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 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 The greatest percent increases during that period were among year olds (214%) and 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 year olds. There was a 30% decrease in heroin admissions by year olds. Heroin admissions are admissions where heroin was the primary substance at admission.

DEFINITIONS Papaver Somniferum Opiate = Rx derived from opium Opioid = All Rx with morphine-like actions

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 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:

ADDICTION MEDICINES 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 INSUFFICIENT EVIDENCE REGARDING EFFICACY o CONTRADICTORY EVIDENCE o TOO EXPENSIVE NALTREXONE $ PER DAY o CORRECT DOSE? o SIDE - EFFECTS

BARRIERS MEDICATION o CANDIDATE SELECTION TOOLS NEED TO BE RESEARCHED - WHO WILL BENEFIT MOST? o POTENTIAL FOR ABUSE o POTENTIAL FOR DIVERSION o “MAGIC BULLET THEORY” o DELIVERY SYSTEM

BARRIERS PATIENT o COMPLIANCE o SELECTION o STIGMA o COST/INSURANCE COVERAGE

BARRIERS PHYSICIAN/NURSE o LACK OF AWARENESS o LACK OF TRAINING o LACK OF ONGOING TECHNICAL ASSISTANCE o DO NOT PROMOTE USE o MD’S NEEDED AT ALL PROGRAMS o EXTRA WORK OBSERVATION TIME

BARRIERS COUNSELOR o LACK OF AWARENESS o LACK OF TRAINING o COUNSELORS IN RECOVERY “NOT THE WAY I DID IT” o MORE WORK AFTERCARE

BARRIERS PROGRAM o NEED PHYSICIAN SERVICES o NEED TO INCREASE COMMUNICATION BETWEEN PHYSICIANS AND COUNSELORS o 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 NEED INCREASE IN EDUCATION AND T.A. o PRIVATE MD’S NEED TO BE ABLE TO LINK TO THE SYSTEM o NEED OUTCOME DATA

BUPRENORPHINE OVERVIEW OF THE DRUG ADDICTION TREATMENT ACT OF 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 AN AMENDMENT TO THE CONTROLLED SUBSTANCES ACT (10/17/01) o PRACTITIONER REQUIREMENTS “QUALIFYING PHYSICIAN” o LICENSED o BOARD CERTIFIED IN ADDICTION PSYCHIATRY o CERTIFIED IN ADDICTION MEDICINE BY ASAM OR AOA o INVESTIGATOR IN BUPRENORPHINE CLINICAL TRIALS o 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 ( MG) CALLED TEMGESIC® AVAILABLE IN THE U.S. AS AN PARENTERAL FORM CALLED BUPRENEX® LOW DOSES FOR PAIN TREATMENT AS COMPARED TO ADDICTION TREATMENT ( 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 2 & 8 MG SUBLINGUAL TABLETS MADE BY RECKITT & COLMAN CALLED SUBUTEX® o 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 DOSES USED FOR OPIOID ADDICTION TREATMENT IS 1 -2 MG UP TO MG o 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 IF TAKEN S.L. BUP>>>>>>NALONXONE o IF TAKEN I.V. NALOXONE>>>>>BUP

BUPRENORPHINE SAFETY 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 o REPORT OF 53 CASES OF HEPATITIS IN FRANCE SINCE 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 SCANT STUDIES o DEATH CASE REPORT ASSOCIATED WITH IV BUPRENORPHINE AND BENZODIAZEPINES o CANNOT GIVE WITH ReVia o AVOID MEDICATIONS THAT ARE METABOLIZED BY THE CYTOCHROME P450 3A4 SYSTEM o 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 opioid- free for 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 tamper- resistance as compared to Suboxone.

OD prevention project

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 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 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 In 4 day lead in maintained abstinence was 32% in the treatment group vs 11% in the placebo group (all got behavioral treatment) o Better abstinence rates with 7 day lead in Good adherence to medication o 74% had 4 injections o 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 Decreased cravings and less depression and anxiety o 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)

ADDICTION MEDICATIONS ARE FOR THE BRAIN. 12 STEP IS FOR THE SOUL.