eMedicine Specialties > Psychiatry > Addiction

Sedative, Hypnotic, Anxiolytic Use Disorders: Treatment & Medication

Author: Christopher L Sola, DO, Assistant Professor in Psychiatry, Mayo Clinic School of Medicine; Medical Director of Inpatient Medical Psychiatry Program, Department of Psychiatry and Psychology, Mayo Clinic
Coauthor(s): Amit Chopra, MD, Resident Physician, Department of Psychiatry, Mayo Clinic, Rochester; Abhinav Rastogi, MBBS, MRCPsych, Resident Psychiatrist, Stratford Road Day Centre, Birmingham, UK
Contributor Information and Disclosures

Updated: Jan 29, 2010

Treatment

Medical Care

Treatment of sedative-hypnotic overdose

• 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 hemodynamic status.
  • 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.
• Benzodiazepines are the most commonly prescribed and abused sedative-hypnotics, but they produce less respiratory depression than barbiturates. Long-acting metabolites often cause intoxication that lasts for several days. Benzodiazepine overdose is most dangerous in combination with other sedative-hypnotics.
  • Benzodiazepine antagonist, flumazenil, is available for the treatment of benzodiazepine intoxication.⁶ 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 benzodiazepine dependence. (Weinbroum A et al, 1993; Wiviott SD, Source book of substance abuse and addiction, 1996).
  • Flumazenil is contraindicated in patients with increased intracranial pressure (ICP) or closed-head injury (CHI), those with a history of epilepsy, or those known to have ingested a tricyclic antidepressant (TCA) agent.⁷
  • Flumazenil should be administered in an initial IV dose of 0.2 mg given over 30 seconds, followed by a second 0.2 mg IV dose if there is no response after 45 seconds. This procedure can be repeated at 1-minute intervals up to a cumulative dose of 5 mg. In patients who are physically dependent on benzodiazepines, slowly administer repeated doses of flumazenil. (See Flumazenil).
  • Flumazenil is a short-acting drug; therefore, sedation after an initial awakening may recur. Observe patients with benzodiazepine toxicity for at least 2 hours after recovery from flumazenil for late respiratory depression or resedation.
• 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 severity of the patient's condition.
• Address all potential complications, such as aspiration, pulmonary edema, and respiratory failure due to sedative-hypnotic drug overdose. If a suicide attempt is suspected, then place the patient on suicide precautions and order a psychiatric evaluation.

General principles for treatment of sedative-hypnotic withdrawal syndromes

• 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 basic principle is to withdraw the addicting agent slowly to avoid convulsions.
  • 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.
  • 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.
  • An initial dose is given, usually 30-60 mg of phenobarbital or equivalent. The withdrawal drug is repeated at hourly or 2-hour intervals as needed for 2-7 days.⁶ The patient should be monitored closely for acute changes in vital signs or worsening delirium, as well as for other withdrawal symptoms.
  • After the patient has received similar 24-hour doses for 2 consecutive days, the 24-hour stabilizing dose is given in divided doses every 3-6 hours. This index dose is then tapered, reducing subsequent daily doses by 30-60 mg/day.⁶

Treatment of severe sedative-hypnotic withdrawal

• 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 symptoms.
  • Advanced withdrawal is most safely managed in an intensive care environment, especially 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.
  • Treatment with oral agents: Determine the level of tolerance by giving pentobarbital, 200 mg by mouth and wait 1 hour. Look for signs of nystagmus, ataxia, drowsiness, dysarthria, decreased blood pressure, and decreased pulse. If 2 or more signs are present, stop the procedure and convert to phenobarbital; if not, give pentobarbital (100 mg by mouth) every hour until 2 or more signs are present or a total of 600 mg pentobarbital has been given. Convert to phenobarbital, 30 mg for every 100 mg of pentobarbital given. Then, decrease phenobarbital by 10% of the initial dose per day.
  • Treatment with parenteral agents: Phenobarbital is recommended for most patients due to its long half-life, which allows less frequent dosing once the total daily dose needed to control withdrawal symptoms is determined. Infuse phenobarbital intravenously until the patient shows signs of mild intoxication (nystagmus, ataxia, drowsiness, dysarthria, decreased blood pressure, and decreased pulse). Once that dose is determined, it is the daily dose required to block withdrawal and may be given on subsequent days in divided doses.
  • Short-acting medications, instead of phenobarbital, are indicated for patients with severe hepatic failure and for hemodynamically unstable patients who require very rapid medication titration to control withdrawal symptoms. If a short-acting medication is to be used, choose among midazolam, diazepam, or lorazepam, depending on rapidity of reversal of effects required. Intravenous medication should be given until signs of intoxication or reduction of withdrawal signs occurs. For the short-acting intravenous medications, adjust frequency of administration to duration of action of the medication and reduce the total daily dose 10% per day.

Treatment of mild-moderate sedative-hypnotic withdrawal

• Many patients who have mild dependence on benzodiazepines can be managed by a slow taper of the drug in an outpatient setting. The first step is to objectively determine an approximate level of drug to which the patient is tolerant; patients tend to overestimate or underestimate the amount of drug they have been taking.
• 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.⁶
• The following is a commonly used benzodiazepine equivalence schedule. Diazepam 10 mg is approximately equivalent to the following drugs and doses:²
  • Alprazolam - 1 mg
  • Chlordiazepoxide - 25 mg
  • Clonazepam- 0.5-1 mg
  • Lorazepam - 2 mg
  • Oxazepam - 30 mg
  • Temazepam - 20 mg
  • Zolpidem- 10 mg
• 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) have been used successfully in the treatment of mild sedative-hypnotic withdrawal. The main rationales for using anticonvulsants in substance-abuse patients are their lack of addiction potential, evidence supporting a role of kindling mechanisms in withdrawal syndromes, and their efficacy in comorbid psychiatric disorders. The available data currently support the utilization of carbamazepine as a treatment for detoxification from benzodiazepines and use of gabapentin and topiramate in the treatment of benzodiazepine detoxification.⁸

Consultations

• Neurologist: Consultation is indicated if seizures are unresponsive to usual treatment of the withdrawal symptoms or when neurologic symptoms not explained by the usual symptoms of intoxication or withdrawal are present.
• Psychiatrist: Consultation is indicated in the context of suicidal risk, aggressive behavior, or comorbid psychiatric disorders (eg, mood or psychotic disorders).
• Poison centers: Poison centers may be contacted to obtain information about other possible unknown substances being used, especially in overdose situations.

Diet

Keep nothing by mouth if patient is unconscious.

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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