Steven A. King, MD, MS

Fears about the overprescription of opioid analgesics and the opioid epidemic have resulted in initiatives for physicians to prescribe these medications more judiciously. However, new concerns about patients needlessly suffering untreated or undertreated pain have been raised.

Unfortunately, many lay people and even many health care providers still believe that opioids are the optimal treatment for all forms of pain and that there are no good alternatives. Studies, however, have shown that nonopioid pharmacologic therapies and nonpharmacologic therapies can be as effective and, in many cases, even more effective than opioids.

and meta-analysis of mind-body therapies (MBTs) for patients whose pain is being treated with opioids highlights how useful these modalities can be and the importance of considering them when caring for patients suffering with pain.

The review included 60 studies with 6404 participants. A variety of MBTs were employed, including meditation, hypnosis, relaxation, guide imagery, therapeutic suggestion, and cognitive-behavioral therapy (CBT) depending on the individual studies. The types of pain varied from procedural pain to burn pain to cancer-related pain to chronic pain. The impact of various MBTs on the pain and on the use of opioids were examined.

The findings indicated that meditation, hypnosis, therapeutic suggestion, and CBT were most likely among the MBTs to provide the greatest pain relief with moderate to large improvements. Meditation, hypnosis, and CBT appeared to have the greatest impact on opioid use. The researchers noted that the lack of evidence for the impact of the other MBTs may reflect that there were fewer studies rather than evidence that those MBTs are less likely to have an effect on either the pain or opioid use.

There were also indications that MBTs may provide some benefit for opioid craving and misuse, another reason why their use should be considered for patients on opioids for whom it is believed these medications should be discontinued.

There were differences between the types of pain for which the individual MBTs were studied. Studies that looked at meditation-based therapies primarily focused on chronic noncancer pain while most hypnosis, relaxation, and imagery studies focused on acute, procedural, or cancer-related pain. Whether this provides any guidance as to which type of therapy would be most beneficial for which type of pain is open to question and warrants further study.

It is worth noting that there is a great deal of overlap between many of the MBTs and what might be considered meditation by some could be considered relaxation or even hypnosis by others, so there is often a lack of clear demarcation between them. MBTs are not a magic bullet for the management of pain. They showed a moderate but statistically significant effect on the pain and resulted in a small but statistically significant reduction in opioid use.

In addition to these apparent benefits, MBTs also have one very significant advantage over many of the other treatments for pain: they are essentially free of adverse events. If they are tried and do not provide any benefit, the patient will be no worse off. As with all the other interventions to manage pain, no one can guarantee that MBTs will provide improvement but one can be as close as possible to certainty that they will not have any negative impact on those being treated with them. If the opioid epidemic has taught us anything it is that therapies initiated to help patients can end up having a destructive effect.

There is one very real limitation in the introduction of the MBTs as major treatments for pain. For the most part, in academic centers and hospitals, pain management is primarily considered to be a subspecialty of a single medical specialty—anesthesiology. The only significant exception to this is headache management, which is usually considered to be a part of neurology.

The reality is that few anesthesiologists and neurologists, even those who specialize in pain management, receive much, if any, training in the use of MBTs, nor do most primary care physicians upon whom the management of pain often falls. Thus, most patients with pain are unlikely to come into contact with caregivers who are knowledgeable about MBTs, much less know how to utilize them.

Obviously, the physicians most likely to be trained in the use of MBTs are psychiatrists, and this is one of many reasons why psychiatrists should be more involved in the care for patients with all forms of pain and not just those patients with diagnosable mental disorders.

There is a need for more and better studies on MBTs for pain. However, this can be said of all the other treatments for it. Let us recall that millions of patients have been prescribed opioids for the management of chronic pain although there are virtually no studies demonstrating their efficacy.

1. Garland EL, Brintz CEE, Hanley AW, et al. 

Mind-body therapies for opioid-treated pain: a systematic review and meta-analysis

This article was originally posted on February 20, 2020, and has since been updated. -Ed

Articles

For the millions of patients whose pain is being treated with opioids, mind-body interventions are proving to be important considerations to ease suffering.

Mind-Body Therapies for the Management of Pain: How Effective Are They?

Pain is a subjective complaint for which health care professionals largely depend upon self-report by patients. However, we face a special challenge in determining whether pain is present, its severity if it is, and how it is responding to treatment in patients who are cognitively impaired. A recent review of the problem of pain among patients who suffer 

 identifies many of these issues and current recommendations for addressing them.


	Dementia largely occurs among older patients who, while not inevitably experiencing 

, are more likely than younger patients to suffer from many disorders that can cause pain, such as arthritis, cancer, 

, and shingles. Furthermore, some disorders such as 

 and stroke can cause both severe pain and dementia.

Although there has long been a widely propagated myth that as people age they are less likely to experience pain, there is little to support this view. Studies have indicated that as many as 60% to 80% of residents of nursing homes with dementia and over 50% of those in the community with it experience pain.


	The greatest challenge to health care providers is determining whether patients with dementia are experiencing pain. Although patients with mild to moderate dementia may still be able to respond appropriately when asked if they are experiencing pain, those with more severe dementia are probably unable to gauge how much pain they feel, so asking them this question is unlikely to provide much information nor will the commonly used instruments to measure pain such as numerical rating scales.

