American Psychiatric Association

1000 Wilson Boulevard

Suite 1825

Arlington. VA 22209

Telephone 703.907.7300

Fax 703.907.1085

E-mail apa@psych.org

Internet www.psych.org

> January 13, 2006

Andrew C. von Eschenbach, M.D., Acting Commissioner

Division of Dockets Management (HFA--305)

Food and Drug Administration

5630 Fishers Lane, Rm. 1061

Rockville, MD 20852.

**RE: Notice: "International Drug Scheduling; Convention on Psychotropic
Substances; Single Convention on Narcotic Drugs; Butorphanol;
Delta--9--tetrahydrocannabinol (Dronabinol); Gamma-Hydroxybutyric Acid;
Ketamine; Khat; Tramadol; Zopiclone; Buprenorphine; Oripavine"**

**(Docket No. 2005N--0479)**

Dear Acting Commissioner von Eschenbach:

The American Psychiatric Association (APA), the national medical
specialty society representing more than 37,000 psychiatric physicians,
nationwide, appreciates the opportunity to submit these comments
concerning the Food and Drug Administration's (FDA's) notice on
international drug scheduling, published in the Federal Register on
December 13, 2005, with the title, "International Drug Scheduling;
Convention on Psychotropic Substances; Single Convention on Narcotic
Drugs; Butorphanol; Delta--9--tetrahydrocannabinol (Dronabinol);
Gamma-Hydroxybutyric Acid; Ketamine; Khat; Tramadol; Zopiclone;
Buprenorphine; Oripavine."[^1]

The United States is a party to the 1971 Convention on Psychotropic
Substances (hereinafter, referred to as the "1971 Convention"). Under
Article 2 of this 1971 Convention, when WHO notifies the United States
that it has information regarding possible changes to the drug schedules
of the Convention, the Secretary of State must then notify the Secretary
of the Department of Health and Human Services (HHS), who must then
provide an opportunity for comments on the relevant issues.[^2]

FDA is soliciting comments on these drugs, in order to prepare a
response from the United States to the World Health Organization (WHO),
which will then consider whether to recommend certain international
restrictions on these drugs. FDA's articulated concerns are the medical
usefulness and potential for abuse or diversion of those drugs. The WHO
Expert Committee on Drug Dependence will make final decisions on its
scheduling review that includes buprenorphine, as a follow-up to its
thirty-third meeting, held in Geneva, Switzerland in September of
2002.[^3]^,^ [^4]

APA will confine these comments to the FDA's two questions posed in the
notice with regard to buprenorphine: "1.1 If buprenorphine is
transferred from Schedule III of the Convention on Psychotropic
Substances, 1971, to Schedule I of the Single Convention on Narcotic
Drugs, 1961, do you think that its availability for medical use will be
affected? (Yes/No);" and "2.2 If ''yes,'' how do you think the transfer
will impact its medical availability?"[^5]

APA maintains that the availability of buprenorphine for medical use,
which is now primarily for treating opioid addiction, will be likely to
be substantially diminished by a change from Schedule III of the 1971
Convention to Schedule I of the 1961 Convention. In the following
comments, APA will detail the manner in which buprenorphine's
availability will be restricted by that kind of schedule change and the
reasons why restricting its availability will have an adverse
international impact.

**Opioid Addiction**

The magnitude of the opioid addiction problem, both in the United States
and internationally, is substantial and growing. One contributing factor
to this growth is the increasing use of opiate-derivative pain killers.
According to a 2004 survey by the Substance Abuse and Mental Health
Services Administration (SAMHSA), addiction to pain killers, which
includes prescription drugs, well exceeds heroin addiction in the U.S.
and the category of illicit drugs with the most new users was pain
killers. Opioid pain killers are on the rise as drugs of choice for many
addicts. According to the White House Office of National Drug Control
Policy (ONDCP), "(a) rough estimate of the hardcore addict population in
the United States places the number between 750,000 and 1,000,000
users."[^6] Fortunately, buprenorphine can be used effectively to treat
this and other types of opioid addiction.

