A brief refresher with useful tables, figures, and research summaries

According to Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria, a substance use disorder refers to substance use that causes significant problems, including health, disability, and behavioral symptoms that affect an individual’s life. Substance use disorders are classified as mild, moderate, or severe, depending on how many of the diagnostic criteria are met.

In this section, we review the following topics:

• Diagnostic criteria for substance use disorders

• Alcohol use disorder and withdrawal

• Opioid use disorder and withdrawal

• Stimulant intoxication and withdrawal
  
  

The DSM-5 criteria for diagnosis of a substance use disorder are listed in the following table.

The Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based method for use in community-based clinics for identification, early intervention, and treatment of substance use, abuse, and dependence on alcohol and illicit drugs.

• Screening: The SBIRT quickly assesses for at risk behavior, severity of use, and assists in predicting the levels of treatment needed and can be used in a variety of healthcare settings.

• Brief intervention: SBIRT begins with a short conversation to increase insight and awareness of use, provide feedback and advice, and motivate the patient toward behavior change.

• Referral to treatment: Once a screen is positive, referral is made for additional treatment and support services.

The estimated prevalence of 12-month alcohol use in the United States based on the DSM-5 classification is 14%. Alcohol use disorders can affect anyone, regardless of social status, age, race, or gender. More than 20% of patients in most medical settings are affected by alcohol use disorders (rates are higher in psychiatric wards, trauma wards, and burn services).

Assessment of the DSM–5 criteria for alcohol use disorder can be achieved by asking patients the following questions. The presence of at least two of these symptoms during the same 12-month period indicates a diagnosis of alcohol use disorder.

A thorough social history and detailed history of alcohol consumption is important to obtain in the evaluation of alcohol withdrawal; 50% of middle-class people with alcohol use disorders have experienced alcohol withdrawal, and the rates are much higher in the hospitalized and homeless. Fewer than 10% of patients experience seizures during withdrawal. Withdrawal seizures often occur within 36 hours after cessation of alcohol use.

In a systematic review and meta-analysis of hospitalized patients, predictors of severe alcohol withdrawal syndrome (e.g., delirium tremens and/or seizure) included prior episodes of alcohol withdrawal as well as low platelet and serum potassium levels. Death is a serious consequence of alcohol withdrawal syndrome, usually resulting from hyperthermia, cardiac arrhythmias, complications of withdrawal seizures, or concomitant medical disorders.

The following table lists criteria for diagnosing alcohol withdrawal:

The Clinical Institute Withdrawal Assessment of Alcohol scale, revised (CIWA-Ar), shown in the following table, can be used to assess presence of alcohol withdrawal and need for medication to prevent seizure:

(Source: Recognition and Management of Withdrawal Delirium [Delirium Tremens]. N Engl J Med 2014.)

Predictors of delirium during alcohol withdrawal:

• CIWA-Ar scores >15 (especially when accompanied by a systolic blood pressure >150 mm Hg or a pulse rate >100 beats per minute)

• recent withdrawal seizures

• prior withdrawal delirium or seizures

• older age

• recent misuse of other depressant agents

• concomitant medical problems, including electrolyte abnormalities (e.g., low levels of potassium, magnesium, or both); low platelet counts; and respiratory, cardiac, or gastrointestinal disease
  
  

Major treatment goals of alcohol withdrawal are to:

• control agitation

• decrease the risk of seizures

• decrease risk of injury or death

• prevent relapse
  
  

Benzodiazepines (e.g., diazepam, lorazepam, chlorazepate, chlordiazepoxide) are the mainstay of treatment. No single drug in this class has been shown to be superior to others. Required treatment doses vary widely by patient. Patients who do not respond to high doses (and are intubated) may require additional sedation.

Alternative drugs for withdrawal include phenobarbital, carbamazepine, oxcarbazepine, valproic acid, or gabapentin. Dexmedetomidine can be used as an adjunctive agent to treat delirium.