Thus, it falls on healthcare providers to find alternative methods for identifying pain in those who can’t respond. Determining whether pain is present primarily consists of observing patients. Of greatest use in determining pain in patients who can’t self-report are observations of:
	• Facial responses
	• Vocalization
	• Body movement or body posture

Although there have been multiple instruments (the review identified 19) that have incorporated these observable behaviors, the review considered them to be of poor or unproven reliability, to lack evidence of validity, and none had been tested for sensitivity to change. Thus, it is impossible to determine which one of these scales is be more reliable or valid than the others.

It is worth noting that two observational measures that may be useful for cognitively intact patients-improvement in levels of functioning and reduction in the use of analgesic medications-may be of limited use for patients with dementia whose functioning is already significantly limited by the cognitive impairment and who have little control of what medications they take and when they take them.


	Even when pain is identified in patients with dementia, there are still multiple challenges with regard to treatment. Although analgesic medications may be beneficial, as with all geriatric patients, cormorbid conditions and reduced renal and hepatic function can make it difficult to find the optimal balance between pain relief while avoiding adverse effects. Furthermore, because of limitations in self report patients with dementia and pain may be unable to report those adverse effects when they do occur.


	Recommendations with regard to pharmacologic management of pain among those with dementia follow. It should be noted, however, that these recommendations are based primarily on those for geriatric patients in general as there is little research on their efficacy specifically for patients with dementia:
	1. Acetaminophen is considered the first-line medication although there is limited research beyond 3 months of use (ie, that would be considered being used for chronic pain)
	2. Because of their potential adverse effects the use of 

 should be avoided.
	3. Opioids may be effective in managing pain although it is still an open question whether their benefits outweigh their potential adverse effects. One issue that the review doesn’t address is how much whatever benefits ascribed to opioids for patients with dementia may be due to their sedating effects. Considering that measurement of their efficacy would be primarily based on observation of the patients, sedation might be confused with patients actually experiencing a reduction in pain.
	4. Other medications commonly used for the management of chronic pain, most notably the 

serotonin-norepinephrine reuptake inhibitors

, may be effective but they can have adverse effects that might exacerbate other medical problems. Moreover, similar to the opioids, can have sedative effects that might be mistaken as providing analgesia.
	5. Another issue not mentioned by the review is that of scheduling of medications. For patients in nursing homes, analgesic medications are often prescribed on a prn basis which means that patients with dementia who are unable to report they are having pain are unlikely to receive them. During my career, I have often observed that cognitively impaired patients who are prescribed prn sedative medications for agitation and prn medications for pain will receive the former because agitation is easily observable but won’t receive the latter because pain is not.


	As with the treatment of chronic pain for patients of any age, nonpharmacologic treatments should be considered and may be effective. They have the added benefits of essentially being free of adverse effects so therefore, unlike medications, are unlikely to exacerbate any other medical problems. However, as with pharmacologic therapies, there is limited research on these treatments for this patient cohort and the recommendations are primarily based on those for geriatric patients without dementia.

The most promising nonpharmacologic treatments for these patients are: exercise and/or movement therapies, massage and/or human touch, heat and relaxation therapies, human interaction and presence. Unfortunately, other interventions that may be effective for the management of chronic pain in cognitively intact patients, most notably psychologically based therapies such as cognitive-behavioral therapies, are of markedly limited use for patients with dementia. Other therapies that do not require direct involvement of the patient such as music therapy may be more effective.

Many of the treatments for chronic pain provided by physical and occupational therapists are focused on educating patients by teaching them alternative methods to manage their pain and how to perform tasks using different body mechanics. Obviously, learning new material would be difficult for many patients with dementia.


	Health care providers must rely on observation of patients with dementia to determine if they are experiencing pain. Agitation on the part of these patients may be a reflection of pain. Health care providers should be especially observant for indications of pain among patients who are suffering from disorders that frequently cause pain such as rheumatologic disorders, Parkinson disease, diabetes.

Therapies to manage the pain must always be weigh potential benefits against potential adverse effects. Even though we have known about the difficulties of managing pain in patients with dementia for almost 30 years, we still have made relatively little progress on how best to evaluate their pain and how to treat it.

1. Achterberg W, Lautenbacher S, Husebo B, et al. 

. 2020;5:1-8.
	2. Sengstaken EA, King SA. 

The problems of pain and its detection among nursing home residents

How do you determine whether pain is present and its severity as well as how it responds to treatment in patients who are cognitively impaired? Some answers to these questions.

Pain and Dementia

Slideshows

How can clinicians determine the presence of pain in cognitively impaired patients? And how do you know the medication is working if your patient can’t tell you?

Identifying and Managing Pain in Cognitively Impaired Patients

When physicians prescribe medications, usually the only thing we need to consider is how the drugs will affect the person for whom we are prescribing. We make choices based on the problems for which they are being prescribed and the risks and benefits based on the overall health of the patients. We rarely have to give much consideration to what, if any, impact the medications may have on the medical status of the patients’ families.

However, three new studies highlight how important it is that when physicians prescribe opioids there can be significant and even potentially fatal consequences for the family members of those for whom they are being prescribed.

The first study examined opioid overdoses among family members of people prescribed opioids using data supplied by a commercial insurance provider that provided information on both the patients and family members.

 The findings indicate that although opioid overdoses by the family members of those prescribed opioids were relatively infrequent, they occurred at almost three times the rate as for members of families where no one was prescribed an opioid. Furthermore, the risk of family member overdoses correlated with the dosage of the prescribed opioids. The risk of overdoses was present across all age groups from children to adults and prescription of long acting/extended release opioids and fentanyl patches increased the risk for overdoses.

