Opioid Use Disorder (OUD)

• The prevalence of opioid use disorder has increased significantly with the opioid epidemic (which remains ongoing) in many Western nations.
  • In the United States, 0.8% of adults surveyed met the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for OUD in the past year
  • In Canada, the prevalence estimates are not well known, but one survey estimates that 9.6% of Canadian adults who used opioid medications report some form of problematic use.^[1]
  • In Europe, opioid use disorder rates are lower than in North America, and between 0.36 to 0.44%.^[2]
• Males are more likely than females to have an opioid use disorder.^[3]
• Problems associated with opioid use usually develop in the late teens or early 20s.^[4]

• In those being treated for opioid use disorder, relapse following abstinence is common.^[5]
• Long-term mortality rates can be as high as 2% per year (due to related infections, overdose, accidents, injuries, or other general medical complications).^[6]
• Between 20 to 30% of individuals can achieve long-term abstinence.
• Individuals are at particular risk for both accidental and/or deliberate opioid overdose.^[7]

• Opioid use is also associated with opioid-induced depressive episodes, which although temporary, can be intense enough to cause suicide attempt, and completed suicides.^[8]
• Antisocial personality disorder and conduct disorder is also more common in those with opioid use disorder.^[9]
• Marital difficulties such as divorce and job difficulties are associated with opioid use disorder.^[10]
• In some cases, there may be a forensic history associated with drug-related crimes (e.g. - burglary, robbery, larceny, possession/distribution of drugs, forgery, stolen goods).

• Chronic opioid use disorder can cause a variety of medical problems including dry mucous membranes, decreased gut motility (causing severe constipation), changes in vision (due to pupillary reconstruction).
• Individuals who inject opioids intravenously can have sclerosed veins (“track marks”) and puncture marks in the upper extremities.
  • Peripheral edema, cellulitis, abscesses, and skin lesions can also develop.^[11]
  • Tetanus and Clostridium botulinum infections are also rare but extremely serious consequences of injection opioid use.^[12]
  • Other systemic infections include bacterial endocarditis, hepatitis (up to 90% have hepatitis C), and HIV infection (anywhere between 10 to 60%).^[13]
    • Immune compromise can also lead to opportunistic infections such as tuberculosis.
  • Individuals who use heroin or other opioids intranasally (“snorting”) can develop nasal mucosal irritation and/or perforation of the nasal septum.
• Males can develop erectile disfunction from chronic use, and females can have reproductive dysfunction including irregular menstruation.^[14]

• Impulsivity and novelty seeking are temperamental traits that increase the risk for any substance use disorder including for opioids.^[15]

A problematic pattern of opioid use leading to clinically significant impairment or distress, as manifested by at least 2 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.
6. Continued 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 taking opioids solely under appropriate medical supervision.

• Opioid use disorder is characterized by compulsive, prolonged self administration of opioids for no legitimate medical purpose or, if it is for a medical condition that requires opioid treatment it is used in significant excess of the amount needed for that condition.^[16]
• The dependence on opioids can be so intense that daily activities are planned around the obtaining and administration of opioids.^[17]
• Opioids may be purchased via the illegal market or obtained from a physician (or multiple) via falsification or exaggeration of medical problems.^[18]
• Most with opioid use disorder have significant tolerance and experience withdrawal when opioids are abruptly stopped.
• Even after stopping opioids, intense cravings can occur even if seeing drug-related stimuli (e.g. - seeing powder-like substances that resemble heroin).
  • These cravings can contribute significantly to relapse.^[19]
• Common side effects of opioids include constipation,^[20] sedation, respiratory depression, dizziness, nausea, and vomiting.

Opioids are a class of substances that bind to the opioid receptors, including Mu1 (μ1), Mu2 (μ2), Delta (δ), Kappa (κ). It is commonly used as an analgesic to treat pain, but is frequently a substance of abuse. Common opioids include morphine, codeine, hydromorphone, methadone, and drugs of abuse like heroin. They can be classified on the basis of their chemical structure as:

1. Opium alkaloids (codeine, morphine)
2. Semisynthetic derivatives of the natural alkaloids (hydrocodone, hydromorphone, oxycodone, buprenorphine, diamorphine [heroin])
3. Synthetic opioids
   • Anililopiperidines (fentanyl, alfentanil, sufentanil, remifentanil, carfentanil)
   • Diphenylpropylamine derivatives (propoxyphene, dextropropoxyphene, methadone, diphenoxylate, loperamide)
   • Others (pentazocine, butorphanol, nalbupine, levorphanol, tramadol)
4. Opioid antagonists (naloxone and naltrexone).

