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Journal of the Formosan Medical Association (2018) xx, 1e4

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Case Report

Clinical management of gamma-

hydroxybutyrate (GHB) withdrawal delirium
with CIWA-Ar protocol
Po-Chiao Liao a, Hu-Ming Chang b, Lian-Yu Chen b,c,*

a
Department of Psychiatry, Taipei Medical University Hospital, Taipei, Taiwan
b
Taipei City Psychiatric Center, Taipei City Hospital, Addiction Psychiatry Department, Taipei, Taiwan
c
Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan

Received 2 March 2018; received in revised form 31 May 2018; accepted 4 June 2018

KEYWORDS Gamma-hydroxybutyrate (GHB) is a synthetic drug used mainly for recreational purpose.
Gamma- Although the prevalence of GHB abuse is low in Taiwan, GHB has become increasingly popular
hydroxybutyrate; in certain subpopulations such as clubbers and men who have sex with men (MSM). GHB depen-
GHB; dence could be associated with severe withdrawal syndrome including hallucinations and
CIWA-Ar; delirium. Despite systematic studies on detoxification and management of GHB withdrawal
Withdrawal delirium have been performed, no validated measurement for severity of GHB withdrawal syndrome
is available. Here we present a case of GHB withdrawal delirium that was treated successfully
with fixed and symptom-triggered benzodiazepine dosing regimen based on Clinical Institute
Withdrawal Assessment for AlcoholeRevised (CIWA-Ar) scale. The utilization of CIWA-Ar in such
cases could offer useful guidance for benzodiazepine dosing. To the best of our knowledge,
this is the first case report of GHB withdrawal delirium in Taiwan.
Copyright ª 2018, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).

Main text short half-life, it has caused significant drug-induced coma

Gamma-hydroxybutyrate (GHB) is a popular drug of recre-
ational use for its effects of euphoria, sedation, amnesia
and sex-stimulation.1 Due to its low therapeutic index and
* Corresponding author. Taipei City Psychiatric Center, Taipei City
Hospital, No. 309, Songde Rd., Xinyi Dist., Taipei City, Taiwan.
E-mail address: lianyu0928@gmail.com (L.-Y. Chen).
or mortalities in western countries.2 In addition to its risks
for physical dependence and lethality in overdose, GHB use
is associated with more severe withdrawal syndrome
compared to other club drugs, causing a disproportionate
number of GHB users to seek medical help for potentially
life-threatening withdrawal syndrome.3
As national survey in Taiwan has shown a relatively low
prevalence of GHB use,4 an increasing trend of GHB use in
certain subpopulation such as clubbers and men who have

