MANAGING THE MONSTER PART 2: Starting, Managing, Tapering Benzodiazepines

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

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