tx 4 melton saunders

Caring for Specific Popula2ons

Sarah T. Melton, PharmD,BCPP,BCACP,CGP,FASCP

E. Kyle Cook, APN, NNP-‐BC

Disclosure Statements

•  Sarah T. Melton has no financial rela5onships with proprietary en55es that produce health care goods and services.

•  E. Kyle Cook has disclosed no relevant, real or apparent personal or professional financial rela5onships.

Learning Objec5ves 1.  Describe the role of each member of the interprofessional

team (e.g., physician, nursing, clinical pharmacist, addic5on counselor, and peer recovery) in providing outpa5ent medica5on-‐assisted care for the pregnant woman with opioid dependence in Appalachia.

2.  Assess whether the pregnant pa5ent is mee5ng desired outcomes in an outpa5ent opioid treatment facility.

3.  Discuss how the interprofessional team communicates treatment plans with outside providers (e.g., obstetricians, neonatologist, primary care) during the pregnancy to ensure best possible outcomes for the mother and baby.

4.  Design a comprehensive outpa5ent program to meet the referral and popula5on needs of indigent, pregnant women with opioid dependence in rural Appalachia.

Caring for Pregnant Women Addicted to Opioids in Rural Appalachia:

An Interprofessional Collabora<on

Wednesday, April 23, 2014, 1:30 pm – 2:45 p.m.

.

Sarah T. Melton, PharmD,BCPP,BCACP,CGP,FASCP

Learning Objec5ves 1.  Describe the role of each member of the interprofessional team

(e.g., physician, nursing, clinical pharmacist, addic5on counselor, and peer recovery) in providing outpa5ent medica5on-‐assisted care for the pregnant woman with opioid dependence in Appalachia.

2.  Assess whether the pregnant pa5ent is mee5ng desired outcomes in an outpa5ent opioid treatment facility.

3.  Discuss how the interprofessional team communicates treatment plans with outside providers (e.g., obstetricians, neonatologist, primary care) during the pregnancy to ensure best possible outcomes for the mother and baby.

4.  Design a comprehensive outpa5ent program to meet the referral and popula5on needs of indigent, pregnant women with opioid dependence in rural Appalachia.

•  Mission To merge cu@ng edge medical care and an authenCc recovery community to heal lives broken by addicCon

•  Loca5on •  Southwest Virginia •  Russell County, VA •  3rd highest overdose death rate in the Commonwealth •  Only provider for pregnant women with opioid addic5on in

a 4-‐county region

Treatment Team •  Samuel Melton, MD, FAAFP, ABAM

•  Margaret Gregorczyk, MD

•  Hope Fennewald, LPC, CSAC

•  Sarah Melton, PharmD, BCPP

•  Angie Muncy, Peer Recovery Coach •  Steve Ray, Peer Recovery Coach •  Dwight Sullins, Peer Recovery Coach

Pregnancy Referrals

•  Local Community Service Boards •  Department of Social Services

•  Court, proba5on system

•  Obstetricians •  Self-‐referral

Program •  Mo2va2onal

Enhancement Therapy

•  Communica2on with obstetrician and pediatrician before & a@er delivery

•  One-‐on-‐one mee2ng with physician and cer2fied substance abuse counselor

•  Comprehensive drug-‐of-‐abuse history

•  Treatment agreement (signed by pa2ent and provider)

Program

•  Educa5on and baseline laboratory studies •  Induc5on onto buprenorphine •  Group therapy with other pregnant women •  Stabiliza5on and maintenance of therapy •  Prepara5on for delivery, pain management,

breas\eeding, contracep5on

Program •  Insurance accepted like all medical condi5ons •  Witnessed urine drug screening, breath alcohol each visit •  Pill/film counts (each visit and at random) •  Program is zoned based on stability and support level

•  Zone 0: 3 5mes/week visits at start of program •  Zone 4: Poten5al of monthly visits when pa5ent is

working, volunteering, or ac5vely engaged as a caretaker of children

•  Mandatory support sessions between visits (NA, AA, Celebrate Recovery)

•  Monthly individual counseling visits with the addic5on counselor required

•  Assessment for mood or anxiety disorders as well as other medical condi5ons.

