AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Throughout history, humans have sought chemical agents to ameliorate the effects of stress and attenuate feelings of discomfort, tension, anxiety, and dysphoria. Consequently, sedatives, anxiolytics, and hypnotics were created. The oldest of these is ethanol. By the 19th century, bromide salts, choral hydrate, and paraldehyde were used in medicine. Subsequently, barbiturates were synthesized in 1903, followed by meprobamate in 1950. By 1959, the benzodiazepine chlordiazepoxide was created, giving rise to at least 3000 different benzodiazepines, of which 50 are currently marketed.

The therapeutic value of these agents as anxiolytics and hypnotics has been well established, and they continue to serve an important role in managing many debilitating anxiety symptoms in the context of both psychiatric disorders and medical illness. However, the toxic effects of these drugs have also been established, including various withdrawal syndromes, dependence, and tolerance.

Pathophysiology

No conclusive data explain how sedative-hypnotics function. Gamma-aminobutyric butyric acid (GABA) is the most widely distributed inhibitory neurotransmitter in the central nervous system. GABA opens chloride (Cl) channels, causing an influx of Cl ions. The influx of Cl ions causes hyperpolarization of the neuron, subsequently inhibiting neuronal discharge. Benzodiazepines and barbiturates potentiate the actions of GABA in a similar fashion via specific receptors, which are located near the GABA receptors. The GABA (A) receptor subunit, composed of multiple forms (eg, alpha, beta, gamma) has been proposed as the functional unit on which benzodiazepines and barbiturates operate.

Benzodiazepine receptors in the CNS have been classified as BZ1 and BZ2 subtypes, based on relative affinities for different benzodiazepines and nonbenzodiazepines. As an example, imidazopyridines (eg, zolpidem) may act via the BZ1 receptors, although contradictory evidence exists regarding this. GABA is believed to facilitate the affinity these drugs have for their receptors. The action of hyperpolarization is reversed by the influx of calcium into the cell.

The long-term pharmacodynamics interaction of benzodiazepines with the GABA receptor is thought to be extremely complex. Long-term use of benzodiazepines and barbiturates is thought to result in down-regulation of inhibitory GABA receptors and configurational changes of the receptor-agonist complex, resulting in diminished agonist sensitivity. These changes are potential mechanisms of tolerance, dependence, and withdrawal. The abrupt cessation of benzodiazepines, as in the case of a patient discontinuing a benzodiazepine after long-term use, is thought to result in the classically described acute withdrawal symptoms as the inhibitory pressure is removed, leaving a relative excitatory state.

Frequency

United States

Approximately 12.5% of the adult population uses a prescribed anxiolytic in the course of a year, while about 2% of the population takes one on any given day. More than half of these drugs, especially benzodiazepines, are prescribed by primary care physicians. In 1988, approximately 88 million prescriptions were written, most for emotional distress. Benzodiazepines are one of the most commonly prescribed drugs in this country.

International

In Western Europe and parts of Asia, use of a hypnotic in the course of a year approaches 25-30%.

Race

Use of hypnotics is higher in whites than in other races.

Sex

Male-to-female ratio is 1:2.

Age

Sedatives, anxiolytics, and hypnotics are commonly prescribed for people in the sixth and seventh decades of life; however, nonmedical use is highest in people aged 18-25 years, with rates of 0.7-1.9%.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Patients who abuse or become dependent on benzodiazepines may fall into 2 broad categories. The first category contains patients being prescribed benzodiazepines for the symptomatic treatment of a psychiatric disorder. Such patients risk developing dependence, particularly if they have a history of alcohol or prescription drug abuse, are being prescribed high doses, or are prescribed the anxiolytic for longer than 1 month. Of note, some patients are safely maintained at the same dose for many years without apparent loss of efficacy. Patients with a family history of alcoholism may be genetically predisposed to benzodiazepine dependence, as evidenced by the likelihood that they will report more positive mood effects compared with those without a family history.

The second category includes patients who use benzodiazepines in the setting of alcohol or polydrug abuse or dependence. Sometimes these individuals may use benzodiazepines to manage chronic anxiety or insomnia, to prolong the effects of methadone, to lessen the undesirable effects of other drugs (eg, methamphetamine), or when no other drugs are available. Sedative-hypnotics such as secobarbital and pentobarbital are thought to be more likely to become primary drugs of abuse than benzodiazepines.

