The document discusses addiction replacement therapy (also known as opioid substitution therapy) for treating opioid use disorder. It begins by outlining the objectives and magnitude of the global and Egyptian opioid problems. It then describes medication-assisted treatment using opioid agonists/antagonists like methadone and buprenorphine. The benefits of opioid substitution therapy include reducing illegal opioid use and associated harms while increasing social functioning. Common myths about substitution therapy are addressed. Treatment algorithms are provided to guide patient assessment and selection of optimal replacement therapies like methadone, buprenorphine or naltrexone based on their different pharmacological profiles and patient characteristics.

1. Leut.Col.Dr.Yasser AbdEl-Ghany El-Ghazzawy
PsychiatricHospital, Maadi Armed Forces MedicalComplex
Addiction Replacement
Therapy

2. AddictionReplacementTherapy

3. Objectives
Magnitudeoftheproblem
1
2
3 AddictionReplacementTherapy(OpioidSubstitutionTherapy)
“Medication-AssistedTreatment(MAT)”forOpioidusedisorder
Agonist/ Antagonistpharmacology
4 OpioidSubstitutionTherapy(OST):
 Methadone
 Buprenorphine
 Comparison / Flowchart for assessment and management
 Harm reduction concept
 History of OST
 The perfect drug
 Benefits of OST
 Myth about substitution therapy/ challengesand threats.
 Inclusion Criteria and special groups.

4. Magnitude of theproblem
Worldwide:
1
In Egypt:
2

5. Magnitudeof theProblem
Consequences of theopioid crisis:
• Increased HIVand HCV.
• Risingincidenceofinfants born dependentonopioidsas a result of
opioiduse duringpregnancy.
Worldwide
In2020, 2.7 million peopleaged 12 orolder, inU.S with
OUD
OpioidUseDisorder:
Overdose deaths:
• The UnitedNations attributes76% of addiction-related
deaths worldwidetoopioids
• More than quadrupled from 1999

6. Magnitude of theProblem
In Egypt:
All indicatorspoint to an increaseinthebehaviorof drugabuse by
injection,whichis accompanied by an increasein the rates of
infection(HIV,HBV, HCV)
• By the end of2020, the
cumulativenumber of people
infectedwithHIV/AIDS was:
18,196,ofwhom 6,080 are
injectingdrug users, representing
33.5 %ofthe total number of
cases detectedfrom 1986to
2020.
• Out of the total6080,in
the last fiveyears only:
4803, or 79%.
• In 2019and 2020alone, the
percentageof HIV through
injectingdrugs increased by
31% compared tothe previous
twoyears.

7. Magnitude of theProblem
In Egypt:
• A Survey bythe
government shows that the
narcotic problem costs the
country’s economy $800
millionannually
• According to theUNODC
51% of injecting drug users are
infectedwith HCV with the
highestNumbers in Egypt
globally(10%) .
• In additionto 150,000 new
infections annually.
UNOCD= UnitedNationsOffice onDrugs and Crime

8. “Medication-AssistedTreatment(MAT)”
for Opioid Use Disorder
1
Detoxification
2
Early and late
recovery
3
Maintenance
Methadone
Buprenorphine
Naltrexone
Alpha-2-AdrenergicAgonist
Medications (Lofexidine)

9. Agonist/Antagonist
o Affinityfor
binding plus
efficacy
o Methadone
PureAgonist
o Affinityfor
binding butlow
efficacy
o Buprenorphine
PartialAgonist
o Affinityfor
binding butno
efficacy;blocks
action of
endogenous
andexogenous
ligands.
o Naltrexone
PureAntagonist

10. Heroin/Methadone Buprenorphine Naloxone/Naltrexone
FullAgonist PartialAgonist Antagonist
Activity
Zone
Affinity
Zone

11. Patternof OpioidReceptorActivation

12. HarmReduction
WhatisHarm
Reduction?
Can be viewedas the preventionof adverse
consequencesofillicitdrug use without
necessarilyreducingtheirconsumption.
A range of different strategies withthe goal
of minimizingthe riskof the patient
contractinginfectiousdiseases,overdosing,
orsufferingother consequencesrelated to
the use of substances.
The increasingnumbers of patients
infectedwithbloodbornediseases
through sharing injectingequipment,
the model ofharm reductionhas been
adaptedinEgypt

13. HarmReduction
Vaccinationagainst
HBV
ProtectedSex
Harmreduction
strategies:
Overdose reversal
medications supply
(Naloxone)
Treatmentfor
infectiousdiseases
(HCV/HIV)
Reducestigmaassociated
with substanceuseand
co-occurringdisorders
NotSharing
Needles
OpioidSubstitution
therapy(OST)

