This is slide about opioid use disorder and how it is treated in Nepal

1. Substance Use Disorders
(Opioid Use Disorder)
Dr. Dikshya upreti
PG Resident
Department of Psychiatry
Nepal

2. Terminology
Dependence: A cluster of physiological, behavioral, and cognitive phenomena
in which the use of a substance or a class of substances takes on a much higher
priority for a given individual than other behaviors that once had greater value.
Behavioral dependence: Substance-seeking activities and related evidence of
pathological use patterns are emphasized.
Physical dependence refers to physical (physiological) effects of multiple
episodes of substance use.
Psychological dependence, also referred to as habituation, is characterized by
a continuous or intermittent craving (i.e., Intense desire) for the substance to
avoid a dysphoric state.

3. • Abuse: Use of any drug, usually by self-administration, in a manner that
deviates from approved social and medical patterns.
• Misuse: Similar to abuse, but applies to drugs prescribes by physician that are
not used properly
• Addiction: The repeated and increased use of a substance, the deprivation of
which gives rise to symptoms of distress and an irresistible urge to use the
agent again and which leads also to physical and mental deterioration.
• Intoxication: A transient condition following the administration of alcohol or
other psychoactive substance, resulting in disturbances in level of
consciousness, cognition, perception, affect or behaviour, or other
psychophysiological functions and responses.

4. • Withdrawal: A group of symptoms of variable clustering and severity
occurring on absolute or relative withdrawal of a substance after repeated,
and usually prolonged and/or high dose, use of that substance.
• Tolerance: Phenomenon in which, after repeated administration, a given dose
of drug produces a decreased effect or increasingly larger doses must be
administered to obtain the effect observed with the original dose.
• Cross-tolerance/cross dependence: Refers to the ability of one drug to be
substituted for another, each usually producing the same physiological and
psychological effect.
• Neuroadaptaion: Neurochemical or neurophysiological changes in the body
that result from the repeated administration of a drug.
• Codependence: Term used to refer to family members affected by or
influencing the behavior of the substance abuser.

5. Substance Use Disorder (According to DSM 5)
A maladaptive pattern of substance use leading to clinically significant
impairment or distress, as manifested by 2 (or more) of the following,
occurring within a 12-month period:
1.Recurrent substance use resulting in a failure to fulfill major role obligations
at work, school, or home
2.Recurrent substance use in situations in which it is physically hazardous
3.Continued substance use despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of the substance
4.Tolerance
5.Withdrawal

6. Substance Use Disorder
6. the substance is often taken in larger amounts or over a longer period than
was intended
7. there is a persistent desire or unsuccessful efforts to cut down or control
substance use
8. a great deal of time is spent in activities necessary to obtain the substance, use
the substance, or recover from its effects
9. important social, occupational, or recreational activities are given up or
reduced because of substance use
10. the substance use is continued despite knowledge of having a persistent or
recurrent physical or psychological problem that is likely to have been caused or
exacerbated by the substance
11. craving or a strong desire or urge to use a specific substance.

7. Changes from DSM IV to DSM 5 and ICD 10 to ICD 11
• A significant change with DSM-5 is that there no longer are separate
diagnoses of substance abuse and substance dependence.
• DSM-5 essentially merges the criteria for these two diagnoses, and has
added another criterion related to craving (which was not in either set of
diagnostic criteria for DSM-IV). These changes have resulted in essentially
eleven criteria that can be used to make a diagnosis of an “SUD,”.
• Disorders due to substance use or addictive behaviors in ICD 11
• These options contrast with ICD-10 when only Substance Dependence and
Harmful Substance Use were available.

9. Opioid-Related Disorders
• Opiate: It refers to natural alkaloids derived directly from the poppy plant.
• Opioids: they are broader class of xenobiotics that are capable of producing
opium-like effects on binding to opioid receptors.
• Endogenous neural polypeptides such as endorphins and enkephalins are
natural opioids.
• Opioids have been used for analgesic and other medicinal purposes for
thousands of years, but they also have a long history of misuse for their
psychoactive effects.

10. • Opium is derived from Papaver somniferous, an annual plant with white or
red flowers growing on a central bulbous pod.
• Toxic part: Unripe fruit capsule, latex juice
• Latex is obtained by lacerating the immature seed pods; the latex leaks out
and dried to a sticky brown residue.
• Seeds are non- poisonous and are called ‘khaskhas’ which constitutes a
condiment in cooking.