• Direct toxic actions
• • 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.
  • 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.
  • In the United States, barbiturates are subject to more stringent federal control and are less commonly used, while benzodiazepines are more prone to abuse or dependence because of their perceived safety and more frequent prescribing.
• 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: Early human studies in the 1960s established that discontinuation from high doses of diazepam or chlordiazepoxide taken for 1 month produce a withdrawal syndrome. 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 upon the biological half-life of the drug. 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 withdrawal 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. Symptoms may fluctuate throughout this time, making it difficult to assess whether the symptoms are due to symptom reemergence or symptom rebound.
  • 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.

Physical

The most vital aspects in assessing sedative-hypnotic intoxication or withdrawal are detailed mental status and neurologic examinations, as independent mood, psychotic, or anxiety disorder may also be present.

• Physical findings of intoxication include the following:
• • Hypothermia and hypotension
  • Head, eyes, ears, nose, and throat - 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 (For higher functions, see below.)
• 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.
  • Attitude is variable.
  • Orientation: The patient can be completely disoriented, with obfuscation of higher functions. Tasks such as computation, abstraction, memory (anterograde memory in benzodiazepines, as seen in Rohypnol misuse), and concentration can be impossible to perform.
  • Perception may be altered based on level of intoxication, with a wide range of disturbances, including hallucinations and illusions.
  • Speech - Speech is often slurred.
  • Mood - The patient may report a variety of mood states.
  • Affect - Affect is variable but could be labile, euphoric, dysphoric, and the intensity ranging from blunt to flat.
  • Thought process and content - Dependent upon the level of intoxication, the thought process and content may range from paranoia to bizarre content. Patients may have suicidal ideation, since patients with depression, anxiety, and dependence personality traits have a higher daily use of sedatives.
  • Judgment is impaired.
  • Insight also is impaired, dependent upon the degree of toxicity.
• Physical signs of withdrawal syndromes including the following:
• • Vital - Hyperthermic temperature above 100°F; pulse rate tachycardic above 100 (beats per minute); respiration rate possibly tachypneic above 20; blood pressure variable, eg, starting off hypertensive, later stages hypotensive
  • Head, eyes, ears, nose and throat - Possible dilated pupils as a secondary effect of sympathetic hyperactivity
  • Cardiovascular - Tachycardia, palpitations, with hypertension in earlier phases of withdrawal; later, hypotensive from fluid losses (sweating and hyperventilation)
  • Pulmonary - Tachypnea
  • Gastrointestinal - Variable bowel sounds, depending on the type of autonomic predominance (parasympathetic or sympathetic) at the time of presentation
  • Musculoskeletal - Tremulous state and dehydration, potentially leading to muscle spasms and rhabdomyolysis
  • Neurologic - Tremors, increased deep tendon reflexes, ataxia, with or without dyskinesia (For clinical findings pertaining to the higher centers, please see below.)
• Mental status examination findings in withdrawal syndromes include the following:
• • Appearance - Hygiene will vary, depending on length of time experiencing withdrawal symptoms. The patient may be alert but high-strung.
  • Behavior - Patient may display psychomotor agitation, or responding to internal stimuli
  • Attitude - Patient could be hostile if very irritable.
  • Orientation - Depending on how severe the withdrawal symptoms are, the patient may be disoriented to person, place, or time. Patient may have problems with memory, concentration, abstraction, and performance of intellectual tasks.
  • Perception - Patient may exhibit increased sensory perception (smell, sight, taste, touch). There can be abnormal sensation of movement. Depersonalization or derealization is possible.
  • Speech - Speech can vary, but speech can be rapid, tremulous, or, sometimes, idiosyncratic.
  • Mood - Patient often reports feeling anxious but may also describe other feelings (eg, sadness).
  • Affect - Affect may be expansive, labile, irritable, dysphoric, and, most likely, anxious.
  • Thought process and content - Variable, but may present with disorganized thought, auditory, visual and tactile hallucinations, and delusions.
  • Judgment - May be impaired
  • Insight - May be compromised

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Withdrawal syndromes

Delirium tremens and other alcohol-related syndromes
Pheochromocytoma
Thyrotoxicosis
Anxiety disorders
Psychotic illnesses
Anticholinergic or sympathomimetic drug overdoses
Schizophrenia
Seizure disorders
Mood disorders