Certainly one might expect that the availability of opioids in a household would increase the risk of someone other than the patient taking the medications and overdosing. The authors note that the overdoses in children are quite probably accidental while those in adolescents and adults are more likely to be the result of intentionally taking the opioids. However, in either case they acknowledge that health care professionals need to make patients aware that they need to closely monitor the opioids prescribed for them and do their best to prevent family members using them to prevent misuse and potentially life threatening overdoses from occurring.

A second study examined the association between opioids prescribed for parents and the risk of suicide attempts by their children aged 10 to 19 years.

 It, too, found that while suicide attempts by children of parents who were prescribed opioids were relatively rare, they occurred at more than two times the rate for children whose parents were not prescribed opioids.

The authors of the study noted that other factors such histories of substance use disorder, depression, or suicide attempts by the parents or substance use disorder or depression in the children who overdosed did not fully explain the results.

It is also worth noting that the study found that the greatest risk for suicide attempts among children were those where one or both parents were taking a prescribed opioid and a medication for insomnia, either a benzodiazepine or a “Z drug,” although over two times as many were using a benzodiazepine rather than a Z drug.

The researchers did not have an explanation for their results apart from the potential accessibility of medications with which children can attempt suicide in their home but do recommend that when physicians prescribe opioids for parents, they make them aware of the issue and tell them and their children’s health care providers to watch for behaviors that might indicate suicide is being considered.

Finally, a third study looked at opioid and benzodiazepine prescriptions for family members of people whose prescriptions for these medications had been discontinued. The authors identified patients who had filled prescriptions for opioids or benzodiazepines for a 30 day or more supply during the 10 year period between 2007 and 2016. Based on the total number of prescriptions filled during the period, the 10% of patients who filled the most prescriptions were identified as “high-volume users” and those who were in the bottom 50% with regard to the least number filled were “low-volume users.”

When opioid prescriptions were discontinued among high-volume users, 0.2% of family members filled a prescription for an opioid within 2 days and 0.5% within 14 days. The same results were found among high-volume benzodiazepine users with regard to filling a prescription for a benzodiazepine during those periods.

Among low-volume users, only .06% of family members of opioid or benzodiazepines users whose prescriptions were discontinued filled prescriptions for the respective medications within 2 days after discontinuation while 0.4% of family members of low-volume opioid users and 0.3% of benzodiazepine users filled prescriptions for the medications within 14 days after discontinuation.

Although the authors appreciated that the percentages of family members filling prescriptions after discontinuations was quite small, they noted that their findings did raise the concern that family members might have sought prescriptions for opioids or benzodiazepines in order to continue to provide the medications to those whose prescriptions have been discontinued. Another possible explanation is that the patients originally prescribed the medications were either willingly or unwillingly sharing them with family members and when the prescriptions were discontinued, the family members had to seek their own prescriptions in order to continue their use.

Certainly considering the large numbers of patients in the US who have opioid prescriptions for chronic pain and in light of current recommendations that in most of these cases opioids are not appropriate, doctors may feel they are under increased pressure to stop prescribing these medications.

 It is possible that family members subsequent seeking of opioid prescriptions may be a growing problem and something clinicians need to be aware of.

The last two studies highlight concerns physicians should have about the over prescription of benzodiazepines, a topic that has unfortunately taken a backseat to the opioid epidemic. Another new study notes the important role that both benzodiazepines and opioids can play in mortality and ongoing opioid use following noncardiac surgery.

 The study examined the use of opioids and benzodiazepines during the 6 months prior to surgery and found that patients who had been prescribed both medications had a greater 30 day mortality rate and long-term risk of mortality.

Use of opioids, benzodiazepines, or both prior to surgery all were associated with persistent opioid use following it. 43% of preoperative opioid users and 23% of benzodiazepine users were persistent opioid users while 65% of those who used both medications became persistent users of opioids. This was in contrast to only 12% of patients who took neither opioids nor benzodiazepines preoperatively who became persistent opioid users.

Despite the fact that there has been little literature to support the co-prescription of opioids and benzodiazepine and much to recommend against it, it still continues to occur not infrequently. How hard it has been to change the habits of doctors who are doing the coprescribing is demonstrated by another new study.

This study examined the impact of the 2016 Centers for Disease Control and Prevention guideline on the use of opioids for chronic pain, which strongly advised against the co-prescription of these with benzodiazepines. A small but statistically significant decrease in the rates of co-prescription was seen in the two years following the release of the guideline among patients using opioids for extended periods. However, there was no change in what the researchers described as “intensity of co-prescription” measured by the number of days both medications were prescribed concurrently. Curiously, although the study found that there was a reduction in co-prescription for patients with Medicare Advantage no reduction was seen among patients with commercial insurance.

One other interesting finding of the study was that in most cases the same physician prescribed both the opioids and benzodiazepines, which suggests that the problem was not due to lack of coordination between physicians where different ones were prescribing each medication.

None of the findings of any of these studies indicate that physicians should cease to prescribe either opioids or benzodiazepines to patients who truly require them. They do, however, highlight the many issues associated with their use that they may not need to consider when prescribing other medications but do with these two classes.

Dr King is in private practice in Philadelphia.

1. Khan NF, Bateman BT, Landon JE, et al. Association of opioid overdose with opioid prescriptions to family members. 

2. Brent DA, Kur K, Gibbons Rd. Association between parental medical claims for opioid prescriptions and risk of suicide attempt by their children.

3. Barnett ML, Hick TR, Jena AB. Prescription patterns of family members after discontinued opioid or benzodiazepine therapy of users. 