Program

•  Medica5ons not allowed in the program •  Benzodiazepines

•  Gabapen5n •  Pregabalin •  Carisoprodol and other muscle relaxants

•  Seda5ve-‐hypno5cs •  Other controlled substances

Monitoring

•  Pa5ents earn a discharge warning for viola5ng any treatment requirement •  Posi5ve urine drug screens for substances other than

buprenorphine •  Incorrect pill count •  Nonadherence with appointments for group, counseling, or

support group mee5ngs •  Not showing for random urine drug screen or pill count •  Rude or disrup5ve behavior at either office or pharmacy •  Evidence of aberrant behavior

•  Prescrip5on Monitoring Program results •  Early refills •  Lost prescrip5ons •  Doctor shopping

Outcomes – In Progress July 2012 -‐ present

•  41 pregnant females •  Average age: 25 years •  70% first pregnancy •  75% enter very early in pregnancy, others in 2nd or 3rd

trimester •  Average dose of buprenorphine = 11 mg daily •  85% also use tobacco •  Number of neonates with Neonatal Abs5nence Syndrome

(NAS) requiring extended stay in hospital: 16 •  Length of stay ranged from 3 days to 3 weeks; most had

stays less than 1 week •  Dose of buprenorphine does NOT correlate with NAS

Outcomes – In Progress July 2012 -‐ present

•  Most neonates had minimal NAS, those with most severe NAS came into program late into pregnancy or con5nued to test posi5ve for illicit substances

•  6 pa5ents remained in program ajer delivery •  Program “too strict” •  Transporta5on difficulty •  Family not suppor5ve •  Return to using illicit substances

•  3 pa5ents discharged during pregnancy •  4 discon5nued treatment on their own

Recurrent Issues

•  Physical, sexual, and emo5onal abuse •  Exposure to violence •  HIV and Hepa55s-‐C at-‐risk behaviors •  Concomitant drug use •  Co-‐occurring psychological issues •  Lack of family support •  Insecurity about paren5ng skills •  Legal issues •  Lack of educa5on, training for employment •  Nutri5on

Take Home Messages from Our Team

•  More pregnant women are addicted than we realize

•  All pregnant women should be screened for substance abuse with appropriate screening instruments

•  Urine drug screens during pregnancy are helpful to iden5fy substance abuse and help prevent or limit NAS


•  Buprenorphine is not a perfect answer as babies are ojen born dependent, but bener than illicit use of substances and alcohol

•  Pregnant women with addic5on need to be treated with care and kindness – s5gma prevents many from seeking appropriate treatment

•  Pregnancy can be a powerful mo5vator for pa5ents to work on recovery •  Teachable 5me •  Benefit from lots of support with weekly visits


•  There are some mothers who have already hurt their babies with alcohol and drugs before they come into treatment, and some mothers simply will not or cannot accept help for their addic5on

•  Pregnant women must be held accountable like other pa5ents with regard to support sessions, counseling, relapses, etc.


•  It is impera5ve to maintain close contact with the obstetricians, especially at the 5me of delivery •  Post-‐delivery and post C-‐sec5on pain can be

managed with extra buprenorphine rather than switching to the usual opioids, which may increase relapse rates

•  Keeping mothers in treatment ajer delivery is challenging


•  Consider advoca5ng for pregnant mothers to remain in treatment 6 months ajer delivery to avoid involvement of Child Protec5ve Services •  This allows 12 months of therapy AND lets

recovery be part of their recovery from pregnancy so they can see that they can stay abs5nent when not pregnant

Resources for Prac5ce

hnp://store.samhsa.gov/product/TIP-‐51-‐Substance-‐Abuse-‐Treatment-‐Addressing-‐the-‐Specific-‐Needs-‐of-‐Women/SMA13-‐4426

hnp://www.who.int/substance_abuse/ac5vi5es/pregnancy_substance_use/en/

NEONATAL ABSTINENCE SYNDROME

TREATMENT CHOICES AND

CHALLENGES

E. Kyle Cook, APN, NNP-‐BC

Opioids are not the only type of drugs that cause withdrawal symptoms .

Other substances can cause withdrawal symptoms in a baby and cause neonatal drug

withdrawal syndrome (ICD-9 code 779.5) (ex: Caffeine, tobacco)

Most a re exposed to mul2p le c l a s s ifica2ons o f d rugs wh i ch can cause w i thd rawa l symptoms i f t he baby i s dependent

and the source o f the d rug i s i n te r rupted a t b i r th

Withdrawal vs NAS

Morphine would be both an opiate and an opioid

Methadone would be an opioid but not an opiate

So all opiates are opioids, but not all opioids are opiates..

