peter coleman md the coleman institute richmond va. usa
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Rapid Benzodiazepine Detoxification Using Low Dose Flumazenil
- A small case series
Peter Coleman MDThe Coleman Institute
Richmond Va. USA
BackgroundTraditional methods of detoxification for
patients dependent on Benzodiazepine usually involve substitution and slow taper
These methods have low patient acceptance and low success rates
Rapid Benzodiazepine Detoxification using FlumazenilEarly work by Gerra
Further experience by O’Neil and Currie
RBD program begun in Richmond Va. in 2007
History of RBD at TCI First 10 patients detoxified in hospitalSubsequently moved to outpatient procedure
with home infusion pumpFlumazenil infusion begun at 1mg IV over 24
hours, and advanced as tolerated.Most patients seemed to do very well, but
some had an increase in withdrawal symptoms
Current Study Questions1. What is the successful completion rate for a
Flumazenil assisted detoxification?2. How severe are the withdrawal symptoms
during the detoxification?3. How severe are the withdrawal symptoms
following the detoxification?4. Are there indicators that will predict which
patients will do well?5. Are there medications that are helpful for
withdrawal symptoms during and after the detoxification?
Current Study - OverviewObservational study All patients from February 2010 until
December 2010
Current Study – Participants12 patients who were scheduled to receive a
RBDPre-procedure telephone screening using :
Beck AnxietyBeck DepressionBenzo Withdrawal Scale
Usual treatmentNo exclusions because of the study
Benzodiazepine Withdrawal Scale 1. Confused or disoriented 0 1 2 3 4 2. Tense 0 1 2 3 4 3. Dizzy or lightheaded 0 1 2 3 4 4. Weaker than usual 0 1 2 3 4 5. Heart pounding 0 1 2 3 4 6. Difficulty concentrating 0 1 2 3 7. Mentally less active than usual 0 1 2 3 4 8. Hands or fingers feel trembly 0 1 2 3 4 9. Clumsy or uncoordinated 0 1 2 3
4 10. Nervous or anxious 0 1 2 3 4 11. A feeling of unreality 0 1 2 3 4 12. Numb, tingling in the extremities 0 1 2 3
4 13. Irritable or grumpy 0 1 2 3 4 14. Noises and sounds seem louder0 1 2 3 4 15. Perspired 0 1 2 3 4 16. As if I were moving 0 1 2 3 4 17. Shaky or jittery 0 1 2 3 4 18. Detached or withdrawn 0 1 2 3
4 19. Heaviness in limbs 0 1 2 3 4 Total Possible Score = 76
RBD Procedure – Day 1Routine History and physicalRoutine Lab work and EKGPre-treatment with Lyrica (Pregabalin) 50-
75mgInfusion of Flumazenil at 1mg over 24 hoursObservation in clinic for 3-4 hoursPRN meds – Clonidine, Propranolol, Zyprexa,
and Phenobarbital
RBD procedures – Subsequent DaysDaily visitsFlumazenil advanced each day by 1 mg over
24 hours, unless there was withdrawal discomfort
Monitored in clinic for 3-4 hours if Flumazenil increased
PRN meds – Clonidine, Propranolol, Zyprexa, and Phenobarbital
RBD - Completion• Completion of Detoxification defined as a
negative Drug screen
RBD AftercarePatients encouraged to use Lyrica for at least
7 days post completionContinue PRN medsFollow up with their local Physician and
TherapistFollow up phone calls with TCI at:
2 weeks4 weeks2 months3 months
Results – Completion of DetoxificationCompletion of Detoxification 83% (10/12)
One patient stopped after 12 hours
One patient stopped after 3 days
Results – Detoxification Discomfort
We defined the detoxification as “comfortable” when there was no more than a 10% increase in symptoms on the withdrawal scale
Overall 58% - (7/12) - had a comfortable detoxification