11. Active principles
1) Phenanthrene derivatives:
A) Natural alkaloids
• Morphine (10%): White powder/crystals, bitter taste and alkaline in
reaction)
• Codeine (0.5%)
• Thebaine(0.3%)
B) Semi-synthetic opioids: They are produced by chemical modification
of an opiate and includes hydromorphone, diacetylmorphine (heroine,
brown sugar or smack), oxymorphone and oxycodone.

12. C) Synthetic opioids: These compounds are not derived from opiate, but binds to
an opioid receptor and produce opioid effects clinically.
It includes methadone, fentanyl, pentazocine, tramadol and meperidine
(pethidine).
2) Benzy-isoquinolone derivatives (no significant CNS effects)
1) Papaverine (1%)
2) Noscapine (6%)

13. Mechanism of action
• Opioids act as neurotransmitters released from neurons that arise in the
arcuate nucleus and project both to the VTA and to the nucleus accumbens,
and release enkephalin.
• Naturally occurring endogenous opioids act upon a variety of receptor
subtypes.
• The three most important receptor subtypes are:
µ- receptor
δ- receptor
κ-opioid receptor

14. Mechanism of action

15. Mechanism of action
• The brain makes a variety of its own endogenous opioid-like substances,
sometimes referred to as the “brain’s own morphine.”
• These are all peptides derived from precursor proteins called pro-
opiomelanocortin (POMC), proenkephalin, and prodynorphin.

16. • Exogenous opioids in the form of pain relievers (such as oxycodone,
hydrocodone, and many others) or drugs of abuse (such as heroin) are also
thought to act as agonists at µ-, δ-, and κ-opioid receptors, particularly at µ sites.
• The primary effects of the opioid drugs are
mediated via the opioid receptors, which
were discovered in the first half of the
1970s (published in 1973).
μ-opioid
receptors
κ-opioid
receptors
δ- receptor
• Analgesia
• Respiratory
depression
• Constipation
• Drug
dependence
Analgesia
Diuresis
Sedation
Analgesia

17. Epidemiology
• More than 246 million people worldwide are estimated to have used illicit
drugs and, of these, over 27 million are considered to be problem drug users –
people who either suffer from a drug use disorder or are dependent on illicit
drugs. Nearly half of these – 12.2 million people – inject drugs.
• In Nepal, substance use by medical students ranges from 12.8% to 15% for
cannabis, 4% for hashish, 1.12% for lysergic acid diethylamide, 0.22% for
opioids, and 0.22% for amphetamine.
Khanal P, Ghimire RH, Gautam B, Dhungana SK, Parajuli P, Jaiswal AK, et al. Substance use among
medical students in Kathmandu valley. J Nepal Med Assoc. 2010;49:267–71.

18. Etiology
Psychosocial Factors:
• Opioid dependence is greater low socioeconomic status than in higher SES
groups.
• About 50 percent of urban heroin users are children of single parents or
divorced parents and are from families in which at least one other member
has a substance related disorder.
• Higher in children with evidence of behavioral problems in school or other
signs of conduct disorder.

19. Biological and Genetic Factors
• Individuals who abuse a substance from any category are more likely to abuse
substances from other categories.
• Monozygotic twins are more likely than dizygotic twins to be concordant for
opioid dependence.

20. PsychodynamicTheory
• In psychoanalytic literature, the behavior of persons addicted to narcotics has
been described in terms of libidinal fixation, with regression to pregenital, oral,
or even more archaic levels of psychosexual development.

21. The opioid-induced disorders include such common phenomena as opioid use
disorder:
1. Opioid intoxication
2. Opioid withdrawal
3. Opioid-induced sleep disorder
4. Opioid induced sexual dysfunction

22. • Heroin, the most commonly abused opioid, is more lipid soluble than
morphine. This allows it to cross the blood–brain barrier faster and have a
more rapid and pleasurable onset than morphine.
• Heroin was first introduced as a treatment for morphine addiction, but heroin,
in fact, is more dependence producing than morphine.
• Codeine, which occurs naturally as about 0.5 percent of the opiate alkaloids in
opium, is absorbed easily through the gastrointestinal tract and is
subsequently transformed into morphine in the body.