Note: Patients require high-dose, intravenous thiamine before receiving glucose-containing substances to prevent Wernicke encephalopathy. Be cautious when administering fluids because some patients may also have thiamine- or alcohol-related cardiomyopathies.

The following table describes suggested treatment of alcohol withdrawal:

(Source: Recognition and Management of Withdrawal Delirium [Delirium Tremens]. N Engl J Med 2014.)

Treatment strategies to prevent relapse of alcohol misuse include behavioral interventions and pharmacotherapies.

Behavioral interventions:

• Cognitive behavior therapy (CBT): CBT involves the use of education, relaxation techniques, and stress management aimed to address individual goals and problem-solving skills. CBT is used in the treatment of a variety of psychiatric disorders, ranging from depression to obsessive compulsive disorder and substance use disorders. This type of therapy is particularly useful in patients who are highly motivated.

• Behavioral therapies based on conditioning: These forms of psychotherapy apply classical conditioning techniques developed by Ivan Pavlov. In the context of alcohol misuse, patients think about cues that induce craving and are exposed to cues in the absence of drinking and rewarded for their abstinence. The evidence of efficacy for this particular intervention is not as strong as evidence for the efficacy of CBT.

• Motivational enhancement therapy: This therapy uses patients’ insights to help reduce or abstain from drinking alcohol. The level of evidence for the efficacy of this type of therapy is high and similar to CBT.

• Twelve-step facilitation: Alcoholics Anonymous (AA) programs encourage a supportive environment, spiritual focus, and a buddy system to encourage abstinence. Although the evidence for this type of intervention is mixed, such programs can be substantially beneficial for many individuals. Other community-based or professionally led group programs that have less of a spiritual focus are also available and can provide significant help.
  
  

Pharmacotherapy

Medications are underutilized in the treatment of alcohol use disorders. The FDA has approved three oral medications (naltrexone, disulfiram, and acamprosate) and a long-acting injectable formulation of naltrexone for the treatment of alcohol dependence.

The following table describes medications used in the treatment of alcohol use disorder and associated adverse effects and mechanism of action:

(Source: Pharmacotherapy for Adults With Alcohol Use Disorder (AUD) in Outpatient Settings. Agency for Healthcare Research and Quality 2011.)

Following a peak in 2012 of more than 250 million opioid prescriptions dispensed in the United States, national opioid prescribing rates have steadily declined to more than 190 million prescriptions in 2017. In 2016, according to the Centers for Disease Control, more than 11.5 million people reported misuse of prescription pain medications in the past year. The potential for harm from opioids is great, and overdose-related deaths have continued to rise as these medications have become the epicenter of a crisis in the United States.

An opiate is a natural substance derived from the opium of a poppy plant. The term opioid, on the other hand, is a broad category referring to all natural, synthetic, and partly synthetic substances that interact with opioid receptors in the body and brain. Opioids typically act as full agonists to the mu-opioid receptor, resulting in an analgesic or sedative effect. These agents can also produce depressive effects on the central nervous system and the sensation of euphoria; the euphoric and sedative effects are driving forces behind misuse. Opioids include a wide spectrum of substances, from natural (morphine, codeine) to semisynthetic formulations (e.g., oxycodone and hydromorphone) and synthetic agents (e.g., fentanyl and methadone).

Opioid use disorder (OUD) describes a pattern of use leading to changes in behavior or distress. As with other substance use disorders, the DSM-5 diagnostic criteria require the presence of at least 2 of 11 specified symptoms or behaviors (see table of diagnostic criteria below) within a 12-month period.

Risk factors for the misuse of opioids include:

• history of substance use disorder

• severe or chronic pain syndromes

• demographic vulnerability (e.g., unemployment or poverty)

• comorbid mental disorders
  
  

Presenting symptoms associated with OUD include:

• use of an opioid for longer than the intended treatment period

• use in the absence of medical need

• use of an excessive dose where a medical need does exist

• planning of daily activities around acquisition of the opioid and its use
  
  

Screening tools:

• Single-Question Drug Screen

  • How many times in the past year have you used an illegal drug or a prescription medication for nonmedical reasons? (A positive screen is 1 or more days.)

