Benzodiazepines and Pain

Quick . . . name a class of prescription medications that, by most evidence, appears to be overprescribed and abused and the use of which has resulted in an increasing number of emergency department visits.

If you said “opioids,” you would be right. This is probably the answer most health care professionals would give. However, there is another response that is given much less frequently but would be equally true: benzodiazepines.

I wish I could say that this inattention to benzodiazepines is something new, but my personal experience indicates it is not. Twenty years ago, I coauthored one of the first papers that examined the use of benzodiazepines by patients with chronic pain and found that these agents were overprescribed.¹ With rare exception since that time, the lectures I have attended on overprescription of medications have focused on opioids. When I have raised the issue of overuse of benzodiazepines, the speakers have either responded that they were unaware of any problem or offered the odd response that the audiences were interested in opioids, not benzodiazepines.

Two reports from the CDC indicate the scope of the problem with benzodiazepines. From 2004 to 2008, there was a 111% increase (going from 144,600 to 305,900) in the estimated number of emergency department visits involving nonmedical use of opioid analgesics.² For the same period, there was an 89% increase (from 143,500 to 271,700) in such visits for benzodiazepines. Data from the National Vital Statistics System multiple cause-of-death file from 2010 show that opioid analgesics were involved in 75% of pharmaceutical overdose deaths; benzodiazepines were in second place, with involvement in 29% of such deaths.³ Benzodiazepines were also involved in 30% of opioid-related deaths-far more than any other class of drugs. This indicates that combining benzodiazepines and opioids may be especially dangerous.

Of course, patients who use prescription drugs for nonmedical purposes may be purchasing drugs illicitly, so it is difficult to determine how many of those in the CDC studies may have had prescriptions written for them by physicians. However, 2 studies on opioid prescriptions in the Department of Veterans Affairs health care system indicate that benzodiazepines continue to be frequently prescribed for patients with chronic pain.

In the first study, the authors found that 32% of patients taking what they defined as high doses of opioid analgesics for chronic noncancer pain and 25% of those taking what was considered a traditional dose of opioids for the pain were also taking a benzodiazepine.⁴ In contrast, only 10% of patients who were not receiving an opioid were given a prescription for a benzodiazepine.

The second study involved patients receiving methadone or a long-acting form of morphine for chronic pain. In this study, at least 28 days of a benzodiazepine had also been prescribed for 26% of the patients at the same time as they were taking the opioid.⁵

Concerns about benzodiazepine use by patients with chronic pain

Even by the time of my study,¹ the use of benzodiazepines by patients with chronic pain was generally contraindicated. Since that time, additional studies have only strengthened this premise-most notably research indicating that benzodiazepines reduce the analgesic effects of opioids and that their long-term use can result in hyperalgesia, thereby exacerbating the pain by lowering the pain threshhold.⁶

There are the additional problems well known to psychiatrists. Benzodiazepines can be addictive. In fact, from my experience, it is often more difficult to discontinue benzodiazepines than opioids. Many times after patients have told me that they are willing to do anything to reduce their pain and I have recommended trying to discontinue benzodiazepine use, they have modified their responses to “anything but that!”

Although benzodiazepines can be effective for the treatment of anxiety for short periods, they are, with rare exceptions, not generally indicated for chronic anxiety in the absence of a diagnosable anxiety disorder. However, few of the patients with chronic pain that I have seen during my career have had a diagnosis of an anxiety disorder at any time while receiving these medications. Furthermore, many of those who have anxiety also have associated depression, which may be exacerbated by the benzodiazepines. Obviously, treatment with an antidepressant would be a far better choice for these patients-especially in light of the fact that SNRIs can provide marked analgesia in addition to their antidepressant and anxiolytic benefits. Even for medication management of brief periods of anxiety, buspirone may be a better choice.

Benzodiazepines have been and continue to be frequently used for the treatment of insomnia. In fact, this was the most common reason why the patients in my study were taking benzodiazepines.¹ Studies of patients with chronic pain who had difficulty in sleeping show that benzodiazepines interfere with the same stages of sleep most likely to be problematic. The patients I studied found that the benzodiazepines provided little benefit for improving sleep. With the availability of the non-benzodiazepine sedative hypnotics, including zolpidem, zaleplon, and eszopiclone, there is now little rea-son for benzodiazepines to be used to aid sleep.

Benzodiazepines are also frequently employed as muscle relaxants, but there is limited literature to support this. Whether they provide much direct muscle relaxation or whether their benefits are primarily related to their sedating effects is open to question. There are better choices if a muscle relaxant is indicated, such as cyclobenzaprine and tizanidine, which do not carry the potential problems that are associated with benzodiazepines.

Although there has been a growing focus on the abuse of opioid analgesics, with the development of tamper-resistant formulations and the requirement that physicians take risk evaluation and mitigation strategy (REMS) programs to prescribe certain opioids, benzodiazepines have not received similar attention.

There is no doubt that abuse of opioid analagesics is a major problem that needs to be addressed. But ignoring problems associated with benzodiazepine use is injurious to the nation’s public health.

References:

1. Governale L. Outpatient prescription opioid utilization in the US, years 2000-2009. July 22, 2010. http://
www.fda.gov/downloads/AdvisoryCommitteesMeetingMaterials/Drugs/AnestheticandLifeSupportDrugsAdvisoryCommittee/ucm220950.pdf. Accessed May 20, 2013.

2. Centers for Disease Control and Prevention. Primary Care and Public Health Initiative. Balancing pain management and prescription opioid abuse: educational module. October 24, 2012. http://www.cdc.gov/primarycare/materials/opioidabuse. Accessed May 20, 2013.

3. Centers for Disease Control and Prevention. Suicide among adults aged 35-64-United States, 1999-2010. MMWR Morb Mortal Wkly Rep. 2013;62:321-325.

4. Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity: a literature review. Arch Intern Med. 2003;163:2433-2445.

5. Ilgen MA, Zivin K, Austin KL, et al. Severe pain predicts greater likelihood of subsequent suicide. Suicide Life Threat Behav. 2010;40:597-608.

6. Pereira A, Gitlin MJ, Gross RA, et al. Suicidality associated with antiepileptic drugs: implications for the treatment of neuropathic pain and fibromyalgia. Pain. 2013;154:345-349.