Benzodiazepine

Intoxication and
W i t h d r a w a l : Assessment and Management
David W. Galarneau,

MD

a,

*, Erich J. Conrad,

MD

KEYWORDS
 Benzodiazepine  Intoxication  Tolerance  Withdrawal  Dependence  Addiction

HOSPITAL MEDICINE CLINICS CHECKLIST

1. Benzodiazepines are one of the most commonly prescribed classes of medication. In addition to their beneficial therapeutic effects, there are inherent
risks with their use, including abuse, dependence, intoxication, and
withdrawal.
2. Benzodiazepines act on gamma-aminobutyric acid (GABA) A receptors, exerting a calming effect, as well as producing drowsiness and facilitating sleep.
They hold US Food and Drug Administration approved indications for generalized anxiety disorder, panic disorder, insomnia, and seizure disorder.
3. Slurred speech, ataxia, and incoordination can occur with mild to moderate
intoxication. A paradoxic agitated confusion or delirium can occur on occasion, in certain populations.
4. Development of stupor or coma can occur at more severe stages of intoxication. Benzodiazepines rarely lead to death when ingested alone.
5. Clinical interview and examination, collateral information, and urine toxicology
are the cornerstones of the evaluation of benzodiazepine intoxication.
6. The management of intoxication includes evacuation of the gastrointestinal
tract, as well as assessment and management of the airway if needed.
7. Chronic use of benzodiazepines routinely leads to tolerance, dependence,
withdrawal, and addiction.
8. Tolerance and withdrawal have been linked to neuroadaptive changes
involving GABAergic and glutamatergic receptors in the central nervous system that are induced by chronic drug use.
CONTINUED

Disclosures: The authors have no conflicts of interest or funding sources to disclose.

a
Ochsner Health System, The University of Queensland, New Orleans, LA, USA; b Louisiana
State University School of Medicine, New Orleans, LA, USA
* Corresponding author.
E-mail address: dgalarneau@ochsner.org
Hosp Med Clin 4 (2015) 513525
http://dx.doi.org/10.1016/j.ehmc.2015.06.005
2211-5943/15/$ see front matter 2015 Elsevier Inc. All rights reserved.

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CONTINUED

9. Benzodiazepine discontinuation can lead to 4 distinct syndromes: recurrence

or relapse, rebound, pseudowithdrawal, and true withdrawal.
10. There is a great variability to withdrawal symptoms and syndromes: they differ
between and within people as well as agents.
11. Frequent symptoms of withdrawal include anxiety, insomnia, restlessness,
agitation, irritability, and muscle tension. Uncommon but serious symptoms
are psychosis, seizures, confusion, paranoid delusions, hallucinations, and
persistent tinnitus. Death can ensue if withdrawal is severe and not managed
properly.
12. Although a variety of factors exist, time course and severity of the withdrawal
syndrome are most commonly linked to the dose, duration of use, and duration of drug action.
13. In addition to pharmacokinetic and drug-specific factors, there are a variety of
clinical factors that influence the withdrawal syndrome, including degree of
mental disorder, polysubstance abuse, chronic comorbid medical conditions,
age, gender, and educational level.
14. The evaluation and assessment of benzodiazepine withdrawal involves clinical
interview and history taking, physical and mental status examination, and
basic laboratory work (including urine toxicology and blood alcohol level).
15. The first step in the management of benzodiazepine withdrawal is the determination of the appropriate setting for detoxification.
16. There are 2 primary options for detoxification: tapering, or substitution and
tapering.
17. Adjuvants to a benzodiazepine detoxification regimen include anticonvulsants
and cognitive behavior therapy.
18. The best prevention for benzodiazepine dependence and addiction is careful
prescribing.

OVERVIEW

Benzodiazepines have been one of the most commonly prescribed medications since
their introduction in the 1960s. They have long eclipsed the use of barbiturates, primarily because of their improved safety profile. Continued controversy exists
regarding what role the benzodiazepines should have in the treatment of anxiety disorders, and whether there is potential long-term risk with the development of dementia.14 In addition to the beneficial therapeutic effects, there are inherent risks with use,
including abuse, dependence, intoxication, and withdrawal, which every clinician
needs to be able to recognize and manage.
PHARMACOLOGY

What is a benzodiazepine?
Benzodiazepines are a class of psychotropics that exert a variety of effects, including
hypnotic, anxiolytic, anticonvulsant, myorelaxant, and amnesic.5 Benzodiazepines are
agents that hold US Food and Drug Administration approved indications for generalized anxiety disorder, panic disorder, insomnia, and seizure disorder. They have
similar mechanisms of action, but have differing pharmacokinetic properties that

Benzodiazepine Intoxication and Withdrawal

provide each agent with its own unique niche in a broader spectrum of general class
effects. Boxes 1 and 2 list the specific pharmacokinetic properties of the differing
agents.
Where do benzodiazepines exert their therapeutic effects?
Benzodiazepines act on gamma-aminobutyric acid (GABA) A receptors.6 As depicted
in Fig. 1, the GABAA receptor is a pentamer spanning the plasma membrane and forming a chloride channel. There are 19 different subunits that can compose the receptor
complex: a1 to 6, b1 to 3, g1 to 3, d, , q, r1 to 3.6 Classically, the pentamer is made up
of 2 b subunits, 2 a subunits, and 1 g subunit. There are 2 GABA recognition sites per
GABAA receptor complex, and an increase in the concentration of GABA results in an
increase in the mean channel open time.7 It seems that this complex is responsible for
the anxiolytic, sedative, and anticonvulsant effects of benzodiazepines. The GABAA
receptor is modulated by several classes of drugs that bind allosteric sites on the receptor complex. The mechanism of action of benzodiazepine agonists is to enhance
GABAergic transmission by increasing the frequency of channel opening in response
to GABA.8 The benzodiazepine binding site is positioned between the a and g
subunits.7
INTOXICATION

What are the clinical signs and symptoms of intoxication?

Slurred speech, ataxia, and incoordination can occur with mild to moderate intoxication. A paradoxic agitated confusion or delirium can occur on occasion, particularly in
older adults or those with a history of traumatic brain injury.9,10 Box 3 provides more
details on benzodiazepine effect and intoxication.
Is intoxication dangerous?
Development of stupor or coma can occur at severe stages of intoxication. Benzodiazepines rarely lead to death when ingested alone; a lethal dose has not been established for any of the benzodiazepines.10,11 The few deaths that have occurred involved

Box 1
Benzodiazepine dose comparisons (approximate)
Clonazepam (Klonopin): 0.25 mg
Triazolam (Halcion): 0.25 mg
Alprazolam (Xanax): 0.5 mg
Lorazepam (Ativan): 1 mg
Diazepam (Valium): 5 mg
Clorazepate (Tranxene): 10 mg
Temazepam (Restoril): 10 mg
Flurazepam (Dalmane): 15 mg
Oxazepam (Serax): 15 mg
Chlordiazepoxide (Librium): 25 mg

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Box 2
Half-life and potency of various benzodiazepines
Short half-life, high potency
Alprazolam (Xanax)
Lorazepam (Ativan)
Triazolam (Halcion)
Short half-life, low potency
Oxazepam (Serax)
Temazepam (Restoril)
Long half-life, high potency
Clonazepam (Klonopin)
Long half-life, low potency
Chlordiazepoxide (Librium)
Clorazepate (Tranxene)
Diazepam (Valium)
Flurazepam (Dalmane)

short-acting, high-potency benzodiazepines such as alprazolam or triazolam, or

administration of benzodiazepines by an intravenous route.10
On rare occasions, patients have been simultaneously intoxicated and in withdrawal. This condition is most typically seen as a result of chronic daily use of very

Fig. 1. GABAA receptor. BZD, benzodiazepine.

Benzodiazepine Intoxication and Withdrawal

Box 3
Benzodiazepine effect and intoxication
Beneficial effects
Decreases activity
Reduces excitement
Exerts a calming effect
Alleviates anxiety
Induces drowsiness
Facilitates sleep
Paradoxic effects (most often seen in the elderly)
Agitated confusion
Delirium
Mild to moderate intoxication
Slurred speech
Ataxia
Incoordination
Severe intoxication
Respiratory depression
Stupor
Coma
Death (rare when ingested alone)

high doses of benzodiazepines. Management of this condition is complex and best

accomplished in an inpatient setting.
Benzodiazepines seem to not cause damage to peripheral organ systems in either
long-term use or acute overdose.10 Benzodiazepines have a ceiling effect in terms of
respiratory depression, and for the most part escalating doses plateau in a nonlethal
state, which is in contrast with barbiturates, for which no ceiling effect exists. However,
in rare cases, respiratory depression is possible with the use of benzodiazepines, such
as in patients with severe chronic obstructive pulmonary disease.12 In addition, in patients with severely impaired liver function, benzodiazepines that rely on metabolism
through the liver can build up and be toxic. Despite their safety in single-agent overdose,
benzodiazepines can be fatal in mixed overdoses,11 especially if in combination with
neuronal inhibiting agents, such as alcohol, major tranquilizers, or opiates.
How is intoxication evaluated and assessed?
Clinical interview and examination, collateral information, and urine toxicology are the
cornerstones of the evaluation of benzodiazepine intoxication.
What is the management of intoxication?
In a benzodiazepine overdose, assessment and maintenance of the airway are essential. If necessary, intubation and ventilator support are initiated. Evacuation of the

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gastrointestinal tract with a large-bore orogastric tube may be necessary, because

some agents can slow gut motility or form concretions in the stomach.10 Activated
charcoal and a dose of cathartic should be given, and repeated doses of charcoal
may be needed for agents with extensive enterohepatic circulation in order to speed
elimination.10
Flumazenil is a competitive benzodiazepine receptor antagonist and can reverse the
effects of benzodiazepines. Flumazenil exceeding 1 mg has been associated with seizures and cardiac arrhythmias; therefore, slow titration is recommended.10 Patients
physiologically dependent on benzodiazepines, or who have ingested benzodiazepines in combination with other substances that lower the seizure threshold, are at
highest risk for seizures when given flumazenil.13
As intoxication wanes, it is important to be vigilant for the development of a withdrawal syndrome.
WITHDRAWAL

What are tolerance and withdrawal?

When benzodiazepines are used routinely (ie daily or near daily) they can lead to the
development of tolerance and withdrawal. Box 4 provides brief definitions of these
terms, as well as other common addiction terms. Benzodiazepine and alcohol withdrawal share many similarities, which are a function of the properties of the GABA
receptor.
What are the molecular underpinnings of tolerance and withdrawal?
Tolerance and withdrawal have been linked to neuroadaptive changes in the central
nervous system that are induced by chronic drug use. In the case of benzodiazepines,

Box 4
Addiction terminology
Tolerance
The diminishing effect of a drug resulting from repeated administration at a given dose.
Withdrawal
A characteristic group of symptoms that occurs on the abrupt discontinuation or decrease in
intake of a drug.
Dependence
An adaptive state associated with a withdrawal syndrome on cessation of repeated drug
intake.
Physical dependence
Dependence that involves physical-somatic withdrawal symptoms (eg, fatigue).
Psychological dependence
Dependence that involves emotional-motivational withdrawal symptoms (eg, dysphoria and
anhedonia).
Addiction
A state characterized by compulsive engagement in rewarding behavior or compulsive drug
use, despite adverse consequences.

Benzodiazepine Intoxication and Withdrawal

chronic use leads to a diminution of GABAergic neuronal inhibition coupled with a

compensatory excitation of the glutamate system.7 These neuroadaptive changes
serve to counterbalance the uptick in benzodiazepine-induced GABA release. They
serve to dull or mollify the benzodiazepine response, thus leading to tolerance.
When the benzodiazepine agent is rapidly removed, an excitatory state ensues,
thus producing withdrawal. As withdrawal progresses and finally ceases, there is a return toward the original balance between GABAergic and glutamatergic tone, although
the initial set point is not necessarily reached.
Specific examples of neuroadaptation include the following:
 Tolerance: GABA receptor downregulation (through decreased receptor number,
decreased GABA receptor function, and diminished protein synthesis for GABA
receptors)7
 Withdrawal: GABA receptor upregulation and enhanced function (as shown by
greater affinity for GABA, increased affinity of the benzodiazepine receptor for
benzodiazepines, increased benzodiazepine receptor number)7
Thus it must be noted that although benzodiazepines act on the GABA receptor,
their use is intricately associated with the glutamatergic system as well. This association is especially notable in the withdrawal syndrome, in which some of the symptoms are secondary to increased glutamatergic activity.
What are the possible clinical manifestations of benzodiazepine discontinuation?
Benzodiazepine discontinuation can lead to 4 distinct syndromes: recurrence or relapse,
rebound, pseudowithdrawal, and true withdrawal.10,14 Box 5 outlines these syndromes.
Although the 4 syndromes mentioned earlier are distinct entities, there exists
considerable overlap in the clinical setting. In addition, a subgroup of patients experience a protracted withdrawal syndrome, most commonly after the discontinuation of
long-term benzodiazepine use.10,15 The syndrome is characterized by an irregular and
unpredictable daily course, as well as qualitative and quantitative differences in symptoms from the initial symptoms that were present before benzodiazepine initiation, as
well as those present in the acute withdrawal period.10,15

Box 5
Benzodiazepine discontinuation syndromes
 Recurrence or relapse: a recurrence of symptoms (such as insomnia or anxiety) for which the
benzodiazepine was initially taken. Recurrence is not necessarily linked to physiologic
dependence and is common. Recurrence can present rapidly or slowly, over days to months.
 Rebound: symptoms that develop within hours to days of discontinuation and, although
qualitatively similar to those for which the agent was prescribed, are significantly more
intense than what was experienced before initiation of drug treatment.
 Pseudowithdrawal: an overinterpretation of symptoms, when an expectation of withdrawal
leads to the experiencing of abstinence symptoms. Most notably, pseudowithdrawal has
been observed in patients who discontinued placebo medication or continued
benzodiazepine use but thought it had been stopped, although it is not confined to these
populations.
 True withdrawal: the emergence of somatic and psychological signs and symptoms of the
withdrawal syndrome after discontinuation of benzodiazepines in individuals who are
physically dependent on the drug. True withdrawal can be suppressed, either by restarting
the discontinued drug or by initiation of a cross-tolerant agent.

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What are the clinical signs and symptoms of withdrawal?

The signs and symptoms of withdrawal are numerous; Box 6 provides a comprehensive list.10,14 Considerable variation exists regarding which symptoms are experienced by individual patients and in what sequence. Any combination can be
experienced throughout the withdrawal syndrome, and none are pathognomonic of
benzodiazepine withdrawal.
Frequent symptoms of the withdrawal syndrome include anxiety, insomnia, restlessness, agitation, irritability, and muscle tension. Less frequent symptoms include nausea,
diaphoresis, lethargy, myalgias, coryza, hyperacusis, blurred vision, nightmares, depression, hyperreflexia, and ataxia. Uncommon but serious symptoms are psychosis, seizures, confusion, paranoid delusions, hallucinations, and persistent tinnitus. Clinicians
must exercise constant vigilance during a complicated withdrawal syndrome, because
it can end in death if it is not managed properly and in a timely fashion.
What affects the time course, duration, and severity of withdrawal?
There is a great variability to withdrawal syndromes: they differ between and within people as well as agents. This variability is accounted for by a variety of factors, which are
Box 6
Benzodiazepine withdrawal signs and symptoms
Tachycardia
Hypertension
Fever
Diaphoresis
Anorexia
Diarrhea
Nausea
Agitation
Anxiety
Irritability
Restlessness
Insomnia
Nightmares
Tremor
Hyperreflexia
Tinnitus
Sensory disturbances
Delirium
Hallucinations
Paranoid delusions
Seizures
Death

Benzodiazepine Intoxication and Withdrawal

discussed later. These variables have commonly been divided into drug variables and
clinical variables.14 Three factors are of particular interest and are linked most
commonly to the time course, duration, and severity of withdrawal. These 3 factors,
which are classified as drug variables, are the dose, duration of use, and duration of
drug action.10 In terms of withdrawal severity, dose and duration of use are most important. In relation to latency of onset of the syndrome, the elimination half-life is primary.10
Physiologic dependence can develop after just 2 weeks of daily use, but a clinically
significant withdrawal syndrome is most commonly seen after discontinuation of a
daily therapeutic dose lasting 4 to 6 months.10,14 This period can be shortened to 2
to 3 months if the daily dose used is supratherapeutic.10
What are the drug variables affecting withdrawal?
As noted earlier, there are a multitude of drug variables that affect the withdrawal syndrome. Perhaps one of the most important factors is the pharmacokinetics of the agent
in question. The onset, duration, and severity of the withdrawal syndrome are all linked
to the elimination half-life, which correlates with the decline in serum drug levels.10
 Short-acting benzodiazepines
 Onset of withdrawal: within 24 hours of cessation
 Peak severity: within 1 to 5 days
 Duration of withdrawal: 7 to 21 days on average
 Long-acting benzodiazepines
 Onset of withdrawal: within 5 days of cessation
 Peak severity: within 1 to 9 days
 Duration of withdrawal: 10 to 28 days on average
Withdrawal symptoms are usually more severe or intense for short-acting, high-potency benzodiazepines.10,14,16 Severity of the withdrawal syndrome is also linked to
higher doses and longer use.10,14,16 Examples of the severities of characteristic withdrawal syndromes are presented in Box 7; however, these serve only as examples
and, in practice, much variability exists.
Continuous use of benzodiazepines for greater than 1 year may also predispose patients to protracted withdrawal, independent of the severity of the withdrawal symptoms.15 Although most withdrawal syndromes tend to gradually resolve over a
period of 3 to 6 weeks, protracted withdrawal can persist for months or even years.14
What are the clinical variables affecting withdrawal?
In addition to pharmacokinetic and other drug variables, there are a variety of clinical
factors that also influence the withdrawal syndrome.14 Degree of mental disorder is

Box 7
Severity of characteristic withdrawal syndromes
 Daily benzodiazepine use for 10 days or less: transient insomnia
 Short-term (<23 months), low-dose therapeutic use: mild and easily managed withdrawal
symptoms
 Short-term, high-dose use (>4 or 5 times the therapeutic range): a moderate to severe
withdrawal syndrome
 Long-term (>1 year), low-dose therapeutic use: a moderate to severe withdrawal syndrome.

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correlated to the severity of withdrawal symptoms, as well as difficulty in discontinuing

benzodiazepine use.10,14 High initial anxiety or depression is associated with
increased withdrawal symptoms, and the reduction of anxiety symptoms is a predictor
of success in achieving and maintaining sobriety.10,14
Comorbidity is also linked to the severity of the withdrawal syndrome. This link holds
for the abuse of additional substances, as well as chronic medical conditions.10,14
The withdrawal syndrome is complicated by the use of concomitant substances.14,17 The specific effects seen are directly related to the properties of these
substances. Neuronal inhibitors, such as alcohol and opiates, produce additive or
overlapping effects that can lead to an exacerbation of symptoms.10 Moderate alcohol
use is a more significant predictor of benzodiazepine withdrawal severity than the
pharmacokinetics of the agent itself. Neuronal excitatory agents such as cocaine
and stimulants produce a variable clinical picture, often leading to a mixed syndrome
or a masking of symptoms.10 However, polysubstance abuse and multidrug detoxification is more the rule than the exception, because benzodiazepines are most often
used in combination with other psychoactive drugs, rather than as initial or primary
agents of abuse.10,17
For the most part, patients with comorbid chronic medical illnesses experience a
more severe withdrawal syndrome than their healthy cohorts,10,18 particularly for conditions involving the adrenergic system. This tendency must be taken into account
when deciding when to initiate a benzodiazepine detoxification program. As a general
rule, it should not be initiated until the patient is in a stable medical condition, especially if improvement in the comorbid medical condition is anticipated in the near future
with current medical management.
In general, older age is associated with a more severe withdrawal syndrome,9,10 in
part because of the decreased efficacy of the hepatic microsomal enzyme oxidase
system with age.9 A reduction in the efficacy of this system leads to longer elimination
half-lives and a more protracted and severe withdrawal syndrome.9,10 All benzodiazepines use this system for degradation and excretion, with the exceptions of lorazepam, temazepam, and oxazepam, which are primarily excreted renally.
Female gender is associated with increased withdrawal severity in the tapered
cessation of a long-term therapeutic benzodiazepine, but gender is not implicated
in abrupt cessation of long-term use.10 The GABAA receptor contains a binding site
for the neurosteroid pregnenolone,7 which may play a role in gender differences concerning the benzodiazepine receptor. Increased withdrawal symptoms have been
associated with decreased educational level.10
Box 8 summarizes the factors discussed earlier that influence the withdrawal
syndrome.
How is withdrawal evaluated and assessed?
Box 9 outlines the steps routinely taken in the evaluation and assessment of benzodiazepine withdrawal.
What is the management of withdrawal?
Clinicians must consider carefully the findings of the evaluation and assessment in order to decide what would be the best setting for the management of withdrawal. For
low-dose users, motivational interviewing may be used and the patient advised how to
quit or reduce the dose gradually. For patients dependent on sedative hypnotics, a
scheduled detoxification is likely to be necessary.14,16

Benzodiazepine Intoxication and Withdrawal

Box 8
Factors affecting the withdrawal syndrome
Drug variables
Elimination half-life
Potency
Dose
Duration of use
Clinical variables
Degree of mental disorder
Polysubstance abuse
Chronic medical conditions
Age
Gender
Educational level

There are 2 primary options for detoxification: tapering or substitution and

tapering.10 With the taper method, patients are slowly and gradually weaned from
the benzodiazepine on which they are dependent, using a fixed-dose taper schedule
with the dose being decreased on a weekly to every-other-week basis. The rate of
discontinuation for long-term users (>1 year) should not exceed 5 mg of diazepam
equivalents per week, or 10% of the current dose per week, whichever is smaller.10
Anticipating the needs of the patient, clinicians should be aware that the first half of
the taper is usually smoother, quicker, and less symptomatic than the last half. For the
final 25% to 30% of the taper, the rate or dose reduction schedule should be slowed to
half the previous dose reduction per week, and the reduction accomplished at twice
the original tapering interval.10 If symptoms of withdrawal occur, the dose should be
increased slightly until the symptoms resolve and the subsequent taper schedule
can be commenced at a slower rate.
If patients are unable to complete a simple taper program as outpatients, they may
require a substitution and taper program, or even a period of hospitalization.10 Substitution and taper methods use cross-tolerant long-acting benzodiazepines to
Box 9
Evaluation and assessment of benzodiazepine withdrawal
 Take a sedative-hypnotic use history: dose, duration of use, substances used, clinical
response, attempts at abstinence, previous detoxifications, and complications of
withdrawal experienced in the past.
 Take a psychiatric history, including substance abuse.
 Take a medical history, family history, and psychosocial history.
 Perform a physical and mental status examination.
 Collect a urine toxicology and blood alcohol level.
 Procure basic laboratory work.
 Determine the appropriate setting for detoxification.

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substitute, at equipotent doses, for the sedative hypnotics on which the patient is
dependent. With longer acting benzodiazepines, there is negligible interdose serum
level variation. With tapering, a more gradual reduction in serum levels occurs,
reducing emergent withdrawal symptoms. However, there are reported cases in which
only the primary agent is capable of controlling withdrawal symptoms.19 This finding
tends to be true for high-potency agents such as alprazolam or clonazepam.
Phenobarbital has also been used in substitution and taper regimens and offers the
added advantage of rarely inducing behavioral disinhibition, in addition to possessing
broad clinical efficacy in the management of withdrawal from all classes of sedativehypnotic agents.10 If impaired hepatic function or increased liver tests are present,
then oxazepam or lorazepam are good substitutions.
Nonbenzodiazepine agents have been used as adjuvants to benzodiazepines in
detoxification protocols.20,21 Most notably, anticonvulsants such as valproic acid
and carbamazepine have shown efficacy in preventing withdrawal seizures. This strategy is particularly appealing in patients with comorbid bipolar disorder, because valproic acid and carbamazepine are well-established mood stabilizers.
In addition to pharmacologic approaches, psychotherapy has been used to help
manage withdrawal symptoms. In particular, there are data that show the utility of
cognitive behavior therapy.14
Inpatient detoxifications are best for patients who have polysubstance dependence,
mixed alcohol and other sedative-hypnotic use, high-dose hypnotic sedative use,
erratic behavior, incompatible use histories, involvement with illicit sources, and
extensive mental health issues.10
After detoxification is complete, most patients benefit from a comprehensive recovery program that includes both 12-step meetings and a formal rehabilitation program.
In addition, note that the best prevention for benzodiazepine dependence is careful
prescribing.
PERFORMANCE IMPROVEMENT

There are no large-scale randomized controlled trials to compare different treatment

options in the management of benzodiazepine withdrawal. Future research could
help elucidate which management strategies are most beneficial, or whether there
is a difference in clinical outcome.
CLINICAL GUIDELINES

American Psychiatric Association clinical guidelines.

Substance Use Disorders (May 2006)
 Practice Guideline
 Guideline Watch
 Quick Reference Guide
Available at: http://psychiatryonline.org/guidelines.
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