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Transcript
SOLOMON’S JUDGEMENT
Alcohol/Illicit drug use, misuse
and dependent use
Pharmacological interventions in
pregnant substance misusers
Dr Mary Rowlands
Consultant Psychiatrist in
Substance Misuse, ENDAS
LECTURE OVERVIEW
Introduction –evidence limitations
 Classification of misuse & dependence
 Gender & stigmatisation
 Effects of selectively clinically important drugs
 Evidence base of prescribing in pregnancy
 Interactive learningClinical multiagency practice & care pathways

Evidence-based practice
is mostly extrapolated
from non-pregnant studies




Evidence base for effects of illicit drugs on
pregnancy (database search Medline, PsychLit)
Evidence base for pharmacology interventions in
pregnancy now established (BAP 2004)
Pharmacological studies: Secretion of nonprescribed/prescribed drugs in breast milk
Clinician weighs these limitations, social care
needs and complex clinical presentation of
pregnant drug misuser in the assessment of risk
to foetus to guide multi-agency management
Differences between ICD-10 & DSM-4





ICD-10 classification of Harmful use
(physical, psychological harms causing
damage to health)
Nature of harm identifiable and specified
criticism is it is limited to health
Continuous use for >1 month
Time similar to DSM-4 in intermittent use of
>12 months
DSM(IV) abuse emphasises social
complications including impairment of adult
functional roles, recurring in physically
hazardous situations , legal, interpersonal;
never met criteria for dependence
Dependence definitions are more
specific and similar




Control loss (compulsion), tolerance,
withdrawal, (neuroadaptation) secondary
symptoms of salience & persistence
ICD-10 difference-reinstatement after
abstinence
DSM-4 difference is social,occupational, or
recreational activities given up or reduced
DSM5(2010) will emphasise that difference
between abuse and dependence is the addicted
state i.e. it is a behavioural difference in terms
of pathological “disease” definition
Legality, availability & potency of
abused substances changed in 20th
Century



Cultural assimilation
of “alien drugs “ is
poor
Legal until 1920
Contrasts with lifting
of wartime alcohol
restrictions




Unchanging social
disapproval of
female substance misuse
denigrates women
Modern social pressures
are hypocritical
expecting women to
match men in amounts
abused e.g. binge
pattern
Greater stigmatisation and adverse childcare
outcomes compared to male drug misusers

Greater physical
complications from
substance misuse
compared with males
for same quantity of
substance because

there are gender
differences in body
mass,

and fat to water
distribution for water
soluble drugs
e.g.alcohol

More common for
substance
dependent women
to be in physically
and emotionally
abusive
relationships
Mary Hepburn: Empowering women to
make informed reproductive health choices
•Prevalence of drug
misuse has increased
in both genders 2:1in
terms of recent drug
related deaths but
•M:F drug specialist
service users is 3:1
•improved was 4:1
Common themes in pregnant
drug misusers
 Ambivalence-fear
of maternal role
 Versus motivation to change++
 Low self esteem, extreme guilt
 Associated deprivation,domestic
violence
 Reduced fertility but not infertile
Common themes in pregnant
drug misusers
 Irregular / absent periods
 No contraception
 Unplanned pregnancy common,
further turmoil
 Risky chaotic lifestyle,
 Salience of drug seeking
 Poor multiagency attendance,
avoids Social Service and antenatal
Alcohol-our favourite drug
Use <1 to 1 alcohol unit daily in pregnant (RCOG)
Non-pregnant
Hazardous use:>2-5 units daily (RCPsych)
Harmful use: >5 units daily
likely physical damage, especially binges
Foetal alcohol syndrome
 May have modified syndrome
 Dose related effect including
repeated binges & individual
susceptibility
Foetal Alcohol Syndrome


