MEDICATION SUPPORTED RECOVERY
Steven Kipnis MD, FACP, FASAM
Medical Director, NYS OASAS
Objectives:
• Overview of Opiate misuse and the consequences of this
misuse
• Barriers to the prescribing of addiction medications
• Overview of addiction medications used in opiate use
disorder (Buprenorphine, Naloxone, Vivitrol)
• Prescription drugs when taken as directed for legitimate
medical purposes can be safe and effective.
• Prescription drug misuse occurs when a medication is
not used by the person it was written for , or in the
intended manner.
• Diversion is the unauthorized,rerouting or appropriation
of a medication
• DIVERSION – HOW ONE OBTAINS MEDICATION
• MISUSE – HOW ONE USES MEDICATION
Admissions to NYS OASAS Certified Chemical Dependence
Programs by Primary Substance and Age Group, CY 2007-2012
•
•
.
Prescription opiates admissions
increased from 9,969 in 2007 to
23,913 in 2012, a 140% increase.
Prescription opiates admissions
increased for all age groups
between 2007 and 2012. The
greatest percent increases during
that period were among 18-24
year olds (214%) and 25-34 year
olds (214%).
Prescription opiates admissions
are admissions where the primary
substance at admission was
OxyContin or another synthetic
opiate.
•
•
Heroin admissions increased
from 57,320 in 2007 to 61,583 in
2012, a 7% increase. The greatest
percent increase during that
period was 85% among 18-24
year olds. There was a 30%
decrease in heroin admissions by
35-44 year olds.
Heroin admissions are admissions
where heroin was the primary
substance at admission.
DEFINITIONS
Opiate = Rx derived from opium
Opioid = All Rx with morphine-like
actions
Papaver Somniferum
OPIATE INTOXICATION
•
MOST COMMON
•
MIOSIS
•
NODDING
•
HYPOTENSION
•
DEPRESSED RESPIRATION
•
BRADYCARDIA
•
EUPHORIA
•
FLOATING FEELING
OPIATE OVERDOSE
• CLASSIC TRIAD SEEN IN OVERDOSE
•
•
•
MIOSIS
COMA
RESPIRATORY DEPRESSION
• PULMONARY EDEMA
• SEIZURES
•
DEMEROL, DARVON, TALWIN
WE CAN PREVENT THESE DEATHS
OPIATE WITHDRAWAL - EARLY
•
•
•
•
LACRIMATION
YAWNING
RHINORRHEA
SWEATING
SENSE OF ANXIETY AND DOOM, THOUGH NOT LIFE
THREATENING
OPIATE WITHDRAWAL - MIDDLE PHASE
•
•
•
•
•
•
RESTLESS SLEEP
DILATED PUPILS
ANOREXIA
GOOSEFLESH
IRRITABILITY
TREMOR
OPIATE WITHDRAWAL - LATE PHASE
•
•
•
•
•
•
•
•
•
•
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INCREASE IN ALL PREVIOUS SIGNS AND SYMPTOMS
INCREASE IN HEART RATE
INCREASE IN BLOOD PRESSURE
NAUSEA AND VOMITING
DIARRHEA
ABDOMINAL CRAMPS
LABILE MOOD
DEPRESSION
MUSCLE SPASM
WEAKNESS
BONE PAIN
OPIATES
•
MANY OF THE
COMPLICATIONS OF OPIATES
ARE DUE TO THE ROUTE OF
USE AND NOT THE DRUG
ENDOCARDITIS – VALVE REPLACEMENT
ARTERIAL INJECTION
21
Hser et al, Arch Gen Psychiatry.
2001;58:503-508
ADDICTION MEDICINES
•
•
•
•
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ACAMPROSATE
ANTABUSE
ANTICONVULSANTS
BACLOFEN
BUPRENORPHINE
CLONIDINE
METHADONE/LAAM
•
•
•
•
•
•
•
NALTREXONE
NALOXONE
NEURONTIN
NICOTINE REPLACEMENT
THERAPIES
SSRI’S
ZYBAN
VACCINES
BARRIERS
•
•
•
•
•
•
MEDICATION
PATIENT
PHYSICIAN/NURSE
COUNSELOR
PROGRAM
SYSTEM
BARRIERS
• MEDICATION
o
o
o
INSUFFICIENT EVIDENCE REGARDING EFFICACY
CONTRADICTORY EVIDENCE
TOO EXPENSIVE
• NALTREXONE $2.50 - 4.43 PER DAY
o
o
CORRECT DOSE?