4. Sigurdsson MI, Helgadottir S, Long TE, et al. Association between preoperative opioid and benzodiazepine prescription patterns and mortality after noncardiac surgery.

5. Jeffery M, Hooten WM, Jena AB, et al. Rates of physician coprescribing of opioids and benzodiazepines after the release of the Centers for Disease Control and Prevention Guidelines in 2016. 

Three studies highlight how important it is that when physicians prescribe opioids there can be significant and even potentially fatal consequences for the family members of those for whom they are being prescribed.

When Medications Affect More Than the Patient: Opioids and Family Members

The association between psychiatric disorders, most notably depression and anxiety, and pain is well established. However, mental health professionals, and especially psychiatrists, are still often excluded from treating patients with pain as many of our non-psychiatrist physician colleagues still often believe that there is little for them to do in the care of patients with pain unless it is clearly secondary to a psychiatric disorder. The results of two new studies highlight the importance of addressing mental health problems in patients with pain.

The first study examined the effects of MDD on the outcomes for 260 patients who underwent total knee arthroplasty (TKA).

 Patients completed baseline measures before the surgery that included the Patient Health Questionnaire to evaluate the presence of MDD and others to evaluate pain, level of functioning, and overall quality of life. The testing was repeated at a year following the surgery.

The patients were divided into four groups:

 Those who didn’t suffer from MDD either at baseline or follow-up

 Those who suffered MDD at baseline but not at follow-up

 Those who didn’t suffer MDD at baseline but did at follow-up

 Those who suffered MDD both at baseline and follow-up

At baseline there were no significant differences between the groups with regard to knee function. However, there were significant differences between them at one-year follow-up. Patient with MDD at both baseline and follow-up were found to have significantly less net improvement than patients in the other three groups. Patients who did not have MDD at baseline but did at follow-up also had less improvement than patients who never had MDD or those with MDD that had resolved by follow-up. Patients in the latter two groups had similar levels of improvement.

Visser and colleagues conclude that patients with MDD can still benefit from TKA. They emphasize that the presence of the psychiatric disorder is not a contraindication to the surgery, but it is important to at least begin to treat symptoms before patients undergo TKA. Moreover, it is important to monitor the mental health of patients who have undergone the surgery to determine whether depression is developing and needs to be treated. Also noted was the difficulty in determining whether the psychiatric disorder caused the reduction in benefits from the surgery or if the reason for continuing or new-onset depression was the lower level of improvement following the surgery.

The second study comprised 284 patients with chronic low back pain (CLBP) with or without radiculopathy who were evaluated on their first visit to chronic pain clinics in Portugal.

 The instruments used to evaluate patients included the Hospital Anxiety and Depression Scale (HADS), Brief Pain Inventory, and the Shortened Treatment Outcomes in Pain Survey. The latter two were again used at one-year follow-up to gauge the levels of pain and physical functioning.

During the year, the patients underwent what was described as “the usual multidisciplinary approach” to CLBP. Although the article does not include what was meant by this, it notes that among the services provided by the clinics were “general medical therapy, invasive approaches, physical therapy, and psychological assessment and/or cognitive behavioral therapy.”

At baseline, 51.4% of patients had depression and anxiety symptoms on the HADS while 21.5% had only anxiety, 6.7% only depression, and 20.4% neither. Study findings indicate that patients who suffered from both depression and anxiety symptoms at baseline had significantly worse outcomes with pain severity and disability at the one-year follow-up. The presence of either depression or anxiety alone at baseline also affected both of these measures but at a lesser level.

The researchers concluded that depression and anxiety symptoms at the onset of treatment of CLBP were predictive of treatment outcomes even at the pain clinics where it was expected that psychological issues would be addressed.

Both studies highlight the potentially significant impact the presence of psychiatric disorders and/or their symptoms can have on response to treatments for chronic pain. In patients with chronic pain, the presence of depression or anxiety is often discounted as being secondary to the pain and therefore expected to resolve once the pain improves. Furthermore, because of this, once treatments for the pain are instituted, the psychiatric disorders may be ignored.

Patients with CLBP may be expected to be offered some psychologically based treatments at a pain clinic, but that is not always guaranteed. Moreover, it is much less likely that someone undergoing a TKA would be offered similar services. Even if that person was in treatment for MDD, it is quite possible that the issue of pain may not come up during treatment because patients and psychiatrists may think that knee pain and the response to surgery may have little connection with one’s mental state. Even if MDD is identified prior to surgery, it may be overlooked as a possible factor in the level of a patient’s benefits as a result of the TKA.

These studies demonstrate that for many patients with chronic pain conditions and even those who undergo appropriate surgical therapies such as TKAs, the assessment of mental health at the onset and throughout treatment is of vital importance. Without the active involvement of mental health professionals including psychiatrists in the care of patients with pain, the effectiveness of treatment may be markedly reduced.

 Visser MA, Howard KJ, Elli HB. The influence of major depressive disorder at both the preoperative and postoperative evaluations for total knee arthroplasty outcomes. 

 Oliveira DS, MendonÃ§a LVF, Sampaio RSM, et al. The impact of anxiety and depression on the outcomes of chronic low back pain multidisciplinary pain management: a multicenter prospective cohort study in pain clinics with one-year follow-up. 

The association between psychiatric disorders, most notably depression and anxiety, and pain is well established. However, mental health professionals, and especially psychiatrists, are still often excluded from treating patients with pain.

