Opioid Abuse and Dependence  

Part 1

Summary

- Heroin and prescription opioid abuse is a major health concern. An opioid is a synthetic or natural agent that stimulates opioid receptors and produces opium-like effects. Opiates are opioids that are naturally derived from the opium poppy (e.g., morphine). 
Commonly abused opiates include codeine, heroin, morphine, and opium.Commonly abused opioids include fentanyl, oxycontin, oxycodone, and hydrocodone.
- From a diagnostic perspective, it is imperative that to understands the difference between opioid abuse and dependence.
- Comorbid medical and psychiatric illnesses, as well as other substance abuse, should be assessed.
- Be aware of methods for screening and detection of opioid use in clinical settings.
- Evidence-based treatments include detoxification followed by maintenance therapy using opioid agonists, as well as psychosocial and supportive therapies.
- Treatment is long-term and involves modifying deeply-ingrained behaviors through use of medications and psychosocial therapies.
Definition
They are used to treat pain but may also be abused because of their euphoric effects.
Opioid abuse as a maladaptive pattern of opioid use leading to clinically significant impairment or distress occurring in personal, social, or job-related responsibilities, within a 12-month period.
Opioid dependence is characterized by a maladaptive pattern of opioid use, leading to clinically significant impairment or distress, occurring in a 12-month period, including symptoms of tolerance and withdrawal, despite knowledge that continued opioid use is the cause of these problems.
 
Classification by Diagnostic and Statistical Manual, 4th edition, text revision (DSM-IV-TR) 

A) Opioid Abuse
- Maladaptive pattern of opioid use leading to clinically significant impairment or distress in any of the following over a 12-month period:
- Failure to fulfill major job obligations at work, school, or home
- Recurrent opioid use in hazardous situations, such as driving or operating heavy machines while impaired
- Opioid-related legal problems
- Social and interpersonal problems caused by or exacerbated by opioid use.

B) Opioid Dependence
- Defined as 3 or more of the following within a 12-month period:
- Tolerance (marked increase in amount; marked decrease in effect)
- Withdrawal symptoms (after ceasing drug)
- Use of substance in larger amount and for longer period than intended
- Persistent desire or repeated unsuccessful attempts to quit
- Much time/activity to obtain and use substance and to recover from its effects
- Important social, occupational, or recreational activities given up or reduced
- Use continues despite knowledge of adverse consequences (e.g., failure to fulfill role obligations, use in physically hazardous situations).

Types of Opioids
-Opioids can be taken orally, injected, snorted, or smoked.
 
Types Include:
- Naturally occurring opium derivatives (opiates): morphine
- Partially synthetic: heroin, oxycodone, oxymorphone
- Synthetic: fentanyl, alfentanil, levorphanol, meperidine, methadone, codeine, propoxyphene, buprenorphine.

Opioids May be either short-acting or long-acting, which depends on the way they are formulated. Examples include:

- Short-acting opioids: morphine, hydromorphone, oxycodone
-Long-acting opioids: sustained-release formulations of morphine or oxycodone, transdermal fentanyl.

Diagnostic Approach

It is imperative that the physician differentiates between opioid abuse and dependence, as it is critical in decisions about initiating pharmacologic therapy (i.e., substitution or detoxification). The diagnosis of opioid abuse or dependence is clinical, and therefore a thorough history and psychiatric and medical examination, along with appropriate laboratory tests, are essential for making a diagnosis. The goal is to establish a diagnosis of opioid abuse or dependence as well as to ascertain whether there are any comorbid medical and psychiatric illnesses, or simultaneous abuse of other substances.

History

Diagnosis should be made according to the DSM-IV-TR criteria, which differentiate between opioid abuse and dependence. 
Opioid abuse
- A maladaptive pattern of opioid use leading to clinically significant impairment or distress in personal, social, or job-related responsibilities (e.g., failure to fulfill major obligations at work, school, or home) within a 12-month period.
- Failure to fulfill major job obligations at work, school, or home.
- Recurrent opioid use in hazardous situations, such as driving or operating heavy machines while impaired.
- Opioid-related legal problems.
- Social and interpersonal problems caused by or exacerbated by opioid use.

