#6 Get Hip to Sedative-Hypnotic Use Disorders

August 11, 2022 | By Zina Huxley-Reicher

With Dr. Ximena Levander

Decrease your anxiety managing sedative-hypnotic use disorders! By the end of this episode, you will have practical tips on how to discuss benzodiazepine use, plan a taper, and support your patient throughout the process. We’re joined by Dr. Ximena Levander @XimenaLevander (OHSU).

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Credits

• Producer: Kenny Morford, MD
• Show Notes: Zina Huxley-Reicher, MD; Natalie Stahl, MD, MPH
• Infographic and Cover Art: Zina Huxley-Reicher, MD
• Hosts: Carolyn Chan, MD and Kenny Morford, MD
• Reviewer and Show Runner: Carolyn Chan, MD
• Technical Production: Castos
• Guest: Ximena Levander MD

Production Partner: ACAAM

CME Partner: VCU Health CE

Show Segments

• Intro, disclaimer, guest bio – 0:50
• Case from Kashlak; Definitions – 05:44
• Where people obtain benzodiazepines, types – 06:21
• Urine Drug Screen interpretations – 09:30
• Sedatives/hypnotics other than benzodiazepines – 12:20
• Clinical indications and risks of benzodiazepines – 13:30
• Symptoms of benzodiazepine withdrawal – 15:40
• Clinical scores for management of withdrawal – 17:50
• Benzodiazepine equivalencies – 21:00
• Planning and adjusting a benzodiazepine taper – 24:50
• Adjunct medication and treatment for a benzodiazepine taper – 31:15
• What to do if patient seems “stuck” and struggling with taper – 38:22
• If when to consider continuing lower-dose benzodiazepines instead of finishing taper – 39:50
• Pick of the week: 45:14

Sedative-Hypnotic Use Disorder Pearls

1. It is essential to understand where your patient obtains benzodiazepines. Ask patients if they were prescribed or not prescribed (another prescription vs. pressed pills) pills.
2. Routine immunoassay urine drug screens may not detect benzodiazepines, such as clonazepam, alprazolam and novel benzodiazepines. You may need to order confirmatory urine testing that uses GC/MS.
3. Many patients have been prescribed benzodiazepines long-term and may be experiencing iatrogenic harms, including physical dependence, falls, impaired driving skills, use disorders, etc. 
4. Slower and longer tapers have better outcomes for patients (Sokya, 2017). However, short tapers may be necessary and often are completed inpatient or in a medically supervised facility.
5. Consider adjunctive medications to help treat acute and protracted withdrawal symptoms during and after completing benzodiazepine tapers (Peng, 2022).
6. Based on a patient’s risk factors and indication for the medication, it may be okay to continue a lower/safer dose of the medication, rather than completely discontinue the medication.
7. Due to fentanyl contamination in counterfeit benzodiazepine pills, discuss opioid overdose prevention and prescribe naloxone to patients use non-prescribed benzodipazines.

Types of Benzodiazepines

It’s important to know where patients are getting their benzodiazepines. Ask the following questions on their benzodiazepine source. 

• Are they prescribed to the patient by a clinician?
• Are they non-prescribed regulated benzodiazepines (through someone else’s prescription)?
• Unregulated (typically pressed) pills purchased from the street
• Pills purchased through the internet or “dark web? 

Pressed pills from the street can contain fentanyl (Green, 2016). Thus, educate patients on this and provide naloxone and overdose prevention when appropriate. It is also important to discuss other benzodiazepine harm reduction tools, including the risks of mixing benzodiazepines with other medications that cause respiratory depression and the importance of starting low and going slow. 

Other Sedatives and hypnotics

Ask your patients if they use non-benzodiazepine sedatives, such as gabapentinoids (e.g., gabapentin, pregabalin), barbiturates, muscle relaxants, and z-drugs such as zolpidem as there may be an increased risk of adverse events for a patient taking multiple of these substances.

Interpreting Urine Drug Screens for Benzodiazepines

When prescribing benzodiazepines or trying to determine what patients are taking from other sources, urine drug screens can be a helpful tool but require thoughtful interpretation. Particularly for benzodiazepines, urine drug screens (immunoassays) have significant limitations as they are designed to detect specific benzodiazepine metabolites (Kale, 2019).  It is important to understand what metabolite the immunoassay is designed to detect (Craven, 2014). For example, benzodiazepine immunoassay screens are often negative for clonazepam and alprazolam as well as novel benzodiazepines that are not tested for on routine screening urine drug screens.

Confirmation testing with gas chromatography can be helpful to detect specific types of benzodiazepines. Importantly, all testing should be discussed with patients ahead of time as a way to gather information and facilitate a conversation rather than used for punitive purposes. 

