An introductory guide to methadone as a treatment for opiate dependence. Developed by a substance misuse practitioner and registered nurse working with a community drug team.

1. Methadone
A Potted Guide
By Paul Molyneux

2. A Short History
• During World War II the supply of opium was cut off from Germany. As a
result, painkilling morphine became a medicine in short supply.
• German chemist set about making a synthetic alternative. They developed
a compound that acted as an opioid receptor agonist that successfully
relieved pain.
• That compound was methadone, however it was originally named
dolophine (Hanson et al. 2009).
• Methadone as a treatment for opiate dependence was developed in the
1960s as a medical response to the post-World War II heroin epidemic in
New York City (Joseph et al. 2000).
Paul Molyneux

3. Why Methadone?
• In the UK the treatment of opiate dependence is based on
the substitution model in which an alternative to illicit
opiates is prescribed to reduce the need to use those drugs.
• Methadone is seen as the gold standard of substitute drug
for a number of reasons:
Desirable properties of methadone as a substitute medication
 As effective when taken orally as when injected
 Long acting (24-36 hour half life). Allows for daily dosing
Relatively non-euphoriant
 Little need to increase dose over time (i.e. tolerance)
(Seivewright, 2009)
Paul Molyneux

4. • Studies that compared methadone to placebo where eventually deemed
unethical due to methadone’s clear superiority (see Dole et al. 1969; Newman & Whitehill
1979)
• A 2009 Cochrane meta-analysis concluded that:
“Methadone is an effective maintenance therapy intervention for the treatment of
heroin dependence as it retains patients in treatment and decreases heroin use
better than treatments that do not utilise opioid replacement therapy” (Mattick et al.
2009).
• Interestingly, the authors also noted that:
“It does not show a statistically significant superior effect on criminal activity or
mortality” (Mattick et al. 2009).
Paul Molyneux

5. Dosing
• Donny et al. (2002) have divided methadone dosing into
three levels:
Level 1 Level 2 Level 3
Low dose Medium dose High dose
<60mg 60-100mg >100mg
Holds the client, i.e. Reduces cravings Full narcotic
stops withdrawals for opiates blockade
• In reality, dosing is far more nuanced than this.
• Studies have consistently shown that higher doses of
methadone (>60mg per day) result in lower levels of heroin
use and increased retention in treatment over lower doses of
methadone (<60mg per day) (Seivewright 2009).
Paul Molyneux

6. Preparations
Liquid
• The form of methadone most widely used, usually as a 1mg in 1ml
mixture.
• Other strengths include a 2mg in 5ml linctus (used for terminal cough -
unlicensed as substitute medication), and 10mg in 1ml.
• Also available in sugar free and colouring free preparations.
Paul Molyneux

7. Preparations Cont.
Tablet
• Prescribing of methadone in tablet form is roundly discouraged in the
United Kingdom.
• Tablets prove popular with clients as they can be easily diverted and sold
illicitly. They command a high market value as they cannot be diluted or
adulterated (Preston 2003)
• Often used when the carrying of liquid methadone is unfeasible (e.g.
holiday prescriptions).
Paul Molyneux

8. Preparations Cont.
Injectable Ampoules
• Considered useful for small minority of clients who have difficulty giving
up injecting (needle fixation?).
• Generally, clinicians will only prescribe if there is evidence of complete
abstinence of street drug use (e.g. clean urine samples).
Paul Molyneux

9. Prescription Breakdown
9%
Oral Liquid
11%
Tablet
Injectable
Ampoule
80%
Paul Strang et al. (1996)

10. Adverse Effects - Serious
• Overdose:
– This can occur at 40mg for a non-tolerant adult and 10mg or lower for
a child (this is why safe storage is vital!!!)
– Risk of overdose is exacerbated by other CNS depressant drug use (e.g.
alcohol, BNZs)
• Polymorphic ventricular tachycardia:
– A life-threatening arrhythmia that generally occurs in higher doses.
– ECG monitoring is suggested when dose titrated above 100mg (MHRA
2010)
Paul Molyneux

11. Adverse Effects - Minor
• Constipation
• Sweating
• Weight gain
• Dental problems
• Nausea
• Amenorrhoea
• Depression/lethargy
• Reduced sexual desire
(Seivewright, 2009)
Paul Molyneux

12. Withdrawal
• Withdrawal from methadone, though less acutely
severe than those of morphine or heroin, are far
more prolonged (Rassool 2009).
• Withdrawal symptoms usually emerge after 24-36
hours after cessation and can last several weeks.
Paul Molyneux

13. Withdrawal Symptoms
Nausea & Rhinnorrhea
Tremor vomiting (runny nose)
Lacrimation
(tearing)
Withdrawal
Symptoms
Muscular aches
and pains
Tachycardia
Anxiety
Diarrhoea
Rassool (2009)
Paul Molyneux

14. Question Time
Paul Molyneux

15. Bibliography
Dole V.P., Robinson, J.W., Orraca, J., Towns, E., Searcy, P., Caine, E. (1969)
Methadone treatment of randomly selected criminal addicts. New
England Journal of Medicine, 280, 1372-5.
Donny, E.C, Walsh, S.L., Bigelow, G,.E., Eissenberg, T., Stitzer, M.L. (2002) High-
dose methadone produces superior opioid blockade and comparable
withdrawal suppression to lower doses in opioid dependent human.
Psychopharmacology, 161, 202-12.
Hanson, G.R., Venturelli, P.J., Fleckenstein, A.E. (2009) Drugs and Society. 10th
ed. Massachusetts: Jones and Bartlett Publishers.
Joseph H, Stancliff S, Langrod J (2000). Methadone maintenance treatment: a
review of historical and clinical issues. Mt. Sinai J. Med. 67 (5-6), 347–64
Newman, R.G., Whitehall, W.B. (1979) Double blind comparison of
methadone and placebo maintenance treatments of treatments of
narcotic addicts in Hong Kong. Lancet, 2, 485-8.
Paul Molyneux

16. Bibliography
Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy
versus no opioid replacement therapy for opioid dependence. Cochrane
Database of Systematic Reviews 2009, Issue 3.
MHRA. (2010). Methadone 1mg/ml Oral Solution. Available:
http://www.mhra.gov.uk/home/groups/par/documents/websiteresources
/con105829.pdf. Last accessed 23 July 2011.
Preston, A. (2003). The Methadone Briefing. Available:
http://www.drugtext.org/library/books/methadone/section3.html. Last
accessed 24 July 2011.
Rassool, G. (2009) Alcohol and drug misuse: a handbook for students and
health professionals. Oxon: Routledge
Seivewright, N. (2009). Community Treatment of Drug Misuse: More Than
Methadone. 2nd ed. New York: Cambridge University Press.
Paul Molyneux

17. Bibliography
Strang, J., Sheridan, J., Barber, N. (1996) Prescribing injectable and oral
methadone to opiate addicts: results from the 1995 national postal survey
of community pharmacies in England and Wales. British Medical
Journal, 313, 270-2.
Paul Molyneux

18. This presentation was developed by Paul Molyneux (registered nurse) and has
been peer reviewed by Dr D. Butterworth of the Blackburn with Darwen
Alcohol and Drug Service.
Paul.molyneux@gmw.nhs.uk
Paul Molyneux