SUBSTANCE USE

DISORDERS
OPIODS AND OTHER DEPRESSANTS
PSYCHIATRY LECTURE SERIES 23-05-2024
• FACILITATOR-DR.ONGECHA
• PRESENTERS Ali Noor UMB/20-A/294
• Muzamil Saman UMB/20-A/336
• Gideon Chala UMB/20-A/314
• John Abur UMB/20-A/320
• Lauryne Chemutai UMB/20-A/326
• Joseph KarisaUMB/20-A/337
• Romario Omondi UMB/20-A/348
• Christine Wangui UMB/20-A/305
OUTLINE
• Introduction
• Basics of pharmacology of opioids
• Opioids use disorders
• Opioids intoxication
• Opioids withdrawal
• Other opioid disorders
• Unspecified opioid disorders
• Other depressants
INTRODUCTION
• Opioids include the natural drug opium and its derivatives, in addition to synthetic
drugs with similar actions. The natural drugs derived from opium include morphine
and codeine; the synthetic opioids include methadone, oxycodone,
hydromorphone (Dilaudid), levorphanol (Levo-Dromoran), pentazocine (Talwin),
meperidine (Demerol), and propoxyphene (Darvon). Heroin is considered a
semisynthetic drug and has the strongest euphoriant property, thus producing the
most craving.
• 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.
Prescription opioids, which are widely available, have significant abuse liability,
and continued opioid misuse can result in syndromes of abuse and dependence
and cause disturbances in mood, behavior, and cognition that can mimic other
psychiatric disorder
.
• Opioids affect opioid receptors. μ-opioid receptors mediate analgesia, respiratory
depression, constipation, and dependence; δopioid receptors mediate analgesia,
diuresis, and sedation.
• Opioids also affect dopaminergic and noradrenergic systems. Dopaminergic
reward pathways mediate addiction.
• Heroin is more lipid-soluble than morphine and more potent. It crosses the blood–
brain barrier more rapidly, has a faster onset of action, and is more addictive.
OPIOIDS USE DISORDER
• DIAGOSTIC CRITERIA –DSM-5
• A problematic pattern of opioid use leading to clinically significant impairment or
distress, as manifested by at least two of the following, occurring within a 12-month
period
• : 1. Opioids are often taken in larger amounts or over a longer period than was intended.
• 2. There is a persistent desire or unsuccessful efforts to cut down or control opioid use.
• 3. A great deal of time is spent in activities necessary to obtain the opioid, use the opioid,
or recover from its effects.
• 4. Craving, or a strong desire or urge to use opioids.
• 5. Recurrent opioid use resulting in a failure to fulfill major role obligations at work,
school, or home
.

• 6Continued opioid use despite having persistent or recurrent social or

interpersonal problems caused or exacerbated by the effects of opioids.
• 7. Important social, occupational, or recreational activities are given up or reduced
because of opioid use.
• 8. Recurrent opioid use in situations in which it is physically hazardous.
• 9. Continued opioid use despite knowledge of having a persistent or recurrent
physical or psychological problem that is likely to have been caused or
exacerbated by the substance.
.
• 10.Tolerance, as defined by either of the following:
• a. A need for markedly increased amounts of opioids to achieve intoxication or
desired effect.
• b. A markedly diminished effect with continued use of the same amount of an
opioid. Note: This criterion is not considered to be met for those taking opioids solely
under appropriate medical supervision.
• 11. Withdrawal, as manifested by either of the following:
• a. The characteristic opioid withdrawal syndrome (refer to Criteria A and B of the
criteria set for opioid withdrawal).
• b.Opioids (or a closely related substance) are taken to relieve or avoid withdrawal
symptoms.
• Note: This criterion is not considered to be met for those individuals taking opioids
solely under appropriate medical supervision
PREVALENCE
• The 12-month prevalence of opioid use disorder is approximately 0.37% among
adults age 18 years and older in the community population.
• This may be an underestimate because of the large number of incarcerated
individuals with opioid use disorders
• . Rates are higher in males than in females (0.49% vs. 0.26%), with the male-to-
female ratio typically being 1.5:1 for opioids other than heroin (i.e., available by
prescription) and 3:1 for heroin.
• Female adolescents may have a higher likelihood of developing opioid use
disorders.
• .
CONT…..
• The prevalence decreases with age, with the prevalence highest (0.82%) among
adults age 29 years or younger, and decreasing to 0.09% among adults age 65
years and older.
• Among adults, the prevalence of opioid use disorder is lower among African
Americans at 0.18% and overrepresented among Native Americans at 1.25%. It is
close to average among whites (0.38%), Asian or Pacific Islanders (0.35%), and
Hispanics (0.39%).
• Heroin is exclusively a drug of abuse and is most commonly used by patients of
lower socioeconomic status, who often engage in criminal activities to pay for
drugs. Of note, prescription opiate abuse is fast becoming a major public health
problem
ETIOLOGY
• PSYCHOSOCIAL FACTORS
• Low socio-economic status
• Social separation-most of urban heroin users are children of single parents or
divorced parents
• BIOLOGICAL AND GENETIC FACTORS
• Monozygotic twins are more likely than dizygotic twins to be concordant for opiod
dependence
TREATMENT
• Methadone
• Long-acting opioid receptor agonis
• Administered once daily. Significantly reduces morbidity and mortality in opioid-
dependent persons. “Gold standard” treatment in pregnant opioid-dependent
women
• Restricted to legally licensed substance abuse treatment programs. Can cause QTc
interval prolongation; thus, screening electrocardiogram is indicated, particularly
for certain patients such as those with cardiac disease
.
• Naltrexone
• Competitive opioid antagonist, precipitates withdrawal if used within 7 days of
heroin use
• Either daily orally or monthly depot injection. It is a good choice for highly
motivated patients such as health care professionals
• Compliance is an issue.
.

