eMedicine Specialties > Psychiatry > Addiction

Sedative, Hypnotic, Anxiolytic Use Disorders: Treatment & Medication

Author: Joji Suzuki, MD, Fellow in Addiction Psychiatry, Department of Psychiatry, Boston University School of Medicine
Coauthor(s): Christopher L Sola, DO, Clinical Assistant Professor, University of Vermont, College of Medicine; Director of Consultation-Liaison Psychiatry, Department of Psychiatry, Maine Medical Center; Olakunle PA Akinsoto, MD, Consulting Staff, Family Health Center, Jacksonville Medical Center
Contributor Information and Disclosures

Updated: Jun 8, 2006

Treatment

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

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.

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.

Flumazenil (Romazicon)

Benzodiazepine antagonist has a high affinity for the benzodiazepine receptor, making it a competitive antagonist. Flumazenil is short-acting, with a half-life of 0.7-1.3 h. Because most benzodiazepines have longer half-lives, multiple doses of flumazenil may be required to avoid relapse back into a sedative state.

Barbiturates

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

Phenobarbital (Barbita, Luminal, Solfoton)

Chosen for withdrawal because of long half-life and wide therapeutic index. General principle is that sedatives with longer half-lives have less severe withdrawal symptoms. Arbitrary doses are given, and treatment is individualized to respect variable effects in different patients.

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.

Diazepam (Valium)

Depresses all levels of CNS (eg, limbic, reticular formation), possibly by increasing activity of GABA. Individualize the dosage and increase cautiously to avoid adverse effects.

Lorazepam (Ativan)

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.

Clonazepam (Klonopin)

Suppresses muscle contractions by facilitating neurotransmission of GABA and other inhibitory transmitters.

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