Truth about MAT

Exchanging One Drug For Another?

The Truth About Medication Assisted Treatment

For Opioid Use Disorders

NAMI Southwest Ohio

March 08, 2016

Clifford Q Cabansag, MD, DABAM, CTTSAddiction Medicine Physician, Tobacco Treatment Specialist

Disclosures

• NONE

Objectives

At the end of this session each participant will be able to:

• Discuss the language and appropriate terminology of substance use disorders

• State the incidence, prevalence and death rates of opioid use disorders nationally, regionally and locally

• Identify available FDA approved medications for treatment of opioid use disorders & their mechanisms of action

Terminology

• Opiate vs. opioid• Chronic Disease Model• Derogatory language only perpetuates stigma• ‘Dependence’ & ‘Abuse’ not in DSM-5• Use disorder – mild, moderate or severe

• Classification based on # of criteria• Tolerance• Withdrawal• Dependence• Addiction

Opiates & Opioids

• Opiates – Morphine, Codeine & Thebaine• Semi-synthetic opioids

• Derived from natural opiate substrates• Morphine -> diacetylmorphine(heroin), hydromorphone • Codeine -> hydrocodone & oxycodone• Thebaine -> buprenorphine

• Fully synthetic opioids• Fentanyl, methadone, meperidine & propoxyphene

• Endogenous opioids produced in vivo• endorphins, enkephalins, dynorphins & endomorphins

Tomato Tomahto

• OpiATES • 20+ Natural derivatives of Papaver somniferum

• Psychoactive: morphine / codeine / thebaine• OpiOIDS

• Any ligand capable of binding opioid receptor• By default all opiates included

• ALL opiates are OPIOIDS• Only SOME opioids are OPIATES

Trade name vs. Generic

• MS Contin = Morphine Sulphate CONTINuous release• Vicodin/Lortab = hydrocodone + acetaminophen• Percocet = oxycodone + acetaminophen• Darvocet = propoxyphene + acetaminophen• OxyContin = oxycodone (CONTINuous release)• Dilaudid = hydromorphone• Darvon/Actiq/Duragesic patch = fentanyl• Demerol = meperidine• Lomotil = diphenoxylate

The Power of Language

• Addict• Addicted to _• Addiction• Alcoholic• Clean• Dirty• Drug habit• Drug Seeker

E̵ Pt with a substance use disorderE̵ Has a ___ use disorderE̵ Substance use disorderE̵ Pt with an alcohol use disorderE̵ Neg; Free of illicit substancesE̵ Pos; Active useE̵ Substance use disorderE̵ Relief seeking

The Power of Language

• Drug Abuser • Former• Maintenance• Pain Seeker• Recreational• Reformed• Replacement• Substance Abuser

E̵ Pt with SUD E̵ In sustained remissionE̵ Medication Asstd TreatmentE̵ Relief / Treatment SeekingE̵ Non-medical useE̵ In remissionE̵ MATE̵ Pt with SUD

Chronic Model of Disease

• Role of genetics • Pharmacodynamics / Pharmacokinetics

• Risk factors• #1 – Family hx• Childhood / other trauma• Co-occurring disorders• TBI• Early / childhood use

Chronic Model of Disease

Chronic Model of Disease• Trauma

• Not necessary for development of SUD• Does increase risk

• Without adequate treatment• No major or lasting headway can be made with SUD

• Makes treatment of trauma absolutely essential• Must be integrated into treatment

• CBT, Trauma Groups, Seeking Safety, etc.

Chronic Model of Disease• Other risk factors

Chronic Disease Model

DSM-5 Criteria

• Substance Use Disorders• A maladaptive pattern of substance use leading to

clinically significant impairment or distress, as manifested by 2 (or more) of the following occurring within a 12-month period:• Severity specifiers based on 11 criteria

• Merging DSM-IV ‘abuse’ & ‘addiction’ criteria minus legal• Mild: 2-3 criteria• Moderate: 4-5 criteria• Severe: 6 or more criteria

Questions

• (For discussion:Addiction ~ Substance Use Disorder)

• What must be present to have dependence?• Aren’t dependence and addiction the same?• Is it possible to have dependence w/o addiction? • To have addiction without dependence?• What about tolerance & withdrawal?

