A review of the FDA approved medication for the treatment of tobacco, alcohol and opioid use disorders.

1. Benjamin Wilbur Assignment – Topic Paper
Human Services 183 5/11/2017
Medication-Assisted Treatment
Introduction
With the “War on Drug” still being waged on our streets everyday, the hope was that fewer
people would suffer from addiction. The expectation was that with all the money, man-power and
experience of the last 5 decades, things would at least not be getting worse. Unfortunately, the United
States has not been a careful student of the problem. It appears collectively we haven't learned much
from the past (alcoholism of the 17&1800's, see Appendix), others countries solutions to this same
problem (e.g. in the Netherlands and Portugal) or even the solutions that have been shown to work on a
small scale right here in the US (harm reduction through needle exchange, naloxone kits for addicts,
and medication). As a society we still are working hard to deal with addiction by getting rid of the
supply of drugs (see Figure 1.), and punish the addiction out of the addict (see Figure 2.).
1
Figure 1. U.S. Rates of Past Month Drug Use compared to annual spending of Drug Control per 100
people from 1970-2010. (From http://www.mattgroff.com/updating-the-1315-chart/)

2. So clearly throwing money at the drug abuse problem like any problem doesn't fix it. The number of
people abusing drugs has remained relatively constant despite a 100x increase in spending on drug
control (~90% spent on supply reduction). With record number of people enduring the intense trauma
of incarceration (more than any other country in the world, 710 per 100K population), strictest
sentencing guidelines, and record numbers law enforcement officers, are we at least making things
safer? (see Figure 3.) Absolutely not. Rates of property and violent crime have remained basically the
same before and after the era of incarceration (1980-present).
The “War on Drugs” is intellectually dead. No expert can justify the use of money and manpower used
in supply reduction, the police brutality in dealing with “junkies”, or the insanity of incarcerating
addicts. Even with the explosion of new scientific information about addiction over the past century,
2
Figure 2. Number of people incarcerated in America from 1920-2013 with several key drug abuse
related policy changes noted. (From https://endnewjimcrowde.org/about/)

3. addiction treatment and rates of recovery haven't changed much.
So its long past time for some new ideas about addiction. The current model does not explain the
illusive problem of addiction or show how recovery is possible for the masses. If the model is broken,
how can we fix it? Well that's beyond the scope of this paper.
I would like to discuss Medication-Assisted Treatment (MAT) as one of the incremental changes to the
culture of addiction treatment that is long overdue. MAT is defined by the Substance Abuse and Mental
Health Services Administration (SAMHSA) as the use of medications in combination with counseling
and behavioral therapies for the treatment of substance use disorders. According to SAMHSA-HRSA
Center for Integrated Health Solutions website physicians are being actively sought to join the ranks of
health care providers fighting the epidemic of substance abuse (http://www.integration.samhsa.gov/).
Center for Integrated Health Solutions promotes the development of integrated primary and behavioral
health services to better address the needs of individuals with mental health and substance use
conditions, whether seen in behavioral health or primary care provider settings. To say we even need
such a Center is to say our system of health care delivery is broken, seriously broken. Hopefully this is
3
Figure 3. Changes in violent and property crime corelated to inmate and total incarcerated population
from 1960-2007. (From http://cepr.net/publications/reports/the-high-budgetary-cost-of-incarceration)

4. just the beginning of much larger changes in the structure of how health care and addiction treatment
are delivered here in the US.
Medication-Assisted Treatment
Medications have been found to be effective in easing the detoxification process, reducing drug
cravings, reducing the relapse rate and ultimately increasing survival for addicts. Medications have
been FDA approved for curbing addictions to tobacco (nicotine), alcohol and opioids. Research is
ongoing for some drugs that may help cocaine and amphetamine addicts. Even though these
medications have been shown to be safe and effective, some in use for decades in Europe, there use in
the U.S. has been slowed by numerous barriers to there adoption.
Barriers to Adoption
Many states will not pay for the medications. To be readily available for use the medications would
need to be on formulary with Medicaid and available through 340B programs that administer
community health centers. Even when patients have insurance, many private sector physicians are not
using the medications.
Treatment programs have been resistant to the use of medication in the treatment of addictions. There
may be problems of lack of provider education or acceptance of medications as beneficial for patients
with addictions. Treatment programs and health centers may be geographically distant from one
another. There may not be any interaction between physicians and treatment programs, let alone
networking to provide integrated services. Often physicians in private practice don't have any way to
assure that counseling services accompany use of medications in addictions treatment. There are often
workforce issues in implementing MAT. There aren't enough physicians and nurses trained in how to
provide MAT. Often providers, physicians and treatment programs, don't even accept the “medical
model” of addiction thus see no role for medications in treating addiction. Finally, there are significant
4

