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Jane Maxwell, UT Addiction Research Institute, 512 232-0610
“New Drugs”:
Drug Use Trends in Texas Today
Jane Maxwell, Ph.D.
Center for Social Work Research
The University of Texas at Austin
From the terms “Spice” &
“Bath Salts” to…
2C
Phenethylamine
Psychedelics
related to
mescaline
Some were created
in the past to imitate
MDMA
Synthetic
Cathinones
Mephedrone,
methylone, 4-
MEC, MDPV,
Alpha-PVP
Stimulants related
to methcathinone,
MDMA,
amphetamines
Tryptamines
5-MeO-DMT & 4-
AcO-DMT
Psychedelics
related to psilocin
& bufotenin
Piperazines
BZP & TFMPP
Stimulants
Synthetic
Opioids
Acetyl & Butyryl
Fentanyl
U-47700
MT-45
W-18
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
Number of NPS reported by groups
and regions: 2008-2015
0
100
200
300
400
500
600
Africa Asia Europe North Amer.OceaniaSouth & Central Amer
Tryptamines
Synthetic cathinones
Synthetic cannabinoids
Plant-based substances
Piperazines
Phenethylamines
Other substances
Ketamine & PCP types
PCP types
Hallucinogenics
Aminoindanes
Source: UNODC Early Warning Advisory on NPS, July 2015
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
Emerging Synthetic Drug Threats
• Synthetic Cannabinoids
• Synthetic Cathinones (Khat)
• Phenethylamine Hallucinogens
– 2C-X (such as 2C-I, 2C-B, 2C-C)
– DOX (such as DOI, DOB, DOC)
• 25X-NBOMe (25I-NBOMe, 25B-NBOMe, 25C-
NBOMe) Placed in Schedule I in November 2013
Synthetic Opioids (UR47700)
The Synthetics: Calls to US
Poison Control Centers: 2010-2016
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
2010 2011 2012 2013 2014 2015 2016
US Syn Cannabinoids
US Syn Cathinones
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
Synthetic Cannabis Items Identified and
Reported to U.S. NFLIS: 2010-2016
0%
10%
20%
30%
40%
50%
60%
70%
Ax
is T
itle 2010
2011
2012
2013
2014
2015
2016
Khat
• Pronounced “cot”
• Stimulant drug derived from a shrub (Catha edulis) native to East Africa and southern Arabia
• Use is considered illegal, because one of its chemical constituents, cathinone, is a Schedule I drug
• Khat found in the U.S. often comes in by mail from Africa
SOURCE: NIDA. (2011). NIDA DrugFacts: Khat.
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
Synthetic Cathinone Items Identified &
Reported to U.S. NFLIS: 2000- 2016
0
10
20
30
40
50
60
70
2010 2011 2012 2013 2014 2015 2016
MDPV METHYLONE 4-MEC PENTEDRONE ALPHA-PVP ETHYLONE OTHER
Synthetic Cannabis and Cathinone Items
Identified & Reported to U.S. NFLIS:
2000- ½ 2017
Source: US NFLIS.
CANNABIS
# Seizures # Types
2010 3288 19
2011 23686 38
2012 43126 46
2013 34303 47
2014 38734 78
2015 34041 79
2016 22121 82
½2017 5848 47
CATHINONES
# Seizures # Types
2010 632 10
2011 6542 21
2012 13794 31
2013 15572 26
2014 13687 42
2015 14386 46
2016 5720 70
½ 2017 1654 39
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
Marijuana homolog exposures reported to
the Texas Poison Center Network during
1/1/10-5/31/17 (n=3,877)
0
20
40
60
80
100
120
Jan
-10
Ap
r-10
Ju
l-10
Oct-
10
Jan
-11
Ap
r-11
Ju
l-11
Oct-
11
Jan
-12
Ap
r-12
Ju
l-12
Oct-
12
Jan
-13
Ap
r-13
Ju
l-13
Oct-
13
Jan
-14
Ap
r-14
Ju
l-14
Oct-
14
Jan
-15
Ap
r-15
Ju
l-15
Oct-
15
Jan
-16
Nu
mb
er
Month
TX ban 9/1/11 US ban 7/9/12
Alpha-PVP (“Flakka”) Items Identified in U.S.