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Underweight,small in body length at birth
– poor growth and development
– failure to thrive
Irritable or fractitious, tremulous,
Poor sucking response
Heart defects- about 30%
Kidney problems-structural physiological
Hyperactivity
Delayed development-psychomotor & language
KEY Facial features-short upturned nose,
indistinct upper lip & eye-lid narrowing
(receding chin)
Modified versus severe FAS
Stimulants- Physical signs
of intoxication
Tachycardia
 Hypertension
 Sweating
 Pyrexia
 Dilated pupils
But not always because:
 Chronic users develop tolerance

Stimulant Withdrawal

“Crash”- depression, lethargy, hunger

Later- Craving, anxiety, irritability, depression,
suicidal ideation

Extinction- Specific cue related cravings
Amphetamine effect on foetus


Low dose no evidence.
Harmful use:
– Higher dose, increased frequency
– Decreased head circumference
– Length and birth weight
– Growth restriction
– Increased rates of abruption
Severe (Dependence):
– intracranial lesions- cysts
– haemorrhage, infarction
Cocaine most severe stimulant effects
Meta-analysis of studies
showed similar effects to
polydrug misuse whether
or not they misused
cocaine.
 Polydrug misuse was the
norm in one Australian
study.

Cocaine in USA pregnant, dependent
users research associated with severe
socio-economic deprivation

Confounding variable because infant
mortality rates in these areas approached third
world statistics

Increased risk of
abnormal pregnancy
outcomes including
increased rate of SIDS

Cocaine vasoconstriction

Increased abruption
Benzodiazepine effects on
foetus

Diazepam-No proven association:






head & digit abnormalities
isolated reports contaminated by polydrug & alcohol
misuse
Chlordiazepoxide-non reproducible study showed
increased teratogenicity in 0-42 days old foetus
In high doses,?empirical definition>60mg/day/>3/12
Flat, flaccid baby at delivery after recent use
Late pregnancy- increased neonatal hypothermia, hypotonia,
respiratory depression

Neonatal withdrawal symptoms:
-poor feeding in full term, lower APGAR scores
-respiratory depression in premature babies
Hallucinogenic drug effects on
foetus



Plastic effects, unpredictable bad trips so less
reinforcing and addict has more control
Maternal health education that although unimportant
clinically in adult, too little is known of the effect on the
foetus
Ecstacy also has stimulant effects (MDMAmethylene,dioxy, methamphetamine)


Isolated reports of neurotoxic effects in adults related
to frequent use commonly used in moderate doses
No research on effect on foetus, mothers may seek
health education on effect in the first trimester
Cannabis effects on foetus
-most commonly used illicit drug



No consistent morphological abnormalities
Some loose association with reduced birth
weight & height.
Subtle neurobehavioural abnormalities with
heavy drug use described but not evidenced
Heroin dependence
effects on foetus





No increased morphological abnormalities
Reduced birth weight & height.
Premature births
Increased(2.5 x general population)peri-natal
death rates
Increased maternal death rates
Management of SU problems
Assess in therapeutic relationship
 History, MSE, physical, urines,
bloods
 Other investigations as indicated
 Psycho-social investigations
 PPS formulation of problems
 Determine priorities
 Harm reduction

Management
Physical
 Substitute pharmacology: Titration & stabilisation, &/or detoxification
Psychological
 Motivational Interviewing; CBT; Relapse
prevention; Support
Social
 NA; Rehabilitate; Relate; Lifestyle changes;
 Safe environment
Clinical Management is
still pragmatic !!!




Methadone Reduction in the middle trimester
not a graded evidence base but expert consensus
High rate of miscarriage in this group but rate 1 in
5 for all pregnancies so informed consent to start
methadone in first trimester
Drug misusers less often reach full term, but it
may be more related to state of nutrition/placental
function
Increased blood volume in third trimester may
require an increase in Methadone so all
methadone reductions should stop theoretically at
28-30 weeks if client informed maybe later
Methadone in pregnancy
Higher dose titration –
 Higher birth weights,
 Achieves more antenatal care
 Higher NAS