5. regulatory barriers to MAT. Often the state legislature is not educated about the use of medications in
addiction treatment. There may even be statutes on the books blocking such treatment. Certainly there
is little will to increase state funding for addiction treatment, especially to increased spending on
addiction treatment related to the introduction of medications. Given the patch work of state
regulations, Medicaid formularies, outdated attitudes toward using medications to treat addiction MAT
5
Figure 4. State requirements for opioid MAT medications. a. Methadone is only covered by Medicaid in
31 states. b. Buprenorphine has lifetime coverage limits in several states. While this information is not
complete (Yellow = unknown) it certainly demonstrates the lack of education regarding maintenance
treatment. c. Suboxone prescriptions require a prior authorization in most states. d. Counseling and
documentation of counseling are required in most states for Suboxone coverage. (Source: AAAM 2013
Report by ASAM)

6. has an uphill battle on its hand to find acceptance and adoption. In fact SAMHSA has a implementation
checklist that they put together to help anyone in addiction treatment that might want to work to help
get these issues addressed and MAT implemented in their state (http://www.integration.samhsa.gov/
clinical-practice/mat/MAT_Implementation_Checklist_FINAL.pdf appended to the end of this paper).
As of 2005, methadone treatment was still not available in six states: Idaho, Mississippi, Montana,
North Dakota, South Dakota, and Wyoming (SAMHSA TIP-43). I did find information that methadone
is only covered by Medicaid in 31 states and Suboxone is covered by Medicaid in all 50 states
(Advancing Access to Addiction Medication (AAAM), ASAM Report 2013, https://www.asam.org/
docs/default-source/advocacy/aaam_implications-for-opioid-addiction-treatment_final). However, prior
authorization and counseling requirements for the Suboxone to actually be covered (see Figures 4).
MAT for Nicotine Addiction (Tobacco Use Disorder)
Addiction is responsible for more deaths than any other cause (see Table 1). In 2000, tobacco use
accounts for the most deaths followed by alcohol use at #3 and illicit drugs at #9. “Cigarette smoking is
the chief, single avoidable cause of death in our society and the most important public health issue of
6
Table 1. Actual Causes of Death in the United States in 1990 and 2000. (Source Ali H. Mokdad; James
S. Marks; Donna F. Stroup; et al. Actual Causes of Death in the United States, 2000. JAMA.
2004;291(10):1238-1245

7. 7
Figure 5. Tobacco last month use (left) and Tobacco attributable deaths by cause (right). (Sources
(left) 2015 National Survey on Drug Use and Health (right) CDC
https://www.cdc.gov/tobacco/infographics/health-effects/pdfs/pie-chart-2017.pdf?s_cid=bb-osh-
effects-graphic-001)
Table 2. Formulary for Nicotine Addiction (Source
https://www1.nyc.gov/assets/doh/downloads/pdf/csi/tobacco-med-brief-instructions.pdf)

8. our time,” according to the Surgeon General. About 24% of the US population used tobacco last month.
That's a staggeringly high figure given the destruction smoking causes. Smoking tobacco contributes to
death almost entirely from chronic causes (see Figure 5). Tobacco use leads to death from lung cancer,
chronic obstructive pulmonary disease, heart disease, other cancers, strokes and other diseases for a
total of about 480,000 people killed each year. Given the annual total deaths, the daily toll is 1315
people each day.
There are three basic treatments for nicotine addiction nicotine replacement, varenicline, and
bupropion.(see Table 2). All of these treatments have been shown to be more effective than placebo or
counseling alone (see Table 3).
Bupropion (Zyban) is an antidepressant drug. Bupropion increases levels of dopamine and
norepinephrine, brain chemicals that are also boosted by nicotine. Typically, started one week before
8
Table 3. Effectiveness and abstinence rates of individual treatments versus placebo at 6 months
postquit (n=83 different studies). (Source Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use
and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of
Health and Human Services. Public Health Service. May 2008. CPG Table 6.26
https://www.ncbi.nlm.nih.gov/books/NBK63943/)

9. stopping smoking. Due to mild stimulant effects, bupropion has the advantage of helping to minimize
weight gain after you quit smoking. Common side effects include insomnia, agitation, headache and
dry mouth. Patients with a history of seizures or serious head trauma, such as a skull fracture should not
take this drug.
Varenicline (Chantix) is a medication that acts on the brain's nicotine receptors, decreasing withdrawal
symptoms and reducing the feelings of pleasure you get from smoking. Patients should start varenicline
at least one week and possible 3 weeks before they stop smoking. Common side effects include nausea,
headache, insomnia and vivid dreams. Rarely, varenicline has been associated with serious psychiatric
symptoms, such as depressed mood and suicidal thoughts.
Both bupropion and varenicline are generally taken for at least 12 weeks to help reduce the chances of
relapse in early recovery.
MAT for Alcohol Use Disorder
In 2015, about 15.7 million people had alcohol use disorder (see Figure 6). Alcohol consumption is the
cause of approximately 106000 deaths each year between 2006-2010. These deaths are roughly half
9
Figure 6. Number of People 12 or Older with Past Year Substance Use Disorder 2015 (Source
National Survey of Drug Use and Health 2015 )