Answers

• Tolerance• Same amount of substance insufficient• Greater amount to achieve previous effect

• Withdrawal• Characteristic sequelae after discontinuation• Typically opposite effects of substance activity

• Classic examples: alcohol & opioids• Atypical example: cannabis

• Using similar substance to relieve symptoms

Answers

• In order to have dependence:• MUST have both tolerance AND withdrawal• Physiologic symptomatology

• So it IS possible to have dependence WITHOUT‘Addiction’ / Substance Use Disorder

• Examples: caffeine; hospice & chronic pain pts• So what makes the difference between having

only dependence but not an ‘addiction’?

Answers

• The LOSS OF CONTROL & Aberrant Behavior

• SoDependence ≠ ‘Addiction’/Substance Use DisO

• BUTDependence + Aberrant Behavior = SUD

Quiz

• Caffeine

• Clonidine

• Anorexia and Bulimia

• UDS

MAT and Abstinence• “Q: How does the Hazelden Betty Ford Foundation define abstinence

for someone on buprenorphine/naloxone?”• “A: A person who has an opioid use disorder and is taking medication

under the advice and care of a physician to treat the disease is not unlike a post-surgery patient who is using pain medication. If used as directed and not for the purpose of becoming intoxicated, the medication greatly assists in recovery.”

• “Recovery defined by the establishment of new behaviors in this manner is necessary. We view those working a recovery program while using buprenorphine/naloxone as prescribed as being in recovery, and our goal is abstinence.”

• “Clients on maintenance doses of buprenorphine will be expected to pursue 12-Step based counseling and ultimately to taper off the medication, but Seppala says of this group, “They will be taking the medication for probably months.*””

*Addiction Professional, November 7, 2013

Backlash• “Instead of an abstinence model, Betty Ford and Hazelden are embracing

what is known as a harm-reduction form of treatment using pharmaceutical interventions. These medical based treatments use pharmaceuticals like methadone or Suboxone, and other drugs, to limit the “harm” or negative consequences of substance abuse, attempting to keep the individual using a pharmaceutical in smaller amounts than their drug of choice, less often, and staying addicted to the pharmaceutical substitute, but using enough of a substitute not to get dope sick. This is an “evidence-based” treatment, and one that pharmaceutical companies are pushing as they stand to make millions of dollars from the sale of harm-reduction pharmaceutical products.”

• “Hazelden supports medication-based treatments for harm reduction, which is in truth only replacing one drug for another drug.”

• Psychology Today, January 7, 2015

Detox & “Drug-free” Approach

• Traditional model • Detox without subsequent medication support

• Effective for small subgroup: high motivation & stable (Flynn et al., 2003; Van den Brink and Hassen, 2006)

• Otherwise without medications• Up to 90% of detox’d pts relapse in first 1-2 mos (Weiss et al., 2011; Smyth et al. 2010)• Of those relapse – some will die of OD (Kakko et al., 2003)


How many times should you go to rehab?• Reasons given for failure:

• ‘You weren’t ready yet’• ‘You didn’t take it seriously enough’• ‘You didn’t engage in treatment’• ‘You hadn’t hit rock bottom’• ‘You really didn’t want it’

• In what other life aspect would you repeat?• Could it be the treatment was insufficient?• What’s the definition of insanity?


“Detoxification from heroin is good for many things – but staying off heroin is not one of them.”

- Dr. Walter Ling

Chronic Disease Model

“Exchanging one drug for another”

• Is there dependence?• Yes, but recall dependence ≠ substance use disorder

• Was the medication obtained illegally?• No; like other medications obtained by prescription

• Doesn’t MAT make people ‘high’/euphoric?• Routinely, No; may be some mild elevation of mood with

first dose in pt opioid naïve pt but not thereafter• Doesn’t MAT promote self-medication?

• No; pts are monitored regularly and carefully in accordance with evidence-based practice


• MAT• Decreases impulsive substance behaviors• Increases employability• Decreases overall chaos• Helps to develop structure• Increases engagement in socially productive roles• Improves relationships


• MAT definition in 2014 • CMS (Medicaid), SAMHSA, CDC, NIH, NIDA

• “Medication assisted treatment is the use of FDA-approved medications in combination with evidence-based behavioral therapies to provide a whole-patient approach to treating SUDs.”


