Characterizing Benzodiazepine Use in Ambulatory Palliative Care Patients Living with Cancer Courtney Cobert, Amy Dunleavy, Tiffany Khachikian, and Meghal Patel Faculty Adviser: Dr. Kashelle Lockman

Outline Purpose & Methods Results Discussion & Limitations Conclusion & Further Research Outline Tiffany Khachikian – abstract & methods Amy Dunleavy – results Meghal Patel – discussion & limitations Courtney Cobert – conclusion & further research opportunities

67% 5-fold Why Is This Important? Between 1996-2013 Benzodiazepine prescriptions increased by 67% Overdose fatalities increase more than 5-fold Marcus A. Bachhuber, Sean Hennessy, Chinazo O. Cunningham, and Joanna L. Starrels.  Increasing Benzodiazepine Prescriptions and Overdose Mortality in the United States, 1996–2013. American Journal of Public Health: April 2016, Vol. 106, No. 4, pp. 686-688. doi: 10.2105/AJPH.2016.303061 Bachhuber M, et al. American Journal of Public Health 2016; Vol 106, No. 4, pp. 686-688 Bachhuber M, et al. American Journal of Public Health 2016; Vol 106, No. 4, pp. 686-688

Why Is This Important? Since 2013 Benzodiazepines involved in 30% of drug overdose deaths Bachhuber M, et al. American Journal of Public Health 2016; Vol 106, No. 4, pp. 686-688

Why Is This Important? 2016: FDA BBW: BZDs + opioids Extreme sleepiness Respiratory depression Coma Death https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm518697.htm In 2016, FDA requires strong warnings (BLACK BOX WARNING) for opioid analgesics, prescription opioid cough products, and benzodiazepine labeling related to serious risks and death from combined use. Risks of combined use can cause extreme sleepiness, respiratory depression, coma, and death. And yet, in palliative care patients, there is often a need for the combination of opioids with other medications to properly mange pain. For our study: Concurrent medication prescribing (with BZD) and increase risk of respiratory depression: Opioids Gabapentinoids Muscle relaxants Sedative hypnotics

Why Is This Important? “Lots of our patients come to us on benzos!” -UIHC PC clinicians Purpose: Determine prevalence of & indications for BZD use in patients living with cancer & receiving palliative care at UIHC Why Is This Important? UIHC: Observed a high prevalence of benzodiazepine prescribing upon referral to the ambulatory palliative care clinic. Purpose: Determine the Prevalence of benzodiazepine use in ambulatory patients living with cancer and receiving palliative care at UIHC The purpose of the study: Characterize the indication for the benzodiazepine prescription Characterize increase risk with concomitant use with opioids

Patient inclusion criteria: Patient exclusion criteria: PC visit between January 1 and June 30, 2017 Patient ≥ 18 Has a cancer diagnosis Patient exclusion criteria: ≤ 17 years old No appointment during study period Methods A retrospective, single chart review Demographics on everyone; only collected medication information on patients who were prescribed BZDs

Methods Demographic Data Collection Palliative Care Diagnosis Active Treatment or Survivorship Age Death within study period Yes or no Gender Male or Female Type of Cancer Methods Demographic Data Collection Palliative Performance Scale (PPS) Demographics: Age Palliative care diagnosis Active treatment (yes/no) Survivorship (yes/no) Death within study period Palliative performance scale (PPS) Gender (male/female)

Palliative Performance Scale (PPS) 100% Most Active Patient 70% Reduced Ambulation 50% Mainly sitting 30% 0% Death Palliative Performance Scale (PPS) Bed Bound Tool commonly used in palliative care to assess a patient’s functional performance and to determine progression toward end of life Below 70% there is significant signs of disease https://www.vnsny.org/wp-content/uploads/2016/08/VNSNY-Palliative-Performance-Scale-PPS.pdf

Data Collected Risk factors for BZD induced respiratory depression Alcohol consumption Concomitant medication use Frequency of medication use Indication of medication Duration of medication Data Collected Risk factors for BZD induced respiratory depression Risk Factors: Alcohol consumption Prescribed benzodiazepine Prescribed opioid Prescribed sedative hypnotic Prescribed muscle relaxant Prescribed neuropathic pain medications Frequency/type of medication use Indication of medication Duration of medication use

Prevalence of Cancer Diagnosis, n = 114 Results Inclusion and exclusion criteria 93/114 charts reviewed had cancer  81.6% Of the 93 included, 17 patients died during study period due to all cause mortality 58/93 were on at least one BZD  62.4% All other prevalence factors are measured per the 93 patients who had cancer

Results Prevalence of BZD Prescription in Patients with a Cancer Diagnosis, n = 93 Results

Results 62% 38% At least 1 BZD ≥ 2 BZDs Prevalence of BZD Prescription, n = 93 62% At least 1 BZD 38% ≥ 2 BZDs Results

Number of Patients Prescribed BZD by Age Results Remove unable to determine data.. Then you will be able to make the font a good size. Is it better to graph this by raw number of by %?

