Part 1 and 2 of this series on Managing the Monster have outlined the evidence that supports the extreme risk posed by co-prescribing benzodiazepines and opioids. This blog outlines the initiative that Partnership HealthPlan of California is undertaking to reduce this risk, starting with provider education.

Where are we going?

As Partnership dives in to our last phase of the Managing Pain Safely initiative, we are expanding its focus to include co-prescribing of benzodiazepines (BZD).  For the last two and a half years, Partnership has been actively working to reduce the number of members prescribed high dose opioids.  Since the start of the project in January 2014, we have seen a 74% reduction in the proportion of members on high dose opioids (>120 mg MED), PMPM, plan-wide.  This is only 1% away from our initial goal of 75% reduction!    As the project begins to accomplish the goals we initially set out to tackle, it is apparent that there is one crucial area that we have yet to focus on- co-prescribing BZD and opioids.

Why is it important?

As detailed in the last two blogs, the risks of severe complications, including overdose and death, are significantly higher when a patient uses a combination of opioids and benzodiazepines.  While the dangers of opioids alone are significant, they drastically increase when combined with BZD. It has been shown that as much as 80% of unintentional opioid overdoses deaths also involve BZD ¹.  In the past five years, the U.S. has seen a fivefold increase in the number of unintentional BZD associated deaths¹.  Studies have shown that the adjusted hazard ratio for risk from drug overdose for patients currently taking both opioids and BZD for is 3.86.³ This is especially concerning when keeping in mind that compared with opioid abusers, those taking both opioids and BZD are more likely to take the medications for longer periods of time and at higher doses.²

What are we doing?

Given the evidence of the dangers of co-prescribing, PHC leadership has designated this as a priority within this next year.  The MPS team has convened to determine a new goal for the initiative- to reduce the number of members with co-prescriptions of both opioids and benzodiazepines, PMPM.  While final plans and anticipated targets are still being defined, the top strategy of the health plan as of now is to provide education for our providers and our members.  The Plan intends on creating educational material for both providers and members, host a webinar to discuss how to manage patients taking both opioids and BZD, and share provider-site level data detailing who in the practice has prescriptions for both.  PHC is also promoting the CDC guidelines which recommend avoiding co-prescribing. PHC will also be working with community coalitions currently developing and implementing county-wide safe prescribing guidelines acknowledge the dangers of co-prescribing and recommend against the practice.

How will it impact you?

As mentioned, as of now the primary strategy to address co-prescribing will be to create educational materials for the provider and member, share best practices, share provider-site level data, and have 1:1 provider level academic detailing sessions with select provider sites.   PHC is dedicated to support our providers in continuing to grow a knowledge base and develop and utilize tools on safe prescribing.  Throughout the fall of 2016, expect to see more material and discussions on the use of BZD in conjunction of opioids.

Webinar on Co-Prescribing

Managing the Monster: Strategies in Managing Opioid and Benzodiazepine Co-Prescribing

Tuesday October 25, 2016

Noon-1pm

Registration: https://attendee.gotowebinar.com/register/8210921216123819778

References

• Gudin JA; Mogal S; Jones JD; Comer SD. “Risks, Management, and Monitoring of Combination Opioid, Benzodiazepines, and/or Alcohol Use”. Post Graduate Medicine, 2013, 125 (4) 0032-5481
• Jann M; Kennedy WK; Lopez G. “Benzodiazepines: A Major Component in Unintentional Prescription Drug Overdoses with Opioid Analgesics”. Journal of Pharmacy Practice, 2014, 27(1) 5-16
• Park TW; Saitz R; Ganoczy D; Ilgen MA; Bohnert ASB. “Benzodiazepine prescribing patters and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study”. BMJ Open Access, 2015, 350:h2698

This is part 2 of a 3 part series on the dual headed monster of opioids and benzodiazepines. This blog describes strategies for managing and tapering benzodiazepines.

. However, when combined with opioids, benzodiazepines have proven to be very dangerous. In the past five years the U.S. has seen a fivefold increase in the number of unintentional benzodiazepine-associated deaths.  Reviewing data from multiple states, it has been shown that benzodiazepines are a leading cause of fatal drug overdoses, second only to opioid analgesics.² The increase in benzodiazepine and opioid related Emergency Room visits and unintentional deaths has been attributed to the concomitant use of both medications, either illicitly or prescribed.

