How many of you had a flu this winter? Anyone took antibiotics for that? But some people can’t take them because they are allergic. Now, imagine someone suffering from pain, being prescribed opioids and having a negative reaction to them. What if this reaction was addiction to opioids? What if we could measure the risk for addiction the same way we can measure allergy to antibiotics? This article describes why opioid addiction is not an allergy to opioids and that we should not think about it that way, nor try to measure it using opioid risk tools.
We wanted to find out whether we can tell which adult will go into opioid addiction when prescribed opioids for pain. Why? Prescription opioid addiction can have devastating consequences but it is not clear how to identify patients with pain among whom prescription opioids can be safely prescribed.
The Journal of the American Medical Association – JAMA Network Open – commissioned us to do a very special kind of review that is called Diagnostic Accuracy Review. For this study, we chose only the best studies. To illustrate diagnostic performance, data from higher quality studies were extracted and used to calculate likelihood ratios (LR). What are likelihood ratios? Likelihood Ratios bigger than 1 increase the probability of a disease. Likelihood ratio of 1 equals roughly zero increase. Likelihood of 2 equals just about 15% increase.
Opioid Risk Tools
The opioid risk screening tools that are in widespread use are based on low quality studies and are not helpful in identifying patients at higher risk. Among them, the pain medication questionnaire had likelihood ratio of 2.6 (slight increase in likelihood, about 15%). Some risk factors were found in a single high quality study:
A history of opioid or non-opioid use disorder, a mental health diagnosis and concomitant prescription of certain psychiatric medications may increase the risk of prescription opioid addiction.
However, only the absence of a mood disorder appeared useful for identifying lower risk patients (and assessment tools incorporating combinations of patient characteristics and risk factors were not useful).
There are few valid ways to identify patients who can be safely prescribed opioid analgesics. Given the lack of good tools and the mounting evidence that opioids are not effective for chronic pain, such as the recent JAMA trial called Space, prescribers should be aware of tools’ limitations when prescribing opioids for pain. Opioid addiction is not an allergic reaction. Don’t try to measure risk for it and whether it’s safe to prescribe. De-implement opioid risk tools!
|Reference: Klimas, J., Gorfinkel, L., Fairbairn, N., Amato, L., Ahamad, K., Nolan, S., Simel, D., Wood, E. (2019) Strategies to identify patient risks of prescription opioid addiction when initiating opioids for pain: A Systematic review. JAMA Network Open. 2(5):e193365. Doi: 10.1001/jamanetworkopen.2019.3365|
If you enjoyed reading this article, you may also wish reading the article about diagnosing opioid use disorder link here
Looking at an old drug repurposed to treat opioid addiction, a new study found long-acting formulation of morphine (SROM) promising for curbing the opioid epidemic.
Many people who overdose on fentanyl have untreated opioid addiction. Left untreated, opioid addiction can have devastating consequences. One of the reasons for the low treatment rates is that current medications have limited ability to retain people in treatment. The Canadian National Guideline for the Clinical Management of Opioid Use Disorder recommends treatment with slow-release oral morphine, also known as SROM—prescribed as a third line of therapy. In this study, we wanted to compare Kadian® and Methadone for the treatment of opioid use disorder.
|QUICK FACT: Slow release oral morphine (SROM) is given once daily and has been proposed for people who do not tolerate or respond to methadone.|
We looked at the scientific literature up until the May of 2018. Then, we wanted to see if SROM (brand name Kadian®) works as well as methadone in the treatment of opioid use disorder. In the study, we included people of any gender, age or ethnicity.
What did the study find?
We found four unique clinical trials that met inclusion criteria (n = 471), and compared Kadian® with methadone. Meta-analysis of existing clinical trials suggests SROM (slow release oral morphine) may be as effective in retaining patients in treatment and reducing heroin use.
This is the first meta-analysis of slow release oral morphine (Kadian®). We included new studies that increase the validity of the study. We included previously unpublished data obtained from primary trials. A pooling of data for craving and adverse events was not possible due to inconsistent reporting of outcome measures across trials
SROM seems as good as methadone for the treatment of opioid use disorder but retains people in treatment longer.
Why is SROM important?
While methadone is effective for many patients, these findings suggest SROM may provide benefits in addressing some of the limitations of methadone. We need to expand uptake and retention of people on opioid use disorder treatments. These data should compel public health agencies and decision makers to find therapeutic tools for people who have opioid addiction.
