Basics of Benzodiazepine Use Disorder DATE: June 12, 2018 PRESENTED BY: Melissa B. Weimer, DO, MCR
Disclosures Speaker: Melissa Weimer, DO, MCR, has nothing to disclose. Planning Committee: The members of the planning committee (Jessica Gregg, Todd Korthuis, Melissa Weimer, John Mahan, Laura Heesacker, O Nesha Cochran, and Chris Colasurdo) have nothing to disclose. Dr. Korthuis serves as principal investigator for NIH-funded research that accepts donated extended-release naltrexone (Alkermes) and buprenorphine/naloxone (Indivior). 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
Symptom Acute Withdrawal Symptoms: occur after 10-21 days of continuous use Higher dose, longer use = more symptoms Lower dose, shorter term use = less symptoms Insomnia 71% Anxiety 56% Mood swings 49% Muscle twitching 49% Tremor 38% Headache 38% Nausea, vomiting, anorexia 36% Frequency Hypersensitivity to smells, sounds, lights, noise, touch Up to 38% Seizure* 4% Jahnsen, 2015 https://www-ncbi-nlm-nih-gov.liboff.ohsu.edu/pmc/articles/pmc4318457/pdf/dtsch_arztebl_int-112-0001.pdf *Hx of prior seizure = risk of seizure again*
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
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 and feels horrible.
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 outpatient slow taper Enjoy your vacation on a stable dose of lorazepam 1mg BID Start benzodiazepine taper when you return Consider transition to clonazepam or diazepam http://www.globalrph.com/benzodiazepine_calc.htm Taper by 10-25% per week depending on how well patient tolerates each step of the taper and dose availability Start mirtazapine and melatonin for sleep Create sleep routine and cut out naps Refer for cognitive behavioral therapy (CBT) Find hobbies or volunteer work
Taper Example: Clonazepam 0.5mg BID x 2 weeks Check in Clonazepam 0.5mg in AM and 0.25mg in PM x 2 weeks Check in Clonazepam 0.25mg BID x 2 weeks Check in Clonazepam 0.25mg in AM and 0.125mg In PM x 2 weeks Check in Clonazepam 0.125mg BID x 2 weeks Check in Clonazepam 0.125mg QAM x 2 weeks Check in Clonazepam 0.125mg every other day x 2 weeks Check in STOP
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. She has completely isolated herself from family and friends, can not work and feels completely disabled. Her friend recently drove to FL to pick her up because she was so distraught over her use and inability to stop benzodiazepines and her current prescriber is threatening to cut her off. She desperately wants to stop and her friend plans to help her and support her.
Features of a Benzodiazepine Use Disorder vs Benzodiazepine dependence Benzo physiologic dependence Tolerance Withdrawal 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: outpatient prolonged taper Stabilize patient over 1-2 weeks on a dose of long acting benzodiazepines (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 Keep a log and lock on the medications Consider inpatient treatment if this doesn t go well Start very slow taper by reducing clonazepam by 0.25-0.125mg every 2 weeks Add PROPRANOLOL due to patient avoidance of all other meds Taper takes 1 year and is successful Patient engages in NA meetings for support
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 continual 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 TAPER 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 Fastest inpatient taper = 5-7 days Longest inpatient taper = 10-14 days Continue PRN Librium based on CIWA scale as well Work with family on safe discharge plan Advise against working or driving for the next week, minimum Start hydroxyzine, buspirone, trazodone to help with symptom relief Refer for treatment
Alternatives to Benzos for anxiety Prazosin or Clonidine Propranolol Quetiapine Mirtazepine SSRIs Hydroxyzine Buspirone Gabapentin* 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 Consider TRAUMA and PTSD *Beware of possible diversion risk
Final Pearls Patients with significant liver disease Use benzos that undergo glucuronide conjugation Lorazepam, oxazepam CAUTION: Chlordiazepoxide, clonazepam, diazepam Don t attempt to taper opioids and benzos at the same time unless there is a significant safety issue Engage patients in other forms of coping CBT DBT Understand that relapse may occur
Questions? 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
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: gabapentin, carbamazepine or depakote, SSRIs, TCAs, antihistamines (i.e. hydroxyzine), melatonin Limited evidence for AEDs, but still consider
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