10. from chronic disease (57221) and half from acute accidental causes (49544) (see Figure 7).
The FDA-approved medications for alcohol use disorder are disulfiram, acamprosate and naltrexone
(see Table 4). Disulfiram (Antabuse) can help to prevent drinking, although it won't cure alcohol use
disorder or remove the compulsion to drink. If a patient drinks alcohol, the drug produces a very
unpleasant physical reaction that may include flushing, nausea, vomiting and headaches. Evidence to
show that this medication is effective is weak at best if not equivocal (see Table 5). Acamprosate
(Campral®) may help you combat alcohol cravings once a patient has stopped drinking. Acamprosate
10
Figure 7. Alcohol-Attributable Deaths per year average in US 2006-2010 broken down by cause.
Chronic disease (dark) and acute injury (light), due to any alcohol use for all ages. (Source Centers for
Disease Control and Prevention. Alcohol Related Disease Impact (ARDI) application, 2013. Available
at www.cdc.gov/ARDI.)
Alcoholic liver disease 22549
Cancer 13624
Stroke 8480
Heart Disorder 4468
Other chronic 8100
Other acute 3557
Alcohol poisoning 1647
Fall injuries 7541
Homicide 7756
Suicide 8179
Poisoning (not alcohol) 8404
Car Accidents 12460

11. acts on the gamma-aminobutyric acid (GABA) and glutamate neurotransmitter systems and is thought
to reduce symptoms of protracted withdrawal, such as insomnia, anxiety, restlessness, and dysphoria.
Acamprosate has been shown to help dependent drinkers maintain abstinence for several weeks to
months, and it may be more effective in patients with severe dependence. Naltrexone (Revia®) blocks
opioid receptors that are involved in the rewarding effects of drinking and the craving for alcohol.
Naltrexone helps to prevent heavy drinking and reduce the urge to drink. Vivitrol®, the injectable
version of naltrexone, is administered once a month by a health care professional. The injectable
11
Table 4. Formulary for Alcohol Use Disorder (Source Helping patients who drink too much. A
Clinician's Guide 2005 p. 16 NIAAA
https://pubs.niaaa.nih.gov/publications/practitioner/cliniciansguide2005/guide.pdf)

12. 12
Table 5: Summary of Findings and Strength of Evidence from trials assessing efficacy of FDA-
Approved medications for alcohol use disorders. (Source Pharmacotherapy for Adults With Alcohol
Use Disorders in Outpatient SettingsA Systematic Review and Meta-analysis. JAMA.
2014;311(18):1889-1900. doi:10.1001/jama.2014.3628)

13. version of the drug may be easier for people recovering from alcohol use disorder to use consistently.
Unlike disulfiram, naltrexone and acamprosate do not cause any physical reaction if alcohol is ingested.
There is only sufficient evidence to recommend acamprosate and oral naltrexone 50 mg daily. And that
evidence is only modest. While a number of behavioral treatments have been shown to be effective in
the treatment of alcohol addiction, it does not appear that an additive effect exists between behavioral
treatments and pharmacotherapy. Studies have shown that just getting help is one of the most important
factors in treating alcohol addiction; the precise type of treatment received is not as important.
MAT for Opioid Use Disorder
There is a rapidly escalating crisis of drug overdose deaths. The latest available number show that in
2015 the number of deaths exceeded the height of the HIV/AIDS epidemic in 1995 (see Figure 8).
MAT for opioid users is broadly supported with significant supporters including SAMSHA, NIDA,
13
Figure 8. Deaths from Drug Overdoses, Guns, Car Accidents, and HIV/AIDS in the US from 1980-2015
(Source CDC Wonder database queries)
1980
1982
1984
1986
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
2012
2014
0
10000
20000
30000
40000
50000
60000
Drug Overdose
Guns
Car Accidents
HIV/AIDS

14. White House Office of National Drug Control Policy, NIH, Depart of Health and Human Services, and
numerous state governments. With good reason given that, 1) opioid users overdose 2x more frequently
when in abstinence only compared to medication assisted treatments, and 2) 70-90% of individuals
relapse in abstinence only treatment. Effective treatment of OUD has been identified as a national
priority to reduce the rates and societal costs of individual disability associated with OUD, the
infectious disease burden associated with intravenous opioid use (especially hepatitis C [HCV] and
HIV transmission), and escalating rates of accidental opioid overdose deaths and pediatric opioid
ingestions.
Three medications are FDA-approved for the treatment of opioid use disorders, methadone,
buprenorphine with/without naloxone and naltrexone. Methadone is a long-acting synthetic opioid
agonist medication that can prevent withdrawal symptoms and reduce craving in opioid-addicted
14
Table 6: Comparison of medications for opioid use disorders. (Source Connery, HS. Medication-
Assisted Treatment of Opioid Use Disorder: Review of the Evidence and Future Directions. Harvard
Review of Psychiatry 23(2) 2015)

