Title Opioids Used in Conjunction With Benzodiazepines Produce Worse Outcomes in Patients Experiencing Chronic Pain Compared To Sole Opioid Use
Clinical Question For a patient experiencing chronic pain, will the use of benzodiazepines with opioids, compared to opioids alone, produce better outcomes?
Clinical Bottom Line For patients with chronic pain, the use of opioids in conjunction with benzodiazepines produces worse outcomes than opioids alone. This is supported by a cross-sectional study where it was noted that the combination of opioids and benzodiazepines correlated with poor mood and decreased patient function.
Best Evidence  
PubMed ID Author / Year Patient Group Study type
(level of evidence)
25968447Gaunlett-Gilbert/2016 229 patients with chronic pain who were beginning rehabilitationCross-Sectional Study
Key resultsThe study looked at each patient’s medication use/dosage. They used this information to come up with a single morphine equivalent and similar diazepam equivalent dose per patient. The patients were then observed to see how the drug dosage affected their mood and function. It was reported that there was no clear evidence to prove that either of the medications proved beneficial to the patient. In fact, higher dosage of meds had no effect in the amount of pain, fear, or disability experienced by the patient. Higher diazepam doses produced worse outcomes for the patient while higher morphine doses remarkably affected patient function.
Evidence Search ("chronic pain"[MeSH Terms] OR ("chronic"[All Fields] AND "pain"[All Fields]) OR "chronic pain"[All Fields]) AND ("diazepam"[MeSH Terms] OR "diazepam"[All Fields]) AND ("analgesics, opioid"[Pharmacological Action] OR "analgesics, opioid"[MeSH Terms] OR ("analgesics"[All Fields] AND "opioid"[All Fields]) OR "opioid analgesics"[All Fields] OR "opioids"[All Fields]) AND ("drug combinations"[MeSH Terms] OR ("drug"[All Fields] AND "combinations"[All Fields]) OR "drug combinations"[All Fields])
Comments on
The Evidence
Validity: This cross-sectional study was the very first of its kind in terms of observing concurrent opioid and benzodiazepine use. By examining each patient’s medication dosage and calculating single morphine and diazepam doses from them, the study was able to calibrate each patient onto a similar scale, which allowed for more reliable results.
Applicability The subjects in this study were not representative of any particular population, other than having severe chronic pain. Regardless, evidence states treatment with a combination of opioids and benzodiazepines is not practical, resulting in a poor outcome for the patient. Alternative forms of treatment should be used.
Specialty (Oral Medicine/Pathology/Radiology) (Endodontics) (General Dentistry) (Oral Surgery) (Interprofessional CATs)
Keywords Opioids, Benzodiazepines, Pain Management, Chronic Pain
ID# 3169
Date of submission 03/23/2017
E-mail trevinoma@livemail.uthscsa.edu
Author Marcos A. Trevino
Co-author(s) Kylie Barroso
Co-author(s) e-mail kybarr52@yahoo.com
Faculty mentor Edward F. Wright, DDS, MS
Faculty mentor e-mail WrightE2@uthscsa.edu
Basic Science Rationale
(Mechanisms that may account for and/or explain the clinical question, i.e. is the answer to the clinical question consistent with basic biological, physical and/or behavioral science principles, laws and research?)
by Kylie S. Barroso (Austin, Texas) on 05/03/2017
The biological rationale for this question relates to the pharmacodynamic and pharmacokinetic mechanisms of the interactions between opioids and benzodiazepines. Opioids, like morphine, are a powerful narcotic medicine used to treat pain by binding to the µ receptor. Benzodiazepines interact with the alpha 1- GABA receptor which restricts inhibitory interneuron release of GABA. Both of these receptors are located in the central nervous system, which could lead to the cross-reactivity of these two drugs. Benzodiazepine effects, including the reward and anxiolytic effects, are also partially meditated by opioid-controlled mechanisms. It has also been hypothesized that benzodiazepines can alter the pharmacokinetics of opioids by acting as weak inhibitors of enzymes that metabolize opioids. These interactions change the way the medications interact with the body and can cause the undesired outcomes of the patients with chronic pain.
Comments and Evidence-Based Updates on the CAT
None available