Forensic Labs Before and After Chinese
Banned Alpha-PVP Ingredients in October
2015
0
100
200
300
400
500
600
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
Changes in Synthetics
Change in Packaging
Characteristics of Clients Admitted to Texas
Treatment with Primary Problem with Cannabis vs.
Synthetic Cannabis: 2016
28 3240
69
2518
10
24 21
2
15
42 44
69
45
7 4
27
49
15
0
20
40
60
80
Cannabis Synthetic Cannabis
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
Source of Referral to Treatment
0.0 10.0 20.0 30.0 40.0 50.0 60.0
Family Services
Family Member
Parole
Probation
Self
Referral Agency
Syn Cannabis Cannabis All Clients
Other Drugs Currently Used at Treatment
Admission by Clients with Primary Problem with
Synthetic Cannabinoids: 2011-2016
0%
10%
20%
30%
40%
50%
No other drugs Alcohol Cannabis
2011 2012 2013 2014 2015 2016
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
Texas Poison Center Clinical Effects by Year:
2010-2016
0
100
200
300
400
500
2010 2011 2012 2013 2014 2015 2016
Cardio Dermal Gastro
HemeHep Misc Neuro
Exposure Site Reported on Poison Control
Cases: Texas
0%
20%
40%
60%
80%
100%
2010 2011 2012 2013 2014 2015 2016
Residence School Public Area Other/Unk
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
Changes in Psychoactive Substances
Identified in Forensic Laboratories in
US: 2004-2016
0
4000
8000
12000
16000
20000
24000
28000
Psilocin/Psilocybin
Tryptamines
Phenethylamines
MDMA
Synthetic cathinones
SOURCE: National Forensic Laboratory Information System, 2010, 2011, 2012, 2013, 2014, 2015
Glimpses of MDMA Situation in U.S.
0
5000
10000
15000
20000
25000
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
MDMA Items Identified in DEA’s NFLIS Tox Labs: 2004- 2016
MDMA
Synthetic cathinones
Baumann, M.H., et al. The designer methcathinone analogs, mephedrone and methylone, are substrates for
monoamine transporters in brain tissue. Neuron-psychopharmacology 37(5):1192–1203, 2011.
*http://www.ecstasydata.org/stats_su
bstance_by_year.php
Mephedrone and methylone act on the brain like MDMA
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
Phencyclidine
• PCP, Angel Dust, Killer Weed
• Dissolved in embalming fluid (“Fry,”
“Amp,” “Water, Water”).
• Swallowed, sniffed, smoked on joints
dipped in “Fry”.
• Out-of-body strength.
• Dissociative drug like DXM and
ketamine; effects are similar to
cathinones.
Indicators of PCP Trends in
Texas: 1998-2016
0
200
400
600
800
1000
# PCC Calls # Treatment # Tox Items Examined
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
2008 2009 2010 2011 2012 2013 2014 2015 2016
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
A Few Other Substances to
Throw in the Mix…
• Kratom – opioid-like effects
• Krokodil – cheap heroin replacement
• Salvia divinorum – hallucinogenic
effects
• Methoxetamine – “legal ketamine”
• Benzo Fury (5-APB) – stimulant and
hallucinogenic effects
• 2C Phenethylamines
SOURCE: Rosenbaum et al. (2012). Journal of Medical Toxicology, 8(1), 15-32.
Kratom
• Structurally similar to some hallucinogens but no hallucinogenic
activity or effects
• Acts on opioid receptors
• Not scheduled in U.S. Used by natives in SE Asia
• Some users claim it helps with detoxification
• from opioids
• Seems to be a stimulant in lower doses
– Mitragynine
• Seems to be a sedative at higher doses
– 7 hydroxymitragynine
• Often produces a mixed effect
• Onset of effects within 5 to 10 minutes of ingestion; effects last
for several hours
SOURCE: Ken Dickenson, MS, RPh, Hon DSc, July 2013 (Emerging Drug Trends 2013: Beyond Synthetics and Bath Salts).
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
Krokodil
• Russian cheap replacement drug for heroin made from cooking down desomorphine with gasoline, paint thinner, alcohol, iodine, red phosphorous (match heads), etc.
• In Russia, lack of clean needles and methadone, high cost of heroin, poverty, high numbers of HIV+ individuals, etc.
• No confirmed cases of desomorphine in the U.S. since 2 were identified in 2004.
• Injuries that look like krokodil can be due to shared dirty needles, bacteria, toxic adulterants, gangrene, staph infection, MRSA.
