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Withdrawal and psychological sequelae, and patient satisfaction associated with subcutaneous
flumazenil infusion for the management of benzodiazepine withdrawal: a case series
Gary Hulse, George O'Neil, Noella Morris, Kellie Bennett, Amanda Norman and Sean Hood
J Psychopharmacol 2013 27: 222 originally published online 16 May 2012
DOI: 10.1177/0269881112446532

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446532
2013
JOP27210.1177/0269881112446532Hulse et al.Journal of Psychopharmacology

Short Report

Withdrawal and psychological sequelae,

and patient satisfaction associated with
subcutaneous flumazenil infusion for Journal of Psychopharmacology

the management of benzodiazepine

27(2) 222­–227
© The Author(s) 2013
Reprints and permission:
withdrawal: a case series sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/0269881112446532
jop.sagepub.com

Gary Hulse1, George O’Neil2, Noella Morris1, Kellie Bennett1,

Amanda Norman1,3 and Sean Hood1

Abstract
Our group and others internationally have previously reported data on the use of low-dose flumazenil administered intravenously for the management of
benzodiazepine withdrawal. This paper describes the first reported use of subcutaneous flumazenil infusion in the management of acute benzodiazepine
withdrawal. Self-reported withdrawal symptoms and psychological state and anxiety sequelae were collected at baseline and then at intervals to 5
days following initiation of subcutaneous flumazenil infusion. Data indicate that patient subjective benzodiazepine withdrawal symptoms were well
managed, with significant reduction in psychological distress seen over the duration of treatment. Perceived difficulty in performing everyday functions
was positively correlated with withdrawal severity and improved over treatment. Patients reported high treatment comfort, willingness to undertake a
future subsequent treatment using this technique, and willingness to recommend this treatment to a friend. This small proof-of-concept study indicates
that subcutaneous flumazenil infusion has excellent tolerability, efficacy and improvement on measures of psychological distress. Given this technique
is less invasive and requires fewer staff resources compared with intravenous administration, it may prove a significant asset in the management of
benzodiazepine withdrawal.

Keywords
Flumazenil, infusion, subcutaneous, benzodiazepine withdrawal

Introduction
Following long-term benzodiazepine use, between 15–44% of per-
sons become dependent, even while adhering to therapeutic doses,
and upon cessation experience protracted moderate to severe with-
drawal symptoms that, if left untreated, can result in significant
morbidity and, rarely, mortality. Most relapse back to regular ben-
zodiazepine use (Ashton, 1991; Basinska et al., 2010; de las
Cuevas et al., 2000). Benzodiazepine withdrawal management in
primary care commonly involves gradual reduction in benzodiaz-
epine dose, also known as ‘benzodiazepine taper’, with or without
concomitant psychological interventions ranging from supportive
counselling to cognitive behaviour therapy (Lader et al., 2009).
Where a severe withdrawal syndrome or other sequelae are
anticipated, inpatient dose tapering for 2–4 weeks or longer is
usually recommended. These treatment programmes are fre-
quently not cost effective because completion rates and subse-
quent abstinence rates are often low. One study found that only 10
of 44 patients undergoing either fixed or symptom-triggered dose
pathology, panic disorder diagnosis, and history of alcohol/drug
abuse (Schweizer and Rickels, 1998). These factors may also be
predictive of longer-term outcomes; for example, high baseline
levels of psychological distress, anxiety and dosage predict poor
outcomes at 3 months following a supported outpatient dose taper
treatment intervention (O’Connor et al., 2008).
A small but growing body of research has indicated a role for
flumazenil, a benzodiazepine receptor antagonist, in the manage-
ment of benzodiazepine withdrawal (Gerra et al., 2002; Hood
et al., 2009; Lader and Morton, 1992; Quaglio et al., 2005; Saxon
et al., 1997; Savic et al., 1991). Flumazenil has a high first-pass
metabolism, resulting in less than 25% systemic bioavailability
1School of Psychiatry and Clinical Neurosciences, The University of
Western Australia, Perth, Australia
2Australian Medical Procedures Research Foundation (AMPRF), Perth,

taper completed an 8 day inpatient taper protocol and were benzo- Australia
3Department of Addiction Medicine, St Vincent’s Hospital, Melbourne,
diazepine free at the time of discharge (McGregor et al., 2003).
Severity of acute withdrawal has been shown to be associated Australia
with higher dosage of benzodiazepines, the use of multiple benzo- Corresponding author:
diazepines, oral rather than injected use (Seivewright and Dougal, Gary Hulse, School of Psychiatry and Clinical Neurosciences, The
1993), duration of use, shorter half-life benzodiazepines, and University of Western Australia, M521, D Block, QEII Medical Centre,
more rapid taper. Patient variables have also been indicated such Nedlands, WA 6009, Australia.
as higher pretreatment anxiety and depression, personality Email: gary.hulse@uwa.edu.au