Opioid Dependence

A maladaptive pattern of opioid use, leading to clinically significant impairment or distress, including symptoms of tolerance and withdrawal, within a 12-month period, despite knowledge that continued opioid use is the cause of these problems. Defined as 3 or more of the following within a 12-month period:
- Tolerance (marked increase in amount and marked decrease in effect)
- Withdrawal symptoms (after ceasing drug)
- Use of substance in larger amount and for longer periods than intended
- Persistent desire or repeated unsuccessful attempts to quit
- Much time/activity to obtain and use substance and to recover from its effects
- Important social, occupational, or recreational activities given up or reduced
- Use continues despite knowledge of adverse consequences (e.g., failure to fulfill role obligations, use in physically hazardous situations).

According to the ICD-10 Classification of Mental and Behavioral Disorders, diagnosis of conditions due to use of opioids is categorized into 3 pathologic syndromes: 

Opioid intoxication
- There must be clear evidence of psychoactive substance at sufficiently high dose levels.
- There must be symptoms or signs of intoxication, of sufficient severity to produce disturbances in the level of consciousness, cognition, perception, affect, or behavior that are of clinical importance.
- These symptoms and signs cannot be accounted for by a medical disorder unrelated to substance abuse. 
- There must be dysfunctional behavior as evidenced by the presence of at least 1 among the following: apathy, sedation, disinhibition, psychomotor retardation, impaired attention, impaired judgment, interference with personal functioning. 
- At least 1 of the following signs, such as drowsiness, slurred speech, pupillary constriction, decreased level of consciousness, must be present. In severe acute opioid intoxication, respiratory depression, hypotension, and hypothermia will be present.

Opioid Dependence Syndrome

Three or more of the following manifestations should have occurred together for at least 1 month or, if persists <1 month, should have occurred together repeatedly within a 12-month period: 
- A strong desire or sense of compulsion to take opioids
- Impaired capacity to control substance-taking behavior in terms of its onset, termination, or levels of use
- A physiologic withdrawal state when use is reduced or ceased, or use of same substance with intention of relieving or avoiding withdrawal symptoms
- Tolerance: marked increase in amount with marked decrease in effect
- Preoccupation with opioid use: more time spent to obtain, take, or recover from effects of substance
- Persistent opioid use despite clear evidence of harmful consequences. 

Opioid Withdrawal State

There must be clear evidence of recent cessation or reduction of opioid use after repeated, and usually prolonged and/or high-dose, use of that substance. Symptoms and signs compatible with known features of withdrawal state.
 - Any 3 of the following signs must be present for opioid withdrawal state: craving for opioid drug, rhinorrhea or sneezing, lacrimation, muscle aches or cramps, abdominal cramps, nausea or vomiting, diarrhea, pupillary dilatation, piloerection, recurrent chills, tachycardia, hypertension, yawning, or restless sleep. 
- All these symptoms and signs cannot be accounted for by a medical disorder unrelated to opioid abuse. 
- While self-reporting about opioid use is important, collateral history is valuable, as drug-seeking behavior is often associated with legal and social issues the patient may not disclose.

Patients with opioid abuse or dependence may present with chronic constipation, weight loss, or symptoms of either tolerance or withdrawal. Tolerance may manifest as either blunting to the pleasurable effects of opioids, or adverse effects such as nausea and sedation. These can be seen as early as 2 to 3 days following continuous use of opioids, and the individual may seek to increase consumption of the drug to obtain similar drug-reinforcing effects.

Symptoms of withdrawal can occur immediately or up to 72 hours after the last dose of opioid, depending on the half-life of the drug concerned. Initial manifestations include sneezing, yawning, and restless sleep. More severe manifestations include nausea, vomiting, abdominal cramps, diarrhea, backache, muscle spasm, hot and cold flashes, and insomnia.

A high level of suspicion must be maintained for concurrent abuse of other drugs (marijuana, benzodiazepines, and cocaine are the most common in opioid abusers), as well as any comorbid psychiatric illnesses, such as bipolar disorder, attention deficit hyperactivity disorder (ADHD), major depression, anxiety disorders, and personality disorders.  Clinical confirmation of these diagnoses should be made by a psychiatrist in the absence of positive substance abuse on toxicology screen.

