Most practitioners are aware that benzodiazepines and opioids are not recommended to be prescribed concurrently. FDA issued a black box warning for concomitant use in August 2016, and both are listed on the American Geriatrics Society Beers Criteria, separately and in combination, to avoid prescribing for older patients.1,2 Despite this, concurrent prescribing occurs frequently.3

In certain clinical situations, it may be appropriate to prescribe opioids and benzodiazepines together, as long as the patient is appropriately monitored and prescribed the lowest therapeutic dose for the shortest duration necessary. In psychiatric practice, this combination is most often seen when treating anxiety and panic disorders in patients who may also live with chronic pain.

Anxiety and Panic Disorders in Pain Patients

Anxiety disorders, the most commonly diagnosed psychiatric disorders, frequently coexist with chronic pain. First-line treatment for anxiety disorders is selective serotonin reuptake inhibitors (SSRIs), which often take 4 to 12 weeks to see a patient response. Benzodiazepines may be appropriate bridging therapy until the SSRI treatment takes effect. Failure to provide a bridge, however, may result in worsening anxiety, depression, or increased perception of pain despite concurrent opioid use.4

Panic disorders, which can be triggered by uncontrolled pain for which an opioid may be used, may require bridging benzodiazepines; first-line therapy is high dose SSRIs and psychotherapy. Often these patients require benzodiazepines as rescue medication for breakthrough attacks well after the bridging therapy period.4

Benzodiazepines in Pain Patients: How to Monitor Concurrent Therapy

The following should be monitored with concurrent opioid and benzodiazepine therapy:5,6

  • signs and symptoms of ataxia
  • cognitive disorders: confusion, dysarthria, memory impairment, sedation, and somnolence
  • respiratory suppression
  • bradycardia
  • hypotension
  • xerostomia
  • constipation

It is wise to perform a toxicology screening/urinalysis on patients taking this combination, or to at least be aware of recreational substance use, in order to make educated decisions to help keep patients from an accidental overdose. (Details on co-prescribing naloxone below.)

Checking each patient in a national and/or state prescription drug monitoring program (PMDP) and/or controlled substance prescription registry, where one is available, is another way to keep patients safe. These registries show the medication and quantity the patient received and prescriber and pharmacy information. Patients may not remember what medications they take, fail to report information, or may get medication from multiple prescribers.

Tapering Opioids and Benzodiazepines

Any patients taking opioids and benzodiazepines together for 2 weeks or longer should be tapered upon discontinuation. When discontinuing benzodiazepines or high-dose/long-term use opioids, it is recommended to titrate the dose down appropriately to avoid increased risk of neurologic adverse events or seizures.5,6 Doses may be reduced by 10% to 25% weekly, while monitoring for rebound insomnia, withdrawal symptoms, and anxiety. Tapers should be adjusted and individualized based on the patient response, and half-life of the drug. Some patients may need to be tapered more slowly.

For patients with a long history of medication use, consider titrating to 50% of the dose and stabilizing the patient at the 50% dose for several months before proceeding with the taper to decrease adverse events.7 More on opioid tapering and real-world drug monitoring scenarios.

Extra Cautions to Take
It is good practice to prescribe naloxone nasal spray to any patient on concurrent opioid and benzodiazepine therapy for outpatient use, and to counsel both the patient and a family member/friend/caregiver on appropriate use and signs and symptoms of an accidental opioid overdose.

Other medication classes that prescribers should be cautious of prescribing with opioids are:

  • CNS depressants: sedatives, anxiolytics, hypnotics, muscle relaxants, general anesthetics
  • Gabapentinoids

These drugs have the potential to cause serious adverse effects when prescribed concurrently with opioids including respiratory depression and/or risk of opioid overdose.8

It is still the best practice to avoid any concurrent prescribing of opioids and benzodiazepines (or other CNS depressants), and the above uses are not guideline-supported. If opioids and benzodiazepines must be prescribed together, it should be done in the safest way possible for patients: for the shortest duration, at the lowest effective dose, and tapered appropriately.

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Last Updated: May 7, 2021