SIDE - EFFECTS
BARRIERS
• MEDICATION
o
CANDIDATE SELECTION
• TOOLS NEED TO BE RESEARCHED - WHO WILL BENEFIT MOST?
o
o
o
o
POTENTIAL FOR ABUSE
POTENTIAL FOR DIVERSION
“MAGIC BULLET THEORY”
DELIVERY SYSTEM
BARRIERS
• PATIENT
o
o
o
o
COMPLIANCE
SELECTION
STIGMA
COST/INSURANCE COVERAGE
BARRIERS
• PHYSICIAN/NURSE
o
o
o
o
o
o
LACK OF AWARENESS
LACK OF TRAINING
LACK OF ONGOING TECHNICAL ASSISTANCE
DO NOT PROMOTE USE
MD’S NEEDED AT ALL PROGRAMS
EXTRA WORK
• OBSERVATION TIME
BARRIERS
• COUNSELOR
o
o
o
LACK OF AWARENESS
LACK OF TRAINING
COUNSELORS IN RECOVERY
• “NOT THE WAY I DID IT”
o
MORE WORK
• AFTERCARE
BARRIERS
• PROGRAM
o
o
o
NEED PHYSICIAN SERVICES
NEED TO INCREASE COMMUNICATION BETWEEN PHYSICIANS
AND COUNSELORS
NEED LINKAGE TO MD AFTERCARE
• MONITOR DRUG LEVELS
• MONITOR SIDE - EFFECTS
• WRITE RX
o
ENDANGERS PROGRAM INTEGRITY (THERAPEUTIC COMMUNITY)
BARRIERS
• SYSTEM
o
REGULATIONS NEED TO BE CHANGED
• WHO WILL PAY FOR MD SERVICES
o
o
o
NEED INCREASE IN EDUCATION AND T.A.
PRIVATE MD’S NEED TO BE ABLE TO LINK TO THE SYSTEM
NEED OUTCOME DATA
BUPRENORPHINE
•
OVERVIEW OF THE DRUG ADDICTION TREATMENT ACT OF 2000
- AN AMENDMENT TO THE CONTROLLED SUBSTANCES ACT
(10/17/01)
o
REVISION IN LEGISLATION ALLOWS PRACTITIONER TO PRESCRIBE
NARCOTIC DRUGS IN SCHEDULE III, IV, V, OR COMBINATIONS OF
SUCH DRUGS, FOR THE TREATMENT OF OPIOID DEPENDENCE
BUPRENORPHINE
•
OVERVIEW OF THE DRUG ADDICTION TREATMENT ACT OF 2000
- AN AMENDMENT TO THE CONTROLLED SUBSTANCES ACT
(10/17/01)
o
PRACTITIONER REQUIREMENTS
• “QUALIFYING PHYSICIAN”
o
o
o
o
o
LICENSED
BOARD CERTIFIED IN ADDICTION PSYCHIATRY
CERTIFIED IN ADDICTION MEDICINE BY ASAM OR AOA
INVESTIGATOR IN BUPRENORPHINE CLINICAL TRIALS
8 HOURS OF DESIGNATED TRAINING
• HAS CAPACITY TO REFER PATIENTS FOR APPROPRIATE COUNSELING
AND ANCILLARY SERVICES
• NO MORE THAN 30 PATIENTS (INDIVIDUAL OR GROUP) INITIALLY, CAN GO
TO 100 AFTER ONE YEAR (MUST APPLY)
• METHADONE CLINICS CAN HAVE UNLIMITED NUMBERS
o
2013 Rule that methadone clinic can relax take-home scheduling
BUPRENORPHINE
•
THEBAINE DERIVATIVE
o
•
•
MAKES THIS LEGALLY CLASSIFIED AS AN OPIATE
PARTIAL OPIOID AGONIST
INITIALLY USED AS AN ANALGESIC
BUPRENORPHINE
• PARTIAL OPIOID AGONIST
o
VERY HIGH AFFINITY FOR MU RECEPTOR
• WILL DISPLACE MORPHINE, METHADONE
BUPRENORPHINE – WHAT WE THOUGHT
• PARTIAL OPIOID AGONIST
o
DESIRABLE PROPERTIES
•
•
•
•
LOW ABUSE POTENTIAL – True???
LOWER LEVEL OF PHYSICAL DEPENDENCE – True???
SAFETY IF INGESTED IN OVERDOSE QUANTITIES – True???
WEAK OPIOID EFFECT AS COMPARED TO METHADONE
BUPRENORPHINE
• PARTIAL OPIOID AGONIST
o
IF GIVEN TO A PATIENT MAINTAINED ON A FULL AGONIST, IT CAN
PRECIPITATE AN ABSTINENCE SYNDROME DUE TO LOW
EFFICACY AND DUE TO HIGH AFFINITY TO THE MU RECEPTOR
• CANNOT EASILY OVERCOME THE BUPRENORPHINE EFFECT NOR
CAN AN ANTAGONIST OVERCOME ITS EFFECT.
