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 Detached or withdrawn 0 1 2 3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