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Hulse et al. 223
and a short half-life (Roncari et al., 1993). Accordingly, its major
mode of administration for benzodiazepine withdrawal has been
via intravenous administration using multiple bolus infusions of
flumazenil either alone (Lader and Morton, 1992; Saxon et al.,
1997) or in conjunction with tapering doses of benzodiazepines
(Gerra et al., 2002). Our group (Hood et al., 2009) recently
reported on the continuous intravenous delivery of flumazenil for
up to 4 days (2 mg/24 h continuous intravenous flumazenil infu-
sion for 96 h with oxazepam tapering). In conjunction with similar
studies, prima facie evidence exists of the effectiveness of multi-
ple bolus or continuous intravenous infusion of flumazenil in (1)
preventing clinically significant benzodiazepine withdrawal syn-
dromes, and (2) achieving short-term benzodiazepine abstinence.
Notwithstanding positive clinical outcomes, intravenous infusion
over several days is associated with a number of technical and
clinical features that reduce its clinical utility. In particular, diffi-
culty in obtaining peripheral venous access may sometimes
require more invasive central venous cannulation, and the need
for high-intensity medical monitoring during intravenous infusion
makes this is a resource-intensive procedure. Subcutaneous infu-
sion could provide an effective alternative.
This paper describes the first reported use of subcutaneous
flumazenil infusion in the management of acute benzodiazepine
withdrawal in a clinical population, focusing in particular on the
management of withdrawal symptoms and psychological state
and anxiety sequelae during acute withdrawal. The relationship of
patient and drug use variables to withdrawal severity is examined.
Patient acceptability of the procedure is also reported.
Method
Clinical setting
The study was conducted at an outpatient treatment clinic and a
supervised residential facility. The study was conducted under the
auspice of the University of Western Australia Research Ethics
committee (RA/4/1/4185). The data were collected between April
2009 and October 2010.
Design
The study was an observational case series.
Participants
Patients presenting for treatment who were benzodiazepine
dependent (DSM-IV) and wishing to withdraw from and cease
using benzodiazepines were considered for treatment with fluma-
zenil. Inclusion criteria: benzodiazepine dependent (daily use >3
months @ >10 mg per day diazepam equivalents). Exclusion
criteria: less than 18 years of age; medical conditions precluding
cessation of benzodiazepines; known epilepsy; an inability or
unwillingness to consent to participation in the study; and preg-
nancy (urine βHCG positive) or current breast feeding. Patients’
medical assessment included seizure history. Patients were
assessed on an individual basis and a clinical assessment was made
as to whether a previous history of seizures precluded inclusion in
the trial. Known epilepsy was an exclusion criteria. Of note, pre-
existing psychiatric disorders were not an exclusion criterion.
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All participants gave written informed consent, including
understanding of the off-label nature of the use of flumazenil,
before entering treatment, and permission for their clinical records
to be used for research purposes.
Treatment regimen
Subjects were treated with a subcutaneous flumazenil solution
containing 16 mg of flumazenil infused over a 92 h period: 4
mg/24 h period (±20%). The flumazenil infusion was augmented
with a rapid dose taper regimen of 60, 30, 15 mg of oxazepam –
equivalent to 10, 5, and 2.5 mg diazepam (SA Health, 2009) –
over the first 48 h of treatment starting at baseline then 24 and 48
h after the initiation of the infusion. Based on clinical assessment
for residual withdrawal symptoms at the end of the 96 h infusion,
patients were offered a second infusion treatment of up to further
96 h duration. Thus some patients received treatment for up to 8
days. For consistency, this paper reports outcomes for all patients
up to 96 h of treatment. Treatment was provided on an ambulatory
basis. Flumazenil infusions were commenced in the treatment
clinic and the patients then transferred to a residential withdrawal
facility associated with the clinic for monitoring by trained staff.
Medical staff were on 24 h call. Adjunctive anti-convulsive medi-
cations were available if required. Patients returned to the clinic
daily for infusion site inspection and clinical review.
Investigational agent
Commercially available pharmaceutical preparations of flumaze-
nil (e.g. Anexate®, Roche Pharmaceuticals) have a pH of around