I-P titration 10 to 20 mls, 4 hourly using modified
Maudsley guidelines and opiate withdrawal scales
Heroin withdrawal begins at 24 hrs+ for neonate
Methadone withdrawal begins at 2-7 days
 Sub-acute withdrawal may persist for 4-6 months
since slower metabolism in neonates (Bell GL)
 Acute withdrawal monitoring in first month
 increased risk of SIDS, failure to thrive,fits,infection
Methadone Assess/Treatment




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

Quantity, frequency and route of use duration of
opiate (heroin or methadone) use
Stage of pregnancy
Past AND CURRENT treatment response
MMT Plus Comprehensive multi-agency antenatal
care
Contingency planning for lapses in a chronic
relapsing condition, even if a trial of abstinence in
highly motivated
Regular core group reviews
Essential contingency plans
Methadone in pregnancy increases duration,
reduces complications & improves birth
weight
Reduces illicit drugs
 Reduces blood borne virus
risk to mother and baby
 Increases antenatal
engagement
 Reduces foetal distress by
?steady blood opiate levels
 <20ml reduces NAS but
does not reduce illicit
drug use, or infant death rate

Buprenorphine [Subutex] in
pregnancy
Same rationale as
Methadone
 Competative agonist
 Agonist-Antagonist
-less intense opiate
side-effects
 Blocks opiate based
pain relief in labour
 NAS less severe
but less established
evidence



Continue with prepregnant stabilised
patient with informed
consent but initiation
complicated by need
for early withdrawal
Previous
Buprenorphine
stabilization needs to
be considered
Opiates-Postpartum
Neonatal Withdrawal
Syndrome (NAS)




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

Narcan should not be given,
Increases rate of perinatal mortality by
precipitating severe withdrawal
Jittery babies, poor feeding
High pitched cry,vulnerable to fits.
Rx Neonatal Paediatrician,
Obstetrician,or SCBU
May need oromorph
Opiates- Postpartum
follow-up
Methadone exposed foetus
showed no difference in
developmental progress
compared with socially
matched peers, in S
London
(Burns 1996)
Opiates-Postpartum
follow-up

The health and development of a group of children
aged 3-7 years born to and reared by mothers who
abused opiates when pregnant and who remained
on methadone maintenance was compared to a
group of age and socially matched control children.

There was no difference between the two groups in
terms of health and development although smaller
head circumference measurements than the
controls.
Opiates-Postpartum follow-up

More than half of the index children had been on
the child protection register during infancy; all but
one were off the register at the time of the study

Results suggest that drug-abusing women who are
on methadone maintenance and attending a drug
dependency unit may rear and care for their
children as well as parents from a similar social
background who are not drug abusers.
Breast feeding
(DOH) All mothers encouraged
 Low breast milk drug level
3% of maternal plasma level in one
study
 But 1-2 hours after any opiate
medication advised
 Baby immunity improved
 Weaning off gradually helps manage
but insufficient milk drug level to
avoid NAS
Except
 Risk of vertical transmission HIV
 Also in Hepatitis B / C

Breast feeding contraindication if






Pregnant drug misuser is
chaotic, or inconsistent use
Not engaged or stabilised on
methadone
High dose Methadone >80mls
stabilised does not exclude
Cocaine (also passes into
breast milk)
Heavy amphetamine use
increases neonate
jitters, irritability
Benzodiazepines sedate
BAP Recommendations
Categories of evidence for causal
relationships and treatment
Ia: Evidence from meta-analysis of
randomized controlled trials
 Ib: Evidence from at least one
randomized controlled trial
 IIa: Evidence from at least one
controlled study without randomization
 IIb:Evidence from at least one other
type of quasi-experimental study

BAP Recommendations
III: Evidence from non-experimental
descriptive studies, such as
comparative studies, correlation studies
and case-control studies
 IV: Evidence from expert committee
reports or opinions and/or clinical
experience of respected authorities

BAP Recommendations
Proposed categories of evidence for
observational relationships