Benzo Fury• Active ingredient is 5-APB• Stimulant and hallucinogenic properties• Fairly easy to buy via the Internet, at music
festivals, and in clubs - priced at around $15 per pill.
• User-reported effects include:– Increased happiness, euphoria, extreme
mood lift, increased self-acceptance, increased intimacy, closed-eye hallucinations, increased sexual interest
SOURCE: Ken Dickenson, MS, RPh, Hon DSc, July 2013 (Emerging Drug Trends 2013: Beyond Synthetics and Bath Salts).
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
2C-Phenethylamines
• Almost all of the 2C-phenethylamines are produced
in Asia, principally China, but some small labs in
the U.S. are capable of producing 2C (usually 2C-
B).
• In 2011, DEA offices throughout the country began
noting the increasing availability and abuse of 2C
at raves and in nightclubs, particularly by
teenagers and young adults.
• NFLIS labs nationwide identified 253 reports of
phenethylamines in 2010, 336 in 2011, 828 in 2012,
2069 in 2013, 2186 in 2014, 1629 in 2015, 587 in
2016.
“SYRUP” in Texas▪ Codeine cough syrup (purple) and
promethazinesyrup with codeine
(green)continues to be abused.
▪ Codeine cut with Karo syrup, jolly
ranchers, and soft drink.
▪ Promethazine mixed in liter bottle
of lime or other soft drink.
▪ Google “Leaning on Syrup”
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
New “Relaxation” Drinks:
Drank and Lean
Valerian Roots
Melatonin
Rose Hips
“Slow Your Roll”
“Slow Motion Potion”
Legal Lean Syrup
Act - Grape Flavor
Herbal Relaxation
Supplement
• $9.95 from eBay
• Find Legal Lean
Syrup Act - Grape
Flavor Herbal
Relaxation Supplement
on eBay in the category
Health &
Beauty>Vitamins &
Dietary Supplements ...
Jane Maxwell, UT Addiction Research Institute, 512 232-0610
http://www.uclaisap.org/slides/synthetic-drug-training-package.html
New Issues?
• Need better way to disseminate
information on harms of new drugs.
Adults know very little about them. How
can parents talk to their kids when they
have no idea what they are talking about?
• Need information on the new and “more
potent” generation of cannabinoids and
opioids and other new drugs.
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Jane Maxwell, UT Addiction Research Institute, 512 232-0610
Jane C. Maxwell, Ph.D.
Research Professor
Addiction Research Institute
Center for Social Work Research
The University of Texas at Austin
1717 West 6th, Suite 335
Austin, Texas 78703
512 656-3361
To be posted: Google for Texas Drug Trends
8/9/2017
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Update on
treatment
approachesCarlos F. Tirado MD, MPH, FABAMGeneral and Addiction Psychiatry
CARMA Health
ABRI Integrated Health
Restore Fx
Dripping Springs Health Care
MAP Health Management
DisclosureIndivior
Alkermes
8/9/2017
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Outline
Principles of treatment and levels of care
Pharmacotherapies for specific
substances
Clinical characteristics and management
of acute synthetic cannabinoid and
cathinone toxicity
Behavioral therapies for Stimulants
Unifying Principles
▪ Addiction is a chronic, medical disease of the brain.
▪ Aberrant behaviors and unhealthy choices are a consequence of the acute and accumulated toxic effects of the substance on the individual
▪ Addiction resembles other chronic diseases like diabetes and heart disease in regard to genetic transmission, relapsing and remitting course and the important role of personal responsibility in determining how well the disease is controlled
▪ If you treat it as a chronic disease, you have a much better chance for staying sober and in sustained recovery from the disease
▪ People relapse because relapse or recurrence is one of the core features of this and all chronic diseases
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Incorrect assumptions about
CD treatment• Certain addictions are conditions that can be effectively
treated by “detoxification” or “drying out”.
• An episode of treatment is expected to “guarantee” long-
lasting abstinence following termination of treatment.
• If a person relapses after treatment it is often considered a
treatment “failure”.
• Treatment doesn’t work!!! BUT not one size fits all.
Treatment: Basic Elements Screening and Recognition
Treat urgent medical aspects of disease
Make the correct diagnosis (consider all
comorbidities)
Avoid negative stereotypes, judgments and
value-laden interventions
Involve family and significant others
Employ an effective behavioral treatment
Pharmacological (when available) therapies
employed as complimentary treatments to
enhance outcome
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Treatment: Levels of Care Detoxifiction/Medical Withdrawal
(outpatient or inpatient) Detox is NOT a stand alone treatment!!!