4.0. Our earlier experience with intravenous flumazenil infusion
indicated that treatment with continuous subcutaneous flumazenil
infusion for at least 4 days would be necessary, and possibly
longer if protracted withdrawal symptoms were evident. In order
to minimize the likelihood of irritation around the infusion site we
therefore used a flumazenil formulation with a pH of 6.8.
Quantities sufficient for research purposes were manufactured by
Greens Compounding Pharmacy (South Australia) under current
Good Manufacturing Practice (cGMP) guidelines. Greens pro-
vided documentation detailing formulation and autoclaving data.
A certificate of quality assurance was provided by Greens for the
manufactured product. Accelerated aging of the flumazenil drug
solution was conducted by GoMedical Industries (Western
Australia) at 60°C and confirmed drug stability for an equivalent
period of 6 months at 30°C.
Infusion apparatus
Subcutaneous flumazenil infusion was administered via a syringe
pump (Springfusor® 30 syringe infusion pump: GoMedical
Industries, Australia, see Figure 1) connected to a Y infusion
device (the BD Saf-T-Intima® Subcutaneous Infusion Device
with Y adaptor). The Springfusor® consists of a spring-driven
cartridge to drive the syringe and a Flow Control Tubing (FCT) to
control the output from the syringe. The Springfusor® 30 infusion
pump was attached via butterfly needle inserted on the anterior
abdominal wall (Figure 2), and carried in a pouch worn on a belt.
Patients were fully ambulatory with the Springfusor® device in
place.
224 Journal of Psychopharmacology 27(2)
Figure 1.  Springfusor® 30 syringe infusion pump: GoMedical Industries,
Australia
Figure 2.  Subcutaneous infusion site
Assessment and data collection
A structured interview schedule was developed to collect demo-
graphic information, drug use history, psychiatric and physical
comorbidities, and treatment history. Withdrawal symptoms and
cravings and psychological indicators were monitored with vali-
dated clinical instruments and data were collected prospectively.
The Benzodiazepine Withdrawal Scale – CIWA-B (Busto et al.,
1989) – was used to monitor withdrawal symptom severity in all
patients across five data points, at the commencement of the infu-
sion, and thereafter at approximately 24, 48, 72 and 96 h post
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commencement. Throughout the rest of this report these time peri-
ods are referred to as day 1, day 2, day 3, day 4, and day 5 respec-
tively. The K10 (Kessler et al., 2002), and BSI (Brief Symptom
Inventory) (Derogatis and Melisaratos, 1983) were administered
to monitor psychological state. A modified version of the K10 was
used for repeated assessment of symptoms ‘in the last 3 days’. The
GAD7 (Generalized Anxiety Disorder Scale) (Spitzer et al., 2006)
was used to measure baseline anxiety symptoms. As these data
were collected as part of standard clinical care rather than under a
strict research protocol, staff clinical responsibilities took priority
over research data collection beyond standard clinical monitoring,
thus a full data set is not available on all measures. Bloods were
taken from three patients to confirm and monitor plasma flumaze-
nil throughout the study period.
Plasma flumazenil assay
The samples were analysed by an established LC-MS/MS method
for the quantification of flumazenil in plasma. On the day of anal-
ysis, samples were thawed at room temperature and vortex mixed.
Aliquots of samples were extracted into organic solvent hexane:
(dichloromethane, 1:1) using zolpidem-d6 (10 ng/mL in 50% ace-
tonitrile/water) as the internal standard. Two samples from each
participant were analysed to ensure consistency of the quantifica-
tion method (r(11)=0.970, p<0.001).
Statistical methods
Data analysis was conducted to investigate self-reported
withdrawal and psychological distress symptoms over the 96 h
infusion treatment. Data were analysed using SPSS Version 19. A
one-way repeated measures analysis of variance (ANOVA) with
post hoc analysis and paired samples t-tests with Bonferroni cor-
rections were employed to compare differences across the dura-
tion of treatment. Pearson product-moment correlation was used
to examine the strength and direction of the linear relationship
between continuous variables and Spearman’s Rho used with
ordinal variables. Given the small sample size, the authors urge
caution in the interpretation of results, and all analyses should be
considered exploratory.
Results
Patient characteristics
Results from a total of 23 patients are reported; 56% were female.
The mean age was 39 years (standard deviation (SD) 9.6, range
26–66 years). Of the participants, 80% were currently using other