https://doi.org/10.1016/j.jfma.2018.06.005
0929-6646/Copyright ª 2018, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Liao P-C, et al., Clinical management of gamma-hydroxybutyrate (GHB) withdrawal delirium with
CIWA-Ar protocol, Journal of the Formosan Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.06.005
 + MODEL
2 P.-C. Liao et al.
sex with men (MSM) have been noted in Western countries.5
In Taiwan, a web survey examined the prevalence of risky
sexual behaviors and recreational drug use among MSM
group has shown that up to 15.3% of them reported using
GHB in the past 6 months.6 Hence, we present a case with
severe GHB withdrawal delirium who was hospitalized and
treated with benzodiazepines detoxification regimen as
supported by previous study.2 As there was no readily
available assessment tool for GHB withdrawal syndrome,
we further used Clinical Institute Withdrawal Assessment
for Alcohol (CIWA-Ar) scoring to determine the target doses
of benzodiazepines. The case demonstrated that CIWA-Ar
could offer basis to monitor GHB withdrawal and to deter-
mine treatment regimen. The patient has signed the
informed consent and anonymity has been preserved.
Case
A 31-year-old male has a history of alcohol use disorder for
more than 10 years. He started occasional alcohol drinking
at age 20 while he was a college student. He developed
tolerance to alcohol quickly and had alcohol dependence at
age 22 with 15e20 drinks per day. He reported difficulty
quitting, guilty feeling, larger amount and longer period of
alcohol consumption and withdrawal symptoms such as
tremor, anxiety, nausea and insomnia. However, he denied
any history of delirium tremens or withdrawal seizure. Be-
sides, he also used ketamine and MDMA recreationally since
age 23 as he started to go to night clubs. He denied any
psychiatric history or family history of mental illness.
His first use of “Liquid G” (GHB) for recreational purpose
was at age 30. He reported euphoria and relaxation after
using GHB and rapidly developed GHB dependence one
month later. He stopped alcohol drinking within months and
started binge using GHB (up to 20 mL per day). Severe
withdrawal symptoms such as anxiety, restless and nausea
were noted. He reported numerous black-out experiences
and had several traffic accidents due to driving under in-
fluences (DUI) of GHB. He was not able to maintain his work
due to hangover effects of GHB. In spite of his interpersonal
problems with his colleagues and family, he found it diffi-
cult to cut it down. He reported strong craving for GHB
when he felt bored or depressed. He also had guilty feeling
out of his GHB use and was admitted to our substance abuse
treatment ward voluntarily for GHB dependence.
Table 1 CIWA-Ar score and lorazepam dosing of GHB withdrawal treatment.
CIWA-Ar Fixed dose of
score Max lorazepam
Day 1 10 12 mg per day
Day 2 32 16 mg per day
Day 3 30 12 mg per day
Day 4 26 12 mg per day
Day 5 20 12 mg per day
Day 6 14 12 mg per day
Day 7 10 12 mg per day
Day 8 2 8 mg per day
Day 9 2 8 mg per day
Please cite this article in press as: Liao P-C, et al., Clinical management of gamma-hydroxybutyrate (GHB) withdrawal delirium with
CIWA-Ar protocol, Journal of the Formosan Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.06.005
On admission, he was oriented, attentive, with logical
thoughts and denied any hallucinations. Laboratory tests
including complete blood count and biochemistry profile
revealed no abnormalities except hypokalemia (K:
3.2 mEq/L). His urine drug screen was negative for mari-
juana, ketamine, MDMA, methamphetamine, and opioid.
His blood alcohol level was zero. He could cooperate with
medical staff on ward routines. His CIWA-Ar score was 10 on
day 1 morning. However, a few hours later he developed
disorientation to time, place, and person that night. Poor
attention with vivid auditory and visual hallucinations was
noted. He became agitated under fixed dose of lorazepam
of 12 mg/d. His CIWA-Ar was up to 32 due to his delirium;
thus, symptom-triggered lorazepam up to 6 mg was given in
8 h. We rechecked his blood count and biochemistry profile
which simply showed mild hypokalemia (K: 2.9 mEq/L).
Other laboratory results were within normal limits. The EKG
revealed prolonged QTc (0.454 s).
On day 2, we increased the dosage of lorazepam to
16 mg/d and olanzapine 10 mg injection was given for
agitation and delirium. As a systemic review has shown that
olanzapine is equally effective in treatment of delirium as
haloperidol,7 we avoid typical antipsychotics use such as
haloperidol for his QTc prolongation. Extra 2 mg of loraze-
pam was given due to his high CIWA-Ar. On day 3 and 4, his
CIWA-Ar was decreased to 26 under 12 mg/d of lorazepam.
Olanzapine injection was given on day 4 for agitation and
hallucinations. On day 5e7, he gradually became oriented
and auditory and visual hallucinations were much
improved. He started to walk around in the ward and could
cooperate in an interview. He reported lost of memory
during his delirious phase. On day 8, he showed signs of
recovery from the withdrawal delirium and his CIWA-Ar was
decreased to 2; thus, lorazepam was tapered accordingly.
He was then discharged on day 9. The detailed dosing and
CIWA-Ar scores are documented in Table 1.
Discussion
GHB is a recreational drug, mainly used in a liquid oral
form, notorious as a “date rape drug” for its euphoric,
relaxing, and sexually stimulating effects. It has recently
been gaining popularity in western countries with lifetime
prevalence of 0.9e4.7% in the U.S.8 and 0.5e1.4% in
Europe,9 respectively. Although the past-year prevalence of
Symptom-triggered Injection for agitation
dose of lorazepam and delirium
6 mg per day
2 mg per day Olanzapine 10 mg IM
Olanzapine 10 mg IM
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GHB withdrawal delirium with CIWA-Ar protocol
illicit drug use is considered only 0.09% in Taiwan,10
cumulating evidences have supported the increasing use
of GHB in Asia, particularly among MSM, up to 2.3% in the
past 6 months.11 As there is limited study focusing on the
treatment of GHB dependence or withdrawal syndrome,
within our knowledge, this is the first case report of GHB
withdrawal delirium in Taiwan.
GHB, also known as 4-hydroxybutanoic acid and sodium
oxybate, is a naturally-occurring substance found in the central
nervous system. It mainly acts at GHB receptor and GABA-B
receptors. At low doses, GHB stimulates dopamine release
through activation of GHB receptors, while at higher doses it