23. Tolerance and Dependence
• Tolerance to all actions of opioid drugs does not develop uniformly. Tolerance
to some actions of opioids can be so high that a 100-fold increase in dose is
required to produce the original effect.
• For example, terminally ill cancer patients may need 200 to 300 mg a day of
morphine, whereas a dose of 60 mg can easily be fatal to an opioid-naive
person.

24. Comorbidity
• About 90 percent of persons with opioid dependence have an additional
psychiatric disorder.
• The most common comorbid psychiatric diagnoses are major depressive
disorder, alcohol use disorders, antisocial personality disorder, and anxiety
disorders.
• About 15 percent of persons with opioid dependence attempt to commit
suicide at least once.

25. Diagnosis of Opioid Use Disorder
• Opioid use disorder is a pattern of maladaptive use of an opioid drug, leading
to clinically significant impairment or distress and occurring within a 12-
month period.

26. Opioid Intoxication

27. Opioid Intoxication
• Delirium: Opioid intoxication delirium is most likely to happen when opioids
are used in high doses, are mixed with other psychoactive compounds, or are
used by a person with preexisting brain damage or a central nervous system
(CNS) disorder (e.g., epilepsy).
• Opioid-Induced Psychotic Disorder: It can begin during opioid intoxication.
Hallucinations or delusions are the predominant symptoms.
• Opioid-Induced Mood Disorder: It can begin during opioid intoxication.
Opioid-induced mood disorder symptoms can have a manic, depressed, or
mixed nature, depending on a person’s response to opioids.

28. OpioidWithdrawal
• The general rule about the onset and duration of withdrawal symptoms is that
substances with short durations of action tend to produce short, intense
withdrawal syndromes and substances with long durations of action produce
prolonged, but mild, withdrawal syndromes.

29. Opioid Withdrawal Scale
• Clinical Opioid Withdrawal Scale (COWS)
• Objective Opiate Withdrawal Scale (OOWS)

30. Morphine and Heroin withdrawal syndrome
• The morphine and heroin withdrawal syndrome begins 6 to 8 hours after the
last dose, usually after a 1- to 2-week period of continuous use or after the
administration of a narcotic antagonist.
• The withdrawal syndrome reaches its peak intensity during the second or
third day and subsides during the next 7 to 10 days, but some symptoms may
persist for 6 months or longer.

31. Meperidine and Methadone withdrawal syndrome
• The withdrawal syndrome from meperidine begins quickly, reaches a peak in
8 to 12 hours, and ends in 4 to 5 days.
• Methadone withdrawal usually begins 1 to 3 days after the last dose and ends
in 10 to 14 days.

32. Adverse Effects
• The most common and most serious adverse effect associated with the
opioid-related disorders is the potential transmission of hepatitis and HIV
through the use of contaminated needles by more than one person.
• Persons can experience idiosyncratic allergic reactions to opioids, which
result in anaphylactic shock, pulmonary edema, and death if they do not
receive prompt and adequate treatment.
• Another serious adverse effect is an idiosyncratic drug interaction between
meperidine and monoamine oxidase inhibitors (MAOIs), which can produce
gross autonomic instability, severe behavioral agitation, coma, seizures, and
death.

33. Opioid Overdose
• Death from an overdose of an opioid is usually attributable to respiratory
arrest from the respiratory depressant effect of the drug.
• The symptoms of overdose include marked unresponsiveness, coma, slow
respiration, hypothermia, hypotension, and bradycardia.
• When presented with the clinical triad:
i. Coma
ii. Pinpoint pupils
iii.Respiratory depression

34. Treatment and rehabilitation
Overdose Treatment:
• The first task in overdose treatment is to ensure an adequate airway.
• Tracheopharyngeal secretions should be aspirated; an airway may be
inserted.
• The patient should be ventilated mechanically until naloxone, a specific
opioid antagonist, can be given.
• Naloxone is administered intravenously at a slow rate—initially about 0.8
mg per 70 kg of body weight.

35. Opioid dependence
• The mainstay of pharmacological management of opioid dependence is opioid
substitution treatment (OST).
• Globally, the journey of Opioid Substitution Therapy (OST) began more than
50 years back, when Dole and Nyswander used methadone to treat opioid
dependence in New York and published their seminal work in the year 1965.
• 2005: WHO listed methadone and buprenorphine : as medicine used in
substance dependence programs.
• The 2016 report on the Global Status of Harm Reduction reports that OST is
available in eighty countries.