licit or illicit psychoactive drugs in addition to benzodiazepines,
the most common being cannabis (43%), and 80% of patients
smoked tobacco. Four patients had used two or more psychoactive
substances in addition to benzodiazepines and tobacco in the week
prior to admission.
All participants used benzodiazepines daily, with a history of
long-term benzodiazepine use (mean number of years of benzodi-
azepine use was 11.9 (SD 7.8), range 1–29 years), and continued
their benzodiazepine use up until the commencement of flumaze-
nil treatment. Whilst diazepam was the most commonly used ben-
zodiazepine (65%), two-thirds of participants (65%) were
Hulse et al. 225
Figure 3.  CIWA-B scores (mean) by treatment day
currently using multiple benzodiazepines. For ease of compari-
son, benzodiazepine dosage was converted into ‘diazepam equiv-
alent dose’. The mean diazepam equivalent daily dose used by
participants was 169 mg (sd=181), range 20–840 mg. All partici-
pants reported previous unsuccessful attempts to reduce or abstain
from benzodiazepine use. Some of these were under medically
supervised dose taper regimes, others were simply patients’ own
attempts to ‘cut back’. As this data was entirely self-reported it has
not been reported.
A subset of 11 participants completed the GAD7 (Generalized
Anxiety Disorder Scale) to measure baseline anxiety symptoms
(mean=12.5, sd=4.95). A score of 10–14 is considered moderate
(Spitzer et al., 2006). A score of 15–21 indicates a severe level of
anxiety severity. Two patients had scores within in the severe range
(19, 21). The GAD7 also asks participants to rate on a scale of 1–4
the effect of their anxiety symptoms in terms of how difficult it is to
perform everyday functions at work, home and socially. The mean
difficulty rating was 3.09 (SD=0.70) equating to ‘very difficult’.
Severity of withdrawal
Withdrawal symptoms in all study participants (n=23) were
assessed with the CIWA-B at the commencement of the infusion
(day 1), and at 24 h (day 2), 48 h (day 3), 72 h (day 4), and 96 h
(day 5) of treatment, providing five data points. Severity of with-
drawal as measured by the CIWA-B is generally interpreted as fol-
lows: 1–20 ‘mild’, 21–40 ‘moderate’, 41–60 ‘severe’, 61–80 ‘very
severe’ (Busto et al., 1989). Mean withdrawal scores, although
‘mild’ throughout the infusion period, were highest on day 1
(mean=20.2, sd=13.1) and day 2 (mean=19.5, sd=14.8) (Figure 3).
A one-way repeated measures ANOVA was used to compare
21 participants’ withdrawal scores on the CIWA across 5 days.
(Note: as there were missing data for two patients their scores
were excluded from this analysis). Mauchly’s test indicated that
the assumption of sphericity had been violated (chi-square=21.155,
p<0.05), therefore degrees of freedom were corrected using
Huynh–Feldt epsilon. ANOVA results indicate significant change
on the CIWA across the time period, F(3.25, 65)=5.547, p=0.001,
partial η=0.217. Post hoc analysis with Bonferroni corrections
revealed that the CIWA score on day 2 (M=19.85, SD=3.29) was
significantly higher (p<0.001) than the CIWA scores reported on
day 3 (M=15.62, SD=2.78). No other significant differences were
found between CIWA scores on any other days (p>0.05). However,
the number of participants reporting severe to very severe
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Figure 4.  Flumazenil levels (ng/mL) in three participants across 5 days
post commencement of infusion
withdrawal on the CIWA decreased from 11 people at baseline to
six people reporting this high-level severity on day 5.
Patient drug use history was examined to determine any cor-
relation between benzodiazepine use variables and severity of
withdrawal as measured by the CIWA-B. There was a non-
significant low correlation between the number of years of benzo-
diazepine use and mean CIWA score (mean score across the 5
days) (r=0.191, p=0.384) and a non-significant low correlation
between the average daily diazepam equivalent dose and mean
CIWA score (mean score across the 5 days) (r=0.111, p=0.613).
There was a non-significant low correlation between baseline
scores on the GAD7 and mean CIWA score (mean score across the
5 days) (r=0.065, p=0.849). There was a significant correlation
between GAD7 ‘difficulty in performing everyday function’
scores and mean CIWA (r=0.840, p=0.018) Note: N=11.
Psychological distress
Self- reported levels of psychological distress were recorded for 11
participants at baseline (day 1) and for 5 days of flumazenil infusion
using the Kessler Psychological Distress Scale (K10). A significant
difference was found between scores on day 1 (M=27.11, SD=8.831)
and on day 3, 4, or 5 of treatment (M=16.95, SD=7.230),
