Sedative, Hypnotic, or Anxiolytic (Benzodiazepine) Use Disorder

• In the United States, the 12-month prevalences of sedative, hypnotic, or anxiolytic use disorder (DSM-IV criteria) are estimated to be 0.3% in teenagers (age 12 to 17) and 0.2% in adults.^[1]
• The development of this disorder typically follows one of two trajectories:
  • (1) Early age of onset during from teenage years to mid-20s, when the use of the substance is associated with other substances, and with social use (e.g. - at parties).
  • (2) A second, less common, but equally important clinical course, is when an individual is given a prescription from a physician, usually for anxiety, insomnia, or somatic complaints. The individual may develop a tolerance or a need for higher doses of the medication, resulting in a gradual increase in the dose and frequency of self-administration. In these cases, the individual may find multiple physicians to prescribe supplies of the medication.^[2]
• Registry studies suggest on a population level about 15% of all individuals prescribed a benzodiazepine will go on to continue taking one at the 1-year mark, and about 7% had dose escalation beyond recommended dosages.^[3]
  • Individuals at greatest risk for dose escalation were those who had psychiatric comorbidity and substance use disorders.^[4]

• Some individuals who receive these substances by prescription will develop a sedative, hypnotic, or anxiolytic use disorder, while others will not develop a use disorder.
• Similar to alcohol, very significant tolerance and withdrawal can develop to substances in this class.
  • As users with the disorder take more substance to achieve the same euphoria or desired effect, there can be a sudden onset of respiratory depression and hypotension, which can cause death.^[5]
• The social and functional consequences of a sedative, hypnotic, or anxiolytic use disorder are similar to that of alcohol use disorder.
• Significant use of substances in this class can also cause a substance-induced depressive disorder, which in severe cases can lead to suicide attempts and suicide deaths.^[6]
• The risk for acute and chronic toxic effects (e.g. - cognition, memory, falls, confusion) of these substances increase with age.^[7]

• Misuse of substances in this class may be comorbid with other substances (e.g. - alcohol, cannabis, opioid, and stimulant use disorders).
  • For example, individuals may use benzodiazepines to “come down” from cocaine or amphetamines or use high doses of benzodiazepines with methadone to “boost” its effects.^[8]
  • At high doses, these combinations can be lethal (e.g. - mixed with alcohol) although the lethal dosage varies considerably among the specific substances.
• Antisocial personality disorder is associated with sedative, hypnotic, or anxiolytic use disorder when the substances are obtained illegally.^[9]

• Environment factors such as pharmaceutical influence can influence prescribing practices of physicians, who may be inclined to prescribe these medication classes to their patients. Specifically, the prevalence of this substance use disorder correlates with its overall availability (and varies greatly between countries).^[10][11][12]
• Females are at higher risk than males for prescription misuse of sedative, hypnotic, or anxiolytic substances.^[13]

A problematic pattern of sedative, hypnotic, or anxiolytic use leading to clinically significant impairment or distress, as manifested by at least 2 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 be cause of sedative, hypnotic, or anxiolytic use.
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).
    • 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.

• Some withdrawal symptoms such as insomnia can persist for months and contribute to relapse.^[14]
• Depending on the severity of the use, individuals may use in physically hazardous circumstances (e.g. - driving a car or operating machinery while intoxicated).^[15]

• Sedatives, hypnotics, and anxiolytics (also known as depressants) slow down or “depresses” neurotransmission levels and reduce arousal/stimulation in various areas of the brain.
• The most common class of medications misused in this disorder are benzodiazepines (“benzos,” “downers,” “tranks,” “nerve pills”).
  • Alprazolam (Xanax) is the most commonly misused due to its short half-life (commonly called “Xannies,” “Zannies,” or “bars,” – referring to the shape of the pill)
• Other historically more commonly used substance classes include:
  • Barbiturates (e.g. - phenobarbital, secobarbital)
  • Barbiturate-like hypnotics (e.g. - glutethimide, methaqualone [Trade name: Miltown])
  • Carbamates (e.g. - glutethimide, meprobamate [Trade name: Quaalude])
• Although officially considered as a separate substance use disorder under the DSM-5, alcohol use disorder has very similar pathophysiological, intoxication, and withdrawal effects.

• Severity of Dependence Scale (SDS)^[16]

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

• Other mental disorders or medical conditions
  • Individuals with sedative-, hypnotic-, or anxiolytic-induced disorders may have symptoms (e.g. - anxiety) that are similar to primary mental disorders (e.g. - generalized anxiety disorder). The slurred speech, incoordination, and other associated features characteristic of sedative, hypnotic, or anxiolytic intoxication may be the result of another medical condition (e.g. - multiple sclerosis) or from head trauma (e.g. - subdural hematoma).
• Alcohol use disorder
  • Sedative, hypnotic, or anxiolytic use disorder must be differentiated from alcohol use disorder.
• Clinically appropriate use of sedative, hypnotic, or anxiolytic medications
  • Individuals may continue to take benzodiazepines as directed by a physician for a legitimate medical reason for long periods of time. Even if physiological signs of tolerance or withdrawal develop, many of these individuals do not develop symptoms that meet the full criteria for sedative, hypnotic, or anxiolytic use disorder, because they are not preoccupied with obtaining the substance and the use does not interfere with their social or occupational roles.^[17]

• Urine drug screens can identify almost all sedative, hypnotic, or anxiolytic substances.
• Long-acting substances (e.g. - diazepam, flurazepam) can remain positive on urine screen for up to 1 week after use.

• Mild decrease in most aspects of autonomic nervous system functioning, including a slower pulse, a slightly decreased respiratory rate, and postural hypotension.^[18]

• Cognitive behavioural therapy may be helpful during the tapering phase.^[19]

• There are two primary approaches to the management of sedative, hypnotic, or anxiolytic use disorder.
  • The clinician can work with the patient to taper the medication/substance with the aim of abstinence, or consideration of benzodiazepine maintenance therapy with a harm reduction strategy approach.
  • The risks and benefits of each decision need to be carefully weighed, as withdrawal seizures can be a risk factor.
    • Patients with high risk medical conditions or a significant seizure history may benefit from admission to an inpatient service for stabilization and closer withdrawal management.
• There is some evidence for the use of anticonvulsants such as carbamazepine and pregabalin for management of withdrawal symptoms.^[20]