Toxicity syndromes

Electrolyte, metabolic, or endocrine derangements
CNS structural or degenerative disorders
Cerebellar disease
Vasculitic or infectious disorders
Posttraumatic stress disorder

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Careful review of the patient's history and examination will typically suffice; however, further studies may be performed to rule out an underlying pathology with a similar presentation. This is particularly true if the patient presents with severe symptoms or when a reliable history cannot be obtained. Workup depends on the type of presenting disorder, especially if no prior knowledge of ingestion of sedatives is known. If a laboratory workup is necessary, it should include the following:
• • Comprehensive metabolic panel to assess for metabolic encephalopathy seen in hepatic and renal failure, and other electrolyte derangements that can mimic sedative and anxiolytic intoxication.
  • Thyroid panel, as thyrotoxicosis and hypothyroidism can mimic sedative withdrawal and overdose disorders, respectively
  • Toxicity screen, including CNS depressants, cannabis, PCP, and stimulants such as amphetamines and cocaine
  • Serum drug levels if patient is known to take lithium, carbamazepine, valproic acid, or TCAs
  • Blood alcohol level
  • Arterial blood gasses
  • Urinalysis

Imaging Studies

• CT scan of head to rule out space-occupying lesions, intracranial bleeding, and certain CNS infections (eg, toxoplasmosis, Cryptococcus)
• MRI of the head if the CT scan is unremarkable and a space-limiting lesion is suspected, or if intravenous (IV) contrast is contraindicated

Other Tests

• Toxicity screen to rule out the possibility of concurrent drug overdose.
• Consider an EEG in the context of hallucinations to rule out conditions such as temporal lobe epilepsy. In the setting of sedative-hypnotic withdrawal, EEG may show paroxysmal bursts of high-voltage, slow-frequency activities that precede the development of seizures.
• ECG may be helpful to rule out arrhythmias, which can increase the probability of emboli to brain and cause altered mental derangements.