Results of a 2004 survey by the Substance Abuse and Mental Health
Services Administration (SAMHSA) draw a picture of opioid addiction in
the U.S.:

> "In 2004, 6.0 million persons were current users of psychotherapeutic
> drugs taken nonmedically (2.5 percent). These include 4.4 million who
> used pain relievers . . .
>
> "Of the 7.3 million persons classified with dependence on or abuse of
> illicit drugs, . . . 1.4 million were dependent on or abused pain
> relievers.
>
> "Based on a new approach to estimating incidence, the 2004 NSDUH shows
> that the illicit drug category with the largest number of new users
> was nonmedical use of pain relievers. 2.4 million persons used pain
> relievers nonmedically for the first time within the past 12 months.

-   There were significant increases in the lifetime prevalence of use
    from 2003 to 2004 in several categories of pain relievers among
    those aged 18 to 25. Specific pain relievers with statistically
    significant increases in lifetime use were Vicodin^®^, Lortab^®^, or
    Lorcet^®^ (from 15.0 to 16.5 percent); Percocet^®^, Percodan^®^, or
    Tylox^®^ (from 7.8 to 8.7 percent); hydrocodone products (from 16.3
    to 17.4 percent); OxyContin^®^ (from 3.6 to 4.3 percent); and
    oxycodone products (from 8.9 to 10.1 percent)." [^7]

Addiction to opiates, including heroin, is associated with a complex of
negative personal and social consequences, including diminished health
and crime. These are well outlined by the White House Office of National
Drug Control Policy (ONDCP):

> "Long-term effects of heroin use also can include arthritis and other
> rheumatologic problems and infection of bloodborne pathogens such as
> HIV/AIDS and hepatitis B and C (which are contracted by sharing and
> reusing syringes and other injection paraphernalia). It is estimated
> that injection drug use has been a factor in one third of all HIV and
> more than half of all hepatitis C cases in the United States.
>
> "Heroin use by a pregnant woman can result in a miscarriage or
> premature delivery. Heroin exposure in utero can increase a newborns'
> risk of SIDS (sudden infant death syndrome)."[^8]

Countries other than the U.S. are becoming increasingly concerned about
treating opioid addicts and some, especially in Western Europe, are
using buprenorphine to treat them. There is a strong need to continue
the greatest possible access to this beneficial drug, without further
restrictions imposed by re-scheduling it. Unnecessary scheduling
restrictions will have a chilling effect on access to buprenorphine, to
the extent that international drug scheduling influences individual
countries' choices of how to control buprenorphine. Given the influence
of international drug scheduling, the likely result of international
re-scheduling would be reduced access to buprenorphine for legitimate
medical purposes. There is a potential for such a scheduling change to
affect domestic drug classification of buprenorphine from CSA Schedule
III to Schedule II, which could lead to the elimination of office-based
buprenorphine therapy and severely restrict treatment access for
patients.

Pieta Laut, Executive Director of the Public Health Association of
Australia, has advocated for increased international availability for
both methadone and buprenorphine. She recommended in January 2005 that
WHO "include methadone and buprenorphine in the Model List of Essential
Drugs (EDL) . . ." because "(t)here is compelling evidence for the
effectiveness (19), safety (20) and cost effectiveness (21) of
substitution treatment. Apart from a reduction in HIV infection, other
important benefits include substantial reductions in drug overdose
deaths (22), crime (23) and heroin use (24) and also a considerable
improvement in social functioning (25). Methadone and buprenorphine
treatment has now been implemented in a growing number of countries,
especially in western Europe (26). Yet global implementation remains
poor, especially in central and eastern Europe and Asia. There are a
number of barriers to increased implementation of methadone including
competition for scarce health care resources in developing and
transitional countries (though substitution treatment is relatively
inexpensive and cost effective). Including methadone and buprenorphine
in the Model List of Essential Drugs will reduce the financial
disincentive for countries struggling to pay for this treatment."[^9]

