Sedative, Hypnotic, Anxiolytic Use Disorders Clinical Presentation

Patients who abuse or become dependent on sedative-hypnotics may fall into 2 broad categories:

The first category contains patients being prescribed these drugs for the symptomatic treatment of a psychiatric disorder. Such patients have a high risk of developing sedative-hypnotic dependence, particularly if they have a history of alcohol or prescription drug abuse, are being prescribed high doses of sedative-hypnotics, or are prescribed these drugs for longer than 1 month. Patients with a family history of alcoholism may be genetically predisposed to benzodiazepine dependence. Unless dose escalation is evident or deliberate use to produce high or dangerous states of intoxication, there is no reason to assume that chronic benzodiazepine users are abusers.^[7]

The second category includes patients who use sedative-hypnotics in the setting of alcohol or polydrug abuse or dependence. Sometimes, these individuals may use benzodiazepines to manage chronic anxiety or insomnia, to enhance the euphoric effects of opioids, and to lessen the withdrawal associated with cocaine.^[2]

• Direct toxic actions of sedative-hypnotics:

  • Relatively low doses may lead to drowsiness, impaired judgment, and diminished motor skills.
  • A significant impact on driving ability, job performance, and personal relationships is possible.
  • Benzodiazepines may cause dose-related anterograde amnesia; significantly impairing the ability to learn new information while the retrieval of previously learned information remains intact. This effect is exploited when patients undergo uncomfortable procedures, as comfort and postoperative amnesia are beneficial.
  • Other clinical features include slurred speech, ataxia, nystagmus, decreased reflexes, stupor, coma, and cardiorespiratory arrest. The latter are more commonly seen with use of barbiturates (eg, chloral hydrate) due to steep dose-response properties.
  • In the United States, barbiturates are subject to more stringent federal control and are less commonly used, whereas benzodiazepines are more prone to abuse or dependence because of their perceived safety and more frequent prescribing.
  • Benzodiazepines are considered safer because of a higher therapeutic index ratio and flatter dose-response curves. Most cases of coma or respiratory depression usually occur in conjunction with other CNS depressants.
• Withdrawal, symptom rebound, and symptom reemergence: The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) requires 2 or more of the following characteristics to be present for diagnosis of this syndrome: autonomic hyperactivity (eg, sweating, pulse rate >100); increased hand tremor; insomnia; nausea or vomiting; transient visual, tactile, or auditory hallucinations or illusions; psychomotor agitation; anxiety; grand mal seizures.

  • High-dose withdrawal: This is a withdrawal state in the setting of discontinuation of high-dose sedative-hypnotics. Symptoms include anxiety, insomnia, postural hypotension, nausea, vomiting, tremor, incoordination, restlessness, blurred vision, sweating, hyperpyrexia, anorexia, seizures, and delirium. Severe dependence confers increased risk for medical complications including death. Time course of withdrawal symptoms from the last dose taken depend on the biological half-life of the drug. Drugs with a short half-life (eg, alprazolam) may induce a more rapid onset of withdrawal and a more severe withdrawal than drugs with longer half-life (eg, diazepam). Short-acting sedatives-hypnotics can trigger withdrawal in 1-2 days, with symptoms peaking between 1 and 3 days. Withdrawal from longer-acting sedatives-hypnotics may peak in approximately 1 week.
  • Low-dose withdrawal (also called therapeutic dose withdrawal or benzodiazepine discontinuation syndrome): This is a withdrawal state in the setting of therapeutic doses being prescribed. It is thought that withdrawal symptoms generally do not appear if the duration of the treatment is less than 4 months, but it may appear earlier if higher doses are used. While some patients can abruptly discontinue their medications without withdrawal, symptoms associated with this syndrome are the same as high-dose withdrawal, minus seizures and delirium. Depersonalization, heightened perceptions, and illusions have also been described. Symptoms may vary from mild to severe, and a protracted withdrawal syndrome may develop. Patients with a family or personal history of alcoholism or those who also use other sedatives may be at increased risk for this syndrome.
  • Protracted withdrawal syndrome: Some patients who have been maintained on therapeutic doses of benzodiazepines for extended periods may experience a relatively mild form of withdrawal, marked by symptoms of anxiety, irritability, and insomnia, which can last for weeks or months.
  • Symptom rebound: Symptoms for which the sedative-hypnotic was used to treat (eg, insomnia) may return with increased intensity soon after discontinuation of the medication. The symptoms may last from days to weeks but will subside over time.
  • Symptom reemergence: While not a withdrawal syndrome, symptom reemergence describes the reappearance of symptoms of an underlying mood or anxiety disorder after discontinuation of the medication. Unlike symptom rebound, these symptoms will not subside over time.

