may be given in 5-mg increments up to a total of 10 to 20 mg during the first 24
19 Larger methadone doses (i.e., a 20-mg starting dose) may be required for
patients with larger habits. If initial withdrawal symptoms persist 2 to 4 hours after
initial dose administration, the dose can be supplemented with an additional 5 to 10
mg. Federal regulations allow a maximum of 40 mg as an initial dose unless a
program physician documents that 40 mg was insufficient to suppress opioid
20 Once a stabilizing dose has been reached (usually, 40–60
mg/day, but may be as high as 120 mg/day), methadone is tapered by 20% a day for
inpatients or 5% a day for outpatients.
15,19,20 Studies have suggested that slow tapers
are associated with better outcomes. The duration of the taper varies, but a period of
3 to 4 weeks is generally used. The gradual taper may last as long as 6 months. The
most common side effects of methadone are constipation, sweating, and sexual
15,19 A Cochrane review of studies comparing methadone tapers with
other detoxification methods (adrenergic agonists and other opioid agonists) found
that programs vary widely in design, duration, and treatment objectives, but overall
the effectiveness of the treatments was similar.
21 A reasonable starting dose of
methadone would be 20 mg orally. An additional 5 to 10 mg could be administered
after 2 to 4 hours for persistent withdrawal symptoms. The daily dose should be
titrated upward every third day by 10 mg until stabilized on a methadone dose of 60
Buprenorphine, a synthetic partial opioid agonist, was approved by the FDA in
October 2002 for the treatment of opioid dependence. It is a partial agonist at mu
receptors, and in opioid-dependent patients, it prevents withdrawal symptoms.
Because of its partial effects, it produces maximal “ceiling” analgesia with
sublingual doses of 24 to 32 mg, a dosage equivalent to approximately 60 to 70 mg of
oral methadone. Buprenorphine is associated with a milder withdrawal syndrome
compared with full opioid agonists.
Because buprenorphine is a schedule III medication, it can be prescribed in an
office-based setting under the Drug Addiction Treatment Act of 2000. The film and
tablets contain buprenorphine hydrochloride alone or in combination with naloxone.
The naloxone is poorly absorbed orally, and its presence in the combination tablets
is to discourage the IV abuse of buprenorphine. Both forms can be used in an
inpatient setting, but the combination product is preferred in the outpatient setting to
decrease the risk of diversion. When initiating buprenorphine, the first dose should
not be given until more than 4 hours after the last dose of a short-acting opioid, such
as heroin, or 24 hours after a long-acting opioid, such as methadone. As previously
discussed, evaluation of objective opioid withdrawal signs may involve use of
standard rating scales. Induction dosing should begin with 2 or 4 mg on the first day,
which can be repeated every 2 to 4 hours if withdrawal symptoms subside and then
reappear, up to a maximum of 8 mg. The dose can then be titrated the second day in
2- to 4-mg increments to a dose of 12 to 16 mg.
22 Higher doses during induction may
precipitate withdrawal symptoms. In the inpatient setting, the patient may be
stabilized on a relatively low daily dose (e.g., 8 mg/day) and then tapered in
increments of 2 mg/day over the course of several days.
In the outpatient setting, the
patient should be initially stabilized on a daily dose (probably 8–32 mg/day) of
buprenorphine that suppresses withdrawal. The dose should then be gradually
tapered during a period of 10 to 14 days. Buprenorphine is not associated with any
significant adverse effects when used to manage opioid withdrawal. Buprenorphine
(and methadone) detoxification should be accompanied by psychosocial treatments
and support groups as mentioned.
A Cochrane review found that relative to clonidine, buprenorphine is more
effective in alleviating opioid withdrawal symptoms; patients treated with
buprenorphine stay in treatment longer, and are more likely to complete treatment.
The severity of withdrawal appears to be similar for withdrawal managed with
buprenorphine or methadone, but withdrawal symptoms may resolve more quickly
with buprenorphine. The authors of the meta-analysis concluded that although there is
limited evidence comparing buprenorphine with methadone, both agents have similar
effectiveness in the management of opioid withdrawal.
Nonopiate Symptomatic Therapy of Opioid Withdrawal
Although opiate replacement has shown to provide a safe withdrawal, treatment with
opiates is not always necessary. The ability of the α2
-adrenergic agonist, clonidine,
to ameliorate some of the opioid withdrawal symptoms, has led to its widespread use
as a nonopioid alternative. Other α2
-adrenergic agonists (lofexidine, guanfacine,
guanabenz acetate) have also been investigated.