(t(18)=4.006, p<0.001). At baseline 19 of the 20 persons for which
K-10 data were available scored above 16 (high-risk category)
(Andrews and Slade, 2001), while only seven participants reported
such high levels at day 3–5 post-infusion. Psychological distress
was also measured using the BSI for this subset of 11 participants. A
significant difference was reported between the baseline Global
Severity Index (M=89.55, SD=28.38) and scores taken on day 4 or 5
of treatment (M=60.64, SD=26.96), (t(10)=3.334, p<0.001).
Plasma flumazenil levels
Plasma samples were collected from three participants to measure
the flumazenil levels following commencement of infusion and to
validate the method of analysis.
Figure 4 shows that flumazenil was present across the 5 days of
treatment in all participants. Participants 1 and 2 showed the high-
est level flumazenil within the first 2 days following commence-
ment of infusion (4.57 and 2.32 ng/mL, respectively), while the
highest recorded level for participant 3 was on day 3 (1.68 ng/mL).
226 Journal of Psychopharmacology 27(2)
Patient acceptance of procedure
Thirteen patients provided information about acceptability of the
procedure. The majority of these patients rated the subcutaneous
infusion method highly on all three dimensions: How comfortable
was the procedure? In total, 75% of patients rated the procedure as
extremely comfortable (Median=5, Median Absolute
Deviation=0.39, a score of 1 indicating ‘extremely uncomforta-
ble’ and a score of 5 indicating ‘not uncomfortable at all’); Would
you have the procedure again? Some 85% of patients reported that
they would definitely have the procedure again (Median=5,
Median Absolute Deviation=0.39, a score of 1 indicating ‘defi-
nitely not’ and 5 indicating ‘definitely’); Would you recommend
the treatment to a friend? Of the patients, 85% reported that they
would recommend the treatment (Median=5, Median Absolute
Deviation=0.39, a score of 1 indicating ‘definitely not’ and 5 indi-
cating ‘definitely’).
Discussion
Previous studies have shown that intravenous infusion with com-
mercially available pharmaceutical preparations of flumazenil has
efficacy in the management of both acute and long-term benzodi-
azepine withdrawal symptoms. The current study data indicate
that subjective benzodiazepine withdrawal symptoms as assessed
by CIWA-B were well managed by the subcutaneous flumazenil
infusion, and provide proof of concept that continuous subcutane-
ous infusion of flumazenil formulation is a feasible alternative to
intravenous flumazenil administration or benzodiazepine tapering
for the management of acute benzodiazepine withdrawal. Given
the significant benzodiazepine use history of this cohort, it is
apparent that flumazenil is an effective pharmacotherapy for the
management of the acute withdrawal phase for a difficult-to-treat
patient group. Only mild to moderate withdrawal symptoms were
seen, whereas one might otherwise expect to see quite severe
withdrawal symptoms in this patient group.
Although plasma flumazenil levels were collected for three
patients only, these data demonstrate that flumazenil delivered via
the subcutaneous route is associated with flumazenil bioavailabil-
ity via blood from day 1 of the infusion. CIWA symptoms peaked
at day 1 with a significant drop in CIWA score between day 2 and
3. This may suggest that the benzodiazepine withdrawal treatment
action of flumazenil is not determined by blood levels but by cen-
tral nervous system levels, likely associated with increased GABA
receptor occupancy, as has been suggested by other researchers
(Savic et al., 1991). Although data are available regarding recep-
tor occupancy levels with bolus intravenous infusion (Savic et al.,
1991), no data are available to indicate receptor occupancy
achieved with continuous subcutaneous or intravenous flumazenil
infusion as reported here and in our earlier study (Hood et al.,
2009). The use of imaging modalities such as positron emission
tomography to further explore changes in receptor occupancy
over the withdrawal period and associated effects on withdrawal
and psychological sequelae is desirable, and could be examined in
a future research project.
On both measures of psychological distress (K10 and BSI) sig-
nificant improvements were seen over the duration of treatment.
Persons scoring above 16 on the K10 scale have a one in four
chance of having a current anxiety or depressive disorder and 1%
chance of ever having made a suicide attempt (Andrews and Slade,
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2001). While all but one patient screened scored above 16 at base-
line, these had dropped below this level in 60% of participants post-
infusion initiation. Baseline anxiety scores assessed by the GAD7
