tablet (diskette). 

Opioid treatment programs (OTPs) generally 

dispense it as a premixed, colored liquid. The Food 

and Drug Administration (FDA) approved the 

dispersible tablet for the treatment of addiction but 

not for pain management. The 5 and 10 mg strength 

methadone tablets are the only formulations approved 

by FDA for use in pain management. However, other 

formulations, including dispersible tablets, have been 

prescribed for pain control. 

Methadone is becoming increasingly available. 

The amount of methadone distributed or delivered 

by the manufacturers rose dramatically from 2000 

to early 2007, with increases ranging from 9 to 

22 percent annually (Figure 1).3 

5,197 4,911 

4,436

4,080 

3,394 

2,801

2,423 

1,987

Grams of Methadone

Distributed 

Figure 1. Methadone Distribution, 

per 100k Population, 2000–2007 

*Projected

2006 2007*

0 

2005 

1,000 

2004 

2,000 

2002 

4,000 

2001 

5,000 

2000 

6,000 

2003 

3,000 

Source: Feussner using Drug Enforcement Administration data (see note 3). 

The distribution 

of all formulations of methadone (liquid, tablet, 

or dispersible tablet) increased. However, tablets 

distributed with a prescription through pharmacies 

had the largest increase. The number of methadone 

prescriptions dispensed increased by nearly 700 

percent between 1998 and 2006. The strongest 
 

 

 

 

 

 

 

 

 

 

Spring 2009, Volume 8, Issue 1 

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formulation, the 40 mg strength dispersible tablet, had 

the largest increase of all methadone formulations.4 

Methadone-Related Deaths Rising 

Obtaining an accurate picture of methadone deaths 

is very difficult, in part because medical examiners 

across the country do not use the same methods to 

determine or the same terminology to record cause of 

death. For example, distinctions are not made among 

“methadone as the cause of death,” “death related to 

methadone use,” and “death associated with methadone 

use.” Therefore, it is difficult to obtain enough data 

to confirm whether methadone deaths are linked 

more to OTPs or to pain treatment situations. What 

is known, considering the inconsistent information, 

is that the increase in deaths from methadone is part 

of an overall increase in poisoning deaths, most of 

which are unintentional drug overdoses. However, 

methadone-related deaths are increasing at a faster 

rate than other poisoning deaths. According to data 

from the National Center for Health Statistics, from 1999 

to 2005 methadone-related poisoning deaths increased 

by 468 percent, while total poisoning deaths increased 

by only 66 percent.5

 In addition, methadone-related 

poisoning deaths had the greatest percentage increase of 

deaths compared with other opioids.5

 However, even with 

this increase in percentages, the actual number of deaths 

mentioning methadone poisoning continues to be smaller 

than the number of deaths from other opioids or cocaine 

(Figure 2). 

The Researched Abuse, Diversion and Addiction-Related 

Surveillance® System (known as RADARS® System) 

obtains data on prescription drug abuse from many sources, 

including poison control centers, key informant centers, law 

enforcement, and OTPs. Poison control center data from 

2003 to 2006 showed that patients filling prescriptions for 

methadone had the highest fatal poisoning rate for all people 

filling prescriptions. During the same period, according to 

RADARS System data, the source and formulation of the 

methadone could not be determined in 70 percent of all 

Figure 2. Number of Poisoning Deaths Mentioning Specific 

Narcotics and Cocaine, United States, 1999–2005 

Year Cocaine Other opioids 

(codeine, 

morphine, 

oxycodone, 

hydrocodone, 

fentanyl) 

Methadone Other 

synthetic 

narcotics 

(merperdine) 

1999 3,832 2,757 786 732

2000 3,565 2,932 988 784

2001 3,840 3,484 1,456 962

2002 4,612 4,431 2,360 1,301

2003 5,212 4,877 2,974 1,406

2004 5,461 5,242 3,849 1,668

2005 6,228 5,789 4,462 1,744

Source: Fingerhut for the Centers for Disease Control and Prevention (see note 5). 

methadone-associated deaths. However, the tablet form 

of methadone was implicated in 25 percent of reported 

cases, suggesting that methadone may have been prescribed 

and was not dispensed from OTPs.6 

Approximately 35 percent of methadone deaths were 

characterized as resulting from an abuse episode. 