36. History of OST in Nepal
• In 1994, the Mental Hospital Lagankhel in Patan established the first
methadone OST Programme in Nepal, which ran until 2002.
• This programme could not be continued due to lack of social support to
patients and other technical aspects.
• OST programme restarted as a pilot at the TU Teaching Hospital, Kathmandu
under leadership of the Ministry of Home with support from United Nations
Office on Drugs and Crime (UNODC) as an emergency response in 2007.

37. History of OST in Nepal
• The Ministry of Home affairs endorsed the management guidelines for Opioid
Substitution Therapy in 2013 that triggered a strategic change in OST in
Nepal by allowing OST in the private sector through the involvement of
NGOs, registered doctors, private practitioners and hospitals.
• At present time (2016), there are altogether 11 OST sites at 9 different
districts (Kathmandu, Lalitpur, Bhaktapur, Bharatpur, Kaski, Rupendehi,
Morang, Nepalgunj and Bhadrapur) throughout the country, out of which 4
are NGO ran sites and 7 are inside public hospitals.
• Total numbers of 3527 (104 female) received OST services from all OST
sites in Nepal till date and total 887 (19 female) are currently enrolled in the
programme.

38. Goals of Opioid Substitution Therapy
• To reduce or prevent withdrawal symptoms
• To reduce or eliminate non‐prescribed drug use
• To stabilize drug intake and lifestyle
• To reduce drug‐related harm (particularly injecting behavior)
• To engage and provide an opportunity to work with the patient.

39. Methadone Clinical effectiveness
• Methadone is a long‐acting opioid agonist.
• It has been shown to be an effective maintenance treatment of heroin
dependence by retaining patients in treatment and decreasing heroin use more
than non‐opioid based replacement therapy.
• Methadone is most commonly used, followed by buprenorphine. Other
agents such as slow-release oral morphine (SROM), codeine, and
even heroin, are also used, but in a limited number of countries.

40. Methadone
Methadone: first dose is (15)-25-30-(40) mg
COWS-result 3-4 hours after the first dose
• score 0: no
• score 5-12: 5mg
• score 13-24: 7.5 mg
• score 25-36 : 10mg
• score >36 score:15mg
• It may take several weeks to reach the therapeutic daily dose of 60–120mg.
• Stabilization is usually achieved within 6 weeks but may take longer.
• Challenging time: high risk of dropout

41. Methadone cautions
• Intoxication: Methadone should not be given to any patient showing signs of
intoxication, especially due to alcohol or other depressant drugs (e.g.
benzodiazepines).
• Risk of fatal overdose is greatly enhanced when methadone is taken
concomitantly with alcohol and other respiratory depressant drugs, including
benzodiazepines and pregabalin, which can increase the risk of overdose.

42. Methadone cautions
Severe hepatic/renal dysfunction:
• Metabolism and elimination of methadone may be affected, in which case the
dose or dosing interval should be adjusted accordingly against clinical
presentation.
• Because of extended plasma half‐life, the interval between assessments during
initial dosing may need to be extended.

43. Methadone maintenance has several advantages
1. First, it frees persons with opioid dependence from using injectable heroin
and, thus, reduces the chance of spreading HIV through contaminated
needles.
2. Second, methadone produces minimal euphoria and rarely causes
drowsiness or depression when taken for a long time.
3. Third, methadone allows patients to engage in gainful employment instead
of criminal activity.
The major disadvantage of methadone use is that patients remain dependent on a
narcotic.

44. • Methadone maintenance is continued until the patient can be withdrawn from
methadone, which itself causes dependence. An abstinence syndrome occurs
with methadone withdrawal, but patients are detoxified from methadone more
easily than from heroin.
• Clonidine (0.1 to 0.3 mg three to four times a day) is usually given during the
detoxification period.

45. Other Opioid Substitutes
• Buprenorphine: As with methadone and Buprenorphine, buprenorphine is an
opioid agonist approved for opioid dependence in 2002.
• Buprenorphine in a daily dose of 8 to 10 mg appears to reduce heroin use.
Buprenorphine also is effective in thrice-weekly dosing because of its slow
dissociation from opioid receptors.
• After repeated administration, it attenuates or blocks the subjective effects of
parenterally administered opioids such as heroin or morphine.
• A mild opioid withdrawal syndrome occurs if the drug is abruptly
discontinued after chronic administrations.