• Two-Item Screen for Drug Use in Primary Care

  • Question 1: How many days in the past 12 months have you used drugs other than alcohol? (A positive screen is 7 or more days.) If fewer than 7, proceed with question 2.

  • Question 2: How many days in the past 12 months have you used drugs more than you meant to? (A positive screen is 2 or more days.)

• The Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based method for use in community-based clinics for identification, early intervention, and treatment of substance use, abuse, and dependence on alcohol and illicit drugs.

• Rapid Opioid Dependence Screen (RODS)
  
  

The diagnosis of OUD involves identification of a pattern of use that is problematic and leads to clinically significant impairment or distress. In addition to meeting two or more DSM-5 criteria (which can include tolerance or withdrawal) within a 12-month period, diagnosis should involve a clinical history and physical examination.

Once assessment points to a diagnosis of opioid use disorder, severity should be assessed along with a review of comorbid conditions. It is important to take severity and comorbid conditions into account when evaluating the effect of opioids on the patient’s overall well-being and functionality.

• A multimodal approach is important in the treatment of opioid addiction, including medication-assisted therapies and psychosocial behavior therapy.

• Diagnosis and treatment planning with long-term management goals are the first step. Engaging patients or family in shared decision-making is important to success. This begins with sharing the diagnosis with the patient and discussing the treatment options and support mechanisms available.
  
  

Risk of overdose: The risk for overdose should be discussed early to educate patients and family or friends about overdose and possible interventions. If sobriety is desired, patient education is crucial given the risk of overdose after resuming illicit opioid use, due to loss of tolerance after a period of abstinence.

Factors that increase the risk of overdose include:

• history of overdose

• history of substance use disorder

• high opioid dosages

• simultaneous or concurrent benzodiazepine use
  
  

Treatment of overdose:Naloxone (Narcan), an opioid receptor antagonist, rapidly reverses the effects of opioid overdose. It restores breathing in a patient with life-threatening opioid-induced respiratory depression and is therefore important to immediate recovery or rescue following an overdose. The reversal effects of naloxone last for 30–90 minutes, the half-life of the drug, after which the effects of the overdose may return.

• Naloxone can be administered as an injectable, auto injectable, or nasal spray. Police officers and first responders are routinely trained to administer naloxone; family members or friends can also be trained. (See How to Use the VA Intramuscular Naloxone Kit or Naloxone Nasal Spray.)

• Although not considered a treatment for opioid use disorder, naloxone is included in some treatment formulations with buprenorphine. In some cases, it may be is co-prescribed with opioids when the risk of overdose is perceived to be high (e.g., patients prescribed more than 50 morphine milligram equivalents per day or patients with preexisting respiratory conditions such as chronic obstructive pulmonary disease or obstructive sleep apnea). 
  
  

Pharmacotherapy

Medication-assisted treatment (MAT): Opioid agonists are used to reduce or replace abused opioids, improve functionality and quality of life, and prevent overdose or death. Opioid addiction is difficult to reverse because it often causes permanent changes in the brain that create a need for a baseline level of opioid for normal day-to-day functioning that will not diminish with cessation. Medications used to treat OUD aim to reduce cravings and withdrawal symptoms and support the rewiring of brain circuits without creating a new dependence. Three MAT agents that are FDA approved for the treatment of opioid addiction are naltrexone (opioid antagonist), buprenorphine (partial opioid agonist), and methadone (opioid agonist). Buprenorphine and methadone provide basal opioid levels without euphoria or sedation.

• Methadone is a long-acting, full opioid agonist (mu-receptor) that works by blunting opioid cravings and has been shown to reduce drug use and death from overdose. However, methadone is associated with a risk of dependence. It is administered via daily supervised administration in a clinic setting.