• MAT• Decreases deaths• Decreases criminal activity• Increases retention in treatment• Decreases HIV/HepC transmission

• In short – MAT can help improve overall function and pts living a ‘normal’ and productive life

Exchanging One ‘Drug’ for Another

Heroin / Illicit Opioids• Illegal• Avoiding ‘Dope Sick’• Criminal charges / felony• Pharmacologic uncertainty

• Adulterants / ‘Cutting’*• Unemployment• Getting ‘High’ or ‘Buzzed’• Increased criminal behavior• IDU / high risk behavior• Increased HepC HIV STI• Financial ruin• Homelessness• Familial separation

Exchanging One ‘Drug’ for Another

Heroin / Illicit Opioids• Illegal• Avoiding ‘Dope Sick’• Criminal charges / felony• Pharmacologic uncertainty

• Adulterants / ‘Cutting’*• Unemployment• Getting ‘High’ or ‘Buzzed’• Increased criminal behavior• IDU / high risk behavior• Increased HepC HIV STI• Financial ruin• Homelessness• Familial separation

MAT with Methadone/BUP • Legal / Prescribed• Medical treatment• Lawful• Known dosages/potency

• Pharmacologic grade• Employment• No euphoria• Decreased criminal behavior• Daily PO/SL medication• Decreased Communicable Dzs• Financial self-sufficiency• Stable housing• Familial stability


• World Health Organization June 2005• Revised list of “essential medications


• World Health Organization June 2005• Revised list of “essential medications

• Methadone• Buprenorphine• Similar medications

Disparate Treatment

• Compliance comparable to other chronic dz’s• DM1, Asthma, HTN

• Requirements for treatment• Consequences of non-compliance

• CHF, COPD• Grounds for dismissal

Disparate Treatment

• SUD’s are the only conditions in which:• Pt’s are expected to improve their conditions before

being accepted into treatment• Non-compliance / lapse are grounds for dismissal• Withholding known life saving treatment considered• Known life saving treatment withheld or rationed• Active disease considered to be a crime problem• Pt’s expected to discontinue known effective Rx• No/limited insurance coverage for effective treatment

A Question of Duration

• Bear chronic disease model in mind• Range of severity• Some DM2 do well with lifestyle modification alone• Others require 1, 2, 3 or more medications• Still others require insulin

• Likewise with opioid use disorders• Some need only brief intervention• Others need additional group treatment• Some require MAT with Vivitrol• Others require MAT wit BUP or even methadone• Some will require indefinite MAT

A Question of Duration

• Basic risk to benefit analysis• Research: max benefit from prolonged treatment• Best outcomes after min 1 year of stable treatment

• Outcomes only improve with prolonged treatment• Best chances of weaning off after 2 years• Stable treatment

• Worst case scenarios• with continuing MAT: $?• with stopping MAT: relapse, arrest, jail, OD, death

What is the Role of Medication in MAT?

A day in the life of pt with heroin use disorder• Insomnia due withdrawal• Awakened by withdrawal• If not in withdrawal, deathly afraid of it• Various degrees of panic

• Continual crisis management• All resources devoted to answer 1 of 2 questions

• What do I have to do to not be sick?• To keep from becoming sick?


A day in the life of pt with heroin use disorder• A vicious cycle of treating / avoiding withdrawal• A continuous state of “Fight or Flight”• Existence at only a basic level


• Knowledge of negative consequences • INSUFFICIENT TO DETER USE• The Wrong Question: How could they?• Correct Question: What is the nature of the

disease that __________________?• Results in such aberrant behavior


• When under such duress is it realistic? • To expect people to:

• Use their best judgement• Delay gratification• Think long term• Make a logical / sensible / reasonable decision

• Could you?• Basic problem:

• Expecting people whose basic needs remain unmet• In a meaningful purposeful self-actualizing way• CHANGE BEHAVIOR


• Demarcated / Well-defined• Treat withdrawal symptoms – THAT’S ALL• Cravings/symptoms aka

• “The Smoldering Craving” or• “The Committee”

• Left untreated, unable to:• Stop, think, choose another course• Take advantage of otherwise efficacious therapy• Identify triggers, learn and use coping mechanisms


• Demarcated / Well-defined• Treat withdrawal symptoms – THAT’S ALL• With adequate treat of withdrawal symptoms

• (Maybe for the first time)• In a position to ‘do the work of recovery’

• Medication is NOT a magic bullet• Really a small part of treatment but crucial

• MAT places pts in a position to succeed

Take a Deep Breath

Deaths from Prescription Opioid Overdose• 44 people die in US daily due to Rx opioid OD• From 1999-2013:

• Mostly 25-54 years old (but OD’s among 55-64 ↑7x)• Non-Hispanic whites ↑4.3x from 1.6 to 6.8/100k• Non-Hispanic blacks ↑>2x from 0.9 to 2.5/100k• Hispanics slight ↑ from 1.7 to 2.1/100k• First Nations ↑ almost 4x from 1.3 to 5.1/100k• ♂>♀ but gap closing 1999-2010