Unlike most other opioid-related deaths, two-thirds of 

the methadone deaths involved use of multiple drugs, 

especially antidepressants, alcohol, and cocaine.6
 

Methadone Is Safe When 

Used Properly
 

Methadone is safe when used appropriately. It can be 

life saving for individuals dependent on opioids. Any 

practitioner prescribing or dispensing methadone needs 

to appreciate that methadone is powerful, with the 

potential for serious adverse effects. The rising number 

of methadone-related deaths necessitates a review of 

both methadone’s adverse effects and the safe treatment 

practices in OTPs to ensure that methadone is used safely 

and appropriately in those settings. 

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Emerging Issues in the Use of Methadone 

Substance Abuse Treatment 

ADVISORY .............................................................................. 
 

Update on Limited Distribution 

of 40 mg Dispersible Tablet 

As of January 1, 2008, manufacturers of the 

40 mg strength methadone hydrochloride tablets 

(dispersible) have voluntarily agreed to distribute 

only to facilities authorized for detoxification and 

maintenance treatment of opioid addiction and to 

hospitals. The manufacturers’ wholesale distributors 

will no longer supply this formulation to any 

facility not meeting the above criteria.10 

Clinical Issues: Risk Factors 

for Adverse Events Related to 

Methadone Used in the Treatment 

of Opioid Dependence 

•	 Simultaneous patient abuse of substances such as 

benzodiazepines, other opioids, cocaine, or alcohol. 

The majority of people admitted for methadone 

maintenance treatment of heroin and other opioid 

abuse also use other substances, including alcohol, 

cocaine, marijuana, and tranquilizers.7

 Some patients 

continue using heroin, other drugs, and alcohol after 

admission to treatment.8

 Polysubstance abuse, at levels 

that are not necessarily lethal if each substance were 

used alone, may have a synergistic effect with the 

prescribed methadone. This mixing of drugs can cause 

more severe respiratory depression (slow or shallow 

breathing), central nervous system (CNS) depression 

and excessive sleepiness, and abnormal heart rhythms 

(see cardiac screening below). These conditions 

can lead to overdose (poisoning). Other potential 

interactions can slow or stop bowel movements.9 

•	 Interactions between prescribed medications. 

Methadone adversely interacts with numerous 

prescribed medications, potentially causing the same 

serious effects discussed above. The Resource List 

(page 6) provides links to Web sites listing methadone 

drug interactions. 

•	 Methadone accumulation in the body that can result 

in harmful or toxic levels. Methadone is a long-acting 

medication with a long half-life. This half-life varies 

greatly from person to person and ranges between 8 and 

59 hours in different studies.11 Methadone can remain in 

the liver and other tissues such as fat cells from which 

it is slowly released back into the bloodstream. This 

slow release from these tissues may prolong the duration 

of methadone’s action despite low levels in a person’s 

plasma. If the occurrence of this slow release from 

tissues while a person is taking additional methadone 

doses causes toxic levels, methadone can cause 

respiratory depression, low levels of oxygen in the blood, 

or CNS depression—conditions leading to overdose. 

Because these symptoms of overdose may develop 

slowly, warning signs may appear only after the patient 

has left the clinic, too late for medical intervention. 

•	 Methadone’s peak respiratory depressant effects . 

The peak respiratory depressant effects of methadone 

typically occur later and persist longer than its other 

peak effects, particularly during the initial dosing 

period. This phenomenon occurs because methadone’s 

elimination half-life is longer than the duration (4 to 

8 hours) of its action. If a patient takes more doses of 

methadone faster than his or her body can metabolize 

it, serious toxicity or poisoning can result. If a patient’s 

methadone dose is increased too quickly (see next 

bullet), or the patient does not ingest take-home doses 

as directed, respiration can be affected. 

