Hospital Pharmacy - October 2017 - 613

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Hammond et al
patients were evaluated, more consistent findings were the
decrease in BZD requirements when PHB was used in addition to BZD and the relative safety of PHB in these studies.

PHB Monotherapy
Mild-to-moderate AWS. Hendey and colleagues performed a
randomized, double-blind trial at a single center, evaluating
adult patients in the ED with known or suspected AWS.21
Patients were randomized to enteral lorazepam 2 mg or enteral
PHB (260 mg initial dose, 130 mg for subsequent doses),
which were administered per a modified CIWA score. The primary outcome was the change in AWS scores from baseline to
discharge or hospital admission. A total of 44 patients were
included in the analysis (BZD: n = 19; PHB: n = 25). The
mean dose of PHB administered was 509 mg (range, 260-910
mg) and 4.2 mg lorazepam (range, 2-8 mg) in the BZD group.
PHB and BZD were found to significantly decrease the CIWA
score from baseline to discharge (15-5.4 and 16.8-4.2; P <
.0001 for both groups). There were no differences between the
2 groups in the extent of CIWA reduction (P = .40). Patients
who were discharged from the ED were asked to return within
48 hours for AWS symptom evaluation. Nine patients in each
group returned, with no difference found in AWS symptoms
or tolerability of discharge medications (placebo for PHB,
chlordiazepoxide for BZD group).
Young and colleagues prospectively evaluated patients
with acute AWS in the ED.22 Patients with acute drug intoxication were excluded. Patients received an initial PHB infusion of 260 mg, followed by additional 130 mg boluses until
light sedation was reached or adverse effects (eg, altered
mental status, hypotension) were recognized. After the last
dose of PHB, a serum concentration was drawn 30 minutes
later, and patients were observed for at least 1 hour. A total of
62 patients were included in the analysis. The mean serum
PHB concentration was 13.9 µg/mL, with an approximate
increase in serum concentration per mg/kg increase in dose
of 1.65 µg/mL. The majority of patients were safely discharged after a mean ED stay of 3.78 hours. Only 4 patients
did not respond to PHB therapy, evidenced by DT. Therapy
was generally well tolerated, although hypotension (n = 1),
ataxia (n = 1), and lethargy (n = 2) were identified in patients.
Hjermø and colleagues evaluated the effect of PHB therapy in patients with DT at 2 psychiatric departments.23 PHB
was administered at a dose of 100 to 200 mg hourly, while
intravenous diazepam was administered at a dose of 10 to 20
mg hourly. A total of 194 patients were included in the analysis. There were no differences between groups in hospital
LOS or duration of DT (no P values provided). In addition,
there was no difference in development of pneumonia
between groups (P > .05), although respiratory depression
was numerically more common in the PHB-treated group
(3.8% vs 1.1%, P > .05).
Rosenthal and colleagues performed a randomized, openlabel, controlled trial in an inpatient detoxification unit at a

single center.24 Patients with a non-substance-related psychiatric disorder, or opioid (except methadone) or long
elimination half-life BZDs use (eg, diazepam and flurazepam) were excluded. Patients were randomized to a 5-day
detoxification schedule of either PHB or valproate. PHB
was dosed 60 mg enterally 4 times daily on the first day and
then tapered off by day 5. PHB (enteral or intramuscular)
was available as a rescue medication. Outcomes evaluated
were based on symptom severity assessments, including the
Modified Selective Severity Assessment score, which is an
objective scale performed by nurses evaluating symptoms
such as tremor, sleep disturbance, and agitation. This interim
analysis included 42 patients (n in each group not provided).
There was no difference found in the Modified Selective
Severity Assessment score between groups. Patients in the
PHB group received twice as many rescue medications as
the valproate group (39 vs 20, P < .05).
Mariani and colleagues performed a randomized, openlabel, controlled study in an inpatient detoxification unit at a
single center.25 Patients with AW-associated delirium, a non-
substance-related psychiatric disorder, or opioid (except
methadone) or sedative-hypnotic use were excluded. Patients
were randomized into a 4-day detoxification schedule with
either PHB or gabapentin. PHB was dosed 60 mg enterally 4
times daily on the first day and then tapered down to 30 mg
twice daily on day 4, and gabapentin was dosed 1200 mg
once and 600 mg twice on day 1 then tapered to 600 mg once
on day 4. Patients in the gabapentin group were able to
receive rescue PHB as needed. The primary outcome was the
proportion of treatment failure in each group, defined as the
requirement of ≥3 doses of as-needed PHB. A total of 27
patients were included in the analysis (gabapentin: n = 14,
PHB: n = 13). Two patients in each group were defined as
treatment failures (P value not provided). There was no difference in daily withdrawal scores between the groups
throughout the study period. Therapy was well tolerated,
with no patients developing seizures or DT related to AWS.
Summary. The use of oral and intravenous PHB as monotherapy for AWS has been studied in heterogeneous patient
samples in numerous studies with variable study designs and
comparator groups. In summary, it appears that PHB by
either route is as effective as other GABA agonists for the
management of AW and appears to have a clear doseresponse relationship in regard to serum levels; however,
specific serum levels have not been associated with clinical
outcomes and may require patient individualization. These
results are only applicable to patients with mild-to-moderate
AWS and represent surrogate end points.

Clinical Applications and Future
Directions
In total, 9 studies that evaluated PHB in the treatment of
mild, moderate, or severe AWS were included in our

Table of Contents for the Digital Edition of Hospital Pharmacy - October 2017