• ♀↑> 400% vs ♂↑ 273%

CDC National Vital Statistics System mortality data, 2015

Deaths & ED utilization fr Rx Opioid OD• Rx drug ODs leading cause of injury death 2013

• 25-64 yr olds drug OD deaths > MV traffic crashes• 2013: 43,982 drug OD deaths

• Of these, 22,767 (51.8%) related to Rx drugs• Of these,16,235(71.3%)opioids; 6,973(30.6%) benzos• Opioid + benzo combo common

• Almost 2 million 12+ yrs old: opioid misuse or depend• 2011: 2.5 million drug misuse ED visits

• 1.4 million related to Rx drugs• 501,2017 visits related to anxiolytics & sleep aides• 420, 040 visits related to opioids

CDC National Vital Statistics System mortality data, 2015

Trends in Heroin Use in US: 2002 - 2013

• Relatively uncommon• ~ Past year users in 2013: 681,000• i.e. 0.3% of pop. 12 years old or older• But % of people using heroin higher in 2013 vs. 2003

• Incidence• 2013: 169,000 past year heroin initiates• Similar # of initiates in most years since 2002

SAMHSA National Survey on Drug Use and HealthShort Report April 23, 2015

Trends in Heroin Use in US: 2002 - 2013

Past-Year Nonmedical Pain Reliever Use Among Adolescents, by National Survey and Gender

2002–2013

Contributing Factors to Opioid OD Epidemic

• Changes in pain management guidelines 1990’s• PHARMA Aggressive marketing of ER opioids• 1997-2011: 643%↑ Rx opioid g / 100k Ohioans• 2012: 67 doses of Rx opioids / 1 Ohioan• Direct consumer marketing• Over-prescribing in general• Unscrupulous MDs / ‘Pill Mills’• Widespread diversion• Mixing of medications

Contributing Factors to Opioid OD Epidemic

Number and age-adjusted rates of drug overdose deaths by state, US 2013

Number and age-adjusted rates of drug overdose deaths by state, US 2014

Statistically significant drug overdose death rate increase from 2013 to 2014, US states

2013 OH Drug OD Data

• Public health crisis - ↑413% deaths 1999-2013• Unintentional ODs in 2013 – 2,110

• Highest # deaths on record, ↑10.2% from previous• Previous high – 1,914 deaths in 2012

• Almost 6 (5.8) Ohioans died daily - 1 death/4h• Unintentional OD leading cause injury deaths

• > MVA, suicide and falls• Trend since 2007 which continued through 2013

2013 OH Drug OD Data

• Opioids (Rx + heroin) main factor → epidemic• Almost ¾ (1,539; 72.9%) ODS involved opioids

• Up from (1,272; 66.5%) in 2012• Heroin deaths continued to ↑ in 2013

• From (233; 16%) in 2008 to (983; 46.6%) in 2013• Surpassed unintentional Rx opioid deaths• More than 2x fatal cocaine deaths

• MULTIPLE DRUG USE largest contributor

Number of unintentional drug OD deaths of Ohio residents and average crude and age-adjusted annual death rates

per 100,000, by county, 2008-2013

Take a Deep Breath

Role of MAT

• Dominant model remains detox• Detox w/o subsequent pharmacologic support

• Decades of evidence show lack of effectiveness• (What’s the definition of insanity?)

• Rx to prevent relapse not offered s/p detox• Treatment goal

• Misplaced emphasis on becoming “drug-free”• No consideration of risk reduction

Role of MAT• First few weeks s/p detox

• Highest risk of OD and death• To pts who want to stop using illicit opioids

• Imperative to provide agonist or antagonist Rx• Pts who choose agonist treatment

• Methadone without withdrawal• BUP with at least minimal withdrawal

• Harm reduction – decreases in:• High risk behavior• Needle use• Life chaos


• Traditional model • Detox without subsequent medication support

• Effective for small subgroup: high motivation & stable (Flynn et al., 2003; Van den Brink and Hassen, 2006)

• Otherwise without medications• Up to 90% of detox’d pts relapse in first 1-2 mos (Weiss et al., 2011; Smyth et al. 2010)• Of those relapse – some will die of OD (Kakko et al., 2003)