Neonatal Abstinence Syndrome (NAS)

•  Constellation of withdrawal symptoms •  CNS

•  Inconsolability, high-pitched crying, skin excoriation, hyperactive reflexes, tremors, seizures

•  GI •  Poor feeding, excessive sucking, feeding intolerance, loose or watery stools

•  Autonomic/metabolic •  Sweating, nasal stuffiness, sneezing, fever, tachypnea, mottling"

Agonist Treatments for Opiate-‐Dependent Pregnant Women

• Methadone, buprenorphine, (BPH) slow release morphine • Cochrane review of 271 pregnant women from 4 trials analyzed • High drop out rate (30-‐40%), with methadone beZer than other treatments • No differences in side effects in mothers, less frequent with BPH in infants • No overall difference in the incidence of NAS, but BPH may be beZer • Maternal dose not associated with NAS

Neonatal Abs2nence Syndrome

• Gene2c factors may be important • Single nucleo2de polymorphisms (SNPs): Single base pair changes that can alter protein’s func2on • SNPs influence opioid dosing, metabolism, and addic2on in adults • No prior studies of gene2c links to NAS

What is Epigene2cs?

•  Changes in DNA (methyla2on, histone modifica2on) affec2ng func2on without a change in the sequence

•  Environmental triggers •  Can lead to gene silencing •  Can be passed on through

genera2ons

Epigene2cs of Addic2on •  Chronic opioid exposure can

lead to methyla2on at CpG sites within the OPRM1 gene

•  Increase in OPRM1 promoter methyla2on -‐ decreased mRNA content and reduced levels of the mu opioid receptor

•  Methyla2on = Gene silencing •  Changes can be passed on to

the next genera2on

Adult Opioid Dependence

• SNPs present in 40-‐50% of the popula2on have been studied in adults • Mu Opioid Receptor (OPRM1) = Site of Ac<on

•  118A>G SNP • Mul2-‐Drug Resistance Gene (ABCB1) = Transporter •  1236C>T SNP; 3435C>T SNP; 2677G/T/A SNP

• Catechol-‐O-‐methyltransferase (COMT) = Modulator

•  158A>G SNP

JAMA. 2013;309(17):1821-‐1827

Candidate Genes for NAS

• Mu Opioid Receptor (OPRM1) = Site of Ac<on 118A>G SNP • (switch that turns on and of opiate receptor on and off)

• Catechol-‐O-‐methyltransferase (COMT) = Modulator • 158A>G SNP

Future Direc2ons

• NIH Grant – “Improving Outcomes in Neonatal Abs2nence Syndrome”

• Randomize 188 infants to receive morphine or methadone (best prac2ce)

• Evaluate long-‐term neurodevelopmental outcomes of infants treated for NAS

• Establish other gene2c factors -‐ Addic<on Array (1350 SNPs), epigene2cs

What we think we know, may not be so

Epigene5cs may play greater role in severity and dura5on of withdrawal more than drug, dose, and dura5on of intrauterine

Intrauterine Drug Exposure

The presence or absence of !NAS !

does not !indicate the severity !

of !intrauterine drug exposure or abuse.

NAS SCORING TOOLS

Finnegan Neonatal Abs5nence Scoring System

Lipsitz Neonatal Drug-‐Withdrawal Scoring System

Ostrea Tool

Neonatal Withdrawal Inventory

Neonatal Narco5c Withdrawal Index

FINNEGAN

Treatment of NAS • Significant variability in treatment (weight, score) with no large, randomized trials • Morphine is the most common and methadone the 2nd most commonly used drug • Sublingual buprenorphine also being studied • Morphine has a shorter half life (dosed every 4 h); methadone dosed every 8 -‐ 12 h • Clonidine, phenobarbital -‐ second line drugs • Some pediatricians are discharging babies on methadone, phenobarb; weaning as an outpa2ent

Treatment of NAS

Morphine vs Methadone

Which drugs should be used in NAS:

• Results from a small clinical trial

• Results in older children, adults • Lectures or ar2cles from “experts”

• We should not translate borderline evidence into standard of care

• We need large randomized, controlled clinical trials to help us decide

Morphine in Newborn Infants • 898 preterm infants received either morphine or placebo for pain control • Morphine group with higher rates of death, severe IVH, PVL, hypotension, worsened respiratory outcome, delayed feeds • At 7 years old, smaller HC and weight, more social problems, less task oriented, weaker short term memory • May develop seizures or increased brain apoptosis (animal models) – Smart Tots ini2a2ve at FDA

Norman et al, Clin Invest, 2013

BP

SaO2

EEG

Weight Based Dosing Regimen • Star5ng dose and escala5on occurs if the infant con5nues to have NAS scores ≥ 8 for 2 consecu5ve scores, or 1 score ≥ 12 • Dosing related to BW and Finnegan score • Wean 10% of the total dose every 24 -‐ 48 hours