2,3,24 Noradrenergic outflow from the
locus coeruleus is increased during opioid withdrawal and is blocked by
administration of mu agonist opioids. Symptoms of opioid withdrawal, therefore, are
partly caused by excessive sympathetic activity in the locus coeruleus. Central α2
adrenergic agonists inhibit locus coeruleus noradrenergic outflow opioid
withdrawal, thereby significantly reducing some of the symptoms.
Clonidine is therefore best used in a multidrug regimen. Contraindications to
clonidine use include diastolic blood pressure less than 70 mm Hg, concurrent
dependence on sedative-hypnotics, and clonidine hypersensitivity or previous
intolerance. The most common adverse effects are sedation and hypotension. A
Cochrane review examined studies comparing clonidine with methadone taper and
found no significant difference in efficacy between the two for the treatment of heroin
24 A separate Cochrane review did find buprenorphine to
be more effective than clonidine in alleviating opioid withdrawal symptoms.
A sublingual or oral test dose of 0.1 mg (0.2 mg for patients >91 kg) of clonidine
is given: if diastolic blood pressure remains more than 70 mm Hg, additional doses
may be instituted. Oral clonidine can be used at a dose of 0.1 to 0.2 mg/dose 2 to 4
times daily to a maximum of approximately 1 mg/day for 2 to 4 days after cessation
of opioids, then tapered and discontinued by 7 to 10 days.
withdrawal consists of other effects such as musculoskeletal aches and pains,
anxiety, insomnia, and gastrointestinal disorders, it is common to use medications
such as dicyclomine, loperamide, and ibuprofen as adjuncts. This is particularly true
when the detox protocol does not contain opiates.
Symptomatic Therapy of Opiate Withdrawal
Bone, muscle, joint or other pain Ibuprofen, naproxen, other NSAID
Insomnia, anxiety Benzodiazepine
Gastrointestinal hyperactivity Loperamide, dicyclomine
Nausea Prochlorperazine, ondansetron
2010. http://www.asam.org/quality-practice/definition-of-addiction.
D.J.’s blood pressure and drug history should be evaluated for clonidine therapy.
Provided his diastolic blood pressure is greater than 70 mm Hg after the clonidine
test dose, he can receive oral clonidine 0.1 mg with additional medications to treat
his withdrawal symptoms, along with psychosocial counseling.
Ultrarapid Opiate Detoxification
Ultrarapid opiate detoxification (UROD) is a method to shorten the opioid
detoxification period by precipitating withdrawal with an opioid antagonist. The
opioid antagonist causes rapid stripping of agonist from opioid receptors. UROD is
performed under heavy sedation or general anesthesia so the patient does not
consciously experience the acute withdrawal symptoms. The protocols for UROD
vary in terms of the setting of the procedure (inpatient or outpatient), opioid
antagonist (naloxone, nalmefene, or naltrexone), anesthetic agent, adjunctive
medications, and duration of anesthesia.
The UROD procedure includes risks, such as vomiting with aspiration;
cardiovascular complications, including cardiac arrest; pulmonary edema; and
25 Some patients have reported residual withdrawal symptoms for several days.
Little information exists regarding referral to ongoing treatment or relapse rates after
26 A review of five randomized, controlled trials found no benefit of UROD
compared with safer, less expensive treatments.
26 UROD has been criticized for
being simply a “quick fix” that fails to address the underlying behavior changes
necessary for recovery. Additionally, it subjects patients to possible morbidity and
mortality when safer, established procedures are available. The high cost of UROD
limits its accessibility. The American Society of Addiction Medicine recommends
against this method of treating opiate withdrawal due to cardiac complications and
Pharmacotherapies for maintenance treatment of
The ultimate goal of outpatient substance use disorder programs is to assist the
addicted patient into a drug-free healthy lifestyle. This results in reductions in
medical conditions for the patient and reduced crime and health care cost for societal
members. Methadone for maintenance treatment of opioid substance use disorder is
federally regulated and is only available through specially licensed opioid treatment
programs. The Drug Addiction Treatment Act of 2000 allows qualified physicians to
prescribe Schedule III, IV, and V medications approved for the treatment of opioid
dependence in an office-based setting.
27 Currently, only buprenorphine, a Schedule III
medication, is approved for this indication.
treatment for his heroin dependence. What therapeutic options are available to him?