Benzo Withdrawal Scale results during detoxification – Comfortable patients
1 2 3 4 5 60
10
20
30
40
50
60
70
80
MPTHEEHGJZMLGLM
Benzo Withdrawal Scale results during detoxification – Uncomfortable patients
1 2 3 4 5 6 7 8 9 10 11 120
10
20
30
40
50
60
70
MHJRKD
Predictors of a Comfortable and Successful DetoxificationWe considered the following:
1. Type of Benzodiazepine2. Level of Benzodiazepine use3. History of previous Substance Abuse4. Pre-treatment Beck Anxiety Score5. Pre-treatment Beck Depression Score6. Pre-treatment Benzodiazepine Withdrawal
Scale
Results – Possible Predictors of Detoxification success
Patients Specific Benzo Benzo Dose High/Low
Substance Abuse Hx Beck Anxiety Beck Depression Initial Benzo
Withdrawal Scale Completed Detox Increase in W/d Sx
MP X H Y 27 NA 21 Y N
THE K H Y 7 17 13 Y N
MH K H Y 27 33 24 Y Y
EH X H N 12 17 33 Y N
GJ K L N 51 37 70 Y N
JR A H N 31 25 7 Y Y
AB K L N 36 13 25 N Y
RB A H N 21 17 33 N Y
ZM A L Y 24 17 18 Y N
LG X L N 9 9 16 Y N
LM V L N 33 32 46 Y N
KD X L N 47 29 57 Y Y
Predictors - 1Type of Benzodiazepine
No obvious difference - numbers were small
Benzodiazepine Dose – High Dose defined as daily use of over:
6mg of Xanax, Klonopin or Ativan, 60mg of Valium
No obvious difference - numbers were small
Predictors - 2 Substance abuse History
If a previous SA Hx 75% comfortable detoxIf no previous SA Hx 50% comfortable detox
Pre-treatment Beck Anxiety ScaleScore less than 20 100% comfortable
detoxScore over 20 44% comfortable
detoxScore over 30 40% comfortable
detox
Predictors - 3Pre-treatment Benzodiazepine Withdrawal
ScaleLess than 30 67% comfortable
detoxOver 30 60% comfortable detoxOver 40 67% comfortable detox
Pre-treatment Beck Depression ScaleLess than 20 67% comfortable detoxOver 30 67% comfortable detox
Summary – predictors of success or withdrawal discomfortNone of the instruments we used were
completely reliable to predict outcomesThere was a large variation on the scales
usedBeck Anxiety Scale was the most predictiveSubstance abuse history was somewhat
predictiveBeck Depression scale was not predictiveThe initial Benzodiazepine Withdrawal Scale
was not helpful
Results – Discomfort after the Detoxification - PAWSDetoxification discomfort defined as more
than a 10% increase in symptoms from the pre-treatment withdrawal scale
67% - (8/12) – had no increase in withdrawal symptoms after the detoxification
Some had dramatic and rapid resolution, while some took up to 3 months
Very incomplete data
Withdrawal Scores after Detoxification – Comfortable patients
1 20
10
20
30
40
50
60
70
80
THEEHGJLGLMKD
Withdrawal Scores after Detoxification – Uncomfortable patients
1 2 3 4 50
10
20
30
40
50
60
MHJR
Results - Adverse eventsNo seizures or other major adverse events
One patient continued to have severe anxiety and had suicidal thoughts. About 4 weeks after the detoxification he was hospitalized by his local psychiatrist. He was put back on benzodiazepines for a time but took himself off them and following this he had an unsuccessful suicide attempt.
Results – Medications to helpWe used prn:
Clonidine 0.1 mgPropranolol 20mgZyprexa 2.5 mgPhenobarbital 30mg
We have tried:DepakoteBusparLamotrigineTrileptal
Further researchThis was a small pilot studyLarger studyMore detailed psychiatric evaluation toolsMore narrowly focused with exclusions for
other drug useMore rigorous follow up
Conflicts of interestNone
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