Outpatient (counseling, therapy, AA/NA, groups, intensive outpatient, partial hospital)
Residential (intensive live-in recovery oriented program). Vary widely in quality, reputation and cost.
Medical management (in conjunction with a behavioral program) - good for SUDs with pharma therapies or significant medical comorbidity.
Are all use disorders the same?
Important similarities and differences between opioids, alcohol, stimulants, cannabinoids, nicotine Withdrawal states and cravings
Risk of accidental overdose
Medical comorbidity and long term health effects
Availability of proven effective medication therapies
Relapse rates after detox or residential treatment
Psychiatric comorbidity
All respond to treatment
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Pharmacotherapy
FDA Approved Medications
Opioids
Methadone
Buprenorphine-Buprenorphine/Naloxone
Naltrexone (oral and injectable)
Not FDA approved
Ibogaine
Clonidine
Latest medication advances
Probuphine
6 month implantable buprenorphine
Each rod contains 80mg buprenorphine (4 implanted)
Stable on 8mg oral buprenorphine for at least 3 months
85.7% opioid free, sig advantage over oral (p = 0.034).
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Latest medication advances
Very Low Dose Naltrexone (methadone)
0.125mg and 0.250mg doses
Sig reductions in withdrawal sx and reduced craving
Possible additive effect with clonidine
Lofexidine (2.4mg and 3.2mg a day)
Alpha agonist (like clonidine) with more favorable cardiovascular profile
Injectable Buprenorphine in development
Pharmacotherapy
FDA Approved Medications
Alcohol
Naltrexone (oral and injectable)
Acamprosate
Disulfiram
Not FDA approved
Topiramate
Gabapentin
Ondansetron
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Pharmacotherapy
FDA Approved Medications
Nicotine
Nicotine replacement
Bupropion
Varenicline
Not FDA approved
Nortriptyline
Clonidine
Pharmacotherapy
FDA Approved Medications
Cannabinoids – None
Buspirone, THC substitution, valproic acid, nefazodone, bupropion, atomoxetine have been tried.
Stimulants - none
See tables
8/9/2017
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Summary
of Cocaine
Medication
Trials
From Stoops & Rush, Exp Review Clin Pharmacology, 2014 May; 7(3): 363-374
Summary of
Amphetamine
Medication
Trials
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Cannabis vs. Cannabinoids:
Effects Seen in Clinical Cases Most symptoms are similar
to cannabis intoxication:
Tachycardia
Reddened eyes
Anxiousness
Mild sedation
Hallucinations
Acute psychosis
Memory deficits
Symptoms not typically seen
after cannabis intoxication:
Seizures
Hypertension
Nausea/vomiting
Coma
Severe agitation
Rhabdomyolysis, renal
failure
Hyperthermia
Respiratory Depression
SOURCES: Hermanns-Clausen et al. (In Press), Addiction; Rosenbaum et al. (2012). Journal of Medical Toxicology; Forrester et al. (2011). Journal of Addictive Disease; Schneir et al. (2011). Journal of Emergency Medicine.
17
Synthetic Cannabinoids: Other
Clinical Factors Overall more severe manifestations of:
Tolerance and withdrawal
Withdrawal associated seizure, tachycardia, chest pain,
palpitations, dyspnea.
Requirement for hospitalization
Psychosis and mania
Unknown how premorbid history, other substance
use interact with specific SC compounds.
SOURCE: Cooper, ZD; Adverse effects of synthetic cannabinoids: management of acute toxicity and withdrawal; Curr Psychiatry Rep (2016) 18:52
18
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Sample Clinical Treatment Protocol for Synthetic Cannabinoid Users
• Direct individual to emergency room via
ambulance
• Consult a regional Poison Control Center
• Acute management consists of:
– Supportive care with the use of benzodiazepines
and low dose neuroleptic, if needed, to control
agitation and anxiety
– Observe until resolution of abnormal vital signs,
vomiting, and psychiatric symptoms
SOURCE: Cheng, Yeo, Brown, & Regan. (2012). American Academy of Emergency Medicine, 19(2), 19-22. 19
Agitation 82%
Combative/Violent behavior 57%
Tachycardia 56%
Hallucinations 40%
Paranoia 36%
Confusion 34%
Myoclonus/Movement disorders 19%
Hypertension 17%
Chest pain 17%
CPK elevations 9%
Clinical Symptoms of Synthetic Cathinone Use in
Patients Admitted to the Emergency Department
(N=236)
SOURCE: Spiller et al. (2011). Clinical Toxicology, 49, 499-505. 20
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Sample Clinical Treatment Protocol
for Synthetic Cathinone Users
• Supportive care
• Aggressive sedation with benzodiazepines and low
dose neuroleptic (for agitation, seizures,
tachycardia, and hypertension)
• Significant hyperthemia may require passive or
active cooling.