A recent study of patients in several European countries undergoing
medically assisted addiction treatment (MAT) with high dosages of
buprenorphine found a division in two groups of countries. In the Czech
Republic, France and Sweden, patients on high-dosage buprenorphine
comprised over 60% of those undergoing MAT. However, in Denmark, Italy,
Luxembourg and Norway, high-dosage buprenorphine patients were less than
25% of MAT patients. The study also found that, of MAT patients in the
European Union, about 20% are in buprenorphine treatment; 77% of those
are in France. France had 83,000 patients in high-dosage buprenorphine
treatment, 13,000 of which were in specialized units, while the
majority, 70,000, were treated in general practitioners' offices. [^10]
This underscores the importance of retaining office-based usage for
buprenorphine. This study strongly emphasizes the widespread,
international use of buprenorphine for addiction treatment, especially
where it is possible to do so in office settings, and the importance of
continued access to this drug.

**Buprenorphine Treatment**

The recent development of buprenorphine therapy for the in-office
treatment of addiction to opiate derivatives is revolutionary.
Buprenorphine has given psychiatrists and other physicians a new tool
with which to offer addicted patients hope for improved lives free from
opioid addiction. One reason that this drug is so essential and
represents such an advancement in addiction treatment is that, unlike
methadone, it can be used to treat patients in the office setting.
In-office buprenorphine treatment is not subjected to the stringent
regulations that govern addiction treatment in methadone clinics. It is
easier and faster for a solo or group practice physician to initiate
buprenorphine therapy for patients, providing incentives for physicians
to establish more locations in which they can treat addicted patients.
Buprenorphine has enabled the medical community to make significant
strides in improving access to treatment:

> "The Drug Addiction Treatment Act of 2000 (DATA 2000) expands the
> clinical context of medication-assisted opioid addiction treatment by
> allowing qualified physicians to dispense or prescribe specifically
> approved Schedule III, IV, and V narcotic medications for the
> treatment of opioid addiction in treatment settings other than the
> traditional Opioid Treatment Program (i.e., methadone clinic). In
> addition, DATA 2000 reduces the regulatory burden on physicians who
> choose to practice opioid addiction therapy by permitting qualified
> physicians to apply for and receive waivers of the special
> registration requirements defined in the Controlled Substances
> Act."[^11]

It has now been several years since buprenorphine received FDA approval.
"In October 2002, FDA approved two sublingual formulations of the
Schedule III opioid partial agonist medication buprenorphine for the
treatment of opioid addiction. These medications, Subutex®
(buprenorphine) and Suboxone® buprenorphine/naloxone), are the first
and, as of this writing, the only Schedule III, IV, or V medications to
have received such FDA approval and, thus, to be eligible for use under
DATA 2000. Office-based treatment with buprenorphine promises to bring
opioid addiction care into the mainstream of medical practice, thereby
greatly expanding access to treatment and bringing new hope to
thousands."[^12] Buprenorphine is presently assigned to Schedule III of
the Controlled Substances Act in the U.S..[^13]

In order to prescribe buprenorphine, licensed physicians (M.D.s or
D.O.s) must possess a DEA number, meet certain requirements and apply
for a waiver from the Center for Substance Abuse Treatment (CSAT), which
is a component of the Substance Abuse and Mental Health Services
Administration (SAMHSA). SAMHSA also promotes clinical uniformity
through its clinical practice guidelines for buprenorphine treatment of
addiction. According to SAMHSA:

> "DATA 2000 permits qualified physicians to obtain a waiver from the
> separate registration requirements of the Narcotic Addict Treatment
> Act to treat opioid addiction with Schedule III, IV, and V opioid
> medications or combinations of such medications that have been
> specifically approved by the Food and Drug Administration (FDA) for
> that indication. Such medications may be prescribed and dispensed.
>
> "Among requirements for physicians is that "they will not have more
> than 30 patients on such addiction treatment at any one time. (Note:
> The patient limit applies to both physicians in solo practice and to
> entire group practices, and is not affected by the number of physician
> or group practice locations.)"[^14]