14. History
During world War II Asa synthetic alternative 1960s
The supplyof
Opiumwas cutoff
from Germany. As
a resultpainkilling
Morphine became a
medicinein short
supply.
Methadone was developed as
a pain killing alternative by
German chemist as an Opioid
receptoragonist successfully
relievedpain.
• Methadone used as
a treatment for opioid
dependenceas a
response topost- world
War IIHeroinepidemic
inNew YorkCity.
• FDA approved for
opioiduse disorder
in1972

15. o One of the most effective treatment options for opioid dependence.
o It is a safe andcost-effective.
o Extensively researched.
AddictionReplacementTherapy
OpioidSubstitutionTherapy(OST)
WHO addedMethadone and Buprenorphine tothe “Listof EssentialMedicines”
"intended to beavailablewithinthecontext of functioning health care systemsat all
times in adequate amounts, in the appropriatedosageforms,with assured quality,and
at a pricetheindividualand the community can afford."(WHO,2009)

16. “ThePerfectDrug”Characteristics:
• Slowonset of Action. • Relieves withdrawalsymptoms.
• Longduration of action.
• Prevents relapse.
• Slowoffset of action.
• Has impact onnegative
reinforcement generated by stress
neural circuits.
• Oral orpreferable depot form.
• Inhibitsthe reinforcing
properties(Euphoria) by drugs and
associated cues.

17. Benefitsof implementing Opioid Substitution
Therapy (OST)
1
4
2
3
The reductionorcessation of opioiduse,andopioidusedisorder-related
symptoms withLessharmrelated tomode of use /impurity of substance.
The reductionorcessation of opioid-relatedoverdosedeaths.
The reductionorcessation of opioid-relatedcriminalactivity
The reductionof injectionand the associated risk of transmission of blood-
borne viruses(HIV),(HBV)and(HCV).

18. Benefitsof implementing Opioid Substitution
Therapy (OST)
5
8
6
7
OST Increases socialfunctioningandretentionintreatment.
Treatment of opioid-dependentpregnant womenwith methadone or
buprenorphineImproves birthOutcomesfortheirbabies
Reduces suicidalityandco-morbidpsychiatricsymptoms
Decreasescraving,Resetstolerance,Relapseprevention,Safeand
comfortablewithdrawal,Controlleduse givenundermedical supervision.

19. Benefitsof OST
Abuse SubstitutionTherapy
vs.
 High chances of HIV & other blood
borne infections
 Not prescribed medically
 Severe withdrawal symptoms
 High chances of overdose and
intoxication injuries
 Craving
 Criminal activity
 Lost productivity
 Infants born dependentson
opioids.
 High cost of medical service
 Low chances of HIV & other blood
borne infections
 Given under medical supervision
 Mild withdrawal symptoms if
discontinued
 Low chances of overdose
 Less Craving
 Less Criminal activity
 More productivity
 less cost of medical service

20. Misconceptions/ Mythabout OST
Patientsare stillAddicted
Addictionis the pathologicaluse of a
substance
OST is medicallysupervised and regulated
Myth
#1
Mythabout
OST
OSTis simplya substituteof
illegaldrugs
OST ensures commitment torecovery
programs that allows persons to function
normally
Myth
#2
Providingmedicationsaloneis
sufficient:
Combiningpharmacotherapy and other
recoveryservicesis mandatory.
Myth
#3
Posters in the Media :
Methadoneis A Narcotic
Thatkills

21. MainrelevantthreatsagainstOST programin Egyptare:
 Risksin caseof a negativeviewandperception by themedia/community,
dependingon the stigmaand low knowledgeofthe harm-related injected drug
use.
 The relatively strong stigmaanddiscriminationagainst peoplewhouse drugs,
as( it is the casein several Arab countries).
 Lack of fundingpossibilitiesand sustainability.
 The riskof diversionis the case ofnon-control and insufficientmonitoring
throughout thewholeprogram.

22. RecommendationforadmissioncriteriaforOST
TheInclusioncriteria:
 Diagnosisofopioiddependence
according toclassificatorysystems,
 Minimumof one tothree yearsof
opioidaddiction;
 Methodofadministration by
injection
 A minimumageof18;
 Historyoffailedtreatment
attempt(s)and long duration ofuse
 Strong motivation and willingto
come daily
 Ableto giveinformedconsent
Specialgroupsare givenpriority over the
general opioiddependent population:
 Pregnant women;
 Peoplewith HIV/AIDS
 Peoplewith viralhepatitis;
 Peoplewith mental health problems;
 Poly-drugusers; and
 In custodial settings (prisons, jails)and
under policearrest.