The goal of eliminating illicit opiate use is the gold standard; however, a more
realistic expectation is reduced use and subsequent harm reduction. Even temporary
reductions in heroin use are a benefit due to reduced risk of developing major health
(HIV, hepatitis C) and social (crime) issues.
2 Medical management of opioid
Methadone maintenance is the most common form of pharmacologic treatment for
opioid dependence. During methadone maintenance, heroin-dependent patients are
stabilized on a dose of methadone that will be sufficient to suppress cravings for 12
to 24 hours without producing euphoria. Studies have shown that patients maintained
on methadone doses of 60 mg or more had better outcomes than those maintained on
28 Most patients do well on a dose range of 60 to 120 mg/day, although
some patients require more and some require less.
metabolized via CYP450 3A4 drugs that induce, this pathway can precipitate
withdrawal in patients maintained on methadone. Drugs that inhibit this pathway
extend the duration of methadone’s effects. The half-life of methadone is typically 25
hours (15–60) but can extend up to 120 hours with frequent dosing.
administered daily at the clinic in a single liquid oral dose. With the aid of daily
counseling and rehabilitation, the goal is to eventually taper the patient from
methadone as well. Patients who relapse repeatedly despite supportive treatment
will require long-term maintenance therapy. This may take years, and it is shown that
longer duration in treatment correlates with better outcomes. Methadone’s efficacy
comes from the fact that it reduces cravings without producing euphoria itself,
injection of other opioids. But, patients have been able to reach euphoric states
through the concomitant IV administration of other opioids. The higher purity heroin
available today has required even higher doses of methadone to achieve cross-
It is often cut (mixed) with fentanyl to increase the opiate effect.
Buprenorphine has the advantage of office-based availability, thus removing the
stigma associated with attending a methadone clinic and providing more places for
patients to receive treatment because methadone clinics are limited as to how many
patients can enroll and may be hundreds of miles away from the patient’s home.
Buprenorphine, and high-dose methadone (60–100 mg) therapies were compared
with low-dose methadone (20 mg), all three therapies were effective in treating
opioid dependence and were superior to low-dose methadone.
to 16 mg/day of buprenorphine with moderate doses of methadone (50–60 mg/day)
have generally shown comparable outcomes, although higher doses of methadone
(>80 mg) appear to be superior to buprenorphine.
30 Low-dose buprenorphine seems
to have worse outcomes compared to low-dose methadone.
are more likely to be employed, have less medical comorbidity, and a shorter
duration of drug use compared to methadone clinic patients.
formulations of buccal and sublingual buprenorphine and absorption rates are
different between some of them. All are compared to the original buprenorphine
sublingual tablet (Subutex and Suboxone) regarding pharmacokinetics, blood
levels and efficacy. There is also a buprenorphine implant available which was
found similarly effective to lower doses of buprenorphine sublingual.
maintenance treatment buprenorphine combined with naloxone is the standard of care
with pregnancy or allergy to naloxone the only two reasons not to use the
Buprenorphine has a long half-life of around 35 hours (24–60 hours) and it
produces a relatively mild withdrawal when discontinued.
safer alternative to methadone because life-threatening respiratory depression is
much less likely to occur than with a pure mu agonist, unless another CNS depressant
is taken concurrently. Most deaths involving buprenorphine have been caused by a
combination of the drug with benzodiazepines and through injection of the
22,36 Naloxone bolus doses often are ineffective in reversing
respiratory depression caused by buprenorphine because of its prolonged occupancy
on mu receptors. Continuous infusion of naloxone is necessary to overcome
buprenorphine-induced respiratory depression.
37 Another safety advantage compared
to methadone is the lower risk of prolonging QTc.
buprenorphine is also metabolized by CYP450 3A4.
The narcotic antagonist naltrexone can block the euphoriant effects of heroin and
other opiates, prevent the development of physical dependence, and afford protection
from opioid overdose deaths. Although naloxone is similar to naltrexone, it is
impractical because of its short duration of action and its extremely poor absorption
when taken orally. Naltrexone is orally active and provides a dose-related duration
of opioid blockade. An oral dose of 100 mg of naltrexone will block opiate effects
for 2 days, and 150 mg for 3 days. Thus, dosing on Monday, Wednesday, and Friday
is possible; however, it is recommended to use 50 mg QAM because it is easier to
remember for the patient and will result in better adherence. Naltrexone is also
available in an injectable extended-release formulation for once-monthly use.