• Buprenorphine
• Partial opioid receptor agonist
• Sublingual preparation that is safer than methadone, as its effects reach a plateau
and make overdose unlikely.
• Comes as Suboxone, which contains buprenorphine and naloxone; more
commonly used, as this preparation prevents intoxication from intravenous
injection.
• Available by prescription from office-based physicians.
OPIOID INTOXICATION
• Clinical Presentation
• Opioid intoxication causes drowsiness, nausea/vomiting, constipation, slurred
speech, constricted pupils, seizures, and respiratory depression, which may
progress to coma or death in overdose.
• Meperidine and monoamine oxidase inhibitors taken in combination may cause
the serotonin syndrome: hyperthermia, confusion, hyper- or hypotension, and
muscular rigidity
DIAGNOSTIC CRITERIA-DSM5
• A. Recent use of an opioid.
• B. Clinically significant problematic behavioral or psychological changes (e.g., initial
euphoria followed by apathy, dysphoria, psychomotor agitation or retardation,
impaired judgment) that developed during, or shortly after, opioid use.
• C. Pupillary constriction (or pupillary dilation due to anoxia from severe overdose)
and one (or more) of the following signs or symptoms developing during, or shortly
after, opioid use: 1. Drowsiness or coma. 2. Slurred speech. 3. Impairment in
attention or memory.
• D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication with another
substance.
SPECIFY IF
• With perceptual disturbances: This specifier may be noted in the rare instance in
which hallucinations with intact reality testing or auditory, visual, or tactile
illusions occur in the absence of a delirium. Coding note: The ICD-9-CM code is
292.89. The ICD-10-CM code depends on whether or not there is a comorbid
opioid use disorder and whether or not there are perceptual disturbances
TREATMENT
• Ensure adequate airway, breathing, and circulation.
• Ventilatory support may be required
• In overdose, administration of naloxone (opioid antagonist) will improve
respiratory depression but may cause severe withdrawal in an opioiddependent
patient
• Immediately administer 0.8 mg of naloxone (Narcan) (0.01 mg/kg for neonates),
an opioid antagonist, intravenously and wait 15 minutes.
• If no response, give 1.6 mg intravenously and wait 15 minutes.
If still no response, give 3.2 mg intravenously and suspect another diagnosis.. .
OPIOIDS WITHDRAWAL
• SYMPTOMS
• Sweating, dilated pupils, piloerection (―cold turkey‖), fever, rhinorrhea, yawning,
nausea, stomach cramps, diarrhea (―flu-like‖ symptoms).
• While not life threatening, abstinence in the opioid-dependent individual leads to
an unpleasant withdrawal syndrome characterized by dysphoria, insomnia,
lacrimation, rhinorrhea, yawning, weakness, sweating, piloerection,
nausea/vomiting, fever, dilated pupils, abdominal cramps, arthralgia, myalgia,
hypertension, tachycardia, and craving.
PREGANT WOMAN WITH OPIOID
DEPEDENCE
• Neonatal addiction is a significant problem . About ¾ of all infants born to
addicted mothers experience withdrawal symptoms.
• Neonatal withdrawal- unlike in adults, opioid withdrawal is harzardious to fetus
and can lead to miscarriage or fetal death
• Maintaining a pregnant with opioid dependence on a low dose methadone (10-40
mg OD) may be the least harzadoius course to follow.At this dose neonatal
withdrawal is usually mild and can b e managed with low doses of
PAREGORIC(drug indicated for diarrhea)