46. Other Opioid Substitutes
Buprenorphine
• Relative safety and ceiling effect: induction can be made fast
• Can precipitate withdrawal
• upto 8mg on day 1
• Upto 24mg(32mg)
Target-dose is the dose when a patient is comfortable
• Does not experience any withdrawal
• Does not experience craving for illicit opiates
• Does not use illicit opiates anymore.
• May last 1 year or lifelong
• End of OST considered on individual basis

47. Other Opioid Substitutes
• Levomethadyl: Levomethadyl is an opioid agonist that suppresses opioid
withdrawal. It is no longer used, however, because some patients developed
prolonged QT intervals associated with potentially fatal arrhythmias
(Torsades de pointes).

48. Buprenorphine Methadone
Receptor affinity Partial agonist at µ-opioid receptor,
antagonist at κ-receptor
Full agonist at µ, δ- κ
opioid receptor
Formulation Tablet 2 mg Liquid 0.5% (5mg/ml)
Route of administration Sublingual Oral (drinking)
Maximum dose/day 52 mg No limit
Use in pregnancy Safe Safe/First choice
Sedating effect + ++
Withdrawal in case of forced
or voluntary abrupt cessation
Mild to moderate Moderate to severe
Respiratory depression -/+ +/-
Risk of fatal overdose Very low +
retention greater retention in treatment greater drop‐out from
treatment

49. Pregnant Women with Opioid Dependence
• Neonatal addiction is a significant problem.
• About three fourths of all infants born to addicted mothers experience the
withdrawal syndrome.
• OST is the only medically recommended option to treat opioid dependence
but not Opioid withdrawal
• 2-3 rd trimester: dose might need to increase
• Contraception need to be offered to women who enter treatment for opioid
dependence
• Breastfeeding: should be recommended

50. Neonatal Withdrawal
• Although opioid withdrawal rarely is fatal for the otherwise healthy adult, it is
hazardous to the fetus and can lead to miscarriage or fetal death.
• Maintaining a pregnant woman with opioid dependence on a low dose of
methadone (10 to 40 mg daily) may be the least hazardous course to follow.
• If pregnancy begins while a woman is taking high doses of methadone, the
dosage should be reduced slowly (e.g., 1 mg every 3 days), and fetal
movements should be monitored.

51. Treatment of symptoms of opioid withdrawal
Symptom Treatment
Diarrhea Loperamide 4mg
Nausea, vomiting, stomach cramps Metoclopramide
prochlorperazine
Stomach cramps Mebeverine
Agitation, anxiety and insomnia Diazepam
Muscular pains and headaches Paracetamol, aspirin or non‐steroidal
anti‐inflammatories.

52. Psychotherapy
• Individual psychotherapy, behavioral therapy, cognitive-behavioral therapy,
family therapy, support groups (e.g., Narcotics Anonymous [NA]), and social
skills training may all prove effective for specific patients.
• Social skills training should be particularly emphasized for patients with few
social skills.
• Family therapy is usually indicated when the patient lives with family
members.

53. • Narcotic Anonymous Narcotics Anonymous is a self-help group of abstinent
drug addicts modeled on the 12- step principles of Alcoholics Anonymous
(AA).
• The outcome for patients treated in 12-step programs is generally good, but
the anonymity that is at the core of the 12-step model has made detailed
evaluation of its efficacy in treating opioid dependence difficult.

54. Education and Needle Exchange
• Although the essential treatment of opioid use disorders is encouraging
persons to abstain from opioids, education about the transmission of HIV
must receive equal attention.
• Persons with opioid dependence who use intravenous or subcutaneous routes
of administration must be taught available safe- sex practices.

55. References
• The Maudsley prescribing guidelines in psychiatry 13th edition
• Kaplan & Sadock's synopsis of psychiatry behavioral sciences/clinical
psychiatry, eleventh edition
• Stahl’s essential psychopharmacology, fourth edition
• https://health.bmz.de/ghpc/casestudies/Opioid_substitution_therapy_in_Nepal
/GHPC_Nepal_FinalWEB.pdf