Procedures

• Consider a lumbar puncture, depending on the symptoms. If seizures are suspected, complete an EEG.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Initially, treat a patient who has taken an overdose of sedative-hypnotics like any other patient with drug intoxication.
  • Provide an adequate airway and ventilation.
  • Stabilize and maintain the cardiovascular system.
  • Once initial measures have been carried out, consider inducing emesis, performing lavage, and administering activated charcoal to a patient who has orally ingested the drug, depending on the time of ingestion and level of consciousness. Emesis, lavage, and/or activated charcoal prevent absorption of the drug into the system and absorption of the drug or active metabolites through enterohepatic recirculation.
  • Laxatives may be used to induce catharsis.
• If the patient overdosed on barbiturates, administer intravenous sodium bicarbonate to alkalinize the urine, which increases the rate of barbiturate excretion. The dose of bicarbonate varies depending on the patient's metabolic state. Urine pH should be monitored and maintained at 7.5.
• Dialysis may be required, depending on the gravity of the patient's condition.
• Benzodiazepines are the most commonly prescribed sedative-hypnotic, and produce less respiratory depression than do barbiturates. Long-acting metabolites often cause intoxication that lasts for several days. Benzodiazepine overdose is most dangerous in combination with other sedative-hypnotics.
  • A benzodiazepine antagonist, flumazenil, is available for the treatment of benzodiazepine intoxication. It must be used with some caution; in some cases, it has not completely reversed respiratory depression, and it can cause seizures in patients with physical dependence.
  • In a mixed overdose, flumazenil could precipitate tricyclic antidepressant-induced arrhythmias covered by the sedative.
  • Flumazenil should be given in the lowest possible dose. In patients who are physically dependent on benzodiazepines, slowly administer repeated doses of flumazenil.
  • Flumazenil is a short-acting drug; therefore, sedation after an initial awakening may recur.
  • If necessary, this can be treated by repeating doses at 20-minute intervals (see Flumazenil).
• Address all potential complications, such as aspiration, pulmonary edema, and respiratory failure, of overdose. If a clear suicide attempt was made, place the patient on suicide precautions, and order a psychiatric follow up.
• Treatment of withdrawal syndromes is identical for withdrawal from all sedative-hypnotics because all drugs in this category, including barbiturates, sleeping pills, benzodiazepines, and alcohol, exhibit cross-dependence.
• • The first step in treatment is to objectively determine the patient's approximate drug tolerance level because patients often inaccurately estimate the amount of drug they have been taking. Direct observation is ideal, and may be best accomplished in a supervised setting. Any drug causing cross-dependence (eg, phenobarbital) can be used. It is safer to err on the side of overmedicating than undermedicating with the initial dose. That index dose is then tapered, reducing subsequent daily doses by 10% of the initial dose. This typically provides a comfortable taper, especially if the patient is expected to participate in demanding psychological therapy or has coexisting medical conditions. The taper can be accomplished more rapidly if these complicating conditions do not exist.
  • The use of a long-acting barbiturate decreases the severity of withdrawal symptoms, and phenobarbital is chosen in preference to other sedatives because it has a longer half-life. Patients rarely achieve a "high" from phenobarbital as they do from the other drugs, and it is available in multiple dosage forms. The dose of phenobarbital can be given in a constant volume of liquid for each dose so that the patient is not aware of the amount being decreased each day (ie, blind taper).
• If a patient who has been using sedative-hypnotics on a long-term basis presents with advanced withdrawal (eg, elevated vital signs, delirium), it is important to medicate rapidly and in doses sufficient to suppress withdrawal.
  • Administer medications with rapid onset of action to initiate suppression of severe withdrawal signs; they may be administered intravenously for more immediate results. Lorazepam and diazepam have rapid onset when administered intravenously. However, they have a shorter duration of action than when administered orally as first-pass hepatic metabolism is bypassed.
  • The following is a commonly used benzodiazepine equivalence schedule. Diazepam 10 mg is approximately equivalent to the following drugs and doses:
  • Alprazolam - 1 mg
  • Chlordiazepoxide - 30 mg
  • Flunitrazepam - 2 mg
  • Flurazepam - 30 mg
  • Lorazepam - 1 mg
  • Loprazolam - 1 mg
  • Nitrazepam - 10 mg
  • Oxazepam - 30 mg
  • Temazepam - 20 mg
  • After conversion to the equivalent dose of diazepam, the patient should be tapered off diazepam at the rate of 2 mg every 2 weeks over a period of 2-6 months.
  • After stabilization with rapidly acting medications, the patient can be switched to an equivalent dose of a long-acting medication, such as phenobarbital. As long as the patient is awake, significant respiratory depression from the withdrawal medication should not occur. Large doses of long-acting medications may be required (eg, up to 700 mg daily of phenobarbital).
  • Advanced withdrawal is most safely managed in an inpatient setting if the patient has been using high doses of sedative-hypnotics, has a history of withdrawal seizures or delirium tremens, or has concurrent medical illness. If the patient is thought reliable, it is possible to embark on various detoxification regimens in the outpatient setting.
  • A patient can be slowly weaned off the medication; however, this is often unsuccessful if the patient cannot cope with mild withdrawal effects. An alternative is to replace short-acting benzodiazepines (eg, alprazolam) with equivalent dosing of a longer-acting drug (eg, clonazepam), which may provide for a milder withdrawal syndrome during the taper.
  • The weekly tapering dose can be calculated by dividing the total dose by 5 and reducing the dose by this amount weekly. The dose for most patients can be reduced to zero in 4-8 weeks.
• Anticonvulsant agents that do not demonstrate cross-dependence with sedative-hypnotics (ie, carbamazepine, valproate) have been used successfully in the treatment of mild sedative-hypnotic withdrawal, though they have not been studied for use in severe withdrawal. They are given at full anticonvulsant doses for several weeks during the withdrawal.

Consultations

• Neurologist: Consultation is indicated if seizures are unresponsive to usual treatment of the withdrawal symptoms or when there are other neurologic symptoms not explained by the usual symptoms of intoxication or withdrawal, such as persistent headaches.
• Psychiatrist: Consultation is indicated in the context of questions about suicidal risk or if the patient demonstrates aggressive behavior. Additionally, consultation should be obtained when there is suspicion of comorbid psychiatric disorders (eg, mood or psychotic disorders) complicating the treatment of the substance use disorder.
• Poison centers: Poison centers could be used to obtain information about other possible unknown substances being used, especially in overdose situations.