This 30-patient limit posed a substantial treatment barrier because it
was applied to the total number of patients a solo physician, group
practice, clinic or hospital could treat at any one time, regardless of
actual capacity. However, Congress recently recognized the shortfall of
this 30-patient limit. Senate Bill 45, which had bipartisan support and
became Public Law 109-56 on August 2, 2005, was enacted clearly because
the full Congressional intent was to eliminate the 30-patient limit for
group practices, in order to expand access to treatment.[^15] This will
have the effect of substantially expanding patients' access to
buprenorphine treatment.[^16] This legislative change will allow
individual physicians within group practices to treat up to 30 patients,
whereas the total group limit before the amendment was 30 patients.
Through this significant expansion of the nation's buprenorphine
treatment capacity, Congress underscored this public health need that is
substantial and growing.

**Buprenorphine Treatment in the U.S.**

By 2004, only two years after FDA approval, the Center for Substance
Abuse Treatment (CSAT) reported that, \"1,113 physicians are estimated
to have provided treatment using buprenorphine\" with an estimated
63,000 total number of patients treated over the course of the past two
years.[^17]

Recent CSAT statistics show that:

-   Approximately 100,000 patients have been treated with buprenorphine
    by September 7, 2005.[^18]

-   Estimated Total Prescriptions written by January 5, 2006[^19]

> 2003 = 87000
>
> 2004 = 385,000
>
> 2005 = 260,000 (through May 05)

-   DEA has provided ARCOS data for the last several years:[^20]

> 2004: 11.4 million dosage units and 4.1 du/100,000 population.
>
> 2005 (through August): 14.9 million dosage units and 5.3/100,000
> population.  This represents a 30% increase.
>
> If the trend continues for the rest of 2005, then we could estimate 20
> million dosage units by the end of 2005, almost doubling the amount
> for 2004.

-   Physicians who have applied for the waiver/special DEA number:[^21]

> 2002: 1197  applied (1429 certified)
>
> 2003: 1459 applied (809 certified)
>
> 2004:  2098 applied (1798 certified)
>
> 2005: 2647 applied (2734 certified)

-   9954 physicians were trained in buprenorphine treatment by January
    5, 2006.[^22]

Statistics on patient profile characteristics from the CSAT show that
the majority (60%) of U.S. patients undergoing buprenorphine treatment
are addicted to opiates other than heroin. They also suggest that a
large proportion of patients on buprenorphine may have chosen to enter
and/or continue addiction treatment due to the availability and nature
of buprenorphine treatment, as compared with methadone treatment:

-   35% patients are new to substance abuse treatment

-   60% have never been on a medication treatment

-   10% have transferred from methadone[^23]

**Advantages of Buprenorphine in Opioid Addiction Treatment**

[]{.mark}

Buprenorphine was approved for use in office settings because its
properties make it effective for opioid addiction treatment, yet it is
less subject to abuse and diversion than methadone. As SAMHSA notes:

[]{.mark}

> "Buprenorphine has unique pharmacological properties that make it an
> effective and well tolerated addition to the available pharmacological
> treatments for opioid addiction.
>
> "More than 20 years ago, buprenorphine was identified as a viable
> option for the maintenance treatment of individuals addicted to
> opioids. Research conducted over the past two decades has documented
> the safety and effectiveness of buprenorphine for this
>
> indication."[^24]
>
> "Buprenorphine is abusable, consistent with its agonist action at
> opioid receptors. Its abuse potential, however, is lower in comparison
> with that of opioid full agonists. A formulation containing
> buprenorphine in combination with naloxone has been developed to
> decrease the potential for abuse via the injection route."[^25]