Psychiatric Disorders and Pain

Everyone knows the story of Goldilocks and her visit to the home of the three bears, where she was seeking the right balance between the things she discovers to attain the maximum comfort.

Medical professionals face something similar when it comes to prescribing opioids. We don’t want to prescribe too many pain killers, which may contribute to the epidemic of opioid misuse, yet we don’t want to have patients needlessly suffering who might benefit from opioids for pain management. Two recent publications highlight both the concerns regarding this issue and also the limitations in our knowledge regarding how best to achieve the ideal.

The first is a letter signed by over 300 medical professionals to the Centers for Disease Control and Prevention(CDC) regarding its guideline on prescribing opioids for chronic pain issued in 2016.

 The guideline strongly recommends limiting the use of opioids for the management of chronic pain, noting the lack of research to support their use for this and highlighting the potential benefits of using non-pharmacologic treatments and non-opioid medications.

Although the letter doesn’t dispute the CDC guideline recommendations, it expresses concerns that within a year of its publication, “there was evidence of widespread misapplication of some of the Guideline recommendations” including concerns about exceeding its recommended opioid daily dosage limitations.

According to the letter, the guideline has resulted in barriers to patients obtaining needed opioids including amount and dosage limitations set by insurance companies, limitations in dispensing the medications by pharmacies, and doctors themselves limiting or even refusing to prescribe opioids out of fear of legal action if they consider prescribing them in a manner that is different from what the guideline recommends. The letter also states:

Patients with chronic pain, who are stable and arguably benefiting from long-term opioids, face draconian and often involuntary rapid dose reductions. Furthermore, the guideline has created barriers that have resulted in not only unnecessary suffering because of patients being unable to obtain the opioids they require to control their pain but also other problems. In desperation, patients in pain are turning to suicide or illicit drug use or being forced to turn to invasive treatments such as spinal injections that often provide little benefit.

In the letter from the health professionals, they note, appropriately, that there is little objective evidence for their statements and that the letter is mostly based on anecdotes. In fact, the one point that the letter makes that anyone who does pain management can attest to without any doubt is that the non-medication treatments recommended by the CDC, which the letter doesn’t name but includes treatments such as cognitive-behavioral therapy and acupuncture, may not be covered by insurance thus limiting access to them.

The letter expresses concerns about the CDC guideline recommended maximum opioid daily dose of 90 morphine milligram equivalents per day-if clinicians believe a higher dose is required, they should “carefully justify a decision” to do this. (For a dose conversion table for other opioids, see 

www.cdc.gov/drugoverdose/pdf/caclulating_total_daily_dose-a.pdf

This recommendation that physicians should provide a clear justification for higher doses of opioids should not be a substantial obstacle, but a recent study showed that a pain diagnosis is lacking in over 28% of patients prescribed opioids. It appears that opioids are frequently prescribed without much thought whatsoever, much less careful thought.

I am skeptical of several of the points included in the letter. I have read many anecdotes about patients started on opioids for legitimate pain complaints who, as a result of physicians reducing or discontinuing the medications, turned to illicit medications, ie, heroin or illicit fentanyl. However, for the most part, there was information in their stories that didn’t quite fit. Questions remained about whether there was a legitimate reason for prescribing the opioid in the first place and whether at least some of these patients were already suffering from opioid use disorder.

It is worth noting that even when the number of opioid prescriptions was increasing during the last decade of the 20th century and the first decade of the 21st, there was no apparent reduction in the number of unnecessary treatments such as spinal injections despite limited evidence of their efficacy. This suggests that whether opioids are liberally or conservatively prescribed has little to do with the frequency of the provision of such treatments.

The letter calls on the CDC to evaluate the impact its recommendations have on patients and caregivers and that it clarify its recommendations on opioid taper and discontinuation. I agree with the need for ongoing research about the effects of the CDC guideline, but I am troubled by what the letter ignores.

Although the letter indicates that physicians may have misread the guideline as being a requirement, I question how frequent this is. Considering the number of guidelines that have been issued for many different disorders and problems, I hope that health care professionals are aware that guidelines are not laws. As far as I’m aware none, including the CDC, require or expect that every patient be treated according to a specific guideline.

Based on my experience, I believe that most physicians who refuse to continue treatment with opioids or to initiate them based on the CDC guideline may be using it as an excuse, not a reason. It is far easier for physicians to say they are prevented from prescribing an opioid or are required to limit dosage or discontinue it, than to tell patients they (the prescribers) are making the decision. It may take considerable time and effort to explain to patients the reasons for the decision.

There are two other points that the letter overlooks. The first is the reasons why physicians may seek to reduce and possibly discontinue opioids. It is widely thought that the only reason for this is fear of addiction. It is true that this is a problem, and evidence has shown that a significant number of patients taking opioids for chronic pain end up misusing these medications. However, of equal importance is the issue of hyperalgesia where extended use of opioids can actually lower the pain threshold and thereby exacerbate the pain. Although the correct treatment for this is to reduce and discontinue the opioid, the worsening of the pain is often misinterpreted as being due to tolerance or worsening of the condition, which results in an increase rather than a decrease in the dose.

The second overlooked issue is how we should be evaluating the efficacy of opioids or any other treatment for chronic pain. From the letter it would be easy to conclude that measurement of the pain itself is of most importance. However, it is generally agreed that a far better measure of efficacy and one that can be more objectively observed than pain level is the level of functioning.