Classification of MAT Rx’s

• Basic schema• Action• (Route)• Duration of effect• Affinity

• Action• (Full) Antagonist• (Partial) Agonist/Antagonist• (Full) Agonist


• Duration of effect• Short, medium or long acting

• Affinity• Measure of binding of ligand to receptor• (Low) - High


• Action• Antagonist• Short-acting: naloxone IV or IN / Narcan• Long-acting: naltrexone po / ReVia

naltrexone IM / Vivitrol

Antagonist MAT

• Recall high relapse rate (~90%) s/p detox• Suitable for mild OUD / early disease process• Naltrexone 50 mg po daily / Revia• Blocks agonist effects of illicit opioids• PO good for motivated pts• Otherwise increased risk of non-compliance• Option: Naltrexone IM 380 mg monthly / Vivitrol• Trial of PO for toleration before IM• Monitor LFTs q3 mos at first then q6 mos• Must be opioid free before initiating


• Action• (Partial) Agonist/Antagonist

• Action depends on absence or presence of opioids• Opioids absent – agonist effect• Opioids present – antagonist effect

• Buprenorphine / Subutex• Buprenorphine + Naloxone / Suboxone• Route – SL films or tabs• High affinity

Partial Agonist/Antagonist MAT

• Buprenorphine FDA approved for MAT only – SL• BUP has moderate analgesic properties but NOT approved for pain• BUP monoformulation = Subutex• BUP + naloxone = Suboxone

• Role of naloxone?• Good for moderate OUD• Office based • More flexible – at best monthly visits (vs. methadone daily)• Risk of diversion• Low OD risk (except + benzos and/or EtOH)• High affinity

• Able to block illicit opioids• But potential for precipitated withdrawal


• Action• (Full) Agonist• Methadone liquid po for MAT• (Methadone / Dolphine tab po for pain) • Route – both liquid and tab po • Long acting for MAT

• Intermediate acting for pain• Moderate affinity

Full Agonist MAT

• Methadone liquid only for MAT • Restricted access – Methadone Clinics only• Less easily diverted• For severe OUD or pt wanting more structure• Initially daily

• Can progress to 1 month supply in 2.5 years• At higher doses can ‘blockade’ other opioids• QTc prolongation at high doses – baseline EKG

Full Agonist MAT

• Methadone highest efficacy relieving withdrawal• (Dole and Nyswander, 1960’s)• Dominant treatment of OUD in US

• Highest retention (80% at 6 mos)• Decreased HIV & HepC transmission• Interaction with HAART for HIV• Maintains physiologic dependence• Risk of overdose during and if dc’d

Opioid Overdose• Opioid antagonists

• Used to improve breathing• Naloxone

• Short acting• Reverses respiratory suppression > opioid analgesia • May require redosing in cases of massive opioid OD• VERY SAFE – non-toxic even at doses multiple x usual dose

• No effect if no opioids are present• In newborns whose mothers received opioids• Severe withdrawal symptoms with active opioid use• Naltrexone

• Similar to naloxone but longer duration of action• “protects” pts by blocking opioids

Disparate Treatment

Imagine for a moment……• In the ED in atrial fibrillation• In the OR with severe coronary artery disease• In the ICU with COPD exacerbation• On the medical floor with CHF exacerbation• On the phone for pre-auth for insulin

Disparate Treatment

“A methadone patient is monitored more closely than a paroled murderer.”

- Dr. Edwin SalsitzBeth Israel HospitalNew York CityFebruary 2, 1997

Disparate Treatment

Imagine for a moment……• In the ED in atrial fibrillation• In the OR with severe coronary artery disease• In the ICU with COPD exacerbation• On the medical floor with CHF exacerbation• On the phone for pre-auth for insulin

Question

• 2 pts actively using illicit opioids• One takes Suboxone (BUP + naloxone)• The other takes Subutex (BUP only)

• What happens in each case?• Why?

Persons in Substance Use Treatment Receiving Buprenorphine: Single-Day Counts 2009–2013

Retention in Treatment Relative to Dose

Methadone 40 year follow up

Persons in Substance Use Treatment in OTPsReceiving Methadone: Single-Day Counts 2009–2013

Source: SAMHSA, Center for Behavioral Health Statistics and Quality, National Survey of Substance Abuse Treatment Services, 2009 to 2013.

