SOLOMON’S JUDGEMENTAlcohol/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 learning-

Clinical multiagency practice & care pathways

Evidence-based practice is mostly extrapolatedfrom 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 non-prescribed/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

More common for substance dependent women to be in physically and emotionally abusive relationships

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

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 drugUse <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 bingesFoetal alcohol syndrome

May have modified syndrome Dose related effect including repeated binges & individual

susceptibility

Foetal Alcohol Syndrome

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 foetusLow 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 (MDMA-methylene,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; SupportSocial 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 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 pre-pregnant 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) 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 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

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