What is methadone? Case study Why this topic is important How does methadone act differently in pregnancy? Foetal outcomes Neonatal outcomes Post-natal outcomes What I’ve gained from this iSSC Conclusion Further information & References

An opioid agonist. Substituted for opioids eg. diamorphine , preventing the onset of withdrawal symptoms in opioid

dependency. Addictive- so should only be prescribed to the physically dependent on opioids. Administered in a single daily dose, usually methadone oral solution( 1mg/mL). Dose is adjusted according to the degree of dependence.

The NICE guidlines:

Oral methadone and buprenorphine are recommended for maintenance therapy in the management of opioid dependence. Patients should be committed to a supportive care programme including a flexible dosing regimen administered under supervision for at least 3 months until compliance is assured. Selection of methadone or buprenorphine should be made on a case-by-case basis, but methadone should be prescribed if both drugs are equally suitable.

Other drugs used for opioid dependency include:› Bupenorphine› Naltrexone› Lofexidine

• X smoked ~£10 (1 bag) heroin per day for the past 10 years.• X is 7 months pregnant.• Since X found out she was pregnant, she has been coming to the clinic for

methadone maintenance treatment. • She receives 70mls/day.• On this particular day, X went home immediately after coming to the dispensing

unit for her daily methadone. She was sick, approximately 10 minutes after leaving the clinic.

• X came back and asked the doctor for some more methadone.• It was agreed she would receive another 40mls.

Because heroin users can become pregnant• The global average of heroin use prevalence was 0.3% 2003-2004 (Iran

4.4%) (UNODC, 2005)• 80-90% IV heroin users are of reproductive age.• Pregnancy isn’t uncommon (Gaulden, 1964).• 1/3 patients at a high risk clinic were positive for opiod use at some stage in

their pregnancy (Ostrea, Knapp 2001) Because awareness of methadone use in pregnancy should be

increased• Methadone use in pregnancy is advantageous over the alternatives ie.

Pregnant, opioid dependent women on the streets. Care for infants of opioid-dependent mothers could be life-saving.

• Risk of SIDS and BBVs Methadone acts differently during pregnany

• Should be taken into consideration by clinicans when dosing

As pregnancy progresses, methadone metabolism is enhanced resulting in increased clearance.

Methadone EDDP

Half life reduced from 24hrs to 8-20hrs. (Swift & Dudley, 1989) During the 3rd trimester, and oral methadone dose of 50-150mg is required to

achieve a level of 240ng/ml in the maternal circulation. The bioavailability of methadone is normally 40-99% Low levels of methadone in the maternal circulation may result in withdrawal

symptoms. Methadone should therefore be dosed carefully during pregnancy

Hepatic cytochromeN-demethylation

& Microsomal enzymes

Methadone transfer from mother to foetus occurs via the placenta. The placenta may also act as a filter, retain methadone, and alter the methadone.

Methadone EDDP The foetus can metabolise methadone in the liver. Depends on the level of foetal maturation. Capacity significantly less than in the mother, due to the absence of certain

cytochrome enzymes.

Methadone has also been identifed in the amniotic fluid, suggesting oral and cloacal uptake (likely to be a lot less than recieved across the placenta.)

Methadone is also transferred in the breast milk, leading to post-natal exposure of the infant to methadone.

Inconclusive data about how much transfer actually occurs. Thought to be variable, and multi-factorial.

Placental Aromatase

MMT has inarguably improved management of pregnancy and neonatal outcomes in heroin addicts.

High methadone doses in 3rd trimester result in improved foetal growth (Hagopian, 1996)

No serious foetal toxicity has been associated with methadone. Some adverse effects identified, however, this data is inconsistent and there isn’t

an established causal link to methadone use (Lam et al, 1992).› Higher incidence of prematurity.› Intrauterine growth retardation› Increased foetal mortality.

Clinical observations in utero:› Decreased foetal activity› Decreased respiration rate› Decreased heart rate(in contrast to mothers not on oral methadone)

•Decreased average birth weight•Decreased head circumference•Increased morbidity and mortality•Increased incidence of NAS

(Stein et. al. 1999)

Complex disorder, characterised by behavioural and physiological signs and symptoms that are very similar, despite very different causative agents.

Multisystem disorder.› CNS› GI› Autonomic› Respiratory

Acute phase lasts for 7-14 days post-partum High pitched crying particularly characteristic. The pathological severity is assessed using the Finnegan scale

Opiate induced growth reductions:› Decreased postnatal weight gain› Decreased head circumference› Decreased height

These effects decrease with age, but may last for up to 5.5 years...

Increase in:› SIDS› Mortality› Microcephaly› Strabismus› Behavioural effects (mood, attention, cognitive defects)

Up to the age of 5 years, show cognitive impairment. Less interactive aged 5 Aged 7, behaviour at school different: Underachieving, aggressive, disruptive. No difference between effects of heroin and methadone on post-natal outcomes...

Management plans How do you know if a patients lying? Ethical issues Clinical experience Collecting evidence

Methadone Maintentenance treatment is standard procedure in the UK for opioid dependent pregnant women.

Methadone is metabolised faster in pregnancy, so higher doses may be required to acheive the same ‘euphoric’ effect.

Methadone often, but not always, has detrimental effects on the foetus, neonate, and post-natally.

The detrimental effects methadone has on the foetus is less than the effects of diamorphine.

The use of MMT in pregnant women should be encouraged, and seen as harm minimising.

Bristol Specialist Drug Service59-61 Stokes CroftBristol, BS1 3QP0117 923 2077

The methadone maintained pregnancyStein et al. (1999) Clinical Perinatology 26(1):173-83.

The Effects of Maternally Administered Methadone, Buprenorphine and Naltrexone on Offspring: Review of Human and Animal Data

Farid et al. (2008) Current Neuropharmacology, 6, 125-150

www.talktofrank.com Trainspotting (1996)

•Ostrea, EM Jr et al., (2001) Estimates of illicit drug use during pregnancy by maternal interview, hair analysis, and meconium analysis J Pediatr. 138(3):344-8.•Hadman, A. (2009). Neonatal Abstinence Syndrome. Medscape. Available on the world wide web < http://emedicine.medscape.com/article/978763-overview > [January 2010]•BNF•Farid et al. (2008)The Effects of Maternally Administered Methadone, Buprenorphine and Naltrexone on Offspring: Review of Human and Animal Data Current Neuropharmacology, 6, 125-150• Swift, M & Dudley, RM (1989) Altered methadone pharmacokinetics in pregnancy: implications for dosing J Subst Abuse. 1(4):453-60.• Hagopian, GS et al. (1996) Neonatal outcome following methadone exposure in utero. J Matern Fetal Med. 5(6):348-54.• Lam, SK et al. (1992) Narcotic addiction in pregnancy with adverse maternal and perinatal outcome. Aust N Z J Obstet Gynaecol. 32(3): 216-21• Stein, J. Et al. (1999) The Methadone-maintained pregnancy. 26(1):173-83.• Berghella, V. Et al. (2003) Maternal methadone dose and neonatal withdrawal. Am J Obstet Gynecol 190 (6): 1806-7•Gaulden, E.C. et al. (1964) Menstrual abnormalities associated with heroin addiction. Am J Obstet Gynecol. Sep 15;90:155-60.• UNODC (2010). UNODC and Illicit drug facts. Available on the world wide web < http://www.unodc.org/unodc/en/illicit-drugs/index.html?ref=menuside> [January 2010]