Patients selected for naltrexone therapy must be opioid free to avoid precipitation of
withdrawal. For heroin- or morphine-dependent patients, a 4- to 7-day wait is
recommended, whereas longer half-life opiates can require a 10- to 14-day wait.
Patients who are highly motivated to abstain have been most successfully treated with
Because A.X. has had a short duration of opiate misuse, he is a good candidate for
outpatient buprenorphine/naloxone or naltrexone. Methadone is equally effective but
does require enrollment into a clinic, which may or may not be practical for him.
Methadone clinics are considered more effective than the other choices because the
addiction becomes more severe.
Research suggests that physicians consume more opioids, sedatives, and alcohol
than the general public, but less tobacco.
39 The risk is largely based on access to
drugs of abuse, and drug dependence is described as an occupational hazard for
healthcare providers. Fentanyl (injectable as well as transdermal formulations) and
meperidine are primarily, but not exclusively, drugs of abuse among health care
providers. Hospice workers and veterinarians also have access to high-potency
opioids. Studies have noted that substance use was highest in psychiatrists and
emergency medicine physicians and lowest in surgeons and pediatricians.
A comprehensive assessment of addicted health care providers is necessary to
determine whether professional impairment is present, and whether issues involving
public health and safety or violations of ethical standards, such as professional
boundary violations or improprieties, require that the heath care provider be reported
to his or her respective medical board. A physician’s registration with the federal
DEA may need to be suspended. It generally is accepted that health care providers
require longer durations of treatment because they are held to a higher standard of
recovery owing to concerns of public safety, and they may be clever at concealing
Health care providers are often good candidates for naltrexone therapy
(particularly the long action injection) because of the need to remain drug-free
despite continued access to opioids at work.
Opiate Use Disorder Treatment in Pregnancy
QUESTION 1: J.R., a 28-year-old woman, has been maintained on 100 mg of methadone daily for the past
positive. What is the recommend treatment for pregnant patients?
Methadone has been accepted since the late 1970s to treat opioid use disorder
20 Methadone maintenance was determined to be the standard of
care for pregnant women with opioid use disorder by a 1998 National Institutes of
40 Currently, methadone is the only opioid medication
approved by the FDA for medication-assisted treatment of opioid use disorder in
pregnant patients. Women maintained on methadone frequently have regular
menstrual periods, ovulate, conceive, and have normal pregnancies. Heroin-addicted
mothers, however, generally experience more complicated pregnancies because their
lifestyles often predispose them to a poor general state of health and precludes
adequate prenatal medical care.
Infants born to heroin-addicted mothers may also
be exposed to other substances (e.g., alcohol, cocaine, tobacco). These infants tend to
be smaller, to weigh less at birth, and to be born prematurely compared with the
children of women not using opiates.
J.R. should continue methadone maintenance to avoid precipitating a withdrawal
syndrome or a relapse to opiate addiction. Both relapse and withdrawal syndrome
could lead to a spontaneous abortion.
20 A structured methadone maintenance program
provides access to counseling and perinatal medical care which are additional
benefits. The dose of methadone should be titrated individually throughout the
pregnancy and may even need to be increased and switched from QD to BID dosing
due to changes in kinetics that occur during pregnancy.
for either opioid-induced CNS depression or methadone withdrawal after delivery,
Methadone continues to be the standard of care for the management of opioid
dependence in pregnancy; however, a growing body of evidence suggests
buprenorphine may be a reasonably safe alternative.
15 Also most evidence suggests
that infants born to buprenorphine-maintained women have a lower incidence of
neonatal abstinence syndrome and shorter hospital stays.
NEONATAL ABSTINENCE SYNDROME (NAS)
withdrawalsymptoms after birth, and if so, how should they be managed?
Methadone crosses the placental barrier and can cause CNS and respiratory
depression as well as opioid withdrawal in the newborn. In general, the most
common opioid NAS symptoms include restlessness, tremors, a high-pitched cry,
hypertonicity, increased reflexes, regurgitation, tachypnea, diarrhea, and sneezing.
Seizures are associated with, but not necessarily caused directly by, opioid
Management of the neonate’s opioid withdrawal syndrome entails careful attention
to hydration with demand feeding and
symptomatic care. Treatment of opioid NAS should begin when symptoms occur;
prophylactic therapy is not recommended. Mild withdrawal symptoms generally do
not need therapy, but moderate to severe symptoms may require 14 or more days of
Symptoms of physiologic withdrawal are usually apparent within 48 hours of
birth. At this time, treatment can be initiated. Currently, NAS is treated with
41,44–46 Morphine can be started at a dose of 50 mcg/kg given orally four
times daily and titrated to control symptoms. Once the NAS symptoms have
stabilized, the dose can be decreased daily by 20% until discontinuation of the drug.