•	 Poor clinical practice during the start of methadone 

treatment (induction dosing phase). Among patients in 

addiction treatment, the largest proportion of methadoneassociated deaths has occurred during the methadone 

induction phase, usually when (1) treatment personnel 

overestimate a patient’s degree of tolerance for opioids 

or (2) a patient uses opioids or other CNS depressant 

drugs in addition to the prescribed methadone.12 

•	 Cardiac screening. Methadone puts some patients at an 

elevated risk to develop torsades de pointes (a serious 

abnormal heart rhythm). The Center for Substance 

Abuse Treatment convened the National Assessment 

3 
“the initial dose 

of methadone 

shall not exceed 

30 milligrams and 

the total dose for 

the first day shall 

not exceed 40 

milligrams.”

Spring 2009, Volume 8, Issue 1 

Substance Abuse Treatment 

ADVISORY .............................................................................. 
 

of Methadone-Associated Mortality meeting in May 

2003, at which preliminary evidence suggesting proarrhythmic properties of methadone was presented. 

This meeting was reconvened on July 20, 2007, 

and titled Methadone Mortality—A Reassessment. 

One action that emerged was formation of a multidisciplinary expert panel on the cardiac effects of 

methadone, charged with formulating a clinical practice 

guideline to ensure cardiac safety of patients in opioid 

treatment. The expert panel includes key stakeholders 

with backgrounds in addiction medicine, cardiology, 

electrophysiology, pain management, epidemiology, 

and development, as well as representatives from FDA 

and the National Institute on Drug Abuse. The clinical 

practice guideline is expected to be disseminated within 

the next 12 months. 

•	 Poisoning that occurs when methadone is diverted 

for nonmedical use. Deaths can occur when people 

who have no or low opioid tolerance take too large a 

dose or mix methadone with other respiratory or CNS 

depressants. Children also have accidentally ingested 

take-home doses of methadone, with fatal results.1,2,5,6 

Improving Patient Safety in 

Opioid Addiction Treatment 

The increase in methadone-related deaths has resulted in 

changes in recommendations and procedures from the 

manufacturers of the drug itself (see sidebar on page 3), 

FDA (see sidebar on page 5), and SAMHSA. 

Several measures can improve patient safety. These 

include updating induction protocols, educating medical 

and other staff members, monitoring patients’ health 

while in treatment, improving procedures for take-home 

medications, carefully assessing each patient for the use 

of other drugs or medications, and reevaluating patient 

education procedures. 

As with other opioids, methadone may impair mental and 

physical abilities required in operating an automobile or 

heavy machinery. Patients should be cautioned about this 

adverse effect. 

Evidence-based practice guidelines and standards of care 

exist for the use of methadone for opioid dependence (see 

the Resource List on page 6). The standards emphasize 

providing quality care through individualized treatment 

planning, person-focused care, medical supervision, and 

detailed assessment of patients.13 In 2007, SAMHSA sent 

a “Dear Colleague letter”14 to programs recommending 

that they reevaluate their induction procedures. The letter 

stated that, even though 

Treatment Improvement 

Protocol (TIP) 43, 

Medication-Assisted 

Treatment for Opioid 

Addiction in Opioid 

Treatment Programs,

9 

and methadone drug 

labeling state that a 

typical first dose of 

methadone for a patient 

actively abusing opioids 

is 20 to 30 mg, some 

patients need a much lower dose. According to 42 Code 

of Federal Regulations (CFR), Part 8, § 12(h) (3)(ii), “the 

initial dose of methadone shall not exceed 30 milligrams 

and the total dose for the first day shall not exceed 40 

milligrams” (emphasis added). The initial methadone dose 

should be appropriate for the individual patient, with the 

maximum initial dose being 30 mg. Clearly, a 30 mg dose 

should not be the initial dose for all patients.14 There is no 

regulatory dose restriction when methadone is prescribed 

for pain. 