BUPRENORPHINE
• PHARMACOLOGIC USES
o
POTENT ANALGESIC
• AVAILABLE IN MANY COUNTRIES AS A SUBLINGUAL TABLET (0.3 - 0.4
MG) CALLED TEMGESIC®
• AVAILABLE IN THE U.S. AS AN PARENTERAL FORM CALLED
BUPRENEX®
• LOW DOSES FOR PAIN TREATMENT AS COMPARED TO ADDICTION
TREATMENT ( 0.3 - 0.6 MG IM OR IV Q 6 HOURS)
BUPRENORPHINE
• PHARMACOLOGIC USES
o
POOR ORAL BIOAVAILABILITY
• SUBLINGUAL WITH ABSORPTION THROUGH THE ORAL MUCOSA
o
SLOW DISSOCIATION RATE
• PROLONGED THERAPEUTIC EFFECT - SO CAN BE GIVEN EVERY
OTHER OR EVERY THIRD DAY
BUPRENORPHINE
• PHARMACOLOGIC USES
o
TREATMENT OF ADDICTIONS*
•
IN THE U.S.
o
o
2 & 8 MG SUBLINGUAL TABLETS MADE BY RECKITT & COLMAN CALLED
SUBUTEX®
2 & 8 MG SUBLINGUAL TABLETS WITH NALOXONE IN A 4:1 RATIO CALLED
SUBOXONE® - NO LONGER AVAILABLE AFTER 12/12 – ONLY FILM
BUPRENORPHINE
• PHARMACOLOGIC USES
o
o
DOSES USED FOR OPIOID ADDICTION TREATMENT IS 1 -2
MG UP TO 16 - 32 MG
DURATION IS A FEW WEEKS TO YEARS?
• SHORT-TERM TREATMENT IN ADOLESCENTS?
o JAMA article by G. Woody et al, (2008) adolescents aged 15 to 21
did better with long term Suboxone than a short (2 week) detox
protocol using Suboxone
o
TO REDUCE POTENTIAL FOR ABUSE THE COMBINATION
TABLET WAS MADE
• WORKS ON PRINCIPLE THAT NALOXONE IS 100 TIMES MORE
POTENT BY INJECTION THAN BY THE SUBLINGUAL ROUTE
o
o
IF TAKEN S.L. BUP>>>>>>NALONXONE
IF TAKEN I.V. NALOXONE>>>>>BUP
BUPRENORPHINE
• SAFETY
o
o
IF SWALLOWED ACCIDENTIALLY BY A NON- PHYSICALLY
DEPENDENT PERSON DUE TO POOR ORAL BIOAVAILABILITY
THERE IS VIRTUALLY NO OPIOID EFFECT IN ADULT – PEDIATRIC
CASES OF OVERDOSE
REPORT OF 53 CASES OF HEPATITIS IN FRANCE SINCE 1996.
ALL INVOLVED IV BUPRENORPHINE WHICH LEAD TO HEPATITIS
• PERHAPS DUE TO INCREASE BIOAVAILABILITY IF TAKEN IV
Emergency Departments Report Jump in Visits
Linked to Buprenorphine
•
•
•
Emergency departments reported a
significant rise in the number of visits
related to the opioid addiction
medication buprenorphine between
2005 and 2010
The number of buprenorphine-related
visits rose from 3,161 in 2005, to
30,135 in 2010
In 2005, 5,656 physicians prescribed
the drug to 100,000 patients. By 2010,
more than 18,500 doctors prescribed
the medication to over 800,000
patients.
o
The figures come from a report by the
Substance Abuse and Mental Health Services
Administration (SAMHSA) 1/2013
BUPRENORPHINE
• SIDE EFFECTS
o
SIMILAR TO OTHER MU AGONISTS THOUGH LESS SO
• NAUSEA
• VOMITING
• CONSTIPATION
*NO DISRUPTION IN COGNITIVE AND PSYCHOMOTOR
PERFORMANCE
BUPRENORPHINE
• TERATOGENESIS
o
LIMITED REPORTS
• ONE STUDY FOUND NO SIGNS OF PHYSICAL DEPENDENCY IN
NEONATES OF HEROIN ADDICTED MOTHERS TAKING
BUPRENORPHINE
BUPRENORPHINE
• DRUG INTERACTIONS
o
o
o
o
o
SCANT STUDIES
DEATH CASE REPORT ASSOCIATED WITH IV BUPRENORPHINE
AND BENZODIAZEPINES
CANNOT GIVE WITH ReVia
AVOID MEDICATIONS THAT ARE METABOLIZED BY THE
CYTOCHROME P450 3A4 SYSTEM
IF ACUTE PAIN TREATMENT IS NEEDED, MAY HAVE TO SWITCH
TO METHADONE
Pain Management Strategies
• While there are no clinical studies addressing how to
treat pain in patients taking buprenorphine
• As with all patients with pain, non-pharmacologic
therapies and non-opioid analgesics should be used
when safe and likely to work.
