Treatment: Caring for Specific Populations - Dr. Sarah Melton and E. Kyle Cook

1. Caring
for
Specific
Popula2ons
Sarah
T.
Melton,
PharmD,BCPP,BCACP,CGP,FASCP
E.
Kyle
Cook,
APN,
NNP-­‐BC

2. 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.

3. 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.

4. 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

5. 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.

6. • 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

7. 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

8. Pregnancy
Referrals
• Local
Community
Service
Boards
• Department
of
Social
Services
• Court,
proba5on
system
• Obstetricians
• Self-­‐referral

9. 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)

10. 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,
breaseeding,
contracep5on

11. 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.

12. Program
• Medica5ons
not
allowed
in
the
program
• Benzodiazepines
• Gabapen5n
• Pregabalin
• Carisoprodol
and
other
muscle
relaxants
• Seda5ve-­‐hypno5cs
• Other
controlled
substances

13. 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

14. 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

15. 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

16. 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

17. 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

18. Take
Home
Messages
from
Our
Team
• 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

19. Take
Home
Messages
from
Our
Team
• 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.

20. Take
Home
Messages
from
Our
Team
• 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

21. Take
Home
Messages
from
Our
Team
• 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

22. 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/

23. NEONATAL
ABSTINENCE
SYNDROME
TREATMENT
CHOICES
AND
CHALLENGES
E.
Kyle
Cook,
APN,
NNP-­‐BC

24. 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
are
exposed
to
mul2ple
classifica2ons
of
drugs
which
can
cause
withdrawal
symptoms
if
the
baby
is
dependent
and
the
source
of
the
drug
is
interrupted
at
birth
Withdrawal vs NAS

25. 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..

26. 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"

27. 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

28. 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

29. 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

30. 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

31. 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

32. JAMA.
2013;309(17):1821-­‐1827

33. 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

34. 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

35. 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

36. Intrauterine Drug Exposure
The presence or absence of !
NAS !
does not !
indicate the severity !
of !
intrauterine drug exposure or abuse.

37. NAS
SCORING
TOOLS
Finnegan
Neonatal
Abs5nence
Scoring
System
Lipsitz
Neonatal
Drug-­‐
Withdrawal
Scoring
System
Ostrea
Tool
Neonatal
Withdrawal
Inventory
Neonatal
Narco5c
Withdrawal
Index

38. FINNEGAN

39. 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

40. Treatment
of
NAS

41. 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

42. 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

43. Norman
et
al,
Clin
Invest,
2013
BP
SaO2
EEG

44. 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

45. 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

46. ETCH
TREATMENT
ALGORITHM

48. 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

51. 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)

52. 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

53. 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

54. 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

55. LONG-TERM EFFECTS
• BRAIN DEVELOPMENT
• SIDS
• SLEEP
• NUERODEVELOPMENTAL DELAYS
• BEHAVIOR REGULATION
• SENSORY PROCESSING
• COGNITIVE/LEARNING DELAYS
• PSYCHOSOCIAL IMPLICATIONS

56. 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

57. 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.

58. hat
we
what

59. Contact:
E. Kyle Cook, APN, NNP-BC
EKCook@etch.com
Questions?

61. 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.