D Dowell et al. JAMA. Published online March 15, 2016. doi:10.1001/jama.2016.1464 .
No evidence shows a long-term benefit of opioids in pain and function vs no opioids for chronic pain with outcomes examined at least 1 year later (with most placebo-controlled randomized clinical trials ≤6 weeks in duration).
Extensive evidence shows the possible harms of opioids (including opioid use disorder, overdose, and motor vehicle injury).
Extensive evidence suggests some benefits of nonpharmacologic and nonopioid pharmacologic therapy, with less harm.
CDC: “We know of no other medication routinely used for a nonfatal condition that kills patients so frequently,”
1st Six Recommendations (12 total)
1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient. If opioids are used, they should be combined with nonpharmacologic therapy and nonopioid pharmacologic therapy, as appropriate. (Recommendation category: A; evidence type: 3)
2. Before starting opioid therapy for chronic pain, clinicians should establish treatment goals with all patients, including realistic goals for pain and function, and consider how opioid therapy will be discontinued if benefits do not outweigh risks. Clinicians should continue opioid therapy only if there is clinically meaningful improvement in pain and function that outweighs risks to patient safety. (Recommendation category: A; evidence type: 4)
3. Before starting and periodically during opioid therapy, clinicians should discuss with patients known risks and realistic benefits of opioid therapy and patient and clinician responsibilities for managing therapy. (Recommendation category: A; evidence type: 3)
4. When starting opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release/long-acting (ER/LA) opioids. (Recommendation category: A; evidence type: 4)
5. When opioids are started, clinicians should prescribe the lowest effective dosage. (Recommendation category: A; evidence type: 3)
6. Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids and should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids. Three days or less will often be sufficient; more than 7 days will rarely be needed. (Recommendation category: A; evidence type: 4)
- Avoid concurrent benzodiazepines
- Review state prescription drug monitoring program to look for dangerous combination therapies and prior opiod dosing
- Consider risk mitigation strategies (eg. naloxone)
- Suggests urine screening at start to screen for illicit substance abuse which increases risk
USAToday’s review of these guidelines: CDC issues new guideline on opiods
Bottomline: This report is very important for those who prescribe opiods for chronic pain.
Almost all physicians use opiods in their practice and need to keep up with the challenges of pain management and addiction. An update on the problem of non-medical opiod use and heroin addiction from NEJM:
Full article link: Relationship between Nonmedical Prescription-Opiod Use and Heroin Use
The transition from nonmedical use of prescription opioids to heroin use appears to be part of the progression of addiction in a subgroup of nonmedical users of prescription opioids, primarily among persons with frequent nonmedical use and those with prescription opioid abuse or dependence. Although some authors suggest that there is an association between policy-driven reductions in the availability of prescription opioids and increases in the rates of heroin use,16,18 the timing of these shifts, many of which began before policies were robustly implemented, makes a causal link unlikely…
In the majority of studies, the increase in the rates of heroin use preceded changes in prescription-opioid policies, and there is no consistent evidence of an association between the implementation of policies related to prescription opioids and increases in the rates of heroin use or deaths, although the data are relatively sparse. Alternatively, heroin market forces, including increased accessibility, reduced price, and high purity of heroin appear to be major drivers of the recent increases in rates of heroin use…
Fundamentally, prescription opioids and heroin are each elements of a larger epidemic of opioid-related disorders and death. Viewing them from a unified perspective is essential to improving public health. The perniciousness of this epidemic requires a multipronged interventional approach that engages all sectors of society.
Related blog posts:
- Deadly consequences of pain management | gutsandgrowth
- Increased Narcotic Usage in Pediatric Patients with IBD …
- Epidemic of Prescription Drug Overdoses | gutsandgrowth
1. A retrospective study (Inflamm Bowel Dis 2014; 20: 2292-98) of 217 patients with inflammatory bowel disease(108 infliximab-treated, 109 adalimumab-treated) provides data which indicates that combination therapy (mainly with thiopurines) resulted in higher trough levels and lower antibodies to infliximab (ATI) than monotherapy in patients treated with infliximab (IFX). This was not evident in the adalimumab (ADA)-treated patients. Overall, approximately 90% of study population had Crohn’s disease.
Key points from this study:
- The majority of trough level/antidrug antibody levels were drawn due to loss of response. This is a major limitation of this study.
- Among IFX-treated patients, those with combination therapy had trough level of 7.5 mcg/mL compared with 4.6 mcg/mL. In combination therapy patients, the incidence of ATIs was 5.7% compared with 29.8% in monotherapy patients.
