Basics of Benzodiazepine Use Disorder DATE: October 3, 2017 PRESENTED BY: Melissa B. Weimer, DO, MCR
Disclosures Speaker disclosure: One time lecture sponsored by Indivior about overlap of pain and opioid dependence without mention of medication for which I received honorarium. Planner disclosure: None 2 2
Objectives Understand the mechanism of action and pharmacokinetic properties of benzodiazepines Understand that differentiating between benzodiazepine physiologic dependence and benzodiazepine use disorder may be challenging Describe how to safely taper benzodiazepine therapy 3 3
Benzos are positive allosteric modulators Increase the GABA A receptor s affinity for GABA
Benzodiazepine Metabolism Glucuronide Conjugation o Shorter half-life o Inactive metabolites o Safer in liver disease and elderly Lorazepam Oxazepam Temazepam (remember LOT) Oxidation o Longer half-life o More metabolites o Use caution in liver disease Chlordiazepoxide Diazepam Clonazepam
Benzodiazepine Equivalency
Withdrawal Symptoms: occur after 10-21 days of use
Features of a Benzo Use Disorder vs Benzo physiologic dependence Tolerance Withdrawal When severe, these 2 issues can cause problems with their life, ability to cope Benzo dependence alone Benzo use disorder Tolerance Withdrawal Loss of control of use Continued use despite social or interpersonal issues related to use Giving up other activities due to use No longer fulfilling major life obligations Consistent use despite acknowledgement of harms Wanting to cut down, but not being able Taking in larger amounts and longer than intended
Withdrawal Management Soyka, 2017 4-8 weeks to taper, maybe longer, but not too long 10-50% in first week Hospitalize if > 100mg diazepam equivalents Don t withdraw opioids at the same time Adjuncts: pregabalin/gabapentin, carbamazepine, SSRIs, TCAs, antihistamines, melatonin Limited evidence for AEDs, but still consider
Withdrawal Management Calculate benzodiazepine equivalency (http://www.globalrph.com/benzodiazepine_calc.htm) Reduce by 25-30% per day or week, depending on time course Create taper plan based on Time in detox Ability to safely assure taper and monitor patient Other risk factors like opioid use, alcohol use, etc Adjuvant meds Carbamazepine 200mg BID or Divalproic Acid 250mg TID Vistaril 25-50mg QID Buspar 5-10mg TID Trazodone for sleep Consider clonidine or prazosin
Case Example 1 Real case Joe is a 72 yo man with HTN and hyperlipidemia. He developed severe anxiety after retirement approximately 10 years ago and was prescribed lorazepam 1mg BID. He found it helped him at first, but now he feels like it is a crutch and he doesn t like the effect his wife says it has on him. He would like to stop the medication but every time he stops, he becomes sweaty, fearful, anorexic and can not sleep. He would like to stop the medication before he goes on a cruise in 10 days. He has been erratically taking his meds over the last 2 weeks in an attempt to stop them, but has not been able to sleep.
Features of a Benzo Use Disorder vs Benzo physiologic dependence Tolerance Withdrawal Benzo dependence alone Benzo use disorder Tolerance Withdrawal Loss of control of use Continued use despite social or interpersonal issues related to use Giving up other activities due to use No longer fulfilling major life obligations Consistent use despite acknowledgement of harms Wanting to cut down, but not being able Taking in larger amounts and longer than intended
Taper plan Enjoy your vacation on a stable dose of benzos! Start taper when you return Consider transition to clonazepam or diazepam Taper by 10-25% per week depending on how well patient tolerates the withdrawal Start mirtazapine and melatonin for sleep Refer for CBT
Case Example 2 Real case Joanne is a 52 year old female with hx of PTSD and major recurrent depression who seeks care in your primary care clinic for help getting off of benzos. She has been prescribed benzos (diazepam) since age 20 and has tried several times to stop them. She has developed a social phobia about psychiatrists. She can not go longer than 4 hours between doses or she has severe panic, though she does not take them more than prescribed to her Her friend recently drove to FL to pick her up because she was so distraught over her use and inability to stop. She desperately wants to stop and her friend plans to help her and support her.
Features of a Benzo Use Disorder vs Benzo physiologic dependence Tolerance Withdrawal Benzo dependence alone Benzo use disorder Tolerance Withdrawal Loss of control of use Continued use despite social or interpersonal issues related to use Giving up other activities due to use No longer fulfilling major life obligations Consistent use despite acknowledgement of harms Wanting to cut down, but not being able Taking in larger amounts and longer than intended
Taper plan: prolonged taper Stabilize patient over 1-2 weeks on a dose of long acting benzos (clonazepam) mostly equivalent to her current prescription for diazepam Care coordinate with her friend to help manage medication and inform you if there are any issues Start very slow taper of clonazepam by 0.25mg per day every 2 weeks Consider inpatient assistance Add propranolol due to patient avoidance of all other meds Taper takes 1 year and is successful
Case 3: REAL case Jimmy is a 22 year old man with hx of tobacco use who has been ordering a research benzodiazepine (etizolam) from CA for the last year. Total dose of 20mg per day. He also drinks a 6 pack of beer per day. He has received a DWI due to driving while intoxicated. He has had 2 seizures in the past due to attempting to taper his use on his own. He feels restless, anxious, sweaty, and has vomiting. He would like to get back to work for the parks service as soon as possible. His parents have threatened to kick him out of the house if he does not stop his use.
Features of a Benzo Use Disorder vs Benzo physiologic dependence Tolerance Withdrawal Benzo dependence alone Benzo use disorder Tolerance Withdrawal Loss of control of use Continued use despite social or interpersonal issues related to use Giving up other activities due to use No longer fulfilling major life obligations Consistent use despite acknowledgement of harms Wanting to cut down, but not being able Taking in larger amounts and longer than intended
Taper plan Inpatient admission for detoxification Start Depakote 250mg TID, continue 3 weeks Schedule Librium 50-100mg QID x 1 day and then reduce by 25-50mg per day depending on time in detox Continue PRN Librium as well Work with family on safe discharge plan Advise against working or driving for the next week, minimum Start vistaril, buspar, trazodone to help with symptom relief
Alternatives to Benzos for anxiety Gabapentin Prazosin Seroquel Mirtazepine SSRIs Melatonin Vistaril Buspar *List is not in order of preference and not an exhaustive list *Always choose a medication best suited for the specific problem you are attempting to address
References http://www.globalrph.com/benzodiazepine_calc.htm Soyka, Treatment of Benzodiazepine Dependence. NEJM 376; 12. March 23, 2017 http://www.oregonpainguidance.org/app/content/uploads/2016/ 05/Opioid-and-Benzodiazepine-Tapering-flow-sheets.pdf