Phenobarbital is preferred for the treatment of NAS in cases of combined
dependence or benzodiazepine dependence or if maximum doses of opiate have been
If used, phenobarbital is instituted in doses of 5 to 10 mg/kg/day in the first 24
hours, then tapered symptomatically, usually about 20%/day.
If J.R.’s infant displays opioid withdrawal symptoms (e.g., feeds poorly, becomes
tremulous or agitated), morphine at a dosage of 50 mcg/kg orally given four times
daily would be an appropriate intervention. This dosage is given until symptoms
stabilize and then gradually tapered (e.g., 20% each day) during the next week.
Buprenorphine has also shown positive data supporting its use and is a potential
option if morphine is unacceptable.
Methadone is excreted into the breast milk of methadone-maintained mothers. The
amount of methadone in the breast milk is unlikely, however, to have adverse effects
47 Furthermore, studies have found minimal transfer of methadone into
nalbuphine, in infants’ urine.
48 Breast milk offers advantages clearly beneficial to
infants, and J.R. should be encouraged to breast-feed her infant.
The sedative-hypnotics are a diverse group of compounds with broad clinical uses,
including anesthesia, treatment of anxiety, and treatment of insomnia. Ethanol, also a
sedative-hypnotic agent, continues to be the most widely abused substance in the
United States and will be discussed later. Benzodiazepines have become the
prototypical sedative-hypnotic drugs of abuse. Other abused sedative-hypnotic drugs
include carisoprodol and γ-hydroxybutyric acid (GHB). Carisoprodol, a
nonscheduled skeletal muscle relaxant, has an active metabolite meprobamate, a
sedative-hypnotic agent with known abuse potential.
neurotransmitter abused for its euphoric and sedative-hypnotic effects. Although
sedative-hypnotics can be abused as monotherapy, they are more commonly used as
adjuncts to other chemicals such as opiates and EtOH.
Abstinence Syndromes Associated with SedativeHypnotic Dependence
than an afternoon. Will he experience withdrawalsymptoms if he suddenly discontinues alprazolam?
therapy. Withdrawal syndromes seen with sedative-hypnotics are similar to those
seen with alcohol withdrawal and can include insomnia, anxiety, tremors, headaches,
restlessness, nausea, vomiting, hypertension, tachycardia, hypersensitivity to light,
sound, and touch, and perceptual distortions.
50 Generalized tonic–clonic seizures can
occur as isolated seizures or as status epilepticus. The psychoses that develop
resemble the delirium tremens produced by alcohol withdrawal and are usually
characterized by disorientation, agitation, delusions, and hallucinations. During the
delirium, hyperthermia and agitation can lead to exhaustion, rhabdomyolysis,
cardiovascular collapse, and death. Abstinence from short-acting barbiturates and
meprobamate produces symptoms that peak within 1 to 5 days. Discontinuation of
short-acting benzodiazepines (e.g., lorazepam, oxazepam, alprazolam, temazepam)
results in the abrupt onset of withdrawal symptoms, usually within 12 to 24 hours
after the last dose. Long-acting agents, and those with active metabolites, have a
gradual onset of milder withdrawal symptoms compared with the short-acting agents.
Withdrawal symptoms after chronic use of long-acting benzodiazepines typically
occur within 5 days of cessation and peak at 1 to 9 days after the last dose.
B.J. has been abusing alprazolam, taking more than the recommended maximal
dose. Likely, he will experience withdrawal, possibly including seizures, if he were
to abruptly discontinue the alprazolam. His withdrawal from this medication should
Treatment of Sedative Withdrawal
dependence; and the substituting (and gradual taper) of a long-acting benzodiazepine
51 Gradual tapering of the drug of dependence is
appropriate for patients with therapeutic dose dependence or those taking long-acting
sedative-hypnotics, who are not currently abusing alcohol or other substances. A
recent meta-analysis suggests that management of benzodiazepine mono-dependence
by gradual taper is preferable to abrupt discontinuation.
sedative-hypnotics already has a strong association between the drug of choice and
certain desired effects. Therefore, to minimize exacerbating addictive disease,
substitution and taper with a long-acting therapeutic agent is preferred.