Patients are in a critical phase during induction, before their 

bodies achieve a steady state, which is when methadone 

is eliminated from the blood at the exact rate that more 

is added.9 The potential for adverse events during the 

2-week induction process makes it imperative that the 

OTP physician determine the admitting diagnosis, initiate 

treatment, and set the beginning dosages.14 More intensive 

monitoring during the induction phase is essential to 

prevent the adverse events discussed above. Withdrawal 

assessments such as the Subjective Opiate Withdrawal 

4 
 

 

 

 

 

 

 

 

 

 

 

 

Emerging Issues in the Use of Methadone 

Substance Abuse Treatment 

ADVISORY .............................................................................. 
 

Scale (SOWS)15 and the Clinical Opiate Withdrawal Scale 

(COWS)15 are valuable tools during this treatment phase. 

All dosing adjustments must consider the patient’s 

characteristics and status. These can include the patient’s 

dependence level, body mass, other medications, medical 

conditions, and genetic factors. The OTP must maintain a 

balance to provide the patient with enough methadone to 

minimize withdrawal symptoms but not enough to cause 

an adverse event. If the patient develops symptoms of 

withdrawal, he or she could relapse to gain relief. 

To prevent respiratory depression, methadone should be 

administered cautiously to patients with medical conditions 

affecting their breathing, including asthma, chronic 

obstructive pulmonary disease, heart disease, severe obesity, 

sleep apnea syndrome, kyphoscoliosis, or CNS depression.16 

FDA Activity 

•		 In November 2006, FDA announced a revised package insert for methadone, including a black-box warning. 

(See http://www.fda.gov/cder/foi/label/2006/006134s028lbl.pdf.) 

•		 In November 2006, FDA issued “Information for Healthcare Professionals, Methadone Hydrochloride, FDA 

ALERT [11/2006]: Death, Narcotic Overdose, and Serious Cardiac Arrhythmias.” (See http://www.fda.gov/ 

cder/drug/InfoSheets/HCP/methadoneHCP.htm.) 

•		 In July 2007, FDA issued “Public Health Advisory, Methadone Use for Pain Control May Result in Death 

and Life-Threatening Changes in Breathing and Heart Beat.” (See http://www.fda.gov/cder/drug/advisory/ 

methadone.htm.) 

•		 More FDA information is summarized at http://www.fda.gov/cder/drug/infopage/methadone/default.htm. 

Screen Patients for Other Substance 

and Medication Use 

Screening measures can include oral assessments, careful 

observation of patients, and additional random drug tests. 

Some programs use “point of collection” screens or tests 

to determine whether patients have taken substances that 

could interact with methadone. Within limits, these drug 

tests can show whether a patient is taking the methadone 

or diverting it. The tests also can reveal whether the patient 

is taking other illicit substances. With this information, 

treatment providers can prevent potentially dangerous 

interactions with other medications or illicit substances. 

Increase Caution Regarding 

Take-Home Medications 

OTP staff members must balance the desire to keep 

patients and the community safe against their desire to 

help patients normalize their lives by providing doses of 

methadone to take home for unsupervised use. A program 

that is closed on holidays and Sundays may give a patient 

take-home doses, but the program medical director must 

determine that the patient is responsible enough to handle 

opioid medications for unsupervised use. The medical 

director must evaluate the patient and should document the 

evaluation in the patient’s chart. 

The medical director must make take-home decisions 

according to the eight criteria specified in the Federal 

regulations (42 CFR, Part 8, § 12(i)) and the patient’s length 

of time in treatment. Careful assessments determine whether 

patients meet the eight criteria.9 Patients who meet the 

regulatory requirements for unsupervised or take-home use 

of medication should be counseled by program staff on the 

risks of using other drugs or medications.13 Patients should be 

encouraged to sign release forms so that OTP physicians can 

contact other healthcare providers to identify all the patients’ 

prescriptions. All decisions should be documented in patients’ 

charts.17 

5 
 

 

 

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In some States, OTP physicians access State Prescription 

Drug Monitoring programs to determine whether patients are 

receiving prescriptions for medications that could interact 

with methadone. 