Diet

Consider if the patient is unconscious, thereby warranting nothing by mouth.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

A variety of drugs are used both in the acute and the long-term setting for the treatment of sedative, hypnotic, and anxiolytic use disorders. Drug selection depends upon whether toxicity or withdrawal symptoms are being targeted.

Drug Category: Benzodiazepine antagonist

These agents are used in reversing the CNS depressant effects of benzodiazepine overdose. Its ability to reverse the benzodiazepine-induced respiratory depression is difficult to predict.

Drug Category: Barbiturates

These agents are used in some cases to facilitate smooth withdrawals in patients with benzodiazepines and barbiturate dependence.

Drug Category: Benzodiazepines

In dependent patients, these are used in a manner similar to phenobarbital to wean patients from short-acting benzodiazepines. The general principle is that sedatives with longer half-lives have less severe withdrawal symptoms. Various patient-specific dosing strategies are used. If symptoms are severe enough to require inpatient treatment, IV lorazepam or diazepam is used.

After stabilizing the patient, the tapering dose is calculated by dividing the total dose by 5 and reducing by this amount weekly.

Drug Name	Lorazepam (Ativan)
Description	Sedative-hypnotic with short onset of effects and relatively long half-life. By increasing the action of GABA, which is the major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation. Important to monitor patient's blood pressure after administering dose. Adjust dose as necessary.
Adult Dose	1-10 mg/d IV divided bid/tid; adjust dose to response (Dose used in acute treatment of severe withdrawal)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; preexisting CNS depression, hypotension, and narrow-angle glaucoma; breastfeeding mothers
Interactions	Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs; may be antagonized by oral contraceptives
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in renal or hepatic impairment, myasthenia gravis, limited pulmonary reserve, organic brain syndrome, or Parkinson disease

Drug Name	Clonazepam (Klonopin)
Description	Suppresses muscle contractions by facilitating neurotransmission of GABA and other inhibitory transmitters.
Adult Dose	Based on equivalent doses of other benzodiazepines (eg, 1 mg PO of clonazepam for 1-2 mg of alprazolam)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severe liver disease; acute narrow-angle glaucoma
Interactions	Phenytoin and barbiturates may reduce effects; coadministration of CNS depressants increase toxicity
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in chronic respiratory disease or impaired renal function; withdrawal symptoms can result from abrupt discontinuation of the medication Other precautions include history of drug and alcohol abuse; monitor blood counts and liver function tests

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Definitive treatment is a lengthy process, taking months or years. A return to drug use should not be considered a treatment failure, but rather a time to intensify treatment.
• • Current thinking is that patients require a level of treatment based on severity of illness and their readiness to change. Precontemplative patients will have different motivators than those who are actively engaged in maintaining abstinence.
  • Acute inpatient hospitalization is reserved for the most severely impaired patients requiring complicated withdrawals, patients who have been unsuccessful as outpatients, or patients with medical and/or psychiatric comorbidity.
  • Always follow inpatient treatment with outpatient treatment to facilitate the patient's return to the outpatient environment. Intensive outpatient services or even partial hospitalization may be appropriate.

Further Outpatient Care

• Patients with anxiolytic use disorders are frequently treated in the outpatient setting, as most are stable and require minimal monitoring. Some may benefit from enrollment in support groups, such as Pills Anonymous, and attending drug-free outpatient counseling.

Transfer

• After detoxification, the patient may be transferred to the psychiatric unit, if he or she meets criteria for inpatient psychiatric treatment.

Prognosis

• The prognosis for patients with sedative abuse is guarded. In an article by Allgulander, Borg, and Vikander (American Journal of Psychiatry, December 1984), 84% of primary sedative-hypnotic abusing patients had resumed use of sedative-hypnotics 4-6 years after hospital discharge; physical signs of alcoholism had developed in 22%, and 8% had committed suicide. Forty-two percent had been rehospitalized for sedative-hypnotic abuse.