• Lab studies including electrolytes, renal and liver
function tests, cardiac markers, and creatine kinase
should be considered.
SOURCE: Cheng, Yeo, Brown, & Regan. (2012). American Academy of Emergency Medicine, 19(2), 19-22. 21
What do you do if someone has taken a Spice Product or Bath Salts?
• Call your local poison center at 1-800-222-1222
– 57 poison centers around the country have
experts waiting to answer your call.
– Experts can help you decide whether someone
can be treated at home, or whether he or she
must go to a hospital.
• Dial 9-1-1 immediately if they:
– Stop breathing
– Collapse
– Have a seizure
SOURCE: American Association of Poison Control Centers (AAPCC). (2012). Facts about Bath Salts.
…or if they have taken one of these and are having physical symptoms or behaving in a way that is concerning to you
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Behavioral Treatments for
Stimulant Disorders
Community Reinforcement + Vouchers
Contingency Management
Relapse Prevention
Matrix Model
Community Reinforcement +
Vouchers
Promotes lifestyle changes in areas conducive to recovery
Marital/Couples therapy to improve primary relationship
Vocational assistance esp for high risk work
Counseling in alternative social and recreational practices
Individualized skills training (social, mood regulation, time management)
MAT for co-occurring substances.
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Contingency Management
Increase or decrease behaviors by providing immediate reinforcing or punishing behaviors when target behavior occurs.
Usually linked to negative UDSs and level of program adherence
Incentives are usually low level monetary, but social recognition, enhanced status, symbolic items also work.
Relapse Prevention
CBT based
Coping with cravings
Refusal and assertiveness skills
Analysis of how seemingly irrelevant
decisions can affect probability of use
event
Coping and problems solving skills
Strategies to prevent full relapse after a
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Matrix Model
Matrix of treatment modalities
Relapse prevention
Motivational Interviewing
Psychoeducation
Family/couples therapy
12 Step
Done in group sessions and 20 individual sessions over 24 weeks.
Thanks!
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NY State Psychiatric Institute Survey
August 9, 2017
Cooper, ZD; Adverse effects of synthetic cannabinoids: management
of acute toxicity and withdrawal; Curr Psychiatry Rep (2016) 18:52
29
• 3.5 yrs between April 2012-October 2015
• 1358 men/550 women
NY State Psychiatric Institute Survey
August 9, 2017
Cooper, ZD; Adverse effects of synthetic cannabinoids: management
of acute toxicity and withdrawal; Curr Psychiatry Rep (2016) 18:52
30
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NY State Psychiatric Institute Survey
August 9, 2017
Cooper, ZD; Adverse effects of synthetic cannabinoids: management
of acute toxicity and withdrawal; Curr Psychiatry Rep (2016) 18:52
31
Bath Salts in MichiganCase Report – MMWR, May 2011
• First report to summarize epidemiology of bath salt ED cases
• Based on 35 people who had ingested, inhaled, or injected
bath salts and subsequently visited a Michigan Emergency
Department (ED) between 11/13/10 and 3/31/11
• Patients presented with hypertension, tachycardia, tremors,
motor automatisms, mydriasis, delusions, and paranoia
• No relationship found between route of administration and
severity of illness
SOURCE: Cheng, Yeo, Brown, & Regan. (2012). American Academy of Emergency Medicine, 19(2), 19-22. 32
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Opioid Relapse rates following inpatient
treatment.
Relapse rates are v. high: (Pregnant Woman)
6 week program. N=109, 91% relapse, 59% within one week. Program completion delayed relapse by matter of weeks.
extended methadone inpatient detox (avg 15 days). N=73. 27% dropped out. Completers - 1 month, 65% back to using (14% still in residential). 6 months 63% using (9% still in residential).