I have treated many patients with chronic pain over the course of my career with opioids and all have had one thing in common: there is evidence that they are functioning better because of the medications. When these patients are in a fairly stable condition, I try to reduce dosage and, if this is possible, to consider discontinuation. I have never just started a patient with chronic pain on an opioid and then not made an attempt to see if it is still required over time.

The letter calls on the CDC to clarify its recommendations on the tapering and discontinuation of opioids, and I believe this is appropriate. This is another area of pain management with limited research, which the CDC notes. We have very little guidance as to the best ways to taper doses of opioids either with the goal of reducing dosage or discontinuing the medications. A recently published statement calls attention to concerns over rapid and forced tapering for outpatients. This is something that seems to be more for the benefit of health care providers who no longer wish to prescribe opioids than of patients.

Medication management of opioid use disorder: what we know and what we don’t

The National Academies of Sciences (NAS) recently issued a report on the use of medications for opioid use disorder that highlights the efficacy of the three currently available medications for the management of opioid use disorder: methadone, buprenorphine, and extended-release naltrexone. The report emphasizes the problem of the underutilization of these medications.

I am in complete agreement but have one major problem with the report. There is virtually no attention given to the issue of iatrogenic opioid use disorder where patients are appropriately treated with opioids for a legitimate pain problem and end up misusing them.

The report briefly mentions the problem of opioid use disorder among patients with chronic pain. However, it primarily addresses the treatment of opioid use disorder in people with comorbid chronic pain, and it notes the limited research on the efficacy of medication treatment for opioid use disorder. However, there is no specific mention of iatrogenic opioid use disorder and what recommendations there are for its management or the need for future research.

Although the evidence for the existence of iatrogenic opioid use disorder goes back almost 30 years, we still know very little about it. We don’t know if either the physiology or psychology of it is the same or differs from opioid use disorder resulting from the non-medical use of opioids much less whether the treatment for both should be the same.

If methadone and buprenorphine are the appropriate treatment for iatrogenic opioid use disorder, they should also be the first-line treatments for pain because they are just as effective for pain management as other opioids. We would then have something unique in medicine: the same medications that cause the problem are also the appropriate treatment for it.

Why is iatrogenic opioid use disorder so ignored by the NAS report? I can’t be certain, but I believe that an important factor is those involved in writing the report. These are substance abuse experts who probably have limited experience with iatrogenic opioid use disorder and may not even be aware of it. The fact that substance abuse experts involved in the development of DSM-IV and DSM-5 failed to include a separate iatrogenic opioid use disorder diagnosis suggests that they may have limited knowledge about it or think it’s so incredibly rare that it doesn’t warrant a separate diagnosis.

I should note that the letter critical of the CDC guideline also suffers a similar shortcoming. The primary authors of the letter appear to be experts in substance abuse but not in pain management. Many of the over 300 who endorsed the letter are pain specialists and many are addiction specialists, but there are very few who can be considered experts in both and might be expected to be better able to weigh the risks and benefits of opioids.

We need doctors who have training in pain management and addiction medicine. Patients who appear to be receiving only limited benefit from opioids still often refuse to discontinue them out of fear that they will be left to suffer even more than they already are. Patients need to be taught other methods for managing pain apart from opioids for there to be any reasonable expectations that they will agree to reduce the dose or discontinue use.

There are two ways we can address the lack of doctors with expertise in pain management and opioid misuse. Because pain management falls under anesthesiology in most medical schools and hospitals, we could require that anesthesiologists receive training in recognizing and managing substance abuse. Conversely, substance abuse primarily falls under psychiatry, but most psychiatrists receive limited training in pain management.

Although it is doubtful that anesthesiology programs will ever provide much training on substance abuse, I still hope that psychiatry will recognize the important role it can play in pain management. Someone with training in both pain management and substance abuse would be better able to weigh both the benefits and risks associated with the use of opioids in patients with chronic pain and tailor treatment to the needs of individual patients.

 Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain: US, 2016. 

 Health Professionals for Patients in Pain. Professionals call on the CDC to address misapplication of its guideline on opioids for chronic pain through public clarification and impact evaluation. March 6, 2019. 

http://www.healthprofessionalsforpatientsinpain.org

 Sherry TB, Sabety A. Maestas N. Documented pain diagnoses in adults prescribed opioids: results from the National Ambulatory Medical Care Survey, 2006-2015. 

 Darnall BD, Jurrlink D, Kerns RD, et al. International stakeholder community of pain experts and leaders call for an urgent action on forced opioid tapering. 

 National Academies of Sciences, Engineering, and Medicine. Medications for Opioid Use Disorder Saves Lives. Washington, DC: The National Academies Press; 2019.

Medical professionals don’t want to prescribe too many pain killers, which may contribute to the epidemic of opioid misuse, yet they don’t want patients to needlessly suffer.

Goldilocks and the Opioids

Traumatic brain injuries (TBI) and their resultant effects on cognitive function and mental health have been the focus of a great deal of attention recently as a result of increasing recognition of them among the military and athletes, especially football and hockey players. However, there has been much less awareness of chronic pain developing as a result of TBI.

 Current research indicates approximately what percentage of people who suffer TBI develop chronic pain?

 The more severe the TBI, the more likely chronic pain will result.

 No predictive factors have been identified for determining which people who experience TBI are most likely to develop chronic pain.

 Headaches are the most common type of pain experienced by people who suffer with TBI. Which types of headache are most likely to occur?

 Mixed headaches with symptoms of both migraines and tension-type
	

 After headaches, the most common sites of chronic pain that develop as the result of TBI are:

 Regarding recommendations for treatment of chronic pain after TBI, which of the following is most accurate?