Patient Education

• Excellent patient education resources are available at eMedicine's Substance Abuse Center and Mental Health and Behavior Center. Also, see eMedicine's patient education articles Benzodiazepine Abuse, Barbiturate Abuse, and Substance Abuse.
• Family education: Since the abuse and the symptoms affect the entire family, it is necessary to inform them of the issues. In certain cases, they can be enablers.
• Physician education: It is important that the doctor who prescribed the drug know of the effects. Often the patient will seek out many practitioners for the supply. Physicians benefit from feedback on the prescribing practices.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• While no foolproof techniques to prevent malpractice exist, there are ways to reduce exposure to litigation. An estimated 7% of all malpractice claims against psychiatrists result from medication errors and drug reactions. The most common pitfalls are as follows:
• • Failure to evaluate properly
  • Failure to monitor and supervise
  • Negligent prescription practices
  • Failure to treat adverse effects that have been, or should have been, recognized
  • Failure to prescribe the appropriate level of medication for patient's requirements
  • Prescription of addictive drugs to vulnerable patients
  • Failure to refer a patient for consultation or treatment by a specialist
  • Failure to communicate with other medical professionals who are involved with the care of the patient
• All physicians are judged by certain standards of care and guidelines. Their actions are compared to the standards expected of an average physician in their community under the circumstances.
• When treating a patient with any medication, meeting certain expectations can minimize unnecessary litigation.
• • Succinctly record the patient's history, in particular a history of alcohol use and any history of other substance-related disorders, and results of physical examination. If possible, support this information with laboratory tests.
  • Clearly instruct the patient about the use and potential side effects of medication. Obtain an informed consent from the patient, especially if the drug has unpleasant effects.
  • Maintain relevant documentation, especially for changes in medication or instructions. Record the precise number of pills given potentially abused substances, such as sedative-hypnotics or anxiolytics.
  • If the physician is uncomfortable prescribing a particular medication or treating a condition requiring that medication, it is advisable to consult a colleague or research the drug and situation through recently updated reference textbooks or other media.
  • After starting the patient on any sedative, it is advisable to monitor his or her reaction to the medication.
  • Remain aware of current guidelines, drugs recently approved by the Food and Drug Administration, current or recent literature (eg, alternative treatment approaches which do not require these medications), and relevant updates by pharmaceutical companies (eg, reports of surveillance of side effects of these medications). Ignorance is not an acceptable excuse in legal action.
  • Be cautious about approving drugs over the telephone without seeing the patient, and always review the pertinent records.
• Because hypnotics, especially barbiturates, can mimic signs of brain death (eg, no doll's eyes movement or fixed, dilated pupils), be cautious when labeling an overdose patient with brain death.

Special Concerns

• Clinical features of sedative-hypnotic overdose or withdrawal syndromes may mimic other overdose and withdrawal syndromes. Distinguishing withdrawal symptoms and side effects from presumed underlying anxiety symptoms may be difficult; thus, prognosis for sedative abuse is guarded.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Allgulander C, Borg S, Vikander B. A 4-6-year follow-up of 50 patients with primary dependence on sedative and hypnotic drugs. American Journal of Psychiatry. 1984;141(12):1580-2.
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edition, text revision. Washington, DC: American Psychiatric Press, Inc. 2000.
• Bernstein J. Handbook of Drug Treatment in Psychiatry. 3rd ed. 1995.
• Freidman L, Flemming N F. Source book of Substance Abuse and Addiction. 1996.
• Galanter M, Kleber HD, eds. Textbook of Substance Abuse Treatment. 3rd ed. American Psychiatric Publishing;. 2004.
• Gilman, Ruddon, Limgird. Goodman & Gilman: Pharmacological Basis Therapeutics. 9th ed. 1996.
• Kaplan, Sadock. Comprehensive Textbook of Psychiatry VI. 6th ed. 1995.
• Karch Steven B, ed. Drug Abuse Handbook. CRC Press:1997.
• Katzung. Basic & Clinical Pharmacology. 7th ed. 1996.
• Rabe-Jablonska J, Bienkiewicz W. [Anxiety disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association: diagnostic and statistical manual of mental disorders (DMS-IV -- options book]. Psychiatr Pol. Mar-Apr 1994;28(2):255-68. [Medline].
• Simon R. Psychiatry and Law for Clinicians. 2nd ed. 1998.
• Teifion Davies, TKJ Craig. ABC of Mental HealthBritish Medical Journal. BMJ Books. 1998:39-42.
• Weaver MF, Jarvis MA, Schnoll SH. Role of the primary care physician in problems of substance abuse. Arch Intern Med. May 10 1999;159(9):913-24. [Medline].

Article Last Updated: Jun 8, 2006