I: Evidence from large representative
population samples
II: Evidence from small, well-designed, but
not necessarily representative samples
III: Evidence from non-representative
surveys, case reports
IV: Evidence from expert committee reports
or opinions and/or clinical experience of
respected authorities
BAP Recommendations
Strength of recommendation





A: Directly based on category I evidence
B: Directly based on category II evidence or
extrapolated recommendation from category I
evidence
C: Directly based on category III evidence or
extrapolated recommendation from category I
or II evidence
D: Directly based on category IV evidence or
extrapolated recommendation from category
I, II or III evidence
S:Standard of Care based on expert practical
or ethical consensus
BAP
Recommendations
BAP Recommendations
Nicotine & pregnancy




Psychosocial interventions should be offered
since they are effective(A)
Risk:benefit ratio should be considered for
offering nicotine replacement therapy ©
Reduces low birth-weight & pre-term babies
Bupropion(amfebutamone) should be avoided
no published evidence
BAP Recommendations
Alcohol & pregnancy





Women should be advised not to drink
alcohol or at most,one drink per day(S)
Adequate screening should be routine(S)
Psychosocial interventions should be offered
& be the mainstay of treatment(B)
Patients with symptomatic withdrawal should
be offered medical cover for their
detoxification ideally, as an in-patient(D)
Medication to sustain abstinence should be
avoided(D)
BAP Recommendations
Alcohol & pregnancy
Key uncertainties
 Risks of alcohol withdrawal versus
benzodiazepine prescribed versus
continued alcohol consumption to the
foetus and whether any trimester carries
more risk than at other times?
 Risk of acamprosate, naltrexone or
disulfiram in pregnancy?

BAP Recommendations
Opioids and pregnancy
Methadone maintenance results in
improved maternal & foetal health &
should be offered to opioid dependent
pregnant women (B)
 Less data are available for
buprenorphine maintenance but it
appears similar benefits are seen for
mothers & foetus as for methadone(B)
 Detoxification should be avoided in the
first trimester, is preferred in the second
& used with caution in the third.

BAP Recommendations
Opioids and pregnancy

Methadone is the best known substitute
pharmacotherapy in pregnancy & will
usually be the first choice; however,
recent experience with buprenorphine is
encouraging. Clinicians may therefore
consider continuing buprenorphine in
patients doing well on established
treatment. Potential problems with
opioid analgesia during labour must be
anticipated
BAP Recommendations
Opioids and pregnancy
Key uncertainties
 Does Methadone or buprenorphine
have advantages over the other in
terms of maternal or foetal /neonatal
outcomes?

BAP Recommendations
Stimulants and pregnancy
Limited evidence to make any
recommendations except say ‘stop’
 Substitution therapy is not
recommended despite no studies(S)
 What to offer?

Lecture Summary




Use and misuse is quantitatively imprecise in
terms of foetal drug plasma levels achieved,
addictive behaviour/patterns can guide
clinically
The mainstay of treatment for use, misuse is
education and brief interventions.
Awareness of the potential risk of teratogenicity
poor health in mother leading to poorer
neonate outcomes,
Advice aimed at the harm reduction that the
mother can achieve and working to a hierarchy
of health enhancing goals
Lecture Summary
Highest adverse foetal effect of high dose misuse
and dependence especially stimulants and alcohol.
 In the majority of cases pharmacological alcohol
detoxification is not required. Inpatient management is
recommended.
 BAP recommendations for high dose Methadone
maintenance to improve outcomes for mother and
baby, but evidence base for buprenorphine is
increasing, but dose effect is unknown.