Heroine Seizures At The SW Border 2000-2014

Source: EPIC National Seizure System

Heroin Seizures In The US, 2010 - 2014

Source: EPIC National Seizure System

Drug-Poisoning Deaths Involving Heroin 1999-2013

Source: Nat’l Center for Health Statistics / CDC

Success Stories

• We don’t hear about them• When properly treated• Evidenced Based multi-modal therapies • In context of therapeutic alliance • – such pts practically

INDISTINGUASHABLE from general population

OAT Pts Occupations / Fields of Employment

• Teacher• Electrician• Plumber• Social Worker• Psychologist• Chauffer• Drug Counselor• Computer/IT Tech• Accountant• Retail Manager

• Home Security Systems• Restaurateur• Fish Dept Manager• Movie Editor• PhD Student• HVAC Tech• School Principal• Artist• Advertising VP

OAT Pts Occupations / Fields of Employment

• Bus Driver*• Sanitation Driver*• Con Ed Utility*• Subway Signal*• Sales• Secretarial• Administrator• Piano Teacher• Elevator Repair• Lawyer

• Physician• Landscaper• Car Sales/Repair• Videographer• Heavy Equipment• Contractor• Entrepreneur• Musician• Nurse• * Safety Sensitive –

Employer Aware

Conclusions

• Opioid OD signif cause of preventable deaths• Much confusion/misinformation RE: MAT• When used as part of multi-modal treatment: MAT

is effective evidenced based treatment• Risk Minimize / Safe treatment↑ when

• Monitored closely• Managed carefully• Dosed judiciously• In context of therapeutic alliance

Our Most Basic Role - To BELIEVE in our patients…..on THEIR behalf!

René Magritte – La Clairvoyance (1936)

ReferencesAmerican Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Washington DC, American Psychiatric Association, 2013.

CDC National Vital Statistics System, mortality data, 2015.

Dole VP, Nyswander M: A Medical Treatment for Diacetylmorphine (Heroin) Addiction, JAMA 193(8):80-84, 1965.

Flynn PM, Porto JV, Rounds-Bryant J, and Kristiansen PL: Costs and benefits of methadone treatment in DATOS—Part 1: Discharged versus continuing patients. Journal of Maintenance in the Addictions 2(1/2):129–150, 2003.

Kakko J, Svanborg KD, Kreek MJ, Heilig M: 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. Lancet. 361(9358):662-8. 2003.

Ling W, Hillhouse M, Domier C, et al.: Buprenorphine tapering schedule and illicit opioid use. Addiction 104: 256-265, 2009.

McLellan AT, Lewis DC, O’Brien CP, Kleber HD: Drug Dependence, a Chronic Medical Illness – Implications for Treatment, Insurance, and Outcomes Evaluation. JAMA, 284:1689–1695, 2000.

Mello NK, Mendelson JH, Kuehnle JC, Sellers MS: Operant analysis of human heroin self-administration and the effects of naltrexone, J Pharmacol Exp Ther. 1981 Jan;216(1):45-54.

NIDA Media Guide – how to find what you need to know about drug abuse and addiction, 2014.

ReferencesOhio Department of Health, Unintentional Drug Overdose Death Rates for Ohio Residents by County, 2008-2013.

Ohio Department of Health, 2013 Ohio Drug Overdose Data.

Salsitz EA : Opioid Agonist Therapy – The Duration Dilemma. PCSS-MAT Webinar, 3/10/2015.

SAMHSA, CBHSQ, National Survey on Drug Use and Health (NSDUH), 2013.

SAMHSA, Center for Behavioral Health Statistics & Quality, National Survey of Substance Abuse Treatment Services, 2009-13.

SAMHSA, Drug Abuse Warning Network, 2009 & 2011: National Estimates of Drug-Related Emergency Department Visits

SAMHSA, National Survey on Drug Use and Health Short Report, April 23, 2015.

Smyth BP, Fagan J, Kernan K: Outcome of heroin-dependent adolescents presenting for opiate substitution treatment, J Subst Abuse Treat. 2012 Jan;42(1):35-44, Epub 2011 Sep 21.

Strain EC, Stitzer ML, Liebson IA, Bigelow GE: Comparison of buprenorphine and methadone in the treatment of opioid dependence, Am. J. Psychiatry 151: 1025-1030, 1994.

Suzuki, J: A Review of Opioids and Treatment of Opioid Dependence. PCSS-O Webinar, 01/14/2015.

ReferencesWeiss RD, Potter JS, Fiellin D, Byrne M, Connery HS, Dickinson W, et al.: A Two-Phase Randomized Controlled Trial of Adjunctive Counseling during Brief and Extended Buprenorphine-Naloxone Treatment for Prescription Opioid Dependence. Arch Gen Psychiatry. 2011; 68(12):1238–46.

Vanden Brink W, Haasen C: Evidenced-based treatment of opioid-dependent patients, Can J Psychiatry. 2006 Sep;51(10):635-46..

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