• Buprenorphine is partial opioid agonist (mu-receptor) and a mixed opioid agonist–antagonist that allows for some stimulation of the opioid receptors but with tempered effect and less physiological dependence. Buprenorphine can be given in an office-based opioid treatment (OBOT) program on a weekly or monthly basis. Special training may be necessary for practitioners to prescribe buprenorphine for opioid addiction treatment. The combination of buprenorphine and the short-acting opioid antagonist naloxone (Suboxone) counteracts the effect of injection opioids. Buprenorphine can also be prescribed for pain management. See this resource to learn how buprenorphine prescribing differs for pain management versus OUD.

• Naltrexone is a slow-acting opioid antagonist that binds to and blocks opioid receptors to reduce the euphoric and sedative effects of opioids. It is used to treat acute overdose or, after a period of abstinence, to prevent relapse. Naltrexone reduces cravings, prevents relapse after a period of abstinence, and facilitates patient participation in other recovery activities and interventions such as psychosocial and behavioral therapies. Some experts recommend observed dosing or extended-release injectable forms in patients with problems with adherence. Naltrexone is available in both pill and injectable forms. Some experts recommend observed dosing or extended-release injectable forms in patients with problems with adherence.
  
  

For an overview of the three medications, see this NEJM Knowledge+ learning resource.

Nonpharmacologic treatment

Success in treatment of OUD requires a multimodal and continuing care approach. Each patient’s individual needs should be considered regarding MAT treatment options, treatment setting (inpatient, outpatient, or office-based therapy), intensity, and adjunctive or alternative treatment.

Psychosocial therapies such as counseling, behavioral interventions, and the use of support groups are important adjuncts to pharmacologic treatment. The therapies increase individual understanding of opioid addiction and how it is treated.

For more information on treatment in special populations, see the American Society of Addiction Medicine’s National Practice Guideline.

Withdrawal from any opioid, including heroin, resembles severe influenza and is usually accompanied by the following symptoms:

• pupillary dilation

• lacrimation

• rhinorrhea

• piloerection (“goosebumps”)

• yawning

• sneezing

• anorexia

• nausea/vomiting

• diarrhea
  
  

The Clinical Opiate Withdrawal Scale (COWS) can be used to measure symptoms of opioid withdrawal.

Opioid withdrawal is extremely uncomfortable and distressing for the patient but is usually not life-threatening. In contrast, opioid intoxication is much more likely to be life-threatening, and both intoxication and withdrawal carry significant risks of death when combined with benzodiazepines or alcohol.

Treatment: The mainstay of treatment for opioid withdrawal syndromes is usually a long-acting opioid that relieves the major symptoms of withdrawal. Opioids such as methadone are oral drugs but require physicians within licensed addiction-treatment programs to administer them to patients. Another frequently used opioid is buprenorphine, which is combined with naloxone to prevent diversion and injection. Buprenorphine can be prescribed in-office by providers who have completed a specialized training course. Many people with opioid addiction remain on prescribed opioids for their lifetimes. While this may seem counterintuitive, the prescribed opioids prevent overdose death and improve functionality for those addicted to short-acting prescription opioids or illegal heroin.

(Source: Treatment of Opioid-Use Disorders. N Engl J Med 2016.)

Nonopioid therapy can be used to help treat anxiety, insomnia, and other withdrawal symptoms. Some of these indications, such as the use of clonidine to control symptoms of autonomic overactivity, are off-label and not FDA approved.

(Source: Treatment of Opioid-Use Disorders. N Engl J Med 2016.)

Maintenance therapy: To prevent relapse, a combination of rehabilitation, supportive systems, and pharmacotherapies is required. Maintenance therapy may involve use of one of three agents: naltrexone, methadone, or buprenorphine. Naltrexone, a mu-opioid receptor antagonist is used in patients who are fully abstinent. In patients who may not be able to discontinue opioids, treatment options include methadone or buprenorphine.

(Source: Treatment of Opioid-Use Disorders. N Engl J Med 2016.)

Stimulant withdrawal is not life-threatening, although stimulant intoxication is. Stimulant intoxication can lead to seizures. The following table describes the onset, symptoms, and management of stimulant intoxication and withdrawal: