Download Alcohol and Sedative Hypnotics– Ellen A. Ovson, MD

Ellen A. Ovson, M.D., F.A.S.A.M.
Medical Director
Bradford Health Services, Madison, Alabama
“If the patient be in the prime of life and if from
drinking he has trembling hands, it may be well
to announce beforehand either delirium or
convulsions”
Hippocrates circa 400 BC
BAC 20 mg% to 99 mg%
Loss of muscular coordination
Changes in mood, personality, and behavior
BAC 100 mg% to 199 mg%
Neurologic impairment
Prolonged reaction time
Ataxia
Incoordination
Mental impairment
BAC 200 mg% to 299 mg%
Marked ataxia
Nausea and vomiting
BAC 300 mg% to 399 mg%
Hypothermia
Severe dysarthria
Amnesia
Stage I anesthesia
BAC 400 mg% to 799 mg%
Alcoholic coma
Progressive obtundation
Decreased respiration
Decreased blood pressure
Decreased body temperature
Urinary incontinence or retention
Reflexes markedly decreased or absent
BAC 600 mg% to 800 mg%
Often fatal
Death may occur from loss of airway protective
reflexes (obstruction from flaccid tongue)
Pulmonary aspiration of gastric contents
Profound CNS depression
Supportive
Primary goals
Prevent respiratiory depression
Protect airway (prevent aspiration)
Survival is probable with respiratory and
cardiovascular support
IV glucose and thiamine (alcohol impairs
glucogenesis)
Emesis / gastric lavage not indicated (EtOH rapidly
absorbed)
Charcoal does not absorb alcohol
Enhancement of elimination has no role
Hemodialysis is effective, but rarely indicated since
treatment is supportive only
No effective antagonist (flumazenil not effective)
Agitation best managed non-pharmacologically
Rate of metabolism follows zero order kinetics
Independent of time and concentration of the
drug
Elimination occurs at a rate of 15 to 20 mg/dl/hr
Begins 6 to 24 hrs after last drink
Onset sometimes before BAC reaches 0
Early symptoms include anxiety, sleep disturbance,
vivid dreams, anorexia, nausea, and headache
Physical signs include tachycardia, elevation of blood
pressure, hyperactive reflexes, sweating, and
hyperthermia
Tremor of hands/or tongue, 6 to 8 cycles/sec
(exaggeration of normal physiologic tremor on EMG)
Seizures may occur, typically within 48 hrs
Delirium tremens may begin 48 to 72 hrs after
last drink, preceded by symptoms of early
withdrawal
Profound sympathetic hyperactivity (tachycardia,
hypertension, fever, diaphoresis)
Mortality rate 1% to 5%, increases with delayed
diagnosis, inadequate treatment, and concurrent
medical illness
Effect of alcohol exerted through GABA
Sedation, muscle relaxation, increased seizure
threshold
Chronic alcohol exposure leads to adaptive
suppression of GABA activity
Abstinence produces sudden relative deficiency
in GABA activity resulting in anxiety, increased
psychomotor activity, and predisposition to
seizures
Alcohol inhibits sensitivity to autonomic adrenergic
systems
Chronic alcohol uptake results in upregulation
Discontinuation of alcohol results in rebound
overactivity of central and peripheral noradrenergic
systems
Increased sympathetic autonomic activity from the
locus ceruleus contributes to tachycardia,
hypertension, tremor, diaphoresis, and anxiety
In mild withdrawal, may experience perceptual
distortions of visual, auditory, or tactile nature
(too bright, too loud, pins and needles)
Frank hallucinations may develop in severe
withdrawal
Visual hallucinations are most common and
frequently involve animals
Auditory hallucinations begin as unformed
sounds (clicks or buzzing) and may progress to
voices
Often friends and relatives, often accusatory
Tactile hallucinations may involve bugs crawling
on the skin
In milder cases of withdrawal, the patient’s
sensorium is otherwise clear and the patient
retains insight that the hallucinations are not
real
In more severe withdrawal, this insight may be
lost
Generalized major motor seizures
May occur singly or in a burst of several seizures over a
few hours
Onset is usually 8 to 24 hours after last drink and may
occur before BAC zero
Fewer than 3% progress to status epilepticus (but
alcohol involved in 25% of status epilepticus)
Seizures peak 24 hours after last drink,
corresponding with EEG abnormalities
(increased amplitude, photomyoclonic
response, and spontaneous paroxysmal activity)
EEG changes transient
Risk of seizures appears to be genetically
influenced
Increased risk in those with prior history of
withdrawal seizures
Increased risk in those undergoing concurrent
sedative-hypnotic withdrawal
Kindling effect
Increased risk of seizures as an individual
undergoes repeated withdrawals
Delirium tremens generally appears 72 to 96
hours after last drink
Marked tachycardia, tremor, diaphoresis, fever
Global confusion; disorientation to place and
time; may become absorbed in a separate
psychic reality
Hallucinations frequent, may have no insight,
and therefore may be very frightening
Marked psychomotor activity may develop
Severe agitation in some cases
Persistent low level motor activity in others
Severe disruption in sleep-wake cycle is
common; absence of clear sleep for days
Duration is variable, 2 to 3 days in most studies
May last few hours
May last several days (report of confusion lasting
50 days before clearing)
Amount of daily intake and duration of heavy
drinking have not been correlated consistently
to the risk of severe withdrawal
BAC >300 mg% on presentation at higher risk of
DT’s
Withdrawal seizure at presentation increases
risk of DT’s
Older patients at higher risk of confusion and
delirium, may not involve severe autonomic
manifestations of classic DT’s
CIWA, and shortened version CIWA-Ar are most
extensively studied
Documented reliability, reproducibility, and
validity
<9 indicates mild withdrawal, 10 to 18 indicates
moderate withdrawal, and >18 suggests severe
withdrawal
High scores are predictive of seizures and
delirium
ASAM Clinical Practice Guidelines (1997)
reviewed literature on pharmacologic
management of withdrawal
Evidence indicated that the cornerstone of
pharmacologic management of withdrawal is
the use of benzodiazepines
Pharmacologically cross tolerant with alcohol
Produce the similar effect of enhancing GABAinduced sedation
Administration of benzodiazepines alleviates
the acute deficiency of GABA activity that
occurs with sudden cessation of alcohol
All are similarly efficatious in reducing signs and
symptoms of withdrawal
Longer acting agents (diazepam and chlordiazepoxide) may
be more effective in preventing seizures
Longer acting agents may provide a smoother withdrawal
course
Longer acting agents may pose a risk for oversedation in
the elderly and those with liver disease (shorter acting
agents, lorazepam or oxazepam may be preferable).
Rapid acting agents (diazepam, lorazepam, and
alprazolam) offer more prompt control of
symptoms
Rapid acting agents demonstrate greater abuse
potential
Not as extensively studied
Size of studies not adequate to draw
conclusions regarding efficacy in reduction of
seizures and delirium
Benzodiazepines offer greater margin of safety
with lower risk of respiratory depression as well
as overall lower risk of abuse
“Phenobarbital, a long acting barbiturate, still is
used by some programs, as it is long-acting, has
well-documented anticonvulsant activity, is
inexpensive, and has low abuse potential.”
Fixed Schedule
Medication administered in fixed amounts at
scheduled times for five to seven days
However, many patients can go through withdrawal
with only minor symptoms and need little or no
medication
Symptom-triggered therapy
Patient is monitored with structured assessment
scale and given medication only when symptoms
cross a threshold of severity
Studies demonstrate as effective as fixed-dose
regimen, but significantly less medication used
and significantly shorter duration of detox
Facilitates delivery of large amounts of medication
to patients with rapidly escalating symptoms, thus
reducing undertreatment with fixed-dose
schedule
In certain patients, such as those with severe
coronary artery disease, fixed-dose may be used
to prevent development of even minor
withdrawal symptoms
In patients with a history of alcohol withdrawal
seizures, fixed-dose may be used since seizures
usually occur early in the course of withdrawal
Any detox regimen should allow for
individualization with a mechanism to provide
for large amounts of medication rapidly if
needed.
Benzodiazepines should be administered orally
or intravenously
Lorazepam provides good intramuscular and
sublingual absorption
Beta blockers and alpha adrenergic agonists are
effective in ameliorating symptoms by reducing
autonomic manifestations of withdrawal
No demonstrated efficacy in reducing seizures or
delirium
Delirium is a rare side effect of beta blockers
Reduction in autonomic symptoms may mask
progression of withdrawal and hinder reliability of
withdrawal scales
Carbamazepine used in Europe for alcohol withdrawal
Equal efficacy to benzos for patients with mild to
moderate withdrawal
Without toxicity over 7 day course of tx, less
psychiatric distress, faster return to work, no
impairment of learning, no abuse potential
Prevents withdrawal seizure in animal studies
Studies of adequate size to demonstrate efficacy in
preventing withdrawal seizures or delirium not yet
available
Antipsychotics are less effective than
benzodiazepines to prevent delirium
Actually lead to increase rate of seizure
Widely used for agitation in withdrawal
Should never be used except in conjunction
with benzodiazepines
Magnesium generally normal at onset of withdrawal,
drops as withdrawal progresses, normalizes as
symptoms subside
Only one randomized trial of magnesium during
alcohol withdrawal documented
No difference in severity of withdrawal or rate of
seizures, regardless of magnesium correction
Oral magnesium supplementation is without risk
Routine magnesium administration no longer
recommended
Alcohol
No controlled trials comparing ethyl alcohol to
benzos or placebo
IV administration requires very close monitoring
Numerous adverse effects
Use is discouraged by addiction specialists
Phenytoin
Recent studies failed to demonstrate efficacy of
preventing recurrent withdrawal seizures
Benzos are extremely effective in preventing
withdrawal seizures, and the addition of phenytoin
does not lead to improved outcomes
Use of phenytoin in withdrawal has been largely
abandoned
Thiamine
Thiamine deficiency may lead to Wernicke’s disease
and the Wernicke-Korsakoff syndrome
Acute onset
Triad:
Mental disturbance
Global confusion, apathetic state, memory impairment
Paralysis of ocular movements
Sixth nerve palsy: weakness or paralysis of abduction,
invariably bilateral, rarely symmetric
Ataxia
Gait and stance
Neurologic emergency
Treated with immediate administration of
thiamine, 50 mg IV and 50 mg IM
Delay in thiamine administration increases risk
of permanent memory impairment
Administration of IV glucose may exhaust
reserve of B vitamins resulting in acute
precipitation of Wernicke’s disease
IV solutions containing glucose should always be
accompanied with administration of thiamine in
the alcoholic patient
Ocular palsy responds to thiamine
administration within hours
Gait and cognition improve more slowly
As apathy, drowsiness, and confusion recede, a
permanent defect in retentive memory and
learning known as Korsakoff’s psychosis may
persist
Patients with symptoms of Wernicke’s disease,
those to receive IV glucose solution, and those
at high risk of malnutrition should receive initial
dose of thiamine parenterally
Not all seizures in alcoholics are due to withdrawal
Alcoholics are at higher risk for seizures unrelated to
withdrawal
Careful history of temporal relationship of alcohol use
to the seizure should be taken, diagnosis of withdrawal
seizure should be assumed only is there is a clear
history of marked reduction or cessation of drinking 24
to 48 hours preceding the seizure
All patients with first seizure should be
admitted for observation and evaluation
Neurologic exam and brain imaging as a
minimum; EEG and lumbar puncture may be
appropriate
Previous history of withdrawal seizures with
clear history of withdrawal seizure may not
require full evaluation
If seizure is generalized
If no focal deficit on exam
If no history of head trauma
If no suspicion of meningitis
Then, additional testing has a very low yield and may
be safely omitted
Increased risk of seizures for 6 to 12 hours post seizure
Second seizure occurs in 1 of 4
Parenteral rapidly acting benzodiazepine indicated,
followed by oral detox regimen
Phenytoin no more effective than placebo at
preventing recurrent seizures
Since seizure increases risk for DT’s, admission for
treatment with benzos is safe and reasonable approach
Older studies indicated mortality ~30%
Current studies reflect ~1% mortality
Adequate sedation and meticulous medical care often
necessitate ICU admit
Management of fluid / electrolytes in midst of
marked autonomic hyperactivity
Often delirium arises in medically ill patient in
whom alcohol dependence was unrecognized
High index of suspicion for infection; may be
masked by fever, tachycardia, and confusion
Cross tolerant sedative-hypnotics reduce
mortality, but have not been shown to reverse
the delirium or reduce its duration
Goal is to sedate to a point of light sleep, thus
controlling agitation and preventing behavior risking
harm to self or staff, and allowing staff to provide
supportive medical care
IV benzodiazepines provide rapid control
Massive doses (hundreds, even thousands mg of
diazepam) may be required to control agitation
Respiratory support must be available
Reports of continuous infusion of short-acting
agents, but existing evidence suggests no more
effective than bolus dosing of longer-acting
agents
Benzodiazepines may be supplemented with
neuroleptic to manage agitation, but
neuroleptics must never be used alone due to
effect on seizure threshold
Management of withdrawal is only the first- and
at times most easily achieved- step toward the
primary goal of treating the patient’s underlying
addiction to alcohol
Development of a plan to engage the patient in
treatment is a critical component of withdrawal
Medical detoxification first, if applicable
Group therapy
Individual therapy
Experiential therapy
Twelve Step facilitation
Length of stay, regardless of level of care,
correlates directly with rate of sobriety.
Monitoring and accountability enhance that
rate.
Sedative-hypnotic medications decrease excitement,
exert a calming effect, and facilitate sleep.
Among the most widely prescribed drugs in the U.S.
Sedative-hypnotics stimulate the inhibitory
neurotransmitters in the GABA receptors.
Although all sedative-hypnotics are stimulating at low
doses, their primary effect is to decrease CNS function.
Those associated with severe withdrawal states
include: methaqualone, glutethimide, phenobarbital,
and short-acting benzodiazepines such as alprazolam
and triazolam.
Those with less severe clinical withdrawal include:
meprobamate, diazepam, chlordiazepoxide, and
lorazepam.
Mild to Moderate toxicity: slurred speech, ataxia, and
incoordination
In older adults, there may be a paradoxical agitated
confusion and even delirium.
Severe toxicity: stupor and coma
With older non-BZD agents, toxicity may progress
leading to respiratory arrest or cardiovascular collapse.
Overdose on the older agents may be associated with a
variety of agent-specific manifestations, such as the
bullous lesions (barb blisters) with barbiturates.
With the older sedative-hypnotic agents, tolerance
may develop to the therapeutic effects, but not their
lethal effects; therefore, the therapeutic index
decreases.
Toxicity and overdose thus occur with only small
increases over the individual’s regular intake.
On the other hand, benzodiazepines virtually never
lead to death when ingested by themselves.
A lethal dose has not been established for any of the
benzodiazepines.
The few reported deaths involved short-acting, high
potency BZDs such as alprazolam and triazolam, or
administration of BZDs IV.
Inappropriate administration of chlordiazepoxide by
the IM route can lead to erratic absorption, producing
respiratory compromise.
Despite their safety, BZDs continue to be a
major cause of overdose when ingested with
other agents.
Mixed overdoses – such as those in combination
with alcohol, major tranquilizers,
antidepressants, or opiates – can be fatal.
Assessment and maintenance of the airway and, when
required, ventilatory support are the cornerstone in
managing overdose.
Many BZDs slow gut motility and some – such as
phenobarbital, meprobamate, glutethimide, and
ethchlorvinyl – can form concretions in the stomach.
Therefore, gastric lavage is effective, provided that the
patient has an active gag reflex or is mechanically
ventilated.
Gastric lavage with 1.0 g/kg of activated charcoal,
alongwith a dose of cathartic, should be given,
followed by repeated doses of activated charcoal at
0.5-1.0 g/kg every 2-4 hours; alternatively, the charcoal
may be administered by slow continuous nasogastric
infusion.
Some agents have extensive enterohepatic circulation
and repeated doses of charcoal have been shown to
speed their elimination.
Alkalinization of the urine may be helpful in eliminating
phenobarbital, but forced diuresis has not been shown
to be helpful with any of the agents.
Flumazenil is a competitive antagonist with very weak
agonist properties at the BZD receptor; thus it can
reverse the effects of BZDs, but not alcohol or other
sedative-hypnotic agents.
Flumazenil’s primary indication is the reversal of
short-acting BZDs, such as midazolam, after
medical procedures.
It may also be used when BZDs have been
ingested alone in overdose.
Flumazenil is administered by slow IV titration,
not exceeding 1 mg, with monitoring for the
recurrence of sedation.
Flumazenil is very short-acting; therefore signs
of sedation may return in 50-60 minutes.
The use of flumazenil has been associated with
seizures and cardiac arrhythmias, especially
when it is administered rapidly in large amounts
and in patients who have ingested a sedativehypnotic in combination with a substance
capable of causing seizures (i.e., tricyclics).
Patients who are physiologically dependent on
BZDs are at high risk of seizures when given
flumazenil. Thus, flumazenil is not part of the
standard “coma cocktail” (thiamine, glucose,
and naloxone) because it causes rapid BZD
withdrawal.
Sedative-hypnotic withdrawal can occur with both
high- and low-dose use.
The withdrawal syndrome resembles that of acute
alcohol withdrawal syndrome in many ways due to
both binding to the GABA receptor.
The withdrawal syndrome is most likely to occur
following discontinuation of a low dose of at least 4-6
months or a high dose for 2-3 months.
Time course and severity of withdrawal of determined
by (1) dose, (2) duration of use, and (3) duration of
drug action.
Vital Signs
Tachcardia
Hypertension
Fever
Central Nervous System
Agitation
Anxiety
Delirium
Hallucinations
Insomnia
Irritability
Nightmares
Sensory disturbances
Tremor
Ears
Tinnitus
Gastrointestinal
Anorexia
Diarrhea
Nausea
High-Dose (Severe)
Withdrawal
Seizures
Delirium
Death
Withdrawal severity has been related to dose and
duration of treatment.
Latency to onset of withdrawal is related to the
elimination half-life.
Most frequents signs of W/D: anxiety, insomnia,
restlessness, agitation, irritability, and muscle tension
Less frequent: nausea, diaphoresis, lethargy, aches and
pains, coryza, hyperacusis, blurred vision, nightmares,
depression, hyperreflexia, and ataxia
Uncommon: psychosis, seizures, confusion, paranoid
delusions, hallucinations, and persistent tinnitus
Four different etiologies of signs and symptoms of
discontinuation: (1) symptom recurrence or relapse, (2)
rebound, (3) pseudowithdrawal, and (4) true
withdrawal.
Symptom recurrence or relapse is characterized by
recurrence of symptoms for which the BZD was
prescribed and can occur over days or months after
discontinuation.
Rebound is marked by the development of
symptoms within hours to days of
discontinuation that are qualitatively similar to
the disorder for which the drug was precribed
but more intense. Symptoms are of short
duration and self-limited.
Pseudowithdrawal (over-interpretation of symptoms)
may occur when expectations of withdrawal lead to
the experiencing of abstinence symptoms.
True withdrawal is marked by emergence of symptoms
in an individual who is physically dependent on the
drug. It can only be suppressed by reinstitution of the
discontinued drug or another cross-tolerant sedativehypnotic.
Considerable individual variation and variability exist
among patients who discontinue BZDs.
Any combination of sgs and sxs may be experienced
with varying severity throughout the initial one to four
weeks of abstinence.
The clinical picture can consist primarily of subjective
symptoms with few concurrently observable hyperadrenergic signs or vital sign fluctuations.
Discontinuation syndromes commonly occur in
combination. For example, recurrence of anxiety and
insomnia and the sgs and sxs of rebound and
withdrawal overlap. Therefore, sorting out rebound
from withdrawal is unnecessary (if not impossible!).
Prolonged withdrawal has been reported in a small
proportion of patients following long-term BZD use.
Sgs and sxs may persist for weeks to months following
discontinuation and is characterized by its irregular and
unpredictable course.
Patients experience slowly abating, waxing and waning
symptoms of insomnia, perceptual disturbances,
tremor, sensory hypersensitivity, and anxiety.
BZD action in the CNS is mediated by the GABABenzodiazepine-Receptor Complex.
GABA is the primary CNS inhibitory neurotransmitter.
Activation of the GABA receptor induces the opening
of a neuronal membrane-bound chloride channel,
causing hyperpolarization.
Chronic lorazepam use resulting in tolerance to the
ataxia-inducing effects causes down-regulation
(decreased receptor number, decreased GABAreceptor function, and diminished protein synthesis for
GABA receptors).
With abrupt discontinuation, GABA receptors are upregulated with GABA-receptor complex function
enhanced.
BZD pharmacokinetics determine the onset of
discontinuation symptoms following chronic use, with
the elimination half-life dictating the rate of decline of
blood levels.
Onset of action of W/D from short-acting BZDs
(lorazepam, oxazepam, triazolam, alprazolam, and
temazepam) occurs within 24 hours of cessation, with
peak severity within 1 to 5 days.
With long-acting BZDs (diazepam, chlordiazepoxide,
and clonazepam), onset occurs within 5 days and
withdrawal peaks at 1 to 9 days.
Duration of acute withdrawal can be as long as 7-21
days for short-acting and 10-28 days for long-acting
BZDs.
Withdrawal symptoms from short-acting BZDs are
experienced as being more intense than those with
long-acting drugs, and are of more rapid onset.
Higher dose and longer duration place patients are
greater risk for severe withdrawal.
Beyond one year of continuous use, duration of use
becomes a less important factor.
Tolerance develops more rapidly to short-acting BZDs
and withdrawal requires more aggressive medical
attention.
Patients with chronic psychiatric disorders maintained
on BZDs for more than 3-6 months will be physically
dependent on the BZD.
Numerous BZD discontinuation studies highlight the
high (40-100%) prevalence of active concurrent
psychiatric disorders.
Most demonstrate a correlation between the patients’
degree of psychopathology and their withdrawal
symptom severity and difficulty in discontinuing use.
Concurrent use/abuse of other substances complicates
the clinical presentation in withdrawal.
The percentage of alcoholics who regularly use BZDs
ranges from 29-33%.
Comorbid alcohol abuse and anxiety disorders occurs
in 18-19%.
Moderate alcohol use (>1 beer/day) is a more
significant predictor of BZD withdrawal severity than
half-life of the drug.
Patients with high-dose BZD use who present for
inpatient addiction treatment exhibit a high rate (7096%) of concurrent dependence on other substances.
>20% of patients newly admitted to inpatient
treatment reported using BZDs at least weekly; 73% of
heroin users reported greater than weekly use; >15%
of heroin users used BZDs daily. There is also a high
rate of BZD use in methadone clinics.
Studies of adult sons and daughters of alcoholics have
shown increased propensity to develop dependence
when exposed to alprazolam and diazepam. There also
appears to be a linkage of paternal hx of alcoholism
and severity of withdrawal from alprazolam.
BZD withdrawal should be avoided during acute medical
and surgical conditions; continued BZD use rarely has a
negative effect on the acute medical condition.
Special consideration should be given to discontinuing BZDs
in patients in whom the medical condition could be
worsened by adrenergic and psychological stress factors.
In general, patients with chronic medical conditions
experience BZD withdrawal more severely than others.
The use of anxiolytics peaks between the ages of 50
and 65, with hypnotics most frequent in the oldest age
range.
Hepatic microsomal enzyme oxidase system (MEOs)
efficiency decreases with age. Elderly patients’
elimination half-lives are two to five times slower than
younger adults.
Therefore, withdrawal in the elderly may be quite
prolonged, especially with the long-acting BZDs.
Women are prescribed BZDs twice as often as men; hence,
twice as many women as men are likely to become
dependent.