1 year follow ups. Favor those who have been on medication assisted treatment over detox or residential.
Generally slow tapering with opioid substitution delays relapse and can encourage sustained opioid abstinence in a minority of patients.
Given a choice, most opt for substitution. Even pts who initially choose detox, opt for substitution once they experience withdrawal.
Review of Methadone
Fullerton CA, et al, Medication Assisted
Treatment with Methadone: Assessing the
Evidence, Psychiatric Services, Feb 2014,
Vol 65, no 2, 146-157
Review of meta-analyses, systematic
reviews, individual studies of MMT
between 1995-2012
24 trials, meta-analyses and large reviews
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Methadone Full agonist opioid, T ½ = ~22 hrs.
Active at CYP 3A4 and 2D6
Only available through licensed narcotic treatment programs for tx of dependence.
Has been tremendously marginalized as a treatment, but about 180,000 people nation wide are in treatment
When dosed correctly (between 60-120mg) and monitored closely, patients can do well
Good evidence methadone treatment increases participation in treatment programs, decreases heroin and other drug use, reduces HIV and viral hepatitis transmission, prevents early recidivism post release.
Main Findings
MMT v Placebo or no pharmacotherapy
Mostly published between the 1960s-90s.
By far more effective retaining pts in treatment
Improved suppression of heroin use
Reduced drug-related HIV and HCV risk behaviors
Better than brief and extended detoxification protocols, drug-free programs, wait-list controls
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Main Findings
Methadone dosing: Most studies classified dose ranges as Low (<40mg),
Moderate (40-60mg) and High (60-100mg). Literature generally supports higher dosing with
diminishing return at doses over 120mg/day Better tx retention, cocaine abstinence, less use of
heroin, less withdrawal at doses between 60-110mg. One well-designed double blind RTC (Strain et al, 1999)
comparing moderate dose (40-50mg) to high (80-100mg) showed no difference in tx retention, but sig better reduction in opioid positive urine in high dose group.
Medication Therapy All medications used for the treatment of
chemical addictions are best used as one part of a comprehensive psychosocial program of recovery.
All studies of medications for addiction demonstrate greater effectiveness when combined with behavioral therapy
Medications are not a substitute for a comprehensive recovery plan.
Policies and practices that forbid indefinite duration of treatment or deprive individuals access to housing, treatment and other resources when they are on opioid substitution are discriminatory.
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Main Findings Adverse Events:
390% increase in Methadone-related deaths between 1999-2004.
Mostly attributable to misguided opioid analgesia Highlighted toxicity risk, related to QT prolongation and
respiratory depression. Especially during the initiation phase.
Respiratory depression mainly a cumulative factor enhanced by co-administration of CNS depressants.
Generally QT >500ms is associated with increased risk Must be mindful of medications that prolong QT (esp
psychotropics).
Review of Buprenorphine
Thomas, CP., et al, Medication Assisted Treatment with Buprenorphine: Assessing the Evidence, Psychiatric Services, Feb 2014, Vol65, no 2, 158-170
Review of meta-analyses, systematic reviews, individual studies of BMT between 1995-2012
19 studies: 16 RTCs, 1 randomized x-over study, 1 self-report survey, retrospective descriptive study.
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Buprenorphine/naloxone High affinity mu partial agonist and kappa
antagonist. Some CYP 3A4 activity.
Trade name SuboxoneTM
Long-acting (T ½ ~35hrs), less euphorigenic, prevents withdrawal sickness, works for pain, can block full agonist opioids, sublingual
Requires DEA waiver to Rx for opioid dependence
Requires abstinence from full agonist before first dose.
Common SEs: N/V, sedation, edema, HA, constipation
Buprenorphine/naloxone Unfortunately is abusable…BUT good
evidence it can be very effective as a maintenance treatment.
Studies with 6, 12 month and 2-5 year outcomes show dramatic reductions in heroin use (80-90%), other drug use, and much higher retention in treatment
High cost:benefit ratio especially when criminal recidivism factored in.
The data are sometimes at odds with popular beliefs about maintenance treatment
Lavignasse, P, et al. Ann Med Interne, 2002: 153(suppl 3), 1S20-1S26; Kakko J, et al., Lancet,
2003, 361:662-668; Fiellin, DA, et al., Am J Addict, 2008; 17(2): 116-120.