Clinical Uses and Effects of Benzodiazepines

Benzodiazepines are indicated for treatment of generalized anxiety, panic attacks, insomnia, and alcohol withdrawal. Typically, these indications are intended for short-term use, generally not chronic use.

Adverse effects of benzodiazepines include physiological dependence that can develop in as little a few weeks of regular use (Peng, 2022), excessive sedation, falls,  motor vehicle accidents especially in older patients (benzodiazepines are on the BEERS list), rebound anxiety, insomnia symptoms with any dose reduction, and many medication interactions (Soyka, 2017).

Benzodiazepine Withdrawal 

Benzodiazepine withdrawal symptoms may include irritability, GI symptoms, rebound anxiety, insomnia, difficulty concentrating, delirium, seizures, and death (Peng, 2022). The evidence for effective treatment of benzodiazepine withdrawal is limited. In Dr. Levander’s expert opinion, she will use the CIWA-Ar (a validated scale for alcohol withdrawal) to monitor benzodiazepine withdrawal symptoms while someone is in the hospital. The CIWA-B has been used in research studies to assess benzodiazepine withdrawal but does not have clinical correlation data for medication management (e.g., does not give us cutoffs on when to administer medication).

Benzodiazepine withdrawal can be protracted and lead to post-acute withdrawal syndrome (PAWS) that can last weeks (Ashton, 1991).

Developing a Treatment Plan for Benzodiazepine Use

Many patients do not have a sedative-hypnotic use disorder and are not experiencing harm from the medication. In that case, clinicians should discuss the risks and benefits of continuing benzodiazepines with their patients and monitor for any signs and symptoms of impairment/adverse effects. 

For patients who meet DSM-5 criteria for sedative-hypnotic use disorder and those who don’t meet diagnostic criteria but are experiencing harm from the medication, the general approach is to taper someone off the benzodiazepines. A taper plan should be crafted and discussed with your patient before starting. When considering a benzodiazepine taper, we must ask: who are we treating? Are we trying to make ourselves feel better, our clinic system feel better, or our patients feel better? Center the discussion around patient preferences and safety. 

Converting to a Long-Acting Benzodiazepine

When developing a benzodiazepine taper, in Dr. Levander’s expert opinion, she recommends converting to a long-acting benzodiazepine, such as diazepam. Benzodiazepine equivalency charts (GlobalRPH, Ashton manual) can be used as a starting point to guide conversion. These charts have limitations due to individual variability in benzodiazepine metabolism, so be prepared to adjust the dose based on your patient’s symptoms.  

In general, slower outpatient tapers (over weeks to months) are recommended (Soyka, 2017). Rapid tapers (over 3-7 days) are more difficult to tolerate and generally require a supervised environment, such as a medically supervised detoxification facility or hospital. 

Rapid Tapers

Rapid tapers may be indicated if there are significant concerns about safety with the

 continuation of benzodiazepines which may include the following:

• Recent overdose
• Limitations on the ability to perform a prolonged outpatient taper (e.g., not permitted to take benzodiazepines in an addiction treatment program
• Difficulty managing or adhering to a taper schedule  (e.g. lack of transportation to frequent clinic visits)

Rapid tapers are typically done over 3-7 days in a monitored setting. Medically supervised benzodiazepine withdrawal treatment protocols usually involve a fixed taper (20-30% dose reduction/day) with a long-acting benzodiazepine. Non-benzodiazepine adjunctive medications may be offered and continued on discharge since some symptoms of benzodiazepine withdrawal can continue for weeks or even months after taper completion. 

Many clinicians  use the CIWA-Ar scoring system in the hospital setting to monitor symptoms. While the CIWA-Ar was not developed for benzodiazepine withdrawal, it is often the most readily available tool to monitor symptom severity. As previously mentioned, the CIWA-B has been validated to assess benzodiazepine withdrawal (Busto, 1989). Still, its use is more common for research purposes and less common in clinical settings where nurses and other healthcare professionals lack training on how to use it.

Prolonged Tapers

Prolonged outpatient tapers are typically planned over weeks to months. If a patient uses a short-acting benzodiazepine, transition them to a dose-equivalent long-acting benzodiazepine over approximately two weeks. Additional first-line treatment for underlying anxiety disorders and insomnia can be initiated before or during this transition. 

Once fully converted to a long-acting benzodiazepine, per Dr. Levander’s expert opinion, aim for ~10% dose reduction per week. The initial transition period and the end of the taper are times when it is most important to see patients frequently. Clinicians should ensure close follow-up with weekly or at least every two-week visit during the taper. 

The end of the taper tends to be the most challenging for patients. Sometimes it’s necessary to slow the taper down. If a patients continues to be challenges with tapering the medication or do not want to taper further, and have no immediate or significant risks, you should consider continuing them on a lower benzodiazepine dose and periodically revisit risks and benefits with them as appropriate. 

