Editor’s Note: As part of its effort to facilitate responsible opioid prescribing, the American Academy of Addiction Psychiatry(AAAP) hosts a listserv where clinicians can submit clinical questions and receive responses from a rotating panel of pain experts. In conjunction with the AAAP selected 10 of the most common questions or topics related to opioid use that have been submitted, and asked Charles E. Argoff, MD, Director of the Comprehensive Pain Management Center at Albany Medical Center, and Roger Chou, MD, Professor of Medicine and Medical Informatics & Clinical Epidemiology at Oregon Health & Science University in Portland, to provide responses. For additional resources on appropriate opioid prescribing and opioid addiction treatment, please see the AAAP’s PCSS-O and PCSS-MAT programs, which provide guidance on the safe and effective use of opioid medications and on the treatment of opioid addiction.
The Genetic Risk for Substance Abuse
What is known about the genetic risk for substance abuse, and is there a statistical risk calculator for abuse that is based on a patient’s family history?
Dr. Chou: Unfortunately, there is no simple estimate for risk for substance abuse based on genetics or family history. Twin studies suggest that the degree of heritability of addictive disorders ranges somewhere between 40% and 70%, depending on the substance being evaluated. The risk appears to be higher with first-degree relative than more distant relatives, but I am not aware of consistent or reliable estimates of the degree of risk with more distant relatives.
In addition, there is no simple mendelian inheritance pattern with addiction, and it is likely that the genetic relationships are complex. The risk for substance abuse is also dependent on environmental (eg, exposure) and other factors.
The bottom line is that in a patient being considered for opioids, a personal history of substance abuse is the strongest risk factor for future abuse, and a family history is also an important risk factor, though to a lesser degree.
Dr. Argoff: Although there is no simple answer to this question, at least one of the tools currently available to screen for risk for opioid misuse and abuse, the Opioid Risk Tool, incorporates family as well as personal history of substance abuse into risk stratification.
Risk Factors and Impact on Driving
What patient and treatment factors contribute to opioid use disorders?
Dr. Chou: The strongest risk factor for opioid use is a personal history of opioid use or other substance abuse. A family history of substance abuse is another important risk factor. Depression and other psychological comorbidities are another risk factor, as are age between 20 and 40 years in some studies and a history of preadolescent sexual abuse in women. Somatization is a risk factor in some studies.
In terms of treatment factors, there is no clear association between risk for abuse and use of short- vs long-acting opioids, specific opioid, or dose — though there does appear to be a dose-dependent association with risk for accidental overdose.
What is the impact of opioids on cognition and driving?
Dr. Chou: Opioids can slow cognition and decrease reflexes and concentration, particularly when first started and when changing doses. However, some studies of simulated driving tests indicate no impaired driving ability in persons who have been on stable doses of opioids. Similarly, studies suggest no clear increased risk for motor vehicle accidents in patients on chronic, stable doses of opioids. Patients should be counseled about the potential effects of opioids on cognition and driving or work safety, the importance of not driving when feeling impaired, the need to avoid other substances and drugs that can affect cognition and driving safety, and to avoid driving when starting opioids or changing doses.
Short- or Long-Acting Opioids?
Should short-acting or long-acting opioids be used chronically for chronic pain?
Dr. Chou: Although long-acting, round-the-clock opioids have often been suggested for treatment of chronic pain, there is no evidence that they are superior to short-acting or as-needed dosing. Potential benefits of long-acting, round-the-clock opioids are fewer peaks and troughs that in theory might increase the risk for addiction or withdrawal, and more sustained pain control. However, long-acting, round-the-clock opioids also are likely to induce tolerance and probably have contributed to the trends toward use of higher doses. No study has shown that long-acting opioids are safer than short-acting opioids or more effective for pain relief.
The bottom line is that it’s probably OK to use either; if a patient is doing fine on a short-acting opioid, there is no compelling reason to switch him or her to a long-acting opioid, and vice versa.