- According to this study, the dose of the immunomodulator (IM) did not significantly influence the infliximab trough level or antibody formation; that is, more than half of patients were receiving “suboptimal dosed IM” and their infliximab levels/ATIs were similar to those who were optimally-dosed.
- Among those who were receiving combination therapy, the incidence of antibody formation was lower in IFX-treated patients who started IM concurrently with IFX compared with those in which IM was added subsequently.
- There were many other limitations in this study, including the finding that 94% of monotherapy patients had received previous immunomodulator therapy.
Bottomline: This study suggests that combination therapy is beneficial for patients receiving infliximab (in agreement with the previous SONIC study) and may not be beneficial for patients receiving adalimumab; however, only a well-designed prospective study
2. Inflamm Bowel Dis 2014; 20: 2266-70. This study with 749 patients from Sweden showed that a large number of inflammatory bowel disease patients did not receive with iron supplementation: “Only 46% of patients with anemia were treated with iron supplementation or blood transfusion.” This study showed frequent persistence of anemia one year after diagnosis, especially in children. At time of diagnosis, 55% of children and 27% of adults had anemia and 28% and 16% at one year followup, respectively.
My take: Treatment of the underlying IBD, often helps anemia. However, in some patients treating the anemia with iron may help improve symptoms as much or more than other aspects of treatment.
3. Inflamm Bowel Dis 2014; 20: 2433-49. Reviews pain management approaches for patients with IBD. The article emphasizes how pain can be multifactoral and that opiod-induced hyperalgesia may worsen pain.
Related blog posts:
- Monotherapy or Combination Therapy with Adalimumab …
- More Lessons in TNF Therapy (Part 1) | gutsandgrowth
- More Lessons in TNF Therapy (Part 2) | gutsandgrowth
- Durability of Infliximab in Pediatric Crohn’s Disease …
- Microcytic Anemia Review | gutsandgrowth
- Inadequate treatment of anemia in IBD | gutsandgrowth
- Pain changes brain | gutsandgrowth
A big part of a pediatric gastroenterologist’s daily practice is trying to help patients with recurrent abdominal pain. The goals are to determine the reason for the pain and then to offer the best therapy. In many cases, these goals can be quite difficult. With regard to diagnosis, the majority of patients have ‘functional’ pain and the diagnosis is in part a diagnosis of exclusion, trying to rule out other potential etiologies. With regard to treatment, this is also difficult.
Narcotics are not often given for pediatric abdominal pain, but are used under certain circumstances. These medications can have unintended consequences. One consequence of frequent narcotic usage is that individuals may tolerate pain more poorly after receiving narcotics. A useful review of narcotic overuse was published in the New England Journal of Medicine in 2010. (NEJM 2010; 363: 1981).
“Deaths from unintentional drug overdoses in the United States have been rising steeply since the early 1990s …and are the second-leading cause of accidental death, with 27,658 such deaths recorded in 2007.” 11,499 of the deaths in 2007 were due to unintentional narcotic overdose. In comparison, in the same year, there were about 6,000 deaths from cocaine & 2,000 deaths from heroin.
Besides the number of deaths, the other alarming factor has been a sharp rise (10-fold since 1990) in the usage of narcotics in the past two decades. One of the factors driving this increase has been a compassionate interest in relieving pain. The availability of these drugs throughout the country even in remote regions allows these abusable drugs to be more accessible than illicit drugs like cocaine and heroin. While the availability of these medications may increase the rates of suicide, most opioid-overdose deaths are tragic accidents. Often, laboratory tests identify one or more substances in addition to the opioid, indicating that the depressant effects of alcohol or other drugs were additive in causing death.
With regard to gastroenterology/pediatric gastroenterology, another important aspect of narcotics use is the association of increased mortality risk with inflammatory bowel disease. This has been shown by analyzing a registry for infliximab (IFX) (Lichtenstein G, DDW 2010, abstracts#T1039 & T1040.). In the TREAT registry with 6273 patients (3334 treated with IFX), the only risk factors for increased mortality/increased infections were steroids and narcotics. This study also showed that IFX did not increase mortality, serious infections, malignancy or lymphoma in this cohort.
Clin Gastro & Hep 2008; 6: 978. Refractory abdominal pain review. ‘Narcotics over time increase frequency, duration and intensity of pain.’ Practical recommendations:
treat constipation, withdraw narcotics, consider mental health (CBT/hypnosis/psychotherapy/stress mgt), and possible TCA or SNRI therapy.