15. individuals. It can also block the effects of illicit opioids. It has a long history of use in treatment of
opioid dependence in adults and is taken orally. Methadone maintenance treatment is available in all
but three States through specially licensed opioid treatment programs or methadone maintenance
programs. Research has shown that methadone maintenance is more effective when it includes
individual and/or group counseling, with even better outcomes when patients are provided with, or
referred to, other needed medical/psychiatric, psychological, and social services (e.g., employment or
family services). Buprenorphine is a synthetic opioid medication that acts as a partial agonist at opioid
15
Table 7. Formulary for Opioid Use Disorder (Source Connery, HS. Medication-Assisted Treatment of
Opioid Use Disorder: Review of the Evidence and Future Directions. Harvard Review of Psychiatry
23(2) 2015)

16. receptors—it does not produce the euphoria and sedation caused by heroin or other opioids but is able
to reduce or eliminate withdrawal symptoms associated with opioid dependence and carries a low risk
of overdose. Buprenorphine treatment for detoxification and/or maintenance can be provided in office-
based settings by qualified physicians who have received a waiver from the Drug Enforcement
Administration (DEA), allowing them to prescribe it. The availability of office-based treatment for
opioid addiction is a cost-effective approach that increases the reach of MAT and the options available
to patients.
The evidence from several randomized controlled trials shows that both buprenorphine/naloxone and
methadone are significantly more effective at maintaining opioid abstinence than naltrexone or placebo.
(See Table 8.) Relapse rates for patients on placebo only treatments ranged from 70-94%.
Conclusions
Medication-assisted treatment is not widely available for numerous reasons including a lack of trained
providers, numerous regulatory blocks and an attitude of mistrust and opposition among addiction
16
Table 8. Efficacy of medications for opioid disorder compared to placebo. (Source Connery, HS.
Medication-Assisted Treatment of Opioid Use Disorder: Review of the Evidence and Future Directions.
Harvard Review of Psychiatry 23(2) 2015)

17. treatment professional. FDA-approved medications are available for nicotine, alcohol and opioid
addictions. These medications effectively reduce cravings and relapse. The number of lives lost each
year to these addictions make MAT and any other effective technique for controlling this epidemic
demand our full attention.
17

18. Appendix
The rates of alcohol use in America have varied widely. However, even with Prohibition the rate hasn't
varied as much as it did with the Temperance Movement. During the Temperance Movement
(especially 1830-50) colonial rates of heavy consumption finally decreased. Thanks largely to the lead
from the pulpit, some 6,000 local temperance groups in many states were up and running by the 1830s.
The movement existed in a matrix of unrest and intellectual ferment in which such other social ills as
slavery, neglect and ill-treatment of marginalized people, were addressed by liberals and conservatives
alike. Sometimes called the First Reform Era, running through the 1830s and '40s, it was a period of
inclusive humanitarian reform. (From http://www.u-s-history.com/pages/h1054.html) The three largest
movements for reform were temperance/abstinence from alcohol, abolition of slavery, and the women's
rights movement. So what did the First Reform Era do right that we can't seem to replicate now for all
our efforts (money, incarceration)?
18
Figure 9. In the United States the per capita consumption of pure alcohol at present is 2.2 gallons but
as this chart shows, the rate has varied wildly with the rise and fall of prohibition movements, health
concerns, and availability of a good water supply. Adapted from David F. Musto's Alcohol in American
History, Scientific American, April 1996. (From http://www.theathlete.org/drug-
abuse/epidemiology_alcohol.htm, also http://www.fourpoundsflour.com/tomorrow-drinking-like-a-
colonial-american/)

19. 19
Figure 10 Drug overdose death rate by state, age-adjusted. 2015 (Source CDC
https://www.cdc.gov/drugoverdose/data/statedeaths.html)
Figure 11: Buperinorphine treatment capacity per 100K population by state as of 2017. (Source
SAMHSA)

20. I constructed a map of the U.S. showing how many law enforcement organizations in each state have
started carrying Narcan while on duty (see Figure 12).
20
Figure 12. Number of Law Enforcement organizations per state that carry Narcan, the opioid overdose
reversal drug. Pennsylvanian is the national leader with 595, many states in white still don't have a
single department carrying this life saver. (Data from North Carolina Harm Reduction Coalition,
current as of 5/2017)