were not found to correlate with withdrawal severity, although per-
ceived difficulty in performing everyday functions was positively
correlated with withdrawal severity. It is worth noting that the
effect of this indicator of baseline anxiety on withdrawal severity
was apparent even when patients were prescribed augmented oxaz-
epam taper over the first 72 h to ameliorate symptoms. Our finding
is consistent with those of other researchers (O’Connor et al., 2008;
Rickels et al., 1990) on the importance of baseline anxiety as a
predictor of benzodiazepine withdrawal severity. In contrast,
patient drug use variables that have been shown in previous studies
to be associated with more severe withdrawal, namely benzodiaz-
epine dose and years of use, were not significantly associated with
severity of withdrawal symptoms in this study.
Caution must be exercised in interpretation of these data, given
that sample size is small and data were not collected under clinical
trial conditions. Due to the ambulatory nature of this treatment it
is possible that patients may have been able to self-administer
benzodiazepines undetected. Although we consider this unlikely,
any undetected use would affect the validity of CIWA-B scores.
Subcutaneous infusion has considerable benefits over intrave-
nous administration. Patient acceptance of subcutaneous flumaze-
nil treatment was high on the three measured areas of individual
treatment comfort, willingness to undertake a future subsequent
treatment using this technique, and willingness to recommend this
treatment to a friend. In addition, the need for more invasive,
intensive and expensive resources associated with the intravenous
route is ameliorated. Also appealing is the ability for patients to
remain mobile for the duration of their benzodiazepine with-
drawal, either within the environment of an inpatient or residential
treatment facility or potentially even within their home environ-
ment. The urgent need now for future studies providing direct
comparisons between both subcutaneous and intravenous routes,
flumazenil blood levels and clinical outcomes is acknowledged.
Having achieved preliminary encouraging results with both
subcutaneous and intravenous administered flumazenil in the
management of acute benzodiazepine withdrawal, an additional
clinical challenge is to address the high relapse rates that continue
to plague long-term withdrawal management. Appropriate man-
agement may involve the long-term administration of flumazenil
over several weeks or months, with intravenous or subcutaneous
infusion an impractical method for this long-term flumazenil
delivery. Given the good subcutaneous tissue biocompatibility for
flumazenil demonstrated in this study, one possible solution is the
development of sustained release or depot flumazenil formula-
tions. Authors Hulse and O’Neil have conducted animal studies
on an implantable polylactide microsphere and implant flumaze-
nil formulation similar to the biodegradable naltrexone implant
which has been developed and used for the long-term manage-
ment of heroin dependence (Hulse et al., 2009). The evident bio-
compatibility of the current subcutaneous flumazenil formulation
is encouraging, and safety testing of a subcutaneous flumazenil
implant on human subjects is planned in the near future.
A novel subcutaneous flumazenil infusion therapy for the
treatment of benzodiazepine dependence has been presented here
in a clinical sample, providing early evidence of excellent tolera-
bility, efficacy and improvement on measures of psychological
distress. This is a proof-of-concept study; clinical efficacy of
Hulse et al. 227
subcutaneous flumazenil infusion for this indication is yet to be
substantiated in a randomized clinical trial with strict adherence to
a standardized treatment protocol. Nevertheless, this method has
potential advantages over existing therapies and is worthy of
ongoing research evaluation.
Funding
This research received no specific grant from any funding agency in the
public, commercial, or not-for-profit sectors.
Conflict of interest
GON is a Co-Director of GoMedical Industries, Australia, which is a med-
ical device and pharmaceutical development company that manufactures
the Springfusor® syringe infusion pump used in these studies, and has
various patents on pharmacotherapies for the management of substance
abuse. Go Medical Inc. had no right of veto or input into study design, data
analysis or manuscript preparation. No other study member has any finan-
cial interest associated with the investigational product or Go Medical Inc.
and declare that there is no conflict of interest.
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