The most vital aspects in assessing sedative-hypnotic intoxication or withdrawal are detailed mental status and neurologic examinations in addition to comprehensive physical examination.

• Physical findings of intoxication include the following:

  • Hypothermia and hypotension
  • Eyes - Nystagmus, miosis, and diplopia
  • Cardiovascular - Hypotension and bradycardia; patients may develop tachycardia in response to hypotension
  • Pulmonary - Respiratory depression; risk of aspiration
  • Gastrointestinal - Variable
  • Musculoskeletal - Prolonged unconsciousness resulting in skin necrosis and rhabdomyolysis
  • Neurological - Ataxia, dyskinesia, dysarthria, decreased deep tendon reflexes
• Mental status examination findings of intoxication include the following:

  • Appearance - Dependent upon level of intoxication, the patient may be somnolent and disheveled.
  • Behavior - Psychomotor retardation may be seen, but, on occasion, the patient may show inappropriate sexual or aggressive behavior, usually during or shortly after sedative use.
  • Speech - Speech is often slurred.
  • Mood - The patient may report a variety of mood states.
  • Affect - Affect is variable, and it can range from flat, blunt, dysphoric, labile, and even euphoric.
  • Thought process and content - Dependent upon the level of intoxication, the thought content may range from bizarre content to paranoia. Patients may complain of suicidal ideations.
  • Perception - Perception may be altered based on level of intoxication, with a wide range of disturbances, including illusions and hallucinations.
  • Orientation - The patient can be completely disoriented, with obfuscation of higher functions. Tasks such as computation, abstraction, memory, and concentration are usually impaired.
  • Insight and judgment are usually impaired.
• Physical signs of withdrawal syndromes include the following:

  • Vital signs - Hyperthermic temperature above 100°F; pulse rate tachycardic above 100 beats/minute; respiration rate possibly tachypneic above 20; blood pressure variable, eg, hypertensive initially, hypotensive from fluid loses at later stages
  • Eyes - Possible dilated pupils as a secondary effect of sympathetic hyperactivity
  • Cardiovascular - Tachycardia and palpitations
  • Pulmonary - Tachypnea
  • Gastrointestinal - Variable bowel sounds, depending on the type of autonomic predominance (parasympathetic or sympathetic) at the time of presentation
  • Musculoskeletal - Tremors, potentially leading to muscle spasms and rhabdomyolysis
  • Neurologic - Tremors, increased deep tendon reflexes, ataxia, with or without dyskinesia
• Mental status examination findings in withdrawal syndromes include the following:

  • Appearance - Hygiene may vary, depending on length of time experiencing withdrawal symptoms. The patient may be alert but high-strung.
  • Behavior - The patient may display psychomotor agitation.
  • Attitude - The patient may be hostile and irritable.
  • Orientation - Depending on the severity of withdrawal symptoms, the patient may be disoriented to person, place, or time. The patient may have problems with memory, concentration, abstraction, and performance of intellectual tasks.
  • Perception - The patient may exhibit increased sensory perception (smell, sight, taste, touch). Depersonalization or derealization is possible.
  • Speech - Speech can vary and may be rapid.
  • Mood - The patient often reports feeling anxious but may complain of sadness.
  • Affect - Affect may be expansive, labile, dysphoric, and most likely anxious.
  • Thought process and content - This may be variable, but the patient may present with thought disorganization and delusions.
  • Hallucinations - Auditory, visual, and tactile hallucinations may be present.
  • Judgment - This may be impaired.
  • Insight - This may be compromised.