3 rd Quarter 2015 BENZODIAZEPINE CONSIDERATIONS IN WORKERS COMPENSATION: IMPLICATIONS FOR WORK DISABILITY AND CLAIM COSTS By: Michael Erdil MD, FACOEM Introduction Benzodiazepines, sometimes called "benzos", are a class of psychoactive drugs. Benzodiazepines enhance the effect of the neurotransmitters in the brain, resulting in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties. Benzodiazepine medications are prescribed to treat a number of medical conditions including the management of short- term anxiety disorders and insomnia, acute seizures, acute alcohol withdrawal, and other select indications including pre-surgical sedation. Benzodiazepines are also prescribed, at times, to manage musculoskeletal symptoms including low back pain. Examples of some commonly prescribed benzodiazepines with generic and (trade) names include alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium) and lorazepam (Ativan). Different benzodiazepines have unique characteristics including relative strength, duration of action and efficacy for different conditions. Benzodiazepines, like other medications, may have short and long acting formulations. However, there are controversies regarding the long-term use of benzodiazepines to treat many of these conditions due to limited longer-term efficacy, and potentially significant risks including misuse, abuse, addiction, and overdose. Also, there are many more effective treatment options that are associated with lower risks. The 4th Quarter 2014 Medical Advisor reviewed trends in opioid prescribing, opioid efficacy versus risk, and the association of opioid prescription use with workers compensation claim duration and cost. In this newsletter, the focus is on benzodiazepine prescription use in workers compensation, prescription trends, side effects and risks, the potential impact of benzodiazepine use on workers compensation claim cost, and guideline recommendations. For readers who are interested in obtaining additional information, hyperlinks are provided to obtain article abstracts listed in PubMed and other resources. Trends in Benzodiazepine Prescribing The CDC (Center for Disease Control) recently conducted an analysis of a commercial database that included almost 80 percent of the retail prescriptions in the U.S. in 2012 to better understand benzodiazepine and opioid prescribing. The authors estimated 37.6 prescriptions of benzodiazepines and 82.5 prescriptions of opioid pain relievers per 100 persons in the U.S. Rates of prescriptions varied by state and region, with 3.7 times the rate of benzodiazepines prescriptions in the highest (West Virginia) versus lowest (Hawaii) states. Regional benzodiazepine Benzodiazepine prescribing rates per 100 persons by state (MMWR July 4, 2014)
prescribing was highest in the Southeast (see map below). Similar variation was noted for opioid prescribing though the Northeast had the highest rate of high-dose opioid prescribing. The variability was not explained by differences in the health status of the population in different regions, and more likely represents a lack of consensus among prescribers on when and how to use these medications. The report is available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6326a2.htm?s_cid=mm6326a2_w The rate of benzodiazepine prescribing also appears to vary by age in some studies, with one or more prescriptions obtained by 2.6 percent in individuals age 18-35 years, rising to 5.4 percent for age 36-50 years, 7.4 percent for age 51-64 years, and 8.7 percent for age 65-80 years. The proportion of long--term (> 120 days) benzodiazepine use also increased with age from 14.7 percent for individuals, ages 18-35 years to 31.4 percent for ages 65-80 years. Approximately one in four individuals in all age groups in this analysis received long-acting benzodiazepine medications (https://www.ncbi.nlm.nih.gov/pubmed/25517224). There is controversy regarding the frequency of prescribing benzodiazepine because of the potential for significant side effects and the risks discussed below. Of additional concern, it is estimated that 20-50 percent of chronic pain patients on long-term opioids also receive benzodiazepines, and individuals with mental health diagnoses including substance abuse disorders are more likely to receive benzodiazepines, often prescribed at higher doses (https://www.ncbi.nlm.nih.gov/pubmed/24010730, and https://www.ncbi.nlm.nih.gov/pubmed/25279706). The combined prescription of opioids with benzodiazepines increases the risk of abuse and overdose. Despite these considerations, a longer term review has noted that benzodiazepines continue to be commonly prescribed, both in acute and chronic settings, as well as in conjunction with opioids (https://www.ncbi.nlm.nih.gov/pubmed/25906971). Benzodiazepines Side Effects and Risks There are many potential side effects from using benzodiazepines. The frequency and severity of the side effects depend on several factors. For example, benzodiazepine dose, potency, use of long- versus