DIAGNOSTIC CRITERIA –DSM5
• A .Presence of either of the following:
• 1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e., several weeks
or longer).
• 2. Administration of an opioid antagonist after a period of opioid use
• . B. Three (or more) of the following developing within minutes to several days after Criterion A: 1.
Dysphoric mood. 2. Nausea or vomiting.
• 3. Muscle aches.
• 4. Lacrimation or rhinorrhea.
• 5. Pupillary dilation, piloerection, or sweating 6. Diarrhea. 7. Yawning. 8. Fever. 9. Insomnia
• C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social,
occupational, or other important areas of functioning.
• D. The signs or symptoms are not attributable to another medical condition and are not better
explained by another mental disorder, including intoxication or withdrawal from another substance.
.•
Differential Diagnosis
• Other withdrawal disorders. The anxiety and restlessness associated with opioid
withdrawal resemble symptoms seen in sedative-hypnotic withdrawal. However,
opioid withdrawal is also accompanied by rhinorrhea, lacrimation, and pupillary
dilation, which are not seen in sedative-type withdrawal.
• Other substance intoxication. Dilated pupils are also seen in hallucinogen
intoxication and stimulant intoxication. However, other signs or symptoms of
opioid withdrawal, such as nausea, vomiting, diarrhea, abdominal cramps,
rhinorrhea, and lacrimation, are not present.
• Other opioid-induced disorders. Opioid withdrawal is distinguished from the
other opioid-induced disorders (e.g., opioid-induced depressive disorder, with
onset during withdrawal) because the symptoms in these latter disorders are in
excess of those usually associated with opioid withdrawal and meet full criteria for
the relevant disorder.
TREATMENT
• Treatment includes:
• Moderate symptoms: Symptomatic treatment with clonidine (for autonomic
signs and symptoms of withdrawal), nonsteroidal antiinflammatory drugs
(NSAIDs) for pain, dicyclomine for abdominal cramps, etc.
• Severe symptoms: Detox with buprenorphine or methadone.
• Monitor degree of withdrawal with COWS (Clinical Opioid Withdrawal Scale),
which uses objective measures (i.e., pulse, pupil size, tremor) to assess withdrawal
severity.
OTHER RELATED DISORDERS
• Opioid-induced psychotic disorder Opioid-induced psychotic disorder can begin
during opioid intoxication. Clinicians can specify whether hallucinations or
delusions are the predominant symptoms.
• . Opioid-induced mood disorder Opioid-induced mood disorder 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. A
person coming to psychiatric attention with opioid-induced mood disorder usually
has mixed symptoms, combining irritability, expansiveness, and depression.
• Opioid-induced sleep disorder and opioid-induced sexual dysfunction
Hypersomnia is likely to be more common with opioids than insomnia. The most
common sexual dysfunction is likely to be impotence.
Other Depressants
• Sedative-Hypnotics
• Agents in the sedative-hypnotics category include benzodiazepines, barbiturates,
zolpidem, zaleplon, gamma-hydroxybutyrate (GHB), meprobamate, and others.
These medications, especially benzodiazepines, are highly abused , as they are
more readily available than other drugs such as cocaine or opioids.
• The drugs associated with this group have a sedative or calming effect and are also
used as antiepileptics, muscle relaxants, and anesthetics
.