 The current recommendation for headaches is to be treat them as you would treat headaches without an association with TBI.
	

 As yet, there are no clear recommendations for the treatment of non-headache post-TBI pain.
	

Post-TBI non-headache pain is best treated the same as neuropathic pain conditions.
	

 Findings indicate that if chronic pain related to TBI does not resolve after one year, there is virtually no chance it will ever resolve.

 TBI sufferers with PTSD also appear to be more likely to have chronic pain.

 The mechanisms for chronic pain following TBI have been identified.

 Which of the following may be possible explanations for post-TBI pain?

 Disruption in dopamine signaling due to injury to the dopaminergic centers in the brain
	

 An inflammatory process involving the nervous system
	

Studies indicate approximately 52% of civilian patients with TBI will have chronic pain, and 43% of military veterans have chronic pain as a result of service related TBI.

Up to now, there have been no research findings indicating that the development of chronic pain is correlated with the severity of the TBI.

Predictive factors have yet to be identified. A variety of such factors have been proposed, but none has been found to be consistently predictive.

Migraine, tension-type, and mixed headaches appear to be the most common to develop as the result of TBI.

Although it is commonly thought that the pain secondary to TBI is limited to the head and neck, research has shown that it can also be in the upper and lower extremities. Thus, any pain that develops after a TBI, no matter where the location of the pain is, should be considered as potentially resulting from the TBI.

At present, it is recommended that post-TBI headaches be treated as one would treat the same types of headache without the occurrence of TBI. With regard to non-headache chronic pain following TBI, there is little research indicating the best treatment approaches.

Longitudinal studies indicate that post-TBI pain can resolve even several years after its onset. As of yet, no factors that would predict which person’s pain is likely to resolve have been identified. Thus, there is always some possibility the pain will resolve but there is no guarantee of this, and it should not be depended on as likely to occur.

There appears to be an association between the development of post-TBI chronic pain and of PTSD. However, whether this indicates that there may be some underlying mechanism of development shared by pain and PTSD or whether one might make the TBI patient more susceptible to developing the other is still unclear.

Although multiple theories have been proposed, the mechanisms for the development of post-TBI pain have yet to be identified.

All of these have been proposed as possible mechanisms for the development of pain following TBI. As these are not mutually exclusive, it is quite possible that multiple mechanisms may be involved and that the importance of each may vary from patient to patient.

 Nampiaprampi DE. Prevalence of chronic pain after traumatic brain injury: a systematic review. 

 Irvine KA, Clark JD. Chronic pain after traumatic brain injury: pathophysiology and pain mechanisms. 

 Department of Veterans Affairs; Department of Defense. VA/DoD Clinical Practice Guidelines for the Management of Concussion-Mild Traumatic Brain Injury. 2016. 

https://www.healthquality.va.gov/guidelines/Rehab/mtbi/mTBICPGFullCPG50821816.pdf

 Bales JW, Wagner AK, Kline AE, et al. Persistent cognitive dysfunction after traumatic brain injury: a dopamine hypothesis. 

 Gupta R, Sen N. Traumatic brain injury: a risk factor for neurodegenerative diseases. 

Test your knowledge on traumatic brain injuries (TBI) and their resultant effects on cognitive function and mental health.

THE QUIZ: Chronic Pain and Traumatic Brain Injuries

Editor's note: For reader response(s) to this article, 

When we hear of deaths due to opioid overdoses, we usually think of them being accidental. There is a growing body of evidence, however, that in at least some cases, the overdoses were actually intentional and that the presence of pain may play a role in decisions to end lives via opioid overdoses.

We know that deaths from suicides and deaths from opioid overdoses are rapidly rising. Between 1999 and 2016, suicide rates in the United States rose by nearly 30% and the greatest increase has been in the more recent years.

 Between 1999 and 2017 deaths from drug overdoses in the US went from less than 20,000 to more than 72,000 in 2017 with the greatest increase related to opioid overdoses.

A study of people who presented to emergency departments with opioid poisonings due to prescription opioids found that a little over half (53.5%) were unintentional, 26.5% were identified as being intentional, and for 20% it could not be determined whether the poisonings were in fact intentional.

Based on my experience with patients who are in pain, intentionally taking a potential overdose of opioids is often not an attempt to end one’s life. There are patients who, in an attempt to seek relief when in severe pain, may ignore prescription directions and take higher doses than are prescribed. Others may, because of the opioid’s effect on cognition, lose track of how much they have taken and end up ingesting more than prescribed.

Multiple studies have demonstrated that there is a close association between chronic pain and depression and although it is commonly thought that it is always the former that leads to the latter, we know that pain is a common symptom of depression. Obviously, depression is a major risk factor for suicide and chronic pain seems to be one, too.

Although the relationship between pain, mental disorders, suicide, and opioids has, as yet, been the subject of limited research, a recent study that utilized data available from 18 states participating in the National Violent Death Reporting System provides what is probably the best information we have with regard to the relationship between these factors.

The study examined suicides, defined as deaths resulting from the intentional use of force against oneself, between 2003 and 2014. Of 123,181 suicides, 10,789 (8.8%) had evidence of chronic pain with the most common conditions being back pain (22.65%), cancer (12.5%), and arthritis (7.9%). Just over half (51.7%) of those with chronic pain had a mental health problem. Of these, 81.9% had a diagnosis of depression. On average, suicides associated with chronic pain were more likely to occur in older people with the highest incidence among those aged 80 years or older.