Compared with methadone, which is commonly used to treat opioid
addiction, buprenorphine is preferable because it is "less likely to
cause overdose" and "creates a lower level of physical dependence and
makes it easier for patients to discontinue medication."[^26]^,^ [^27]
Even when buprenorphine was initially approved in 2002, its favorable
characteristics for treatment and low risk of harm were noted by the
FDA.[^28]

All of these characteristics make buprenorphine a well-favored addiction
treatment drug. Some major treatment barriers for opioid addicts are
social stigma and access to treatment. Functions of treatment access are
geographic availability, cost, insurance coverage and the stigma of
seeking treatment at a methadone clinic, which the patient may perceive
brands him or her as an addict. When patients can be treated in a
physician's office instead of in a methadone clinic, several barriers to
treatment are automatically reduced. Treatment in a regular medical
office setting is more private, thus, reducing stigma. Access is
improved geographically, since legislation allowing for bupenorphine's
in-office use has enlarged the number of physicians who can offer
addiction treatment beyond just those in methadone clinics.

The manner in which buprenorphine is handled in the U.S. contributes to
its low risk of abuse and diversion. Part of the equation is its use
with a narcotic blocker and part is the level of control on in-office
use by licensed and properly credentialed physicians, through special
waiver requirements and clinical practice guidelines.[^29] When
buprenorphine is combined with naloxone, which blocks opiate effects,
when injected, the user does not get a euphoric "high," there is little
incentive to abuse buprenorphine.

**[Conclusion and Recommendations]{.smallcaps}**

The widespread, international public health problem of addiction to
opioids requires the greatest degree of possible access to beneficial
treatments. Buprenorphine is a major addiction treatment medication that
has proven to be more efficacious and accessible for many patients than
alternatives. Yet, it has a lower risk of diversion and abuse due to its
inherent nature of being less potent, thus, less attractive as a
euphoric agent. This risk of abuse or diversion is further diminished
when buprenorphine is administered under strict physician supervision
and in combination with opiate blocking agents such as naloxone. Its
access is widely enhanced, when it is available for use in physicians'
office settings.

Buprenorphine has become an important part of physicians' addiction
treatment arsenal in many countries, other than the U.S. It must be kept
accessible. The personal and social ramifications of untreated opioid
addiction are far too damaging to be fostered, even unwittingly, by
unnecessary restrictions on available, proven treatments. For all these
reasons, APA strongly recommends against re-scheduling buprenorphine
from Schedule III of the Convention on Psychotropic Substances, 1971, to
Schedule I of the Single Convention on Narcotic Drugs, 1961, as
entertained in the notice. APA also recommends that WHO: 1. focuses on
methods to ensure that only appropriately qualified physicians in any
country can obtain and use buprenorphine for addiction treatment; and 2.
promotes efforts by the international medical community to share their
best practices for the successful use of buprenorphine in opioid
addiction treatment.

Thank you for your consideration of these comments.

![](media/image1.png){width="2.2493055555555554in"
height="0.7444444444444445in"}

James H. Scully Jr., M.D.

Medical Director & C.E.O., American Psychiatric Association

[^1]: FDA Notice: "International Drug Scheduling; Convention on
    Psychotropic Substances; Single Convention on Narcotic Drugs;
    Butorphanol; Delta--9--tetrahydrocannabinol (Dronabinol);
    Gamma-Hydroxybutyric Acid; Ketamine; Khat; Tramadol; Zopiclone;
    Buprenorphine; Oripavine"

    Docket No. 2005N--0479 \[Federal Register: December 13, 2005 (Volume
    70, No. 238\].

[^2]: FDA Notice: "International Drug Scheduling; Convention on
    Psychotropic Substances; Single Convention on Narcotic Drugs;
    Butorphanol; Delta--9--tetrahydrocannabinol (Dronabinol); et al"

    Docket No. 2005N--0479 \[Federal Register: December 13, 2005 (Volume
    70, No. 238\], at 73775.