Despite the data showing the drastic increase in deaths for patients concomitantly using benzodiazepines and opioids, co-prescribing continues to be an alarming trend. It has been shown that taking benzodiazepines is a greater indicator of future long term opioid use than chronic or musculoskeletal pain, with as many as 40% of opioid users also taking benzodiazepines. When compared with opioid abusers, patients who take both opioids and benzodiazepiines are more likely to take the medications for longer periods of time and at higher doses. Concomitant users are also more likely to use or abuse other drugs and have a comorbid psychiatric disorder. This fatal combination has contributed to as much as 80% of unintentional overdose deaths involving opioids.¹  In a study detailing the association between benzodiazepine prescribing and opioid use in US veterans, it was shown that the adjusted hazard ratio for risk from drug overdose for patients currently taking opioids who had a history of taking benzodiazepines was 2.33 (95% confidence interval 2.05- 2.64), and for those who are currently taking both opioids and benzodiazepines the adjusted hazard ratio for risk from drug overdose was 3.86⁴.

Risks in Medication Assisted Therapy. The rates of benzodiazepine use among those who are also taking an opioid agonist, such as methadone or buprenorphine, have been regularly noted in literature.   Individuals may be abusing opioids and benzodiazepines in order to amplify the euphoric effect of opioids.  It has been noted that for individuals participating in methadone maintenance programs, rates of concomitant benzodiazepine use have been as high as 70%.³ For individuals participating in medication assisted treatment for opioid use disorder, it is important to note that there has been evidence that benzodiazepine use can remove the protective ceiling effect of buprenorphine on respiration depression.  Caution is recommended with patients on opioid replacement therapy- ensure that proper regular screening for alternative drugs/ medications is occurring, and consider using an alternative medication for anxiety relief, such as SSRIs. ³

Managing Benzodiazepines.  Benzodiazepines are most often prescribed for their anxiolytic effects, as well as their adjunctive treatment for several neurological and psychiatric disorders such as seizures and alcohol withdrawal, as well as for their muscle relaxant effects.  Opioids and benzodiazepines are often prescribed by different physicians, who may or may not be in communication with one another regarding the patient’s medication regimen. ¹ While assessing risk of co-prescribing, physicians should be aware that benzodiazepines pharmokinetic interactions can be incredibly variable, dependent on multiple factors such as patient age, ethnicity, poly-drug use, and certain medical conditions (such as renal failure). Prior to initiation of a benzodiazepines or opioid analgesics, it is important to complete a comprehensive review of patient history, including checking of your state’s prescription drug monitoring system (CURES in CA), and a standardized risk stratification tool.   It is important to note that in addition to the increasing rates of medically prescribed benzodiazepines, the rates of illicitly used B benzodiazepines, especially in conjunction with opioids, has also been increasing².

In starting to prescribe benzodiazepines, consider the above factors and remember that the benzodiazepines are Beer List drugs that should be avoided if possible in the elderly and frail.

• Start at the lowest possible dose for the shortest period of time.
• Use the formulation best suited to the indication. For instance, use the short acting benzodiazepines for sleep induction. Use the longer acting formulations for chronic daily management of anxiety.
• If anxiety is the indication, use short-term (< 6 weeks) as a bridge to more effective anti-depressant therapy (SNRIs, SSRIs, Buproprion)
• Use in conjunction with other modalities such as cognitive behavioral therapy, and stress reduction strategies.
• Do not stop abruptly but establish a taper schedule.