Level NAS Score Star5ng Dose -‐ 0.4mg/mL

1 8-‐10 0.3 mg/kg/day ÷ q4h 2 11-‐13 0.5 mg/kg/day ÷ q4h

3 14-‐16 0.7 mg/kg/day ÷ q4h 4 17+ 0.9 mg/kg/day ÷ q4h

ETCH Treatment Plan

Holistic multidisciplinary approach – Non-Pharmacological

•  Environment •  Diet •  Cuddlers

– Pharmacological •  Oral Morphine Sulfate

– Symptom-based vs weight-based dosing

• Non-narcotic – Acetaminophen – Simethicone

ETCH TREATMENT ALGORITHM

ETCH Haslam Neonatal Intensive Care Unit

•  152 beds / Level III NICU – 60 beds"•  30-50 % of our NICU admissions

primarily for NAS treatment"•  135 admissions for 2011"•  283 admissions for 2012"•  258 admissions for 2013"

•  Highest daily census: 37 in September, 2012 Average Daily Census for NAS babies

1st Quarter (JAN-MAR) 2nd Quarter (APR-JUN) 2011 8 13 2012 29 24 2013 28 26

Typical course of treatment

90 % of NAS babies

– Wean in 27 days

– No adjunctive meds

– LOS 30 days

–  50% LOS 21 days

10 % of NAS babies

– Require adjunctive meds •  Phenobarbital (27%) •  Phenobarbital

+Clonidine (7%)

– LOS 65 days •  (longest LOS = 155

days)

Physical Challenges

•  Environment •  Work load •  Pharmacy •  Daily NAS rounds •  Repackaging of

doses / stocking Omnicell vending machines

•  Social Work •  Increased DCS

workload •  Family Support •  Staff Support

•  Volunteer Services •  Phone, Door,

Cuddling •  Rehabilitation Services •  Speech therapy •  Physical/occupational

therapy •  Security

Emotional Challenges

Attitudes / Perceptions •  Preventable nature

of condition •  Personal prejudices

Feelings •  Confusion / fear

– HIPPA concerns –  Ethical Issues

Family / Caregiver Issues •  Personal addiction of

parents •  Mental health issues •  Literacy problems •  Comprehension/

retention issues

Fatigue/exhaustion/burnout

Educational deficit regarding the science of addiction

Long Term Follow-‐up of Infants with NAS

• Opioid exposed children more likely to have ADHD, disrup2ve behavior, psych referrals • Polydrug (including opiates) exposed children have smaller brains, thinner cortex, reduced cogni2ve ability and more behavior problems

• Many studies are small -‐ precludes adjustment for use of mul2ple drugs during pregnancy

• No studies of long term effects of prenatal exposure to buprenorphine or prescrip2on opioids

LONG-TERM EFFECTS

• BRAIN DEVELOPMENT • SIDS • SLEEP • NUERODEVELOPMENTAL DELAYS • BEHAVIOR REGULATION • SENSORY PROCESSING • COGNITIVE/LEARNING DELAYS • PSYCHOSOCIAL IMPLICATIONS

Conclusions •  NAS is a complex disorder with many factors

contribu2ng to incidence, severity •  Significant uncertainty -‐ who to treat, when to treat,

how to treat, how to wean, and the op2mal agent(s) to use

•  Concerns of safety and efficacy of NAS treatments – primum non nocere

•  SNPs in the OPRM1 and COMT genes associated with reduced treatment and LOS

•  Epigene2c factors appear to be important

NAS is 100% preventable • The impact of NAS does not end in the NICU. • Long-term benefits to both the healthcare system and society are significant. • Prenatal care in the otherwise healthy woman is widely accepted to be beneficial to mothers and babies. • We must do all we can to promote prenatal care and substance abuse treatment/counseling in this high-risk population. • Incentives to seek help may allow more opportunities for the woman to receive successful treatment with lifelong benefits.

hat we

what

Contact:

E. Kyle Cook, APN, NNP-BC [email protected]

Questions?

Hudak ML, Tan RC, The Comminee on Drugs and the Comminee on Fetus and Newborn. Neonatal Drug Withdrawal. Pediatrics. 2012;129;e540.

Osborn DA, Jeffery HE, Cole MJ. Seda5ves for opiate withdrawal in newborn infants. Cochrane Database of SystemaCc Reviews 2010, Issue 10. Art. No.: CD002053. Osborn DA, Jeffery HE, Cole MJ. Opiate treatment for opiate withdrawal in newborn infants. Cochrane Database of

SystemaCc Reviews 2010, Issue 10. Art. No.: CD002059.

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