As with suicides in persons without chronic pain, the most common method of suicide was by firearms among persons with pain. While only 18.8% of suicides without a history of pain tested positive for opioids, 51.9% of those with pain tested positive. Opioid overdoses were reported to be the cause of death in 16.2% of persons with pain and was the second most frequent method of suicide among this group; it was the cause of death in only 3.9% of suicides when pain was not present.

With regard to other medications, one finding was of special importance. Of the suicides with a history of pain, 47.2% tested positive for benzodiazepines. We have known for years that benzodiazepines are generally contraindicated for persons with chronic pain as extended use can cause hyperalgesia where there is a lowering of the pain threshold and a resulting worsening of pain. Moreover, benzodiazepines are involved in more than 30% of opioid overdose deaths.

 Finally, because benzodiazepines can interfere with the analgesia provided by opioids, it is pointless to prescribe these two classes of drugs simultaneously, although many doctors still continue to do so.

Anyone who has treated patients who have survived suicide is aware that the reasons for making these attempts are usually complex without any one factor being the cause. More than half (64.7%) of suicide notes left behind by those who have a history of pain indicate that a pain condition or the pain itself played a role in the decision to commit suicide.4 An especially interesting finding in the study was that although increases in the availability of prescription opioids and of the more-deadly illicit opioids have frequently been cited as major causes of the rising suicide rates in the US, the number of people with chronic pain who died by opioid overdoses remained approximately the same over the 12-year period studied.

An earlier study found that among patients with chronic pain, those taking higher doses of opioids were at greater risk of death by suicide, which suggests that this is another factor that needs to be considered in assessing suicide risk.

One commonly reported concern about the risk for suicide is that it is likely to increase in patients with chronic pain who have been prescribed opioids that doctors have sought to discontinue. However, another recent study suggests that this may not be true.

 Utilizing data from the Department of Veteran Affairs, the study found that when long-term opioid therapy for chronic noncancer pain was discontinued, pain intensity during the 12 months after discontinuation on average did not increase and that in some patients there was a slight improvement in pain. The authors noted, however, that there is a great deal of individual variation with regard to changes in pain intensity after discontinuation so that every patient must be carefully monitored.

So how should we apply the results of these studies in clinical practice? First of all, because chronic pain appears to be a risk factor for suicide, it is incumbent upon clinicians to carefully and continually monitor their patients with chronic pain for suicidal ideation. Unfortunately, the treatment of pain in this country still falls primarily under the specialty of anesthesiology, the practitioners of which often have little training in identifying those at risk for suicide. This is one of many reasons why psychiatrists need to be more involved in the care of patients with chronic pain.

Second, prescription of opioids to patients with chronic pain may be providing them with a way to commit suicide. This is not a reason to deny opioids to patients who may benefit from them, but it is one more reason for all physicians to be very careful when prescribing opioids. Furthermore, if opioids are prescribed, physicians bear the responsibility of monitoring patients for suicidal ideation because they may be arming patients with a method to complete suicide.

Third, based on current research, we need not fear that discontinuation of opioids in patients with chronic pain will inevitably lead to worsening of the pain and thereby increase the risk that patients will turn to suicide.

Of greatest importance, is the need to continue to improve the care patients with chronic pain receive. We know that many people with chronic pain never receive care close to anything recommended by published guidelines on the management of pain. The myth that opioids are always the most effective treatment for pain is still widespread not only among the general public but also among many physicians who prescribe these medications.

Accidental deaths from opioid overdoses may be difficult to prevent and in many cases the best we can do is to increase availability of opioid antagonists to reverse the effects of the drugs after they have been ingested. But, in those who commit suicide and especially those who do so who suffer from pain, there are many things health care professionals, and especially mental health care professionals, can and should be doing to prevent the overdoses from occurring in the first place.

I want to raise an issue with Dr. King's article Opioids, Suicide, Mental Disorders, and Pain. (Psychiatric Times Nov 2018 vol. XXXV. No. 11). In the article he makes the statement: "Finally, because benzodiazepines can interfere with the analgesia provided by opioids, it is pointless to prescribe these two classes of drugs simultaneously, although many doctors still continue to do so." The reference he gives for this is: Association between concurrent use of prescription opioids and benzodiazepines: retrospective analysis BMJ 2017; 356:j760.

However, that article has nothing to do with the pharmacologic effect of benzodiazepines on opioid analgesia. In fact, a search of PubMed for the effect of benzodiazepines on opioid analgesia yields only one article that gives very weak indirect support for the assertion that benzodiazepines "interfere with the analgesia provided by opioids."
	Benzodiazepine mediated antagonism of opioid analgesia.
	Gear RW, et. al. Pain. 1997 May;71(1):25-9. 

Other RTCs that study benzodiazepines and analgesia yield mixed results with some finding that benzodiazepine reduce pain and none finding an interference with opioid analgesia. For a sampling see:
	 
	Lorazepam as an adjunct to opioid analgesics in the treatment of burn pain.  Patterson DR, et. al. Pain. 1997 Sep;72(3):367-74.

Comparison of a morphine and midazolam combination with morphine alone for paediatric displaced fractures: a randomized study.  Wille-Ledon C et.al. Acta Paediatr. 2011 Nov;100(11):e203-7.

While many deaths due to opioid overdoses are accidental, there a growing body of evidence that some cases were intentional and that the presence of pain played a role in the decision to end life.

Author | Steven A. King, MD, MS