• Benzodiazepines (BDZs):
• Commonly used in the treatment of anxiety disorders.
• Easily obtained via prescription from physician offices and emergency departments.
• Potentiate the effects of GABA by modulating the receptor, thereby ↑ the frequency
of chloride channel opening.
• Barbiturates:
• Used in the treatment of epilepsy and as anesthetics.
• Potentiate the effects of GABA by binding to the receptor and ↑ the duration of
chloride channel opening.
• At high doses, barbiturates act as direct GABA agonists, and therefore have a lower
margin of safety relative to BDZs. They are synergistic in combination with BDZs (as
well as other CNS depressants such as alcohol); respiratory depression can occur as a
complication.
.

• Epidemiology.
• About 6% of persons have used these drugs illicitly, usually by under age 40.
• The highest prevalence of illicit use is between the ages of 26 to 35, with a female-
to-male ratio of 3:1 and a white-to-black ratio of 2:1. Barbiturate abuse is more
common in those over age 40.
.
• DIAGNOSTIC CRITERIA
• . A problematic pattern of sedative, hypnotic, or anxiolytic use leading to clinically
significant impairment or distress, as manifested by at least two of the following,
occurring within a 12-month period:
• 1. Sedatives, hypnotics, or anxiolytics are often taken in larger amounts or over a
longer period than was intended.
• 2. There is a persistent desire or unsuccessful efforts to cut down or control sedative,
hypnotic, or anxiolytic use.
• 3. A great deal of time is spent in activities necessary to obtain the sedative, hypnotic,
or anxiolytic; use the sedative, hypnotic, or anxiolytic; or recover from its effects.
• 4. Craving, or a strong desire or urge to use the sedative, hypnotic, or anxiolytic
• . 5. Recurrent sedative, hypnotic, or anxiolytic use resulting in a failure to fulfill major
role obligations at work, school, or home (e.g., repeated absences from work or poor
work performance related to sedative, hypnotic, or anxiolytic use; sedative-, hypnotic-,
or anxiolytic-related absences, suspensions, or expulsions from school; neglect of
children or household)
 • 6. Continued sedative, hypnotic, or anxiolytic use despite having persistent or
.

recurrent social or interpersonal problems caused or exacerbated by the effects of

sedatives, hypnotics, or anxiolytics (e.g., arguments with a spouse about
consequences of intoxication; physical fights).
• 7. Important social, occupational, or recreational activities are given up or reduced
because of sedative, hypnotic, or anxiolytics
• 8. Recurrent sedative, hypnotic, or anxiolytic use in situations in which it is
physically hazardous (e.g., driving an automobile or operating a machine when
impaired by sedative, hypnotic, or anxiolytic use)
• . 9. Sedative, hypnotic, or anxiolytic 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 sedative, hypnotic, or anxiolytic.
.

• 10. Tolerance, as defined by either of the following:

• a. A need for markedly increased amounts of the sedative, hypnotic, or anxiolytic
to achieve intoxication or desired effect.
• b. A markedly diminished effect with continued use of the same amount of the
sedative, hypnotic, or anxiolytic. Note: This criterion is not considered to be met for
individuals taking sedatives, hypnotics, or anxiolytics under medical supervision.
• 11. Withdrawal, as manifested by either of the following:
• a. The characteristic withdrawal syndrome for sedatives, hypnotics, or anxiolytics
(refer to Criteria A and B of the criteria set for sedative, hypnotic, or anxiolytic
withdrawal, pp. 557–558).
• b. Sedatives, hypnotics, or anxiolytics (or a closely related substance, such as
alcohol) are taken to relieve or avoid withdrawal symptoms.
• Note: This criterion is not considered to be met for individuals taking sedatives,
hypnotics, or anxiolytics under medical supervision.
INTOXICATION SEDATIVE-HYPNOTICS
• Clinical Presentation
• Intoxication with sedatives produces drowsiness, confusion, hypotension, slurred
speech, incoordination, ataxia, mood lability, impaired judgment, nystagmus,
respiratory depression, and coma or death in overdose.
• Symptoms are synergistic when combined with EtOH or opioids/ narcotics.
• Long-term sedative use may → dependence and may cause depressive
symptoms
.• Diagnostic Criteria
• A. Recent use of a sedative, hypnotic, or anxiolytic.
• B. Clinically significant maladaptive behavioral or psychological changes (e.g.,
inappropriate sexual or aggressive behavior, mood lability, impaired judgment)
that developed during, or shortly after, sedative, hypnotic, or anxiolytic use.
• C. One (or more) of the following signs or symptoms developing during, or shortly
after, sedative, hypnotic, or anxiolytic use: 1. Slurred speech. 2. Incoordination. 3.
Unsteady gait. 4. Nystagmus. 5. Impairment in cognition (e.g., attention,
memory). 6. Stupor or coma.
• D. The signs or symptoms are not attributable to another medical condition and
are not better explained by another mental disorder, including intoxication with
another substance.
TREATMENT
• Maintain airway, breathing, and circulation. Monitor vital signs.
• Activated charcoal and gastric lavage to prevent further gastrointestinal
absorption (if drug was ingested in the prior 4–6 hours).
• For barbiturates only: Alkalinize urine with sodium bicarbonate to promote renal
excretion.
• For benzodiazepines only: Flumazenil in overdose.
• Supportive care—improve respiratory status, control hypotension
WITHDRAWAL OF SEDATIVE-
HYPNOTICS
• Abrupt abstinence after chronic use can be life threatening. While physiological
dependence is more likely with short-acting agents, longer-acting agents can also
cause dependence and withdrawal symptoms
• CLINICAL PRESENTATION
• Signs and symptoms of withdrawal are the same as these of EtOH withdrawal.
Tonic-clonic seizures may occur and can be life threatening
Diagnostic criteria-DSM-5
• Diagnostic Criteria A. Cessation of (or reduction in) sedative, hypnotic, or anxiolytic use that
has been prolonged. B. Two (or more) of the following, developing within several hours to a
few days after the cessation of (or reduction in) sedative, hypnotic, or anxiolytic use
described in Criterion A:
• 1. Autonomic hyperactivity (e.g., sweating or pulse rate greater than 100 bpm).
• 2. Hand tremor.
• 3. Insomnia.
• 4. Nausea or vomiting.
• 5. Transient visual, tactile, or auditory hallucinations or illusions.
• 6. Psychomotor agitation.
• 7. Anxiety.
 .