short-acting agents, duration of use, and the use of alcohol or other sedating medications, including opioids and hypnotic agents, can impact side effects. Other factors include older age and medical conditions such as neurologic or lung disease, liver or kidney dysfunction, morbid obesity, and mental health disorders. Benzodiazepines can cause drowsiness, confusion, poor concentration, impaired memory, dizziness, and slow reaction times. As a result, there is a greater risk of falls and fractures in benzodiazepine users, especially in older individuals who may experience significant morbidity and mortality if they sustain hip fractures (https://www.ncbi.nlm.nih.gov/pubmed/9920227). Falls and fractures risks are higher for individuals who also use opioids (https://www.ncbi.nlm.nih.gov/pubmed/23204431) or alcohol. Benzodiazepines are among the most commonly noted prescriptions involving driving under the influence (https://www.ncbi.nlm.nih.gov/pubmed/21545558). Additionally, benzodiazepine use increases the risk of motor vehicle accidents, especially when first starting to use benzodiazepines, or when taking longer acting or higher dose benzodiazepines (https://www.ncbi.nlm.nih.gov/pubmed/20658797). In 2013, the FDA (U. S. Food and Drug Administration) issued a warning about insomnia medications including benzodiazepines due to the risk of motor vehicle accidents. Benzodiazepines could affect mood. The development of irritability, hostility, or depressive symptoms may occur. As with using alcohol, some individuals who use benzodiazepines may experience less inhibition and express antisocial behaviors while taking medications. The term tolerance to medications is used to describe situations in which medications have become less effective over time and require an increased dose to achieve the same effect. With benzodiazepines, individuals may develop tolerance to the hypnotic effects within days to a couple of weeks resulting in less effectiveness to treat insomnia. In the treatment of anxiety, patients may develop tolerance to benzodiazepines within a few months of regular use. Long-term, 2
anxiety symptoms may increase in some patients, and others may have difficulty decreasing the dose of benzodiazepines due to the development of physical dependence or fear of experiencing anxiety with reducing or discontinuing benzodiazepines use. Patients who become dependent on benzodiazepines can develop withdrawal symptoms with sudden, large dose reductions or abrupt discontinuation. The severity of withdrawal symptoms depends on many factors including dosage and duration of benzodiazepine use, the percentage of dose reduction, how quickly the dose is reduced, short- versus long- acting medication, and other medications used in addition to medical conditions. Withdrawal symptoms could include irritability, increased anxiety, insomnia, increased pulse and blood pressure, tremors, and other symptoms. Abrupt cessation and large reductions are of concern and could precipitate seizures as well as death in some individuals. Thus, some patients, especially on higher doses for longer periods of time, may require slow benzodiazepine weaning over a longer period. Benzodiazepines have potential risks for medication misuse, abuse, and addiction. Misuse includes taking prescribed medication for something other than what it was prescribed for (e.g., benzodiazepine used by a patient for insomnia rather than the prescribed indication for anxiety). Abuse includes taking a medication to get high or using a medication in a different route of administration like crushing and snorting a medication. These actions may have adverse consequences. Estimates are that 2.2 percent of adults misuse tranquilizers. However, it is estimated that 16 percent of long-term benzodiazepine users misuse their medications and 4.6 percent abuse benzodiazepines. Addiction involves a compulsion to use drugs with a loss of control and a lack of concern for consequences of use. According to the Substance Abuse and Mental health Administration (http://www.samhsa.gov/data/sites/default/files/benzodiazepi neandnarcoticpainrelieverabuse/benzodiazepineandnarcoticpainrelieverabuse/teds-short-report-064- Benzodiazepines-2012.pdf), substance abuse admissions due to combined benzodiazepine and opioid use increased 570 percent from 200 to 2010, with 33,000 admissions occurring in 2010. Almost half of the patients admitted for substance abuse treatment had mental health disorders. Another concern regarding benzodiazepine use is the development of serious side effects requiring emergency room visits, including overdoses. The CDC recently conducted a survey to estimate the number of emergency room visits resulting from opioid and benzodiazepine abuse. They estimated that in 2010, there were 408,021 visits related to benzodiazepine abuse, alone or in combination with other drugs. Alcohol was involved in 27.2 percent of the benzodiazepine emergency room visits (http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6340a1.htm?s_cid=mm6340a1_w). Sadly, in 2011 there were 16,917 fatal overdoses in the U.S. due to opioid pain relievers (Morbidity and Mortality Weekly Report [MMWR] 7/1/14). The CDC has estimated that benzodiazepines were involved in 31 percent of the opioid overdose deaths. Other studies from West Virginia (https://www.ncbi.nlm.nih.gov/pubmed/22410408), Ontario Canada (https://www.ncbi.nlm.nih.gov/pubmed/21482846) and Washington State (https://www.ncbi.nlm.nih.gov/pubmed/20083827) have also identified an increased risk of overdose involving the combined use of opioids and benzodiazepines in comparison to use of only one or the other medication. The synergistic effect causing an overdose may be in part due to sleep disordered breathing including sleep apnea that has been observed with both benzodiazepines and opioids (https://www.ncbi.nlm.nih.gov/pubmed/18489633). Therefore, caution is advised before prescribing benzodiazepines and opioids to patients with sleep apnea or other risks such as lung diseases including emphysema, and with patients who use alcohol or take other medications that can slow breathing at night. Recent studies evaluating patients using sedatives and hypnotics for anxiety and insomnia have observed an increased risk of premature death associated with use. 3
Benzodiazepines Association with Disability Duration and Claim Costs Studies that have looked at the impact of opioid prescribing in workers compensation have observed an independent effect of increasing duration of disability and claim cost. A recent analysis in Louisiana involving claims reported from 1999 to 2002 followed the claims for seven years post injury. The researchers looked at the risk of experiencing claim costs that were $100,000 or more. They observed 2.74 times increased odds for high claim cost associated with benzodiazepine use alone. The combined use of benzodiazepines and opioids significantly increased high claim cost risk, with 4.69 times elevated odds for combined benzodiazepines and short-acting opioids, and 14.24 times elevated odds for combined benzodiazepines with long-acting opioids (https://www.ncbi.nlm.nih.gov/pubmed/25046322). Benzodiazepine Prescription and Guideline Recommendations The most common conditions treated in workers compensation for which benzodiazepines are prescribed include anxiety, insomnia, and pain due to musculoskeletal disorders such as low back pain. Anxiety disorders are estimated to occur in approximately 5.7 percent of the general population. Although in the setting of chronic pain disorders, anxiety is more frequently noted with an estimate of 15.7 percent of patients. While benzodiazepines are an option for acute stabilization of anxiety disorders, there is limited guideline support for longer term benzodiazepine treatment of anxiety due to significant side effects and risks described above. Besides, there are many safer treatment options. Alternative medication options include a variety of classes of antidepressant agents including Selective Seratonin and Norepinephrine Reuptake Inhibitors (SNRIs), Selective Seratonin Reuptake Inhibitors (SSRIs), Tricyclic antidepressants (TCAs). Examples of SNRI options include duloxetine (Cymbalta) or venlafaxine (Effexor). SSRI examples include escitalopram (Lexapro) or setraline (Zoloft). Examples of TCAs include amitriptyline (Elavil) or nortriptyline (Pamelor). Alternative non-pharmacologic options include treatments like cognitive behavioral therapy. Insomnia and sleep disorders are also common in the general population with some estimates of temporary insomnia in 30 percent and chronic insomnia in 10 percent of the population http://www.aasmnet.org/resources/factsheets/insomnia.pdf. While benzodiazepines are often prescribed for the treatment of insomnia, guidelines only recommend short-term use. Other options to treat primary insomnia (insomnia that is not due to a medical illness) include attention to good sleep hygiene, use of over the counter sedating antihistamines like diphenhydramine (Benadryl), melatonin, or other non-benzodiazepines hypnotics (sleep medications). Benzodiazepines are commonly prescribed for the treatment of low back pain. However, there is a lack of evidence for the efficacy of benzodiazepines to treat acute or chronic low back pain, a risk of significant side effects, and there are guidelines supporting alternatives including: anti-inflammatory agents, physical therapy, manipulation, complementary and alternative treatments, and other options. Official Disability Guidelines (ODG), in general, recommend only short-term use of benzodiazepines for mental health disorders or musculoskeletal conditions due to the risks of psychological and physical dependence. Benzodiazepine prescription beyond four weeks requires clear indications of the rationale for use, the absence of alternatives, and documentation of efficacy. 4