Dr. Argoff: Despite their use and claims of the benefits of long-acting opioids, not a single published study has demonstrated that patients with chronic pain experience greater relief with long-acting opioids compared with short-acting. In fact, at least one head-to-head study demonstrated the opposite conclusion. Each of these broad types of opioid therapies may play a role in the successful management of a specific person’s specific chronic painful condition. We need to work with a patient to understand what regimen may be optimal for that person.
The Efficacy of Long-term Opioids
Is there evidence to support the efficacy of long-term opioids for chronic pain?
Dr. Chou: Evidence to support the efficacy of long-term opioids for chronic pain is extremely limited. No randomized trial of opioids vs placebo has treated patients for more than six months, and most treated patients for fewer than six weeks. In a Cochrane review,there were very limited data from uncontrolled studies (eg, studies of patients originally randomly assigned to receive opioids in a clinical trial and then followed after the trial ended) that some proportion of patients do continue opioids long-term and report continued pain relief, although significant proportions also discontinued owing to adverse effects or lack of efficacy. Clearly, more long-term controlled studies are needed to understand efficacy of long-term opioids vs alternative therapies (placebo, no opioid, and nonopioid alternatives).
Dr. Argoff: I disagree to some extent with Dr. Chou. Population-based controlled studies, by their design, ignore an individual’s response. This is an important omission if we want to know how often an individual does well on opioid therapy for one, two, or more years and how often an individual does not. We need to design a more clinically relevant approach to studying this important matter.
The Evidence for Multimodal Therapy
What is the evidence to support multimodal treatment of pain?
Dr. Chou: For functionally disabling chronic pain, interdisciplinary rehabilitation — a type of multimodal treatment that typically incorporates supervised physical therapy and psychological therapies (eg, cognitive-behavioral therapy) as well as other modalities in an integrated fashion — has been shown in randomized trials to be more effective than single-modality therapies for chronic pain. For low back pain, interdisciplinary rehabilitation has been shown to be as effective as fusion surgery for patients with nonradicular low back pain.
At the same time, there isn’t great evidence that piling on lots of interventions is a more effective or efficient strategy in most patients than using one or a few interventions, particularly in patients with acute pain. Patients more likely to benefit from multimodal therapies are those who have chronic disabling pain that has not responded to single intervention, and those who have risk factors for developing chronic disabling pain.
Dr. Argoff: Unfortunately, given all that is recommended about the multimodal treatment of pain, there is little in the way of large prospective studies regarding such an approach to report. On the other hand, there are many studies to support the observation that a single intervention for chronic pain infrequently results in complete pain relief or even significant pain relief for most of the patients exposed to that intervention.
Upping the Dose vs Combination Therapy
Physicians in my hospital often seem to add a second opioid for treating pain rather than increasing the dose of the initial opioid. Do you have any suggestions for changing this practice that makes nursing care confusing and does not seem to promote patient comfort?
Dr. Chou: This seems to be the kind of thing that could be fairly easily flagged through electronic prescription records and brought to the attention of the physicians, so that they stick with one opioid rather than more. In some cases, there may be a reason to use two opioids (eg, one long-acting and one short-acting for titration or breakthrough pain), but there aren’t too many reasons to prescribe more than one short-acting or more than one long-acting opioid.
Dr. Argoff: This is not a simple question to answer. The first step is to understand why the prescriber is adding another opioid. Whereas some patients sufficiently benefit from a single opioid, others experience optimal benefit when one particular opioid is used as a long-acting agent (eg, a fentanyl patch) and a different opioid compound is used for pain that breaks through this regimen (eg, short-acting oxycodone or oxymorphone).
There has been recent interest in the formal clinical development of a new medication that combines morphine and oxycodone in one preparation, because studies have shown that such a combination may enhance outcome; however, this preparation is not currently approved by the US Food and Drug Administration.
Buprenorphine While Breastfeeding?