Results Indications Anxiety 55% Procedures 26% Sleep 10% n=58 Top indications for prescribing the first BZD. Add %/n

Results Co-Prescribing Prevalence of Concomitant Respiratory Depressant Medications, n=58 Results Co-Prescribing Co-Prescribing of BZD with Other Medications Opioids: 79% Gabapentinoid: 41% Sedative Hypnotic: 15% Muscle Relaxants: 10% Co-prescribing Opioids Prevalence of opioid use: 79% Prevalence of two opioids: 62.3% Gabapentinoids 41.2% Sedative Hypnotics 14.9% Muscle Relaxant 9.7%  

Results Benzodiazepine scheduling frequency Type of BZD Use; n =58 Results Benzodiazepine scheduling frequency **I just used the Frequency of the First Benzo since we just did the indication for first Benzos on slide 13 ** Scheduled or prn does not change the duration of how long they were on the first benzo  

BZD Use by Palliative Performance Scale; Results PPS Make fonts bigger. Again, is it better to have raw #s vs percent? PPS: no correlation between a reported decrease in PPS and increase in benzo 4 people with PPS<30% 50% were on one benzo 50% were on two benzos PPS 40-49% 5/6 were on one benzo 83% 2/5 were on two benzos 40% PPS 50-59% 10/19 were on one benzo 52.6% 3/19 were on two 16% PPS 60-69% 6/11 were on one benzo 55% No one was on two PPS 70-79% 15/21 were on one benzo 71% 6/21 were on two benzos 29% PPS >80% 19/30 were on one benzo 63% 6/30 were on two benzos 20%  

Discussion Similar Studies Cancer center 31% Hospice 58% Our study: 79% Prevalence of benzo/SH + opioid use in palliative care cancer patients  43% decreased to 31% in 2016 at MD Anderson Cancer center Haider A. et al.(S762) J Pain Symp Manage. 2018; 55(2): 690 – 691. Henderson M. et al. Palliat Med. 2006;20(4):407-12.

Discussion Indication 31/58 = 53% Anxiety most common indication  Henderson study: hospice cancer patients  anxiety most common indication (1/3 of prescriptions, but only 78% had indication recorded) Bachhuber found similar results with 56% of prescriptions for anxiety in the general population Some evidence for short term treatment but  increased adverse effects with increased duration of treatment CBT, serotonergic agents Bachhuber M, et al. American Journal of Public Health 2016; Vol 106, No. 4, pp. 686-688 Henderson M. et al. Palliat Med. 2006;20(4):407-12.

Discussion General Population Prevalence 5.6% Co-prescribing 12% Prevalence of benzodiazepine use: 62% vs 5.6% adults in general population Co-prescription of opioid and benzo in general population: 79% vs 12% Bachhuber M, et al. American Journal of Public Health 2016; Vol 106, No. 4, pp. 686-688 Venkata HG, et al. BMJ 2017;356:j76

Discussion Limitations External validity Small sample size Actual frequency of benzodiazepine use Unclear indications Chart review Discussion Limitations Small sample size can undermine external and internal validity

Where do we go from here? Larger Sample Size Consider Prescribers Utilize sites outside UIHC Palliative Care Clinic Expand the time frame assessed; follow patients longitudinally Consider Prescribers Who is prescribing Indication for prescribing Consider only patients on chronic BZDs Assess prevalence of chronic use of BZDs Assess indication of chronic BZD Educate prescribers and patients Analyze their attitudes toward BZDs Educate on BZD risks & drug interactions Where do we go from here? This is the only study done that looked at only benzo use specifically in cancer patients receiving palliative care Based on what we found in our study, there are several areas that can be expanded on to further the knowledge in this area Further research needs to be done with a larger sample size – we only looked at a small population at UIHC in a 6 month time frame Look at prevalence of benzo use at other sites Expand the time frame, maybe even from initiation of care? Prescribers – we only looked at the fact that patients were prescribed a benzo and why Analyze who is prescribing benzos Focus on what indications prescribers are using Consider patients who are only on benzodiazepines chronically – like me mentioned, acute use was included in our study (procedures) which is important but not as relevant to respiratory depression adverse effect from benzos Exclude procedural indications for the medication Educate physicians and patients on proper use of benzos for certain indications Analyze their attitudes Make them aware of risks involved with co-prescribing What they can use instead of benzos for anxiety, etc. **EMPOWER trial if asked about patient education Separate study design Put in system alerts or best practice alerts into the medication records

Summary High prevalence of benzodiazepine prescribing in cancer patients Additional co-prescribing leads to increased risk of respiratory depression and death Effects of these medications need to be considered when developing patient therapy plans

Questions

Sources Bachhuber MA, Hennessy S, Cunningham CO, Starrels JL. Increasing Benzodiazepine Prescriptions and Overdose Mortality in the United States, 1996–2013. Am J Public Health. 2016;106(4):686-688. doi:10.2105/AJPH.2016.303061 Haider A, Azhar A, Naqvi S, et al. Concurrent Use of Opioids and Benzodiazepines or Non-Benzodiazepines Sedative Hypnotics Among Cancer Patients Referred to Outpatient Palliative Care Clinic of a Comprehensive Cancer Care Center (S762). J Pain Symptom Manage. 2018;55(2):690-691. doi:10.1016/j.jpainsymman.2017.12.416 Henderson M, MacGregor E, Sykes N, Hotopf M. The use of benzodiazepines in palliative care. Palliat Med. 2006;20(4):407- 412. doi:10.1191/0269216306pm1151oa Journal of Public Health: April 2016, Vol. 106, No. 4, pp. 686-688. doi: 10.2105/AJPH.2016.303061 Venkata HG, Chauhan G, Ram BS. Co-prescription of Opioids and Benzodiazepines. BMJ. 2017;356(7). doi:10.1136/bmj.j760