Some jurisdictions require that OTPs operate 7 days a week 

to avoid the need for take-home doses. This requirement is 

consistent with the consensus panel recommendations in 

TIP 43.9 According to SAMHSA guidance,17 if the medical 

director determines a patient is ineligible for take-home 

doses, an OTP that closes for Sundays and/or holidays 

should arrange for the patient to take methadone under 

supervision. 

Programs may conduct random call-backs, asking patients 

to return to the facility before their scheduled appointments 

and bring with them the remainder of their take-home 

medication. Staff members can then determine whether 

the correct amount of methadone remains or whether it has 

been diverted.9

 Some States require that patients carry takehome doses in locked boxes or use other secure methods of 

transporting and storing the medication. 

Resource List 

Center for Substance Abuse Treatment. (2005). 

Medication-assisted treatment for opioid addiction in 

opioid treatment programs (Treatment Improvement 

Protocol Series 43, HHS Publication No. SMA 05­

4048). Rockville, MD: Substance Abuse and Mental 

Health Services Administration. Retrieved April 13, 

2009, from http://www.ncbi.nlm.nih.gov/books/ 

bv.fcgi?rid=hstat5.chapter.82676 

Leavitt, S. B. (Ed.) (2006). Pain treatment topics: 

Methadone-drug* interactions (*Medications, 

illicit drugs, & other substances). Glenview, IL: 

Mallinckrodt Pharmaceuticals. Retrieved April 13, 

2009, from http://pain-topics.org/pdf/MethadoneDrug_Intx_2006.pdf 

Methadone (Dolophine) prescribing information. 

Retrieved April 13, 2009, from http://www.fda.gov/ 

cder/drug/infopage/methadone/dolophine_PI.pdf 

National Drug Intelligence Center, U.S. Department 

of Justice. (2007). Methadone diversion, abuse, 

and misuse: Deaths increasing at alarming rate 

(Document ID: 2007-Q0317-001). Washington, DC: 

Author. Retrieved April 13, 2009, from http://www. 

usdoj.gov/ndic/pubs25/25930/index.htm 

Educate OTP Staff 

To ensure good practice, medical and program staff 

members should receive ongoing education that updates 

their awareness about the following: 

•		 Current knowledge, such as lower recommended 

induction dosages;
 

•		 Current information on what is known about 

methadone’s pharmacology, adverse effects, 

abuse potential, and withdrawal symptoms;
 

•		 The risks of misuse of methadone; 

•		 Procedures for obtaining a thorough medical and 

psychosocial history of the patient; and
 

•		 Protocols for appropriate dosing and patient 

monitoring.
 

Educate Patients 

Patients may be less likely to use or handle methadone 

in a risky manner when they know the possible dangers. 

Education methods should engage patients. Brochures, 

pamphlets, and other educational resources need to be presented using language and formats that each patient can 

understand. Early in treatment, in particular, the patient 

may need information presented in ways that are concrete, simple, repetitive, and easy to understand. Because 

the greatest number of OTP methadone-associated deaths 

occur during the induction stage, it is especially important 

to communicate effectively with patients during this phase. 

However, patient education needs to continue during all 

phases of treatment. Patients need the following: 

•	 Information about the safe use and storage of takehome methadone. OTP staff members need to warn
 

patients about the danger of accidental overdose by 

6 
 

 

 

 

Emerging Issues in the Use of Methadone 

Substance Abuse Treatment 

ADVISORY .............................................................................. 
 

people living with the patients or who have access to the 

methadone. Methadone must be kept out of the reach of 

children who may inadvertently drink the colored liquid 

and overdose. Small children, because of their lower 

weight, could easily be poisoned if they consumed a 

methadone dose calibrated for an adult’s weight. 