attenuates dopamine release through activation of inhibitory
GABA-B receptors.12 Like other central nervous system de-
pressants, chronic GHB use could lead to tolerance associated
with down-regulation of inhibitory GABA and GHB receptors.
Thus, discontinuation of GHB use will result in unopposed
excitatory neurotransmission due to decreased GABA- and GHB-
mediated neuroinhibition, causing withdrawal syndrome.13
Among recreational drugs, GHB is at particular risk to
develop overdoses and intoxications, resulting in coma, and
to develop a quick dependence, resulting in severe with-
drawal symptoms.14 The oral absorption of GHB is relatively
fast, with peak concentrations in plasma after 20e45 min,
and half-life of 20e30 min, which explains why regular
users typically use the drug every 1e4 h to prevent the
onset of withdrawal.15 However, that potentiates the risk
for overdose. At doses >60 mg/kg, coma and respiratory
depression can occur. Combination use with alcohol further
increases the risk of respiratory depression.
GHB is well known for its short duration to reach de-
pendency. As our case has demonstrated, tolerance could
occur within 1 weeke6 months. The median time for chronic
GHB users to experience withdrawal syndrome was 18
months, much shorter than those with alcohol use disorders.
Although GHB withdrawal has many similar features to
alcohol withdrawal, including tremor, sweating, anxiety,
agitation and confusion, it is generally more severe, and the
risk for psychosis and delirium is exceptionally high.16 Usually,
GHB withdrawal syndrome develops within the first 6e72 h
(mean 7.5 h). History of short latency and abrupt onset could
help clinicians to differentiate GHB withdrawal from alcohol
withdrawal.17 A systemic review on 27 studies of GHB-related
withdrawal syndromes described the most common with-
drawal symptoms included tremor (67%), hallucinations
(63%), tachycardia (63%), insomnia (58%), and anxiety
(46%).18 The prevalence of GHB withdrawal delirium up to 12%
was higher than alcohol withdrawal delirium (about 5%).
Factors associated with withdrawal delirium was not clear
yet, except one study showed frequent ingestion (ingestion
every 8 h or less) could cause withdrawal delirium.2
As GHB acts at GABA-B receptors and benzodiazepines act
at GABA-A receptors, long-acting benzodiazepines are the
mainstay of treatment for GHB withdrawal.19 A review sup-
ported high dose benzodiazepines (diazepam, 150e200 mgs/
24 h) effective in management of GHB withdrawal delirium.
For refractory delirium, both barbiturate and propofol could
be considered when symptoms persisted despite high dose
benzodiazepine after 24 h.2 In some cases, the psychotic
symptoms are prominent, in which low dose antipsychotics
such as haloperidol or olanzapine was recommended.17
Baclofen, a GABA-B agonist, has also been used for
Please cite this article in press as: Liao P-C, et al., Clinical management of gamma-hydroxybutyrate (GHB) withdrawal delirium with
CIWA-Ar protocol, Journal of the Formosan Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.06.005
3
inpatient treatment of GHB withdrawal and for outpatient
treatment of GBL dependence.3 As it is extremely difficult to
know the amount of GHB consumption by our patients, it is
crucial to have a measurement for the risk of withdrawal
delirium and to offer guide for benzodiazepine dosing.
Up to date, there has been no validated measurement
for GHB withdrawal syndrome severity. We used CIWA-Ar as
an assessment tool for two reasons. First, the clinical fea-
tures of GHB withdrawal syndrome are very similar to
alcohol withdrawal as they are both central nervous system
depressants. Second, benzodiazepines are the mainstay
treatment for alcohol withdrawal as well as for GHB with-
drawal. CIWA-Ar includes 10 items, each score from 0 to 7,
with total scores 70.20 There items are objective measures
of the severity of alcohol withdrawal syndrome including
nausea/vomiting, anxiety, disorientation or auditory/visual
disturbances, etc. It has been used effectively as a guid-
ance on benzodiazepine dosing of alcohol withdrawal
treatment for decades,20 we suggested using CIWA-Ar as a
tool to evaluate the severity of GHB withdrawal. There has
been long-term debate over whether fixed or symptom-
triggered doses of benzodiazepine could reach better
treatment outcome. Generally speaking, symptom triggered
regime is favored over fixed dose regime for decrease in the
quantity of benzodiazepines and shorter treatment duration.
In a randomized clinical trial, the quantity of benzodiaze-
pines decreased by 83.7% and treatment duration decreased
from 62 to 20 h.21 As the management of severe GHB with-
drawal is more complicated than alcohol withdrawal due to
its higher delirium risks and higher doses of medication
needed,16 here we adopted a detoxification method
combining fixed dosing and symptom-triggered dosing
regimen. In addition to regularly given high medications,
additional symptom-triggered benzodiazepines were given
to control his agitation if CIWA-Ar score of 15 or greater.
Here we presented a case of GHB withdrawal delirium
that we treated successfully with fixed and symptom-
triggered benzodiazepine dosing regimen based on CIWA-
Ar scale. It is worthy of our attention that onset of delirium
usually occurs abruptly within 24 h after stopping GHB use.
Although GHB withdrawal symptoms are somewhat similar
to alcohol withdrawal, characterized with autonomic ner-
vous system hyperarousal, the symptoms are usually more
severe and the risks for psychosis and delirium are partic-
ularly high. We as clinicians should pay attention to the
management of intoxication or withdrawal of GHB due to
the increasing popularity among MSM population as well as
in clubbers. The utilization of CIWA-Ar in such case could
offer useful guidance for benzodiazepine dosing regimen.
Conflicts of interest
The authors have no conflicts of interest relevant to this
article.
Acknowledgments
No external funding, apart from the support of the authors’
institutions, was used for this study. The authors declare
that there are no conflicts of interest in this study.
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4 P.-C. Liao et al.

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Please cite this article in press as: Liao P-C, et al., Clinical management of gamma-hydroxybutyrate (GHB) withdrawal delirium with
CIWA-Ar protocol, Journal of the Formosan Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.06.005