Equivalent Doses of Benzodiazepines

• Alprazolam         -0.5mg
• Chloradizepoxide 25mg
• Clonazepam0.5mg
• Diazepam   10mg
• Lorazepam1mg
• Temazepam –       20mg

Tapering Benzodiazepines.  Given the dramatically increased risk of overdose and death with co-prescribing of benzodiazepines and opioids, consider tapering to the lowest possible dose or off, of one or both of these high risk medications. Tapering of benzodiazepines is fraught with obstacles. Rebound symptoms with heighted anxiety and insomnia is common so longer tapers may be required. CDC recommends tapering opioids first due to the difficulty with benzodiazepine tapering. If the patient has memory difficulties that might impair their ability to remember and stay on the opioid taper or the benzodiazepine dose is low, consider starting with the benzodiazepine taper. Some considerations:

• Go slow (3-6 months)
• Expect anxiety, insomnia, and resistance. Provide supportive psychotherapy
• One prescriber, one pharmacy
• Switch from short acting agents such as lorazepam to longer acting agents such as diazepam or clonazepam
• Reduce the daily dose by 5-10% per week
• Early follow-up – 1 week after starting and adjust tapering dose if needed
• Slow taper after ½ of original dose achieved
• Add adjunctive therapy if withdrawal/rebound symptoms are problematic. Drugs to consider are buspirone, clonidine, Vistaril, Inderal

Resources

Gudin JA; Mogal S; Jones JD; Comer SD. “Risks, Management, and Monitoring of Combination Opioid, Benzodiazepines, and/or Alcohol Use”. Post Graduate Medicine, 2013, 125 (4) 0032-5481

Jann M; Kennedy WK; Lopez G. “Benzodiazepines: A Major Component in Unintentional Prescription Drug Overdoses with Opioid Analgesics”. Journal of Pharmacy Practice, 2014, 27(1) 5-16

Jones JD; Mogali S; Comer SD. “Polydrug Abuse: A Review of Opioid and Benzodiazepine Combination Use.” Drug and Alcohol Dependence, 2012, 125(1-2) 8-18

Park TW; Saitz R; Ganoczy D; Ilgen MA; Bohnert ASB.  “Benzodiazepine prescribing patters and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study”. BMJ Open Access, 2015, 350:h2698

written by: Scott Endsley MD and Danielle Carter

NEXT: Part 3: the PHC Reducing Benzodiazepine Initiative

This is first in the three part blog series on benzodiazepines and their dangers in combination with opioid drugs Continue reading →

In 2014, there were over 32,000 cases of pertussis in the United States. This represented a whooping 15% increase in incidence over the prior year (pun intended). The incidence rates for pertussis among babies exceeds all other age groups. The majority of pertussis deaths are in babies less than 3 months of age.

In California in 2015, there were over 10,000 cases of pertussis. Of the counties reporting pertussis, the six top counties with “rates substantially higher than statewide average” were all Partnership counties. These are Marin, Sonoma, Napa, Yolo, Humboldt and Modoc counties. Of worrisome note, only 16% of mothers of infants diagnosed with pertussis in 2015 had been vaccinated during pregnancy with Tdap. A CDC study in 2014 found that only 14% of pregnant women had been vaccinated during the pregnancy.

For many years, the American College of Obstetrics and the Advisory Committee on Immunization Practice recommended an approach to pertussis prevention in neonates called “cocooning”. This consisted of administering Tdap vaccine to all women in the post-partum period, and all other family members and caregivers who are in the infants environs to provide a “cocoon” of protection. This strategy has proved insufficient and ineffective as the epidemic of pertussis continues to grow. One key gap was that cocooning left a minimum of a two month gap of exposure between birth and receiving their first immunization.

Confronted with the inadequacy of the cocooning approach, the recommendations were revised by ACIP in 2013 to recommend the following:

• All pregnant women regardless of prior immunization history should receive the Tdap vaccine during pregnancy.

• Tdap should be given between 27 and 36 weeks of gestation to maximize the maternal antibody response, although it can be given at any point during pregnancy.

• If not given during pregnancy, a Tdap should be given in the post-partum period.

• If a tetanus immunization is needed for wound management during the pregnancy, Tdap is the preferred vaccine.

TAKE HOME: if you care for pregnant women in your practice, ensure that ALL women are offered Tdap during pregnancy, optimally during weeks 27-36.

http://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/tdap-td.html

http://www.cdc.gov/pertussis/pregnant/index.html

https://www.acog.org/-/media/Committee-Opinions/Committee-on-Obstetric-Practice/co566.pdf?dmc=1&ts=20160714T1327084446