•	 Counseling to take methadone exactly as prescribed. 

Patients given take-home doses should be advised 

that taking more methadone than prescribed can cause 

breathing to slow or stop and can cause death. 

•	 Counseling about interactions with other prescription 

and over-the-counter medications. Patients need 

to talk to their healthcare provider about taking or 

stopping other medications. These other medicines may 

interfere with the effectiveness of methadone. They 

may also interact with methadone, potentially leading 

to a toxic buildup of methadone in the body that can 

trigger dangerous and potentially fatal changes in 

breathing or heart beat. 

•	 Information about the signs of methadone overdose. 

These signs include trouble breathing or shallow 

breathing; extreme tiredness or sleepiness; blurred 

vision; inability to think, talk, or walk normally; and 

feeling faint, dizzy, or confused. Patients, especially 

patients new to methadone, need to be told that these 

symptoms can occur even when patients have not 

purposefully abused the medication or taken “extra” 

doses. If these symptoms or signs develop, patients 

should get medical attention immediately. 

Educate Family Members and Significant 

Others 

Many OTP patients have family members and significant 

others who are involved in their treatment and recovery. 

As part of the family education component of treatment 

and recovery, family members and significant others need 

to be educated about the topics listed above. Safe storage 

of take-home doses is particularly important if children 

are present in the residence. To help prevent diversion of 

methadone, patients and family members need to make sure 

that the medication is securely stored at home, preferably 

in a locked safe box, to prevent unauthorized access. Any 

misuse or unauthorized use of a patient’s methadone needs 

to be reported to the appropriate staff at the OTP, and steps 

should be taken to provide immediate medical attention, as 

necessary, in the event of accidental poisoning. 

Notes 

1

Center for Substance Abuse Treatment. (2007). Background information for Methadone Mortality—A Reassessment. Rockville, MD: 

Substance Abuse and Mental Health Services Administration. 

Retrieved April 13, 2009, from http://www.dpt.samhsa.gov/pdf/ 

MethadoneBackgroundPaper_72007_2_.pdf 

2

Center for Substance Abuse Treatment. (2007, July). Summary report 

of the meeting: Methadone Mortality—A Reassessment. Rockville, 

MD: Substance Abuse and Mental Health Services Administration. 

Retrieved April 13, 2009, from http://www.dpt.samhsa.gov/pdf/ 

Methadone_Report_10%2018%2007_Brief%20w%20attch.pdf 

3

Feussner, G. (2007). Drug Enforcement Administration, ARCOS Data. 

Presentation at Methadone Mortality Reassessment Meeting, 

July 20, 2007, Washington, DC. Retrieved April 13, 2009, from 

http://dpt.samhsa.gov/medications/methadonemortality2007/ 

MeetingAgenda.aspx 

4

Governale, L. (2007). FDA: Methadone Utilization Data: Food and 

Drug Administration, Center for Drug Evaluation and Research, 

Division of Surveillance, Research and Communication Support, 

Office of Surveillance and Epidemiology. Methadone Utilization 

in the U.S., 2002−2006. Presentation at Methadone Mortality 

Reassessment Meeting, July 20, 2007, Washington, DC. Retrieved 

April 13, 2009, from http://dpt.samhsa.gov/medications/ 

methadonemortality2007/MeetingAgenda.aspx 

5

Fingerhut, L. (2008). Increases in poisoning and methadone-related 

deaths: United States, 1999−2005. Hyattsville, MD: Centers for 

Disease Control and Prevention’s National Center for Health 

Statistics. Retrieved April 13, 2009, from http://www.cdc.gov/ 

nchs/products/pubs/pubd/hestats/poisoning/poisoning.htm 

6

Dart, R. (2007). RADARS Methadone Study. Presentation at 

Methadone Mortality Reassessment Meeting, July 20, 2007, 

Washington, DC. Retrieved April 13, 2009, from http://dpt.samhsa. 

gov/medications/methadonemortality2007/MeetingAgenda.aspx 

7

Substance Abuse and Mental Health Services Administration. (2008). 