We are running out of options for helping people overcome opioid addiction and abandon contaminated fentanyl. But revisiting this medication, known from cancer treatment, can have a dramatic impact on addiction treatment success because it is not only equally effective as the current treatment options but also better tolerated by patients. Expanding treatment options responds to patients’ needs by offering drugs with fewer side effects.
Kadian® slow-release oral morphine is available in 10mg, 20mg, 50mg, and 100mg capsules, which may be combined as necessary.
|Reference: Klimas, J., Gorfinkel, L., Giacomuzzi, S., Ruckes, C., Socias, E.M., Fairbairn, N., Wood, E. (2019) Slow Release Oral Morphine versus Methadone for the Treatment of Opioid Use Disorder: A Systematic Review and Meta-Analysis. BMJ Open (In Press) 0:e025799. doi:10.1136/bmjopen-2018-025799|
If you enjoyed reading this blog, you may also enjoy reading about a medication for treatment of stimulant use disorder. Link here
In a talk at the 2017 National Institute of Drug Abuse meeting on June 17th, Dr Evan Wood pondered lessons learned and success tips derived from his team’s experiences of building an International centre on substance use. The key ingredients in the recipe for success of research centre on substance use were:
Emphasize research productivity. Integrate educational opportunities and mentorship at every step. Use interdisciplinary approach wherever possible. Integrate research alongside clinical care.
From AIDS to opioids
Historically, the new BC Centre on Substance Use grew out of HIV research centre for excellence. The emergence of powder cocaine in 1990’s led to an HIV outbreak in needle exchange when it was believed to be under control. This helped the team to make a compelling case about their unique situation for funders like the National Institute for Drug Abuse. Next, a centralized database of people treated on anti-retroviral treatment (ART) contains all data on everybody living with HIV in the province. This database enables longitudinal survival analysis of HIV outcomes. Using this data, another prospective cohort study of injecting drug users has demonstrated how the viral load went down between 1996-2004. Furthermore, the first supervised injection facility in North America – Insight – has led to about a dozen of supervised injecting facilities in the area nowadays. In sum, the evolution of the centre from HIV treatment to HIV prevention and now to addiction treatment (because of the population of study) is a result of concentrated efforts by researchers, providers and the community.
The centre’s mission is to provide provincial leadership in substance use and addiction research, education and clinical care guidance and to seamlessly integrate these pillars to help shape a comprehensive, connected system of treatment and care that reaches all British Columbians. (taken from www.bccsu.ca)
International sites with rapidly evolving HIV epidemics in patients with substance use disorder present an opportunity for rapid scale-up of interventions once proven efficacious with a promise of large public health impact (text taken from www.drugabuse.gov). The three speakers in this session moderated by Petra Jacobs, entitled “Research on HIV and Substance Use Disorder: International Perspectives,” including Drs Wood and Korthuis, have presented several research projects supported by NIDA and other institutions. I have attended the session. The discussant, Dr Metzger, closed the session with concluding remarks.
Against the use of opioids for chronic non-cancer pain to people who have active substance use disorders advises the third recommendation in the new opioid therapy guidelines (May 8th, 2017).
However, this “strong” recommendation is based on low quality of evidence from studies that rarely involve people with active substance use disorders (SUD).
Here, we first highlight the main caveats in the research of pain treatment among people with SUDs, why this has been the case and then we offer potential solutions for overcoming the obstacles in clinical research and policy.
Most clinical trials of pain medications exclude people with SUDs. Denying treatment of pain with opioids to people with active SUDs in the absence of evidence, based on a presumed potential for “more” addiction and documented adverse side effects (overdose), is cautious. However, it is also likely influenced by stereotypes and stigma towards people who use drugs and it further discriminates people with SUDs. Instead of stigma, the society should seek better ways of increasing rapid access to evidence-based opioid agonist therapy for prescription opioid use disorders (see Ahamad & Socias, 2016).
Moreover, this approach can lead to unanticipated consequences, such as seeking illicit drugs (see Voon et al, 2015). It is clear that we need more research to better understand pain treatment among people with SUDs and to give better recommendations to clinicians. But what kind of further research? Firstly, we need clinical trials that specifically include people with SUDs, such as people receiving opioid agonist treatment (Ti et al., 2015). If trialists refuse to include people with pain and concurrent SUDs into