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Main Findings
BMT v Placebo Studies published since 1995.
By far more effective retaining pts in treatment at all dose ranges.
Improved suppression of heroin use
Medium (7-15mg) and high doses (>16mg) generally associated with effects on tx retention and reduction in illicit use.
Most studies show no significant impact on reducing non-opioid drug use compared to placebo.
Buprenorphine implant showed good retention over 6 months (66% v 31%). Sig diff in negative urine (40% v 28%). Sig reduction in COWS and SOWS.
Main Findings
BMT v MMT: Dosing in the high to mod range is most significant
factor in outcome.
In general methadone at medium and high doses performed better on primary outcomes of retention and illicit opioid use compared to medium and high dose bupe
In one RCT high-dose bupe matched high-dose methadone and did better than low dose methadone.
Stepped care model: BMT v MMT groups. BMT pts who got to 32mg Bupe but not stable stepped to MMT. Of the BMT who did not require step to MMT, mean dose of bupe was 29.6mg. Mean dose of methadone was ~110mg. Good retention and opioid free UDS in both groups at 6 months (76% and 80%).
8/9/2017
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Review of Naltrexone Krupitsky E, et al., Injectable extended-release
naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomisedtrial. Lancet 2011, Apr 30: 377(9776): 1506-13.
RCT, 13 sites, 250 subjects. Conducted in Russia. Post inpatient, at least 7 days opioid free. 380mg XR-NTX v Placebo. 12 bi-weekly counseling sessions. Measured confirmed abstinence between weeks 5-24.
No positive data on oral naltrexone
No good head to head comparisons with BMT or MMT
Naltrexone (oral and depo) Available for both alcohol and opioid dependence
Trade names ReviaTM and VivitrolTM
Irreversible blockade of opioid receptors (mu, kappa and some gamma)
T1/2: 4h, 13h(b-naltrexol).
50mg daily dose. 380mg monthly dose of depo form. Oral dosing for opioids can be flexible up to 150mg q3 days.
Primary SEs: HA, dizziness, fatigue, anhedonia uncommon
Contraindicated in liver failure and active hepatitis (LFTs >3 times normal).
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Naltrexone There is some risk of liver toxicity so liver
function must be monitored when starting 50mg daily dose for alcohol. 380mg monthly
dose of depo form. Overall response rates are in the 10-20% range
– seems to work better in men with strong family history of alcoholism
Primary SEs: HA, dizziness, fatigue, anhedoniauncommon
Contraindicated in liver failure and active hepatitis (LFTs >3 times normal).
Main Findings Outcomes:
Primary: Confirmed abstinence during weeks 5-24 by UDS and self report Median proportion abstinent weeks was 90% in XR-NTX
v 35.0% in placebo by UDS.
Secondary: Self report opioid free days: 99.2% XR-NTX v 60.4%
placebo. Mean change in craving: -10.1 XR-NTX v 0.7 in
placebo Retention: median retention 168 days XR-NTX v 96
days placebo Relapse during treatment: 1 in XR-NTX group v 17 in
placebo
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Main Findings
Adverse Events:
During trial and one year open-label extension
Low rate of discontinuation due to adverse events
21% had study drug related AE
Injection site reactions in 6.1%
Elevations in LFTs in 16.7%
No deaths, ODs, or severe AEs
Abstinence-Based Outcomes Physicians monitoring studies (PHP)
5 year retrospective review of 16 PHPs 78% long term abstinent within program “long-term random monitoring with swift consequences
for substance use and meaningful leverage to enforce abstinence and continued participation” is key.
Australian 1-year heroin outcomes (ATOS) Comparable rates of self reported past month
abstinence between methadone and residential rehab groups. 65% in MMT and 63% in RR
Median of 138 residential treatment days Higher percentage of overdoses, heroin use days and
daily injecting in RR group v MMT
Hawaii Opportunity Probation with Enforcement (H.O.P.E.) and South Dakota’s 24/7 Sobriety Project for Recidivist Driving Under the Influence. Both with high rates of adherence in lieu of re-
incarceration.
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Cheeseburger, Chips, no
Coke…Pepsi!
Meeting patients and payors where they
are:
Briefer stays for specific goals
Targeted readmission
Outpatient support
Risk management and monitoring
Going “off script”
Prepare for calls by patients and payors for broader array of services