REFERENCES:

Evidenced based guidelines for the
pharmacological management of substance
misuse, addiction and comorbidity:
recommendations from British Association for
Psychopharmacology,
Journal of Psychopharmacology(2004) 293-335

Management of drug misuse in pregnancy Ed
Day & Sanju George
Advances in Psychiatric Treatment, Journal of
Continuing Professional Development, The Royal
College of Psychiatrists,Vol 11,Issue 4, July 2005,
253-261,http://apt.rcpsych.org

REFERENCES:



Methadone Neonatal Withdrawal
Bell GL,Lau K Pediatr Clin North
Amer,1995 Apr;42(2):261-281
Drug Misuse in Pregnancy
Breastfeeding Project (2003)
Breastfeeding and Drug Misuse: An
Information Guide for Mothers:
University of Plymouth.
REFERENCE:


The health and development of
children whose mothers are on
methadone maintenance.
Claire Burns , Margaret O'Driscoll ,
Gem WasonChild Abuse Review
Volume 5, Issue 2, Pages 79-144
(May 1996)
Solomon had no evidence but used “clinical”
judgement that the mother that acted in the best
interest of her child was the true parent
Case Study






Late presenter isolated with partner
Stabilisation as in-patient revealed
minimisaton of use
Informed maternal decision to breast-feed
Complicated attitude from partner-previous
partner died blamed drug services, he had
care of 7 year-old daughter of this
relationship
Medical history of this child of congenitalheart
disease hidden
Social services assessed as safe to return
home with other child at core meeting





Further pre-discharge meeting mother
determined to breast-feed although duration
of stabilisation was short-full risk info given
Neonatal paediatrician found no spcific signs
of withdrawal—did not access maternal
notes(system now changed)
Mother went home and apparently
cooperative with community mid-wives
Not informing them nursing baby in bed
Over a weekend unilaterally rapidly reduced
Methadone dose-pharmacist unaware
recently delivered-used heroin, baby rolled off
bed died of hypothermia
Lessons from local perinatal death of
continued Maternal Heroin Use whilst
prescribed Methadone Post-natally



Risk to baby increased if no evidence of clean urines
and/or unstable drug use even though the addiction
treatment service philosophy and evidence base is
harm reduction
but heroin use must be reduced enough to allow a
suitable environment for safe &sustainable child care
routines and requires urgent review which may need
to be intensive & on-going
e.g. be aware of protracted neonatal methadone
withdrawal, twice weekly drug urinalysis during early
post-natal period > 14 days, supplemented by further
health & social care worker monitoring
If there is evidence of continued drug use then
drug using carer in the household increases
risk of harm to the child post natally
 Risk management is required of the potential
for mother to fall asleep at night whilst feeding
baby, due to heroin use on top of methadone,
but what should be the child protection
consequences of “dirty urines”, in practice
 social services reluctant to implement child
removal if mother is “cooperating”with drug &
obstetric services and prescribed Methadone



Should mother & baby be admitted to increase dose
of methadone for safe monitoring, what about the
risk assessment and management if other children
require child care
Previous parenting may not be relevant since past
drug misuse may have been more stable & less
severe than current drug misuse
If parents are rejecting of services antenatally
and present later in pregnancy more child
protection is needed if parental preference is
for breast feeding, both in terms of access to
the home
 &/or trying to control the script by altering
medication without involvement of keyworker
or prescriber, this behaviour increases risk &
communication from pharmacist essential

Proposed Care Pathway
developed locally



Rapid assessment including health education
for harmful use and access into treatment
ideally no later than early in middle trimester
Prompt Specialist S/m Cons and liaison nurse
involvement, and Cons O&G
S/m Specialist 5ml/week reduction or
stabilise by 32 week ideally then involve
neonatal paediatrician to plan neonatal
management at & post-delivery, into
puerperium
Proposed Care Pathway contd


Locally developing multiagency
guidelines with social services with 4 weekly
core group meetings
For the future aspirations to more shared
care with GPSi and antenatal services but
multiagency pathways must first work in
practice in specialist services before altering
the model of service


Management of primary dependent stimulant
users is a greater issue for amphetamine
rather than cocaine in SW England. Polydrug
use is the norm. Systematic development of
pilot intensive community based psychosocial
programmes is required to improve evidence
of enhanced foetal outcomes
BAP recommendations underscore the
experimental evidence base as well as the
expert consensus for treatment of pregnant
drug misusers which does exist & should be
incorporated in routine joint working between
obstetric, social & substance misuse services