[^3]: FDA Notice: "International Drug Scheduling; Convention on
    Psychotropic Substances; Single Convention on Narcotic Drugs;
    Butorphanol; Delta--9--tetrahydrocannabinol (Dronabinol); et al"

    Docket No. 2005N--0479 \[Federal Register: December 13, 2005 (Volume
    70, No. 238\], at 73775.

[^4]: WHO "Expert Committee on Drug Dependence Thirth-Third Report,"
    2003. Retrieved January 11, 2006, from: <http://www.who.int/en/>

[^5]: FDA Notice: "International Drug Scheduling; Convention on
    Psychotropic Substances; Single Convention on Narcotic Drugs;
    Butorphanol; Delta--9--tetrahydrocannabinol (Dronabinol); et al"

    Docket No. 2005N--0479 \[Federal Register: December 13, 2005 (Volume
    70, No. 238\], at 73775.

[^6]: The White House Office of National Drug Control Policy (ONDCP)
    website: "Heroin." Retrieved January 11, 2006, from
    <http://www.whitehousedrugpolicy.gov/publications/factsht/methadone/index.html>

[^7]: U.S. Department of Health And Human Services, Substance Abuse and
    Mental Health Services Administration (SAMHSA), Office of Applied
    Studies website: "2004 National Survey on Drug Use and Health,
    *REVISIONS AS OF 9/8/2005."*

    Retrieved January 11, 2006, from:
    [http://oas.samhsa.gov](http://oas.samhsa.gov/)

[^8]: The White House Office of National Drug Control Policy (ONDCP)
    website: "Methadone April 2000." Retrieved January 11, 2006, from
    <http://www.whitehousedrugpolicy.gov/publications/factsht/methadone/index.html>

[^9]: Pieta Laut, Executive Director of the Public Health Association of
    Australia, in a letter of 29 January 29, 2005, to The Honorable Tony
    Abbott, MP, Minister for Health and Ageing of New South Wales,
    Australia. Retrieved January 11, 2006, from:
    <http://www.phaa.net.au/Advocacy_Issues/whorecom.htm>

[^10]: European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)
    Annual Report 2005: "Clients and coverage of high-dosage
    buprenorphine treatment (HDBT)." The study involved patients in the
    Czech Republic, Denmark, Germany, France, Italy, Luxembourg,
    Portugal, Sweden and Norway.

    Retrieved January 13, 2006, from:
    <http://issues05.emcdda.eu.int/en/page038-en.html>

[^11]: U.S. Department of Health And Human Services, Substance Abuse and
    Mental Health Services Administration (SAMHSA) website; retrieved
    January 11, 2006 from <http://samhsa.gov/>

[^12]: U.S. Department of Health and Human Services, Substance Abuse and
    Mental Health Services Administration (SAMHSA): "Clinical Guidelines
    for the Use of Buprenorphine in the Treatment of Opioid Addiction;"
    DHHS Publication No. (SMA) 04-3939 (2004); Executive Summary, at pg.
    xv. Retrieved January 11, 2006 from
    <http://buprenorphine.samhsa.gov/>

[^13]: FDA Notice: "International Drug Scheduling; Convention on
    Psychotropic Substances; Single Convention on Narcotic Drugs;
    Butorphanol; Delta--9--tetrahydrocannabinol (Dronabinol); et al"

    Docket No. 2005N--0479 \[Federal Register: December 13, 2005 (Volume
    70, No. 238\], at 73778.

[^14]: SAMHSA. "Summary of Drug Addiction Treatment Act of 2000" (DATA
    2000), referencing "Title XXXV, Section 3502 of the Children\'s
    Health Act of 2000 - Waiver Authority for Physicians Who Dispense or
    Prescribe Certain Narcotic Drugs for Maintenance Treatment or
    Detoxification Treatment." retrieved January 11, 2006 from
    <http://buprenorphine.samhsa.gov/titlexxxv.html>

[^15]: Retrieved January 13, 2006, from:
    [http://thomas.loc.gov](http://thomas.loc.gov/)

[^16]: Senate Bill 45, "Drug Addiction Treatment Expansion Act," passed
    by the 109th Congress, 1st Session; to be effective on the date of
    enactment of the Act:

    "SECTION 1. MAINTENANCE OR DETOXIFICATION TREATMENT WITH CERTAIN
    NARCOTIC DRUGS; ELIMINATION OF 30-PATIENT LIMIT FOR GROUP PRACTICES.