I have a pregnant woman on buprenorphine who very much wants to breastfeed after delivery. Is buprenorphine safe in this scenario?
Dr. Chou: The decision to use medications while breastfeeding is an important one that women should always discuss with their physician. However, continuation of buprenorphine during breastfeeding is considered an accepted practice, owing to the low levels in breastmilk that result in low levels in the infant. Many infants born to mothers on methadone or buprenorphine will have neonatal abstinence syndrome, which may be somewhat attenuated by the small amount of buprenorphine in the breastmilk, though I am not aware of data showing that they can go home from the hospital earlier.
Avoiding Opioid-Induced Hyperalgesia
How does one avoid opioid-induced hyperalgesia (increased sensitivity to pain)?
Dr. Chou: Data to estimate the prevalence and clinical impact of hyperalgesia in humans, or how to avoid it, are quite limited. In clinical practice, it can be very difficult to distinguish hyperalgesia from tolerance. Some evidence suggests that hyperalgesia occurs at relatively high doses of opioids, and should be relatively uncommon at doses below 120 mg morphine equivalents per day. Some research suggests that blocking NMDA receptors (with such agents as dextromethorphan, ketamine, or methadone) may help prevent hyperalgesia, but a lot more research would be needed before using such drugs for these purposes could be recommended, because these come with their own potential harms.
Dr. Argoff: There are truly no good data to support or refute this entity. The quality of currently available studies regarding this matter is generally poor.
The Role of Nonphysicians
How can nonphysicians (eg, psychologists, physical therapists, pharmacists, nurses) who provide pain care to patients in the community best collaborate with physicians?
Dr. Chou: I think it’s important for nonphysicians to provide the same messages regarding the importance of self-care and activity and not to reinforce negative coping behaviors, such as fear avoidance and catastrophizing. Similarly, it’s important that physical and occupational therapists don’t overemphasize findings on imaging (eg, degenerative changes in the back) that are very common and only weakly correlated with pain — but rather stress with patients the importance of movement, and that exercise won’t further damage the back. Consistent messages will help patients move and hopefully improve in function.
It is also important for nonphysicians to communicate to physicians when they are concerned about opioid use patterns (eg, if they see that a patient has gotten refills from different providers) or if patients are not effectively engaging in care; this can help the physician in terms of shaping future care plans.
Dr. Argoff: Communication and respecting each other’s disciplines and approach to patient management are key. We (patients and providers) need to be reminded that no single treatment works for all or is likely to cure a person, and how important it is to personalize the approach to care. This last point is too often lost in today’s algorithmic approach to medical care. This gets back to communicating well with each other to help the patient move forward in his or her specific treatment plan — these can’t be “rubber-stamped” for treatment to be successful.
Finally, it helps all of us to have an understanding of what each of us is doing for the patient — how each of our interventions are likely to help the patient. For example, what is the role of opioid therapy in a multimodal approach to chronic pain management? What is the role of physical and occupational therapies, invasive pain management approaches, or cognitive-behavioral approaches? Most of us know that no one treatment usually cures a person, and it’s extremely valuable to integrate these various options seamlessly into a patient’s treatment regimen.
Dealing With Doctor-Shoppers
I am not trying to stigmatize here, but the vast majority of addicts who show up in pain clinics are not interested in recovery. They are looking for a new source of drug. These folks are easy to spot if you are seasoned; however, even tactful observations about their doctor-shopping, historical addiction, story inconsistencies, and so on are typically met with the kind of anger that comes when your cover is blown. What are your recommendations for dealing with these patients?
Dr. Argoff: This is admittedly a tough group of patients to work with. I think that it is important to keep in mind that opioids represent only one class of pharmacologic therapy for chronic pain. Not only may other nonopioid pharmacologic approaches be medically appropriate to consider for the patient with chronic pain whose other behaviors are described above, nonmedical approaches may also be considered. It important to both treat this patient humanely as suggested above, and to treat that person safely.