Treatment Episode Data Set (TEDS): 1996−2006, National 

admissions to substance abuse treatment services (DASIS Series: 

S-43, HHS Publication No. SMA 08-4347). Rockville, MD: Author. 

8

Hser, Y.-I., Hoffman, V., Grella, C., & Anglin, D. (2001). A 33-year 

follow-up of narcotics addicts. Archives of General Psychiatry, 58, 

503–508. 

7 
9

Center for Substance Abuse Treatment. (2005). Medication-assisted 

treatment for opioid addiction in opioid treatment programs 

(Treatment Improvement Protocol Series 43, HHS Publication 

No. SMA 05-4048). Rockville, MD: Substance Abuse and Mental 

Health Services Administration. 

10Drug Enforcement Administration, Office of Diversion Control. 

(2008). Advisory: Methadone hydrocholoride tablets UPS 40mg 

(dispersible). Washington, DC: Author. Retrieved April 13, 2009, 

from http://www.deadiversion.usdoj.gov/pubs/pressrel/ 

methadone_advisory.htm 

11Food and Drug Administration. (2006). Death, narcotic overdose, and 

serious cardiac arrhythmias. Rockville, MD: Author. Retrieved 

April 13, 2009, from http://www.fda.gov/cder/drug/InfoSheets/

HCP/methadoneHCP.pdf 

12Karch, S. B., & Stephens, B. G. (2000). Toxicology and pathology 

of deaths related to methadone: Retrospective review. Western 

Journal of Medicine, 172, 11–14. 

13Center for Substance Abuse Treatment. (2007). Guidelines for the 

accreditation of opioid treatment programs. Rockville, MD: 

Substance Abuse and Mental Health Services Administration. 

Retrieved April 13, 2009, from http://www.dpt.samhsa.gov/ 

regulations/accreditation.aspx 

14Clark, H. W. (2007). Importance of determining initial methadone 

dose. Dear Colleague letter. Retrieved April 13, 2009, from 

http://www.dpt.samhsa.gov/pdf/dearColleague/09-04-07%20

DearColleagueLetter%20on%20Dosing.pdf 

15Center for Substance Abuse Treatment. (2004). Clinical guidelines 

for the use of buprenorphine in the treatment of opioid addiction

(Treatment Improvement Protocol Series 40, HHS Publication 

No. SMA 04-3939). Rockville, MD: Substance Abuse and Mental 

Health Services Administration.

16Roxanne Laboratories, Product insert, Revised. (2006). 

Retrieved April 13, 2009, from http://www.fda.gov/cder/foi/

label/2006/006134s028lbl.pdf

17Clark, H. W. (2008). Take-home doses. Dear Colleague letter. 

Retrieved April 13, 2009, from http://www.dpt.samhsa.gov/pdf/ 

dearColleague/DearColleagueLetterSundayHolidayTH_ 

012408.pdf

Substance Abuse Treatment Advisory

Substance Abuse Treatment Advisory was written and produced under contract number 270-04-7049 by the 

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the Center for Substance Abuse Treatment (CSAT), Substance Abuse and Mental Health Services Administration 

(SAMHSA), U.S. Department of Health and Human Services (HHS).

Disclaimer: The views, opinions, and content expressed herein do not necessarily reflect the views, opinions, or 

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Recommended Citation: Center for Substance Abuse Treatment. (2009). 

Emerging Issues in the Use of Methadone. HHS Publication No. (SMA) 

09-4368. Substance Abuse Treatment Advisory, Volume 8, Issue 1.

ADVISORY ..............................................................................

Spring 2009, Volume 8, Issue 1

Substance Abuse Treatment

88 HHS Publication No. (SMA) 09-4368 

Printed 2009

Substance Abuse Treatment Advisory 

Emerging Issues in the Use of Methadone