    > \(a\) IN GENERAL- Section 303(g)(2)(B) of the Controlled Substance
    > Act (21 U.S.C. 823(g)(2)(B)) is amended by striking clause (iv).
    >
    > \(b\) CONFORMING AMENDMENT- Section 303(g)(2)(B) of the Controlled
    > Substance Act (21 U.S.C. 823(g)(2)(B)) is amended in clause (iii)
    > by striking \`In any case\' and all that follows through \`the
    > total\' and inserting \`The total\'.
    >
    > \(c\) EFFECTIVE DATE- This section shall take effect on the date
    > of enactment of this Act.

    Passed the Senate July 19, 2005."

    Retrieved January 11, 2006 from the Library of Congress:
    [http://thomas.loc.gov](http://thomas.loc.gov/)

[^17]: International Center for Advancement of Addiction Treatment
    website, "The Opiate AddictionRX.info Newsletter, World Highlights,"
    January 27, 2005:

    "USA: Buprenorphine 2 Years After Approval\
    The director of the Center for Substance Abuse Treatment, H. Westley
    Clark, recently reported, '1,113 physicians are estimated to have
    provided treatment using buprenorphine' ( Alc. & DrugAbuse Weekly,
    Nov. 1, 2004). The total number of patients treated over the course
    of the past two years is estimated by Dr. Clark to be 63,000,
    'mostly in detox' (which is clear, since no physician may treat more
    than 30 patients at one time)."

    Retrieved January 11, 2006 from
    <http://www.opiateaddictionrx.info/enews/Enewsjan05.htm#high09>

[^18]: The figures were provided orally by Robert Lubran, Director of
    Pharmacologic and Alternative Therapies, Center for Substance Abuse
    Treatment (Substance Abuse and Mental Health Services
    Administration, U.S. Department of Health And Human Services) at a
    September 8, 2005, meeting of APA\'s Council on Addiction
    Psychiatry.

[^19]: The figures were provided by e-mail, dated January 12, 2006, from
    the Center for Substance Abuse Treatment (Substance Abuse and Mental
    Health Services Administration, U.S. Department of Health And Human
    Services) to APA.

[^20]: The figures were provided by e-mail, dated January 12, 2006, from
    the Center for Substance Abuse Treatment (Substance Abuse and Mental
    Health Services Administration, U.S. Department of Health And Human
    Services) to APA.

[^21]: The figures were provided by e-mail, dated January 12, 2006, from
    the Center for Substance Abuse Treatment (Substance Abuse and Mental
    Health Services Administration, U.S. Department of Health And Human
    Services) to APA.

[^22]: The figures were provided by e-mail, dated January 12, 2006, from
    the Center for Substance Abuse Treatment (Substance Abuse and Mental
    Health Services Administration, U.S. Department of Health And Human
    Services) to APA.

[^23]: The figures were provided orally by Robert Lubran, Director of
    Pharmacologic and Alternative Therapies, Center for Substance Abuse
    Treatment (Substance Abuse and Mental Health Services
    Administration, U.S. Department of Health And Human Services) at a
    September 8, 2005, meeting of APA\'s Council on Addiction
    Psychiatry.

[^24]: U.S. Department of Health and Human Services, Substance Abuse and
    Mental Health Services Administration (SAMHSA): "Clinical Guidelines
    for the Use of Buprenorphine in the Treatment of Opioid Addiction;"
    DHHS Publication No. (SMA) 04-3939 (2004); Executive Summary, at pg.
    xvii.