• 8. Grand mal seizures.

• C. The signs or symptoms in Criterion B cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
• D. The signs or symptoms are not attributable to another medical condition and
are not better explained by another mental disorder, including intoxication or
withdrawal from another substance.
• Specify if: With perceptual disturbances: This specifier may be noted when
hallucinations with intact reality testing or auditory, vis
TREATMENT
• Guidelines for Treatment of Benzodiazepine Withdrawal
• 1. Evaluate and treat concomitant medical and psychiatric conditions.
• 2. Obtain drug history and urine and blood samples for drug and ethanol assay.
• 3. Determine required dose of benzodiazepine or barbiturate for stabilization,
guided by history, clinical presentation, drug-ethanol assay, and (in some cases)
challenge dose.
• 4. Detoxification from supratherapeutic dosages:
• a. Hospitalize if there are medical or psychiatric indications, poor social supports,
or polysubstance dependence or the patient is unreliable. b. Some clinicians
recommend switching to longer-acting benzodiazepine for withdrawal (e.g.,
diazepam, clonazepam); others recommend stabilizing on the drug that the
patient was taking or on phenobarbital.
.

• . b. Some clinicians recommend switching to longer-acting benzodiazepine for

withdrawal (e.g., diazepam, clonazepam); others recommend stabilizing on the
drug that the patient was taking or on phenobarbital.
• c. After stabilization, reduce dosage by 30% on the second or third day and
evaluate the response, keeping in mind that symptoms occur sooner after
decreases in benzodiazepines with short elimination half-lives (e.g., lorazepam)
than after decreases in those with longer elimination half-lives (e.g., diazepam).
• d. Reduce dosage further by 10–25% every few days if tolerated.
• e. Use adjunctive medications if necessary; carbamazepine, β-adrenergic receptor
antagonists, valproate, clonidine, and sedative antidepressants have been used,
but their efficacy in the treatment of the benzodiazepine abstinence syndrome
has not been established.
• 5. Detoxification from therapeutic dosages:
.• a. Initiate 10–25% dose reduction and evaluate response.
• b. Dose, duration of therapy, and severity of anxiety influence the rate of taper
and need for adjunctive medications.
• c. Most patients taking therapeutic doses have uncomplicated discontinuation.
• 6. Psychological interventions may assist patients in detoxification from
benzodiazepines and in the long-term management of anxiety.
REFERENCES
• DSM-5
• First Aid psychiatric textbook
• Review of psychiatry textbook
• Kaplan and Sadocks textbook for psychiatry
THANK YOU
.