Female gender is also associated with increased withdrawal
severity in patients undergoing tapered cessation of longterm, therapeutic BZD use. However, gender is not a factor
in abrupt cessation.
Determine the reason the patient or referent is seeking
evaluation of sedative-hypnotic use and/or discontinuation.
Take a sedative-hypnotic history.
Elicit a history of other alcohol or psychoactive drug use.
Take a psychiatric history.
Take a family history of substance use, psychiatric, and medical
disorders.
Take a current and past medical history.
Take a psychosocial history.
Perform a physical and mental status exam.
Conduct a UDS.
Complete an individualized assessment with differential
diagnoses.
Determine level of care for Detox and method.
Obtain patient consent and initiate Detox.
Benzodiazepines
alprazolam
chlordiazepoxide
clonazepam
clorazepate
diazepam
flurazepam
lorazepam
oxazepam
temazepam
triazolam
Barbiturates
pentobarbital
secobarbital
butalbital
phenobarbital
Non-barbiturates
Placidyl
Doriden
Quaalude
Dose Equivalent to 30 mg of
Phenobarbital
0.5-1
25
1-2
7.5
10
15
2
10-15
15
15
100
100
100
30
500
250
300
For dependent patients, there are two options for
detoxification: tapering or substitution.
Tapering is indicated for use in: (1) outpatient ambulatory
setting, (2) patient with therapeutic-dose BZD dependence, (3)
patients who are dependent only on BZDs, and (4) patients who
can reliably present for regular clinical follow-up during and
after detoxification.
Tapering is done by decreasing the BZD dose on a weekly to
every-other-week schedule. The rate should not exceed 5 mg
diazepam (12.5 mg chlordiazepoxide or 15 mg phenobarb) or
10% of the starting dose per week, whichever is smaller. The
first 50% of the taper is usually smoother, quicker, and less
symptomatic. For the final 25-35%, the rate and dose should be
cut in half.
Substitution and taper is indicated for those who are
unable to tolerate the taper and those previously
excluded from taper.
Substitution is accomplished with a cross-tolerant longacting BZD or Phenobarbital, with Phenobarbital
having the advantage of less disinhibition and broad
clinical efficacy.
If hepatomegaly or elevated liver enzymes are a
problem, then oxazepam may be substituted.
Lorazepam could be used, but has higher abuse
liability.
Calculate the equivalent dose of chlordiazepoxide,
clonazepam, or phenobarbital using the Substitution
Dose Conversion Table and divide into three to four
daily doses.
Provide prn doses of BZD until substituted drug
reaches steady state.
Gradually reduce the dose.
Sedative-hypnotic tolerance testing may be performed
when the tolerance level is difficult to determine.
Pentobarbital 200 mg is given PO q2 hours for up to
24-48 hours or until signs of intoxication appear; then
total dose administered in divided by number of days
to arrive at daily dose. Phenobarbital is then
substituted with gradual taper.
Signs and symptoms of withdrawal are treated as
needed with 30-60 mg phenobarbital every 1-4 hours.
When the patient has received similar 24-hour
phenobarbital doses for two consecutive days, the
total is divided by 2 to arrive at the stabilizing dose.
This dose is divided over the next 24 hours and then is
tapered.
Carbamazepine has been studied as an adjunct to
traditional detoxification. In one study, significantly
more patients treated with carbamazepine were BZDfree at 5 weeks with less withdrawal severity reported.
Sodium valproate also is effective in attenuating
withdrawal.
Propranol diminishes the severity of adrenergic
symptoms, but should not be used alone.
Clonidine is ineffective in treating BZD W/D.
Buspirone is ineffective as well.
Trazodone decreases anxiety in BZD-tapered patients.
CBT has been shown to improve the rate of successful
alprazolam discontinuation.
Prolonged BZD W/D is associated with sgs and sxs
lasting weeks to months following discontinuation,
probably as a result of long-term receptor site
adaptation.
Propranolol 10-20 mg qid is helpful in attenuating
anxiety or tremors, as are sedating antidepressants for
insomnia.
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