A full taper off the medication may be challenging if patients have been taking benzodiazepines for many years. Data suggests that sustained cessation of use is difficult – approximately ⅓ of tapered patients will return to use (Voshaar, 2006). 

Recently, a new clinical concept has been proposed – complex persistent benzodiazepine dependence which you can read more about in Peng, 2022, 

Adjunctive Medications and Co-occurring Conditions

Consider adjunctive medications, such as gabapentin, carbamazepine, or valproic acid, to help with withdrawal symptoms (Baandrup, 2018). If patients have underlying anxiety, offer treatment (SSRI, buspirone). If they have insomnia, offer CBT-i (CBT for insomnia). Remember to review their other medications (e.g., stimulants), which could contribute to anxiety or insomnia, and lower those dosages as needed. Additionally, behavioral support can be helpful for patients (Darker, 2015). In addition to behavioral health resources in person, many phone apps may be helpful with rebound symptoms of anxiety and insomnia (Breath2Relax, VA CBTi). For patients with co-occurring OUD, it is essential to treat OUD with first-line medications while balancing risks and benefits. 

Links

Josie and the Pussycats (film)

1. Conversion charts/resources: GlobalRPH, Ashton manual
2. Soyka M. (2017). “Treatment of Benzodiazepine Dependence.” The New England journal of medicine, 376(24), 2399–2400. https://doi.org/10.1056/NEJMc1705239
3. Busto, U. E., Sykora, K., & Sellers, E. M. (1989). A clinical scale to assess benzodiazepine withdrawal. Journal of clinical psychopharmacology, 9(6), 412–416.
4. Peng L, Meeks TW, Blazes CK. Complex Persistent Benzodiazepine Dependence—When Benzodiazepine Deprescribing Goes Awry. JAMA Psychiatry. Published online May 18, 2022. doi:10.1001/jamapsychiatry.2022.1150
5. Park TW, Sikov J, dellaBitta V, Saitz R, Walley AY, Drainoni ML. “It could potentially be dangerous… but nothing else has seemed to help me.”: Patient and clinician perspectives on benzodiazepine use in opioid agonist treatment. J Subst Abuse Treat. 2021 Dec;131:108455. doi: 10.1016/j.jsat.2021.108455. Epub 2021 Apr 30. PMID: 34098286; PMCID: PMC8556389.
6. Baandrup, L., Ebdrup, B. H., Rasmussen, J. Ø., Lindschou, J., Gluud, C., & Glenthøj, B. Y. (2018). “Pharmacological interventions for benzodiazepine discontinuation in chronic benzodiazepine users.” The Cochrane database of systematic reviews, 3(3), CD011481. https://doi.org/10.1002/14651858.CD011481.pub2
7. Voshaar, R. C., Gorgels, W. J., Mol, A. J., van Balkom, A. J., Mulder, J., van de Lisdonk, E. H., Breteler, M. H., & Zitman, F. G. (2006). “Predictors of long-term benzodiazepine abstinence in participants of a randomized controlled benzodiazepine withdrawal program.” Canadian journal of psychiatry. Revue canadienne de psychiatrie, 51(7), 445–452. https://doi.org/10.1177/070674370605100706
8. Darker, C. D., Sweeney, B. P., Barry, J. M., Farrell, M. F., & Donnelly-Swift, E. (2015). “Psychosocial interventions for benzodiazepine harmful use, abuse or dependence.” The Cochrane database of systematic reviews, (5), CD009652. https://doi.org/10.1002/14651858.CD009652.pub2
9. CBT-Insomnia App – From the VA
10. Breathe2Relax App – From the VA
11. Harm Reduction Action Center. “Harm Reduction for Benzos”
12. Josie and the Pussycats is the greatest movie of all time!  

Goal

Listeners will develop a framework to approach the evaluation and management of sedative-hypnotic use disorders.

Learning objectives

After listening to this episode listeners will…  

1. Identify common sedative-hypnotic substances, including benzodiazepines and Z-drugs
2. Describe indications and adverse effects of benzodiazepine use 
3. Diagnose sedative-hypnotic use disorder using DSM-5 criteria
4. Recognize symptoms of benzodiazepine withdrawal
5. Develop a patient-centered treatment plan to manage benzodiazepine use disorder, including taper strategies for benzodiazepine withdrawal, evidence-based psychotherapy, and treatment of co-occurring substance use disorders.

Disclosures

Dr. Levander reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Morford, K, Levander, X. Huxley-Reicher, Z, Stahl N, Chan, CA. #6 Get Hip to Sedative-Hypnotic Use Disorders. The Curbsiders Addiction Medicine Podcast. http://thecurbsiders.com/episode-list August 11, 2022