Additional considerations to improve safety in benzodiazepine prescribing include the following: Utilize alternative medications with better efficacy and safety (e.g. SSRIs, SNRIs, TCAs, NSAIDs, etc.) and non-medication options whenever possible. Carefully screen patients for potential risk of misuse, abuse, or addiction. Obtain an in-depth medical and psychological history to screen for medical conditions that could increase the risk of using benzodiazepines. Access the state Prescription Drug Monitoring databases to determine if there are any other benzodiazepine or opioid prescribers, and avoid dual prescriptions. Educate patients regarding alternatives, risks, safe use, and disposal. Also, any potential risks associated with misuse, abuse, and taking other sedating medications including opioids or using alcohol. Restrict initial benzodiazepine prescription to short-term duration at the lowest possible doses with more frequent follow-ups while considering alternative treatment options. In the presence of psychological disorders, consider a psychiatric consultation. Longer term use requires evidence of clear indication supporting use, consideration of alternatives, monitoring for compliance, efficacy and absence of significant side effects. Conclusions Benzodiazepines are an option in the short-term management of acute anxiety and insomnia. However, there is limited evidence of long-term efficacy for the use of benzodiazepines to treat these conditions. The use of benzodiazepines to manage musculoskeletal disorders like low back pain is controversial due to the lack of efficacy and significant side effects. The combined use of benzodiazepines with opioids results in a significantly increased risk of overdose or even death. For the majority of patients, there are alternative treatment options with better efficacy and less risk of side effects. When benzodiazepines are prescribed, physicians have the responsibility to improve patient safety through better screening, education, monitoring, and caution. In addition to guidelines similar to ODG Treatment in Workers Comp and the American College of Occupational and Environmental Medicine Occupational Medicine Practice Guidelines, there are useful recommendations available from several sources, including the following: Patient Resources Choosing Wisely The American Board of Internal Medicine (ABIM) Foundation launched Choosing Wisely in 2012 to provide patients with information to help them make informed decisions about their health care, and to avoid unnecessary medical tests or treatments that could result in more harm than good. ABIM Foundation has partnered with many National Medical Specialty Societies and Organizations, as well as Consumer Reports, to offer patient-friendly materials. Here are some pertinent Choosing Wisely recommendations: American Geriatrics Society. Don t use benzodiazepines or other sedative-hypnotics in older adults as first choice for insomnia, agitation or delirium. http://www.choosingwisely.org/clinician-lists/american-geriatrics-society-benzodiazepines-sedative-hypnotics-forinsomnia-in-older-adults/ American Geriatrics Society. Sleeping Pills for Insomnia and Anxiety in Older People. Sleeping pills are usually not the best solution http://www.choosingwisely.org/patient-resources/treating-insomnia-and-anxiety-in-older-people/ American Society of Anesthesiologists. Physicians should be cautious in co-prescribing opioids and benzodiazepines http://www.choosingwisely.org/american-society-of-anesthesiologists-asa-releases-choosing-wisely-list-for-painmedicine/ 5
Other web sites with useful information include the following: Fact Sheet Benzodiazepines http://www.druginfo.adf.org.au/attachments/391_adf_factsheet_benzo.pdf Discontinuing Benzodiazepines http://www.uvm.edu/medicine/ahec/documents/patienthandoutdiscontinuingbenzos20130312.pdf Insufficient Sleep Is a Public Health Epidemic http://www.cdc.gov/features/dssleep/index.html Getting a Good Night s Sleep http://www.uvm.edu/medicine/ahec/documents/information_about_insomnia_july_2010.pdf Fact Sheet- Dealing with Anxiety Without Medication http://www.druginfo.adf.org.au/attachments/217_fs_76_anxiety_final.pdf For more information email us at mms@aig.com. This document is provided as reference material and is based in part on information derived from third parties. AIG does not assume liability or responsibility for the accuracy or completeness of any third-party material in this document. The information contained herein should not be construed as an endorsement of any kind. AIG assumes no liability in connection with the use of such information. This document is for informational purposes only and is not a substitute for medical diagnosis, advice, or treatment for specific medical conditions. This document does not replace sound clinical judgment or individualized patient care in the delivery of medical care. This document may not be reproduced, distributed, or copied without the prior written consent of AIG. Copyright American International Group, Inc. All rights reserved. 175 Water Street New York NY 10038 10/01/2015 6