23. Methadone
( throughspecializedmethadoneclinics)
Modeof Action
Durationof Action
Preparations Dosing
A fullmu-opioid
receptor agonist
methadoneliquid, Oral
tablets, methadonePowder,
IV methadone
Adequate dosing
ranges from60 – 120
mg,typically
beginning with adaily
doseof20–30mg
with increases of5 or
10mguntil the
optimaldoseis
reached
slowonset of action(30
min. withpeakeffect(2-3
hrs.) with long
elimination ½ life(24-36h)

24. SideEffects
Deaths
1
Respiratory
depression
2
Cardiac
( QTcprolongation) ECG as
baseline andfollow-up during
treatment
3
The mainthreat is
theriskof
overdosing,
especiallyatthe
start oftreatment
and when
methadoneis
combined with other
sedativemedications
or illicitdruguse
Abuseispossible

25. Contraindications:
1 4
2 5
3 6
Does notmeet
DSM 5/ICD-11
criteria
Seriousand problematic
use of alcoholand or
sedative hypnotics
Less than 1yr history
of opioidaddiction
Unable to attend
program as required
Allergicresponse
Cardiac complications
Caution: Highlyactive antiretroviral treatment
medications used in HIV infection treatment affect the
pharmacokinetics of methadone; therefore, it is vital to
practice caution in the case of patients who receive highly
active antiretroviral treatment

26. Buprenorphine
Modeof Action
Durationof Action
Preparations Dosing
History
Partial agonist at
the mu receptor. It
has lowactivitybut
high affinity.
o Poorbioavailabilitywhen
taken orallyand must be
dissolvedsublingually
o Co-administration
withnaloxone (Suboxone®)
(not absorbed sublingually)to
preventthe buprenorphine from
beinginjected(Abuse)
o Other forms : 6-month
subdermal implant and
a once-monthly buprenorphine
injection
o Discoveredin1966
o (FDA) approved in2002
o Onset of effect in 30–
60minutes.
o Peak effect inabout 1–
4 hours.
o Half-life 20–72hours
(36hours onaverage).
Tolerabledose range (4to 24
mg )

27. Comparison( The 3- FDAapproved drugs)
Treatment Methadone Buprenorphine Naltrexone
Pharmacologic action Full opioid agonist Partial agonist Full opioid antagonist
FDA-approved clinical
indication
Opioid-use disorder, pain Opioid-use disorder, pain Opioid-use disorder,
alcohol-use disorder
Routeof
administration
Oral, parenteral Sublingual,
subcutaneous extended-
release injection,
subdermal implant,
transdermal patch
Oral, parenteral
Frequencyof
administration
Daily Orally: daily,every other
day, 3 times a week;
subcutaneously:monthly
implant: every 6 months
Orally: daily,every other
day or every
third day;
intramuscularly:
monthly (Vivitrol)

28. Treatment Methadone Buprenorphine Naltrexone
Challenges • Potentialfor abuse
• cardiac
complications in
cardiac patients
• Higherriskof
overdose
• More severein
withdrawal
Safe in pregnancy and
breastfeeding
• Potentialfor abuse if
not combined with
naloxone
• saferfor peoplewith
cardiacproblems
• Better for modestly
motivated patients
• low risk of overdose
• Less severe
withdrawal so easier
transition in and out
of treatment
Not recommended in
pregnancy
• No potential for
abuse but Less
complianceyet better
in long acting
injections
• Betterfor highly
motivatedpatients
• Hepatic
complications in
hepatic patients
Contraindicated in
pregnancy

29. Is the patient
willing to
participate in
CD treatment?
Is patient
pregnant
and/or has
chronic
pain ?
1. Evaluate key comorbidities
2. Prescribe naloxone to treat overdose
3. Develop a detox plan
4. MI to encourage treatment participation
YES
1. Refer to an ASAM certified
addiction treatment provider
2. Review all three medication
option risks and benefits
NO
Is patient willing to participate in a
methadone maintenance program
and is one locally available?
YES
Refer to methadone
treatment program
NO
Recommended
naltrexone (long-acting
injectable preferred)
unless pregnant
Ifpregnant
MI= Motivational interviewing
ASAM=American Societyof Addiction Medicine
CD=Chemical dependency
OO=opioid overdose
OUD= Opioid-usedisorder
KEY
Continue to monitor for relapse
and maintain contact withCD
treatment provider
No toall
Is patient highly
motivated and/or would
preferto avoid agonist
therapy?
Agreed to treatment
Patient diagnosed with an opioid use disorderthrough assessment

30. No toall
Is patient highly
motivated and/or would
preferto avoid agonist
therapy? Ifyes to any
Recommended
methadone or
buprenorphine
No
Methadone
Buprenorphine
Refertomethadone
clinic and continueto
monitorcomorbidities
Office-based induction and maintenance
strategies perdata waiver training
guidelines.
Maintain contact with CDtreatment
provider to assess progress
Yes
Recommendedlong-acting
naltrexone
Continue to monitor for relapse
and maintain contact withCD
treatment provider
Ifno improvement
Is patient
pregnant
and/or has
chronic pain?
ALGORITHMICAPPROACH TO CHOOSINGTHE OPTIMAL THERAPY : Oesterle,TylerS., et al. "Medication-assistedtreatmentforopioid-usedisorder." Mayo
ClinicProceedings.Vol. 94. No. 10.Elsevier,2019.

31. Thank
You 