The phenobarbital method is used in some drug treatment programs. The
pharmacologic rationale for phenobarbital substitution is that it is long acting,
producing little changes in serum levels between doses, thereby preventing
breakthrough withdrawal symptoms. Lethal doses are many times higher than toxic
doses, and dysphoria occurs with elevated dose, rendering it less desirable for
The standard method involves calculating a phenobarbital replacement dose for
the total daily dose of the sedative-hypnotic being abused. The calculation is based
on phenobarbital equivalents (Table 90-3). If multiple sedative-hypnotics are being
used, the totals for each drug and alcohol (amount of pure ethanol) are summated. The
total phenobarbital substitution dose should be given in divided doses, 3 or 4 times
daily (to avoid dysphoria). Because the calculated dosage is an estimate based on
patient history, which may be inaccurate, it is advisable to administer a test dose if
the calculated replacement dose is more than 180 mg/day. The test dose, generally
one-third the total dose, is given to the patient, who is then observed for 1 to 2 hours.
The patient is observed for mitigation of withdrawal symptoms as well as signs of
overmedication, such as somnolence or incoordination. Once an appropriate dose is
determined, the patient is usually stabilized on that dose for 1 to 2 weeks. After
stabilization, a gradual taper of phenobarbital is instituted, with dosages reduced by
15 mg weekly or every other week, or 10% of the current (starting) dose per week.
For the last 25% to 35% of the taper, the rate is slowed to keep the patient stabilized.
The taper should be held for a few days if withdrawal symptoms occur.
Hypnotic Dose Equivalent to 30-mg Phenobarbital
Pure ethanol 30–60 mL Clonazepam 1–2 mg Pentobarbital 100 mg
Alprazolam 0.5–1 mg Diazepam 10 mg Secobarbital 100 mg
Butalbital 100 mg Flunitrazepam 1–2 mg
Carisoprodol 700 mg Lorazepam 2 mg Triazolam 0.25–0.5 mg
Chlordiazepoxide 25 mg Oxazepam 10–15 mg Zolpidem 5 mg
aNot approved for use in the United States.
B.J. has a substance use disorder to alprazolam. Tapering of alprazolam or
conversion to phenobarbital will both result in a safe withdrawal. His total dose of
alprazolam is 10 mg/day, so if phenobarbital is used he should receive 300 mg
divided 3 or 4 times a day. The total daily phenobarbital dose or alprazolam dose
should be tapered by 10% of the dose per week as tolerated.
γ-Hydroxybutyric acid (GHB), commonly referred to as “liquid ecstasy,” is a potent
“club drug.” Once available as an over-the-counter nutritional supplement, primarily
used by bodybuilders for its muscle building effect, the FDA removed it from the
retail market in 1990 because of widespread reports of poisoning. In 2000, it was
classified as a schedule I drug; however, a GHB-containing product, sodium oxybate,
is available as a schedule III prescription drug for the treatment of cataplexy
associated with narcolepsy. GHB is found in mammalian brain tissue, where it is
derived from conversion of its parent neurotransmitter, γ-aminobutyric acid
It is believed to be a neurotransmitter. Experimental evidence suggests
that the mechanism of action of exogenously administered GHB involves agonist
activity at the GABAB receptor.
γ-Hydroxybutyric acid has CNS depressant effects and is abused for its
euphorigenic properties, disinhibition, and enhanced sensuality. Its psychic effects
are similar to those of alcohol, and include increased libido, short-term anterograde
amnesia, and a dreamy, altered sensorium. It has a steep dose-response curve, and
common adverse effects include dizziness, nausea, weakness, agitation,
hallucinations, seizures, respiratory depression, and coma. Its effects are synergistic
with alcohol. GHB overdose may be fatal, and there is no antidote. Treatment for
GHB overdose is primarily supportive.
Highly addictive, tolerance and physical dependence can occur with regular use of
GHB, and a withdrawal syndrome has been seen in people who have taken high
doses of it (~18 g/day or more, although doses are variable in solution form) with
frequent dosing (every 1–3 hours).
53 Withdrawal symptoms can include muscle
cramps, nausea, vomiting, tremor, anxiety, insomnia, tachycardia, restlessness, and
delirium or frank psychosis. Death caused by pulmonary edema has been reported.
Treatment of withdrawal involves supportive care, including use of benzodiazepines
(e.g., lorazepam or diazepam) for sedation. Withdrawal can last up to 2 weeks.
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