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, and probably that would be the answer most health care professionals would give. However, there is another response that would be 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 that it is not. Twenty years ago, I coauthored what was one of the first papers on a study that examined the use of benzodiazepines by patients with chronic pain and found that they were overprescribed.¹ With rare exception since that time, the lectures I have attended on overprescription of medications have usually focused mostly on opioids. When I raise the question of overprescription of benzodiazepines, the speakers either respond that they are unaware of any problem involving benzodiazepines or, while acknowledging that there is, offer the odd response that the audience is interested in opioids rather than benzodiazepines.

Last year, the CDC reported that from 2004 to 2008 there was a 111% increase (from 144,600 to 305,900) in the estimated number of emergency department visits involving nonmedical use of opioid analgesics.² During the same period, there was an 89% increase (from 143,500 to 271,700) in the number of such visits for benzodiazpines. The New York City Department of Health and Mental Hygiene (NYC DOHMH) reported that in 2009 approximately 25% of unintentional drug overdose deaths involved opioid analgesics other than methadone, while 33% involved a benzodiazepine.³ 

Of course, patients who use prescription drugs for nonmedical purposes may be purchasing drugs illicitly. It is thus difficult to determine how many of the overdoses reported by either the CDC or the NYC DOHMH were for legally prescribed drugs. However, findings from recent studies that looked at opioid prescriptions at the Department of Veterans Affairs health care system indicate that benzodiazepines continue to be prescribed frequently for patients with chronic pain.

Morasco and colleagues⁴ found that 32% of patients who took high doses of opioid analgesics for chronic noncancer pain and 25% of those who took a traditional dose of opioids for the pain were also taking a benzodiazepine. In contrast, only 10% of patients who were not taking an opioid were given a prescription for a benzodiazepine.

Krebs and colleagues⁵ looked at patients who received methadone or a long-acting form of morphine for chronic pain. Their findings show that 26% of the patients had also received a prescription for at least a 28-day supply of a benzodiazepine at the same time as they were taking the opioid.

Concerns about benzodiazepines for chronic pain
The use of benzodiazepines by patients with chronic pain has generally been contraindicated from as far back as 1990. Since that time, the evidence has been strengthened. Most notably, research findings suggest that benzodiazepines reduce the analgesic effects of opioids and that their long-term use can result in hyperalgesia, which can exacerbate pain by lowering the pain threshhold.⁶

In addition, benzodiazepines are known to be addictive. In fact, it is often harder to discontinue benzodiazepines than opioids. Combining benzodiazepines with opioids can increase the risk of death, which makes the frequent co-prescription of these drugs especially worrisome

Although benzodiazepines can be effective for the treatment of anxiety for short periods, they are, with rare exceptions, not generally indicated for the treatment of chronic anxiety in the absence of a diagnosable anxiety disorder. However, based on my experience,  it is rare for patients with chronic pain who are given benzodiazepines to have a true comorbid anxiety disorder. Furthermore, many of those who have anxiety also have associated depression, which may be exacerbated by benzodiazepines. Obviously, treatment with an antidepressant would be a far better choice for these patients-the serotonin-norepinephrine reuptake inhibitors can provide marked analgesia in addition to their antidepressant and anxiolytic benefits. For 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, in our study, this was found to be the most common reason why patients were taking benzodiazepines.¹ The results from studies of patients with chronic pain who have difficulty in sleeping show that the stages of sleep most likely to be problematic are those that are disrupted by benzodiazepines. It is interesting to note that the patients in our study found that benzodiazepines provided little benefit for improving sleep. With the availability of the nonbenzodiazepine sedative hypnotics, including zolpidem, zaleplon, and eszopiclone, there is little reason for benzodiazepines to be used to aid sleep.

Benzodiazepines often have also been used as muscle relaxants, but there is limited evidence for this. Whether benzodiazepines provide much direct muscle relaxation or whether the 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 associated with benzodiazepines.

The overuse of benzodiazepines may at last be attracting the attention it deserves. A New York Times article this summer⁷ reported that a community mental health center in Louisville, an area in which for several years there has been marked concern about prescription opioid misuse, had determined that benzodiazepines were being misused and that it decided to stop prescribing alprazolam. According to the article, hydrocodone, oxycodone, and alprazolam are 3 of the most commonly prescribed controlled substances in Kentucky.⁷ Whether the banning of a single drug is the best way to go is certainly open to debate, but the need for more focus on the prescription of benzodiazepines, especially for patients with chronic pain, is not.

References
1. King SA, Strain JJ. Benzodiazepine use by chronic pain patients. Clin J Pain. 1990;6:143-147.
2. Centers for Disease Control and Prevention. Emergency department visits involving nonmedical use of selected prescription drugs-United States, 2004-2008. MMWR. 2010;59:705-709.
3. New York City Department of Health and Mental Hygiene. Preventing misuse of prescription opioid drugs. City Health Inf. 2011;30:23-30.
4. Morasco BJ, Duckart JP, Carr TP, et al. Clinical characteristics of veterans prescribed high doses of opioid medications for chronic non-cancer pain. Pain. 2010;151:625-632.
5. Krebs EE, Becker WC, Zerzan J, et al. Comparative mortality among Department of Veterans Affairs patients prescribed methadone or long-acting morphine for chronic pain. Pain. 2011;152:1789-1795.
6. Gear RW, Miaskowski C, Heller PH, et al. Benzodiazepine mediated antagonism of opioid analgesia. Pain. 1997;71:25-29.
7. Goodnough A. Abuse of Xanax leads a clinic to halt supply. New York Times. September 14, 2011. http://www.nytimes.com/2011/09/14/us/in-louisville-a-centers-doctors-cut-off-xanax-prescriptions.html. Accessed July 15, 2012.