• Heroin (“H,” “china white,” “dope,” “junk,” “smack”) is an opioid made from morphine, a natural substance taken from the seed pod of the various opium poppy plants grown in Southeast and Southwest Asia, Mexico, and Colombia.
• It is most often used intravenously, smoked, or used intranasally
• Heroin can be a white or brown powder, or a black sticky substance known as black tar heroin.
• Using heroin with crack cocaine is a practice known as speedballing.

• There are numerous screening tools for opioid use disorder. See the above links for more details.

• Like with all substance use disorders, there is a complex interplay between biological, social, psychological, and cultural factors.

• Opioid-induced mental disorders
  • Opioid-induced disorders can include depressed mood that resemble primary depressive disorders (e.g. - persistent depressive disorder, major depressive disorder). However, opioids are less likely to produce symptoms of mental change than other drugs of abuse. Opioid intoxication and opioid withdrawal are different from other opioid-induced disorders (e.g. - opioid-induced depressive disorder, with onset during intoxication) because the symptoms in opioid-induced disorders predominate the clinical presentation and are severe enough to warrant additional independent clinical attention.
• Other substance intoxication
  • Alcohol intoxication and sedative, hypnotic, or anxiolytic intoxication can resemble an opioid intoxication. The absence of pupillary constriction or the lack of a response to naloxone, can suggest these alternative diagnoses. In some cases, however, intoxication can be due both to opioids and to alcohol or other sedatives, and naloxone will only reverse some sedative effects.
• Other withdrawal disorders
  • The anxiety and restlessness associated with opioid withdrawal resemble symptoms seen in sedative-hypnotic withdrawal. However, opioid withdrawal also has rhinorrhea, lacrimation, and pupillary dilation, which are not seen in sedative-type withdrawal. Dilated pupils are also present in hallucinogen intoxication and stimulant intoxication, just like with opioid withdrawal. However, other signs or symptoms of opioid withdrawal, such as nausea, vomiting, abdominal cramps, diarrhea, rhinorrhea, and/or lacrimation are not present.

• Urine drug screens will often be positive for opioids.
  • Generally, the use of heroin, morphine, codeine, oxycodone, propoxyphene will still show up in urine screens 12 to 36 hours after opioid use.^[22]
  • Fentanyl is not detected with standard tests but can be identified by comprehensive assays.
  • Methadone, buprenorphine (or buprenorphine/naloxone combination), and LAAM (L-alpha-acetylmethadol) require special testing, and thus will not show up as a positive result on routine tests.
    • Opioid replacement therapies can be detected between several days to more than 1 week.
  • Laboratory evidence of the presence of other substances (e.g., co caine, marijuana, alcohol, amphetamines, benzodiazepines) is common.^[23]
• Intravenous opioid users should have routine investigations for hepatitis A, B, and C, and HIV
• Liver function tests may also show transaminitis due to hepatitis or from toxic liver injury due to contaminants mixed in injected opioids.

• Given the various medical comorbidities associated with opioid use disorder, individuals with chronic use should have an examination for chronic intravenous use (“track marks”) or recent injection sites throughout the body
• The nasal septum should be examined for evidence of perforation
• A cardiovascular exam should focus on heart murmurs, which may indicate subacute bacterial endocarditis.
• Lymphadenopathy may suggest early viral infection such as with HIV.
• A hepatic exam should be done to look for enlargement, which may indicate acute hepatitis.

• Don't forget about decreased tolerance if a patient has not been on opioids for a while! If restarting opioids, start again at a lower dose then taper up.
• Opioid withdrawal can often be extremely uncomfortable, but withdrawal by itself is not fatal. However, there are many associated complications that can be fatal such as suicide, accidental overdose (if opioids are taken after a period of abstinence and the individual loses tolerance), exacerbation of respiratory issues, and psychiatric comorbidity.
• Withdrawal symptoms typically appear at 72 hours after last use. Common symptoms includes tachycardia, sweating, mydriasis (pupil dilation), myalgia, rhinorrhea, piloerection, GI symptoms (nausea, vomiting, stomach cramps, diarrhea), low mood/anxiety, tremors, and intense cravings.

• The mainstay of opioid use disorder treatment with opioid replacement therapies, most commonly with methadone and buprenorphine/naloxone.

• Evidence-based therapies for opioid use disorder include motivational interviewing, case management, psychoeducation, peer support groups (e.g. - Narcotics Anonymous)