• If acute pain is anticipated, such as for an elective
surgical procedure, adjuvant analgesics and
interventional procedures such as nerve blocks should
be provided as available.
Pain Management Strategies
• For patients with moderate to severe pain who are expected to
require opioid analgesic therapy for the short term, federal
guidelines recommend:
o
holding the buprenorphine and starting short acting opioid
agonists. While the buprenorphine's effects diminish (20-60
hours), the patient may require higher opioid doses to compete
with the presence of buprenorphine on mu-opioid receptors. The
patient should be monitored carefully in the initial period to titrate
the opioid agonist dose downward as its effect becomes greater.
o
Before restarting buprenorphine, the patient should be opioidfree for 12-24 hours to avoid precipitating withdrawal.
Pain Management Strategies
• For patients with mild to moderate acute pain, consider
treating the pain with buprenorphine alone. The total
daily dose of buprenorphine can be increased (to a
maximum of 32 mg sublingual/day); it should be given in
divided doses every 6-8 hours.
• Another option is to continue buprenorphine and use
short-acting opioid agonists at high enough doses to
overcome buprenorphine's partial agonism. Opioids that
have a higher intrinsic activity at the mu-opioid receptor,
including morphine, fentanyl, or hydromorphone, are all
options, while opioids with less efficacy such as
hydrocodone or codeine should be avoided.
Pain Management Strategies
• In a patient who is expected to have an ongoing need for
pain management, consider replacing buprenorphine
with methadone therapy for opioid addiction.
On the Horizon
•
•
•
Implantable buprenorphine – Probuphine
o
6 month duration
o
Being studied by Dr. Walter Ling at
UCLA
• 108 patients and 55 placebo
patients
• 40% in bup group and 28% in
placebo group tested negative for
illegal drugs at 16 weeks.
• At 24 weeks 66% of treatment
group compared to 31% in
placebo group were still in
treatment
Micro - dose Bup for withdrawal taper
Buprenorphine patch
o
For pain and not addiction – much
different dosing
•
OREXO -Introduction of Zubsolv,
newest Buprenorphine product about
to come on the market:
o
While similar to Suboxone,
benefits of Zubsolv include: less
dissolve time, thereby decreasing
the need for long observation time
if dispensing in an OTP setting;
better taste; lower dose of
buprenorphine( 1.4 and 5.7 mg),
decrease cost associated with
purchase; higher bioavailability;
and medication packaging that is
of greater pediatric tamperresistance as compared to
Suboxone.
OD prevention project
http://www.nyhealth.gov/diseases/aids/harm_reduction/opioidprevention/
NALOXONE (NARCAN)
• Opioid antagonist which reverses opioid overdoses
• Pushes most other opioids off the receptors, then sits on
the receptor preventing it from being activated for 30-90
minutes
• Analogy - getting the wrong key stuck in a lock
NALOXONE IN ACTION
• Reverses sedation and respiratory depression
• Causes sudden withdrawal in the opioid dependent
person
• No psychoactive effects
• Over the counter in some countries, but not the US
• Routinely used by EMS
ADMINISTRATION
• Inject into muscle but subcutaneous and intravenous are
fine also
• Acts in 2-8 minutes
• If no response in 2-5 minutes repeat- and if 911 has not
been called do it now!!
• Do not repeat naloxone more than twice
• Lasts 30-90 minutes
Vivitrol
•
•
•
•
Depot naltrexone
Approved for alcohol dependence
Approved for the opioid dependent person
Cost is a factor – but it improves compliance
Vivitrol Studies
• 25% reduction in heavy drinking when compared to
placebo group
o
o
In 4 day lead in maintained abstinence was 32% in the treatment
group vs 11% in the placebo group (all got behavioral treatment)
Better abstinence rates with 7 day lead in
• Good adherence to medication
o
o
74% had 4 injections
64% had 6 injections
New Uses
• Nicotine dependence – men did better than women
o
Women also don’t do as well with NRT: smoke for different
reasons than men??
• Cannabis dependence
o
Actually increased the high and increased cravings
• Amphetamine/Stimulant dependence
o
o
Decreased cravings and less depression and anxiety
Decreased cocaine use if also used opiates
• Low dose naltrexone when coming off agonists
• Too long a period after off agonists and start of vivitrol (can be
10days before naltrexone and 15 daysbefore vivitrol with
methadone tapers)
Does Treatment Work?

Medications +
psychosocial
therapy both
benefit brain
function and
recovery.

Each affects
different parts
of brain and in
opposite ways.
PET scans adapted and retouched from Goldapple et al. 2004
• ADDICTION
MEDICATIONS
ARE FOR THE
BRAIN.
• 12 STEP IS
FOR
THE
SOUL.
steven.kipnis@oasas.ny.gov