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Rapid Benzodiazepine Detoxification Using Low Dose Flumazenil - A small case series

Rapid Benzodiazepine Detoxification Using Low Dose Flumazenil - A small case series. Peter Coleman MD The Coleman Institute Richmond Va. USA. Background. Traditional methods of detoxification for patients dependent on Benzodiazepine usually involve substitution and slow taper

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Rapid Benzodiazepine Detoxification Using Low Dose Flumazenil - A small case series

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  1. Rapid Benzodiazepine Detoxification Using Low Dose Flumazenil- A small case series Peter Coleman MD The Coleman Institute Richmond Va. USA

  2. Background • Traditional methods of detoxification for patients dependent on Benzodiazepine usually involve substitution and slow taper • These methods have low patient acceptance and low success rates

  3. Rapid Benzodiazepine Detoxification using Flumazenil • Early work by Gerra • Further experience by O’Neil and Currie • RBD program begun in Richmond Va. in 2007

  4. History of RBD at TCI • First 10 patients detoxified in hospital • Subsequently moved to outpatient procedure with home infusion pump • Flumazenil 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

  5. Current Study Questions • What is the successful completion rate for a Flumazenil assisted detoxification? • How severe are the withdrawal symptoms during the detoxification? • How severe are the withdrawal symptoms following the detoxification? • Are there indicators that will predict which patients will do well? • Are there medications that are helpful for withdrawal symptoms during and after the detoxification?

  6. Current Study - Overview • Observational study • All patients from February 2010 until December 2010

  7. Current Study – Participants • 12 patients who were scheduled to receive a RBD • Pre-procedure telephone screening using : • Beck Anxiety • Beck Depression • Benzo Withdrawal Scale • Usual treatment • No exclusions because of the study

  8. 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 louder 0 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

  9. RBD Procedure – Day 1 • Routine History and physical • Routine Lab work and EKG • Pre-treatment with Lyrica (Pregabalin) 50-75mg • Infusion of Flumazenil at 1mg over 24 hours • Observation in clinic for 3-4 hours • PRN meds – Clonidine, Propranolol, Zyprexa, and Phenobarbital

  10. RBD procedures – Subsequent Days • Daily visits • Flumazenil 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

  11. RBD - Completion • Completion of Detoxification defined as a negative Drug screen

  12. RBD Aftercare • Patients encouraged to use Lyrica for at least 7 days post completion • Continue PRN meds • Follow up with their local Physician and Therapist • Follow up phone calls with TCI at: • 2 weeks • 4 weeks • 2 months • 3 months

  13. Results – Completion of Detoxification • Completion of Detoxification 83% (10/12) • One patient stopped after 12 hours • One patient stopped after 3 days

  14. 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

  15. Benzo Withdrawal Scale results during detoxification – Comfortable patients

  16. Benzo Withdrawal Scale results during detoxification – Uncomfortable patients

  17. Predictors of a Comfortable and Successful Detoxification • We considered the following: • Type of Benzodiazepine • Level of Benzodiazepine use • History of previous Substance Abuse • Pre-treatment Beck Anxiety Score • Pre-treatment Beck Depression Score • Pre-treatment Benzodiazepine Withdrawal Scale

  18. Results – Possible Predictors of Detoxification success

  19. Predictors - 1 • Type 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

  20. Predictors - 2 • Substance abuse History • If a previous SA Hx 75% comfortable detox • If no previous SA Hx 50% comfortable detox • Pre-treatment Beck Anxiety Scale • Score less than 20 100% comfortable detox • Score over 20 44% comfortable detox • Score over 30 40% comfortable detox

  21. Predictors - 3 • Pre-treatment Benzodiazepine Withdrawal Scale • Less than 30 67% comfortable detox • Over 30 60% comfortable detox • Over 40 67% comfortable detox • Pre-treatment Beck Depression Scale • Less than 20 67% comfortable detox • Over 30 67% comfortable detox

  22. Summary – predictors of success or withdrawal discomfort • None of the instruments we used were completely reliable to predict outcomes • There was a large variation on the scales used • Beck Anxiety Scale was the most predictive • Substance abuse history was somewhat predictive • Beck Depression scale was not predictive • The initial Benzodiazepine Withdrawal Scale was not helpful

  23. Results – Discomfort after the Detoxification - PAWS • Detoxification 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

  24. Withdrawal Scores after Detoxification – Comfortable patients

  25. Withdrawal Scores after Detoxification – Uncomfortable patients

  26. Results - Adverse events • No 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.

  27. Results – Medications to help • We used prn: • Clonidine 0.1 mg • Propranolol 20mg • Zyprexa 2.5 mg • Phenobarbital 30mg • We have tried: • Depakote • Buspar • Lamotrigine • Trileptal

  28. Further research • This was a small pilot study • Larger study • More detailed psychiatric evaluation tools • More narrowly focused with exclusions for other drug use • More rigorous follow up

  29. Conflicts of interest • None

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