Physical Examination

The physician should look for specific signs of opioid use. Signs will depend on whether the patient is acutely intoxicated, has a more chronic problem, has overdosed, or is going through withdrawal.
- Opioid intoxication: miosis, sedation, confusion, slurred speech, memory impairment, hypotension, or shallow or slow respiration.
- Opioid abuse/dependence: miosis, sedation, or evidence of needle marks, scars, or skin necrosis at injection sites.
- Opioid overdose: unconsciousness, pinpoint pupils, apnea (<10 breaths per minute), or very slow pulse rate (<40 beats per minute).
- Opioid withdrawal: dilated pupils, excessive perspiration or lacrimation, rhinorrhea, restlessness, piloerection, aggressive behavior, tachypnea or laborious breathing, hypertension, hypotension, tachycardia, bradycardia, or other cardiac dysrhythmias. Neonates of opioid-dependent mothers often present with seizures during withdrawal.

Urine Drug Tests

A urine drug screen should be ordered initially if there is a clinical suspicion of drug use. The Drug Screen 9 (DS-9) is one of the more common, and tests for opioids (oxycodone, hydrocodone, hydromorphone, morphine, and codeine only), cocaine, marijuana, benzodiazepines, phencyclidine, amphetamines, and barbiturates. The test will report "positive" for opioids in opioid abusers; however, it will not specifically identify which opioid has been taken.

A positive urine screen should be followed by a confirmatory urine test, because certain medications (e.g., antibiotics) can interfere with the test and produce false-positive results. The opioid confirmation urine test by gas chromatography-mass spectrometry is the most specific and sensitive test for identifying opioids. This test will identify the specific opioid in the urine.

The detection times for opioids in the urine are 48 to 72 hours for most opioids, with the exception of methadone, which may be detected up to 7 days after use. A positive opioid confirmation test should lead to a comprehensive evaluation for opioid abuse or dependence if there are no legitimate prescriptions of opioids.
With technological advances, drugs of abuse, including opioids, can also be detected in other body fluids, most commonly saliva and sweat, and in hair. Despite this, urine drug tests remain the most validated and clinically acceptable tests to date.

Other Laboratory Tests

Other tests that should be ordered initially include serum electrolytes, CBC, BUN/creatinine, and LFTs. Due to the risk of associated malnutrition, it is helpful to assess hematologic function and electrolytes. LFTs and renal function are important for assessing whether medication dosing adjustments are required. Beta-hCG may be done if pregnancy is suspected.

Complications of intravenous drug use (e.g., sexually transmitted and needle-transmitted diseases including HIV, hepatitis, and endocarditis) should be investigated. Rapid plasma reagent, hepatitis serology, HIV test, and PPD test should be ordered when the clinical suspicion of injectable drug use is high. Blood cultures are indicated if there are signs or symptoms suggestive of septicemia (e.g., high fever, altered mental state, and vital sign changes) or infective endocarditis (e.g., fever with heart murmur).

Treatment Approach
There is extensive evidence to support the combination of pharmacotherapies with psychosocial treatment for optimal management of opioid dependence.  While detoxification primarily involves judicious use of medications, psychosocial support and supervision are also helpful at this stage. For longer-term treatment, pharmacologic maintenance therapies with adjunctive evidence-based psychosocial treatments are effective in retaining patients in treatment and suppressing illicit opioid use.  Assessment of patient motivation for change, and evidence of family and social support, are important while planning treatment.

Nonspecialists should consult and seek supervision from a practitioner experienced in addictions prior to prescribing pharmacotherapies to patients with opioid abuse or dependence, particularly in special populations such as teenagers, pregnant women, and older adults. In older patients, it is important to assess for cognitive impairment or dementia as that can affect treatment, compliance, and aftercare. In addition, medication doses need to be adjusted based on a patient's age, BMI, renal function, liver function, and nutritional status (albumin). Safe storage of medications is crucial to prevent accidental or intentional overdose, particularly if there are children in the household.

The levels of service for the treatment of opioid dependence should follow the guidelines established by The American Society of Addiction Medicine to determine whether a patient is appropriate for outpatient, intensive outpatient/partial hospitalization, residential/inpatient treatment, or medically-managed intensive inpatient treatment.

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