[^25]: U.S. Department of Health and Human Services, Substance Abuse and
    Mental Health Services Administration (SAMHSA): "Clinical Guidelines
    for the Use of Buprenorphine in the Treatment of Opioid Addiction;"
    DHHS Publication No. (SMA) 04-3939 (2004); Executive Summary, at pg.
    xviii. Retrieved January 11, 2006, from:
    <http://buprenorphine.samhsa.gov/>

[^26]: The White House Office of National Drug Control Policy (ONDCP)
    website: "Heroin." Retrieved January 11, 2006, from
    <http://www.whitehousedrugpolicy.gov/publications/factsht/methadone/index.html>

[^27]: SAMHSA website: "About Buprenorphine Therapy: Evidence of
    Effectiveness:"

    "Studies have shown that buprenorphine is more effective than
    placebo and is equally as effective as moderate doses of methadone
    and LAAM in opioid maintenance therapy. Buprenorphine is unlikely to
    be as effective as more optimal-dose methadone, and therefore may
    not be the treatment of choice for patients with higher levels of
    physical dependence.\
    \
    "Few studies have been reported on the efficacy of buprenorphine for
    completely withdrawing patients from opioids. In general, the
    results of studies of medically assisted withdrawal using opioids
    (e.g., methadone) have shown poor outcomes. Buprenorphine, however,
    is known to cause a milder withdrawal syndrome compared to methadone
    and for this reason may be the better choice if opioid withdrawal
    therapy is elected." Retrieved January 13, 2006, from:
    <http://buprenorphine.samhsa.gov/about.html>

[^28]: FDA Talk Paper, "Subutex and Suboxone Approved to Treat Opiate
    Dependence;" October 8, 2002:

    "The Food and Drug Administration (FDA) announced the approval of
    Subutex (buprenorphine hydrochloride) and Suboxone tablets
    (buprenorphine hydrochloride and naloxone hydrochloride) for the
    treatment of opiate dependence. Subutex and Suboxone treat opiate
    addiction by preventing symptoms of withdrawal from heroin and other
    opiates.

    "These products represent two new formulations of buprenorphine. The
    first of these formulations, Subutex, contains only buprenorphine
    and is intended for use at the beginning of treatment for drug
    abuse. The other, Suboxone, contains both buprenorphine and the
    opiate antagonist naloxone, and is intended to be the formulation
    used in maintenance treatment of opiate addiction. Naloxone has been
    added to Suboxone to guard against intravenous abuse of
    buprenorphine by individuals physically dependent on opiates. Both
    drugs are supplied in 2 mg and 8 mg tablets which are placed under
    the tongue and must be allowed to dissolve.

    "Subutex and Suboxone have been studied in over 2,000 patients and
    shown to be safe and effective treatments for opiate dependence.

    "Buprenorphine is considered to have less risk for causing
    psychological and or physical dependence than the drugs in Schedule
    II such as morphine, oxycodone, fentanyl, or methadone.

    "Subutex and Suboxone are the first narcotic drugs available for the
    treatment of opiate dependence that can be prescribed in an office
    setting under the Drug Addiction Treatment Act (DATA) of 2000. Until
    recently, opiate dependence treatments in Schedule II, like
    methadone, could be dispensed in a very limited number of clinics
    that specialize in addiction treatment. As a consequence, there have
    not been enough addiction treatment centers to accommodate all
    patients desiring therapy." Retrieved January 12, 2006, from:
    [http://www.fda.gov](http://www.fda.gov/)

[^29]: U.S. Department of Health and Human Services, Substance Abuse and
    Mental Health Services Administration (SAMHSA): "Clinical Guidelines
    for the Use of Buprenorphine in the Treatment of Opioid Addiction;"
    DHHS Publication No. (SMA) 04-3939 (2004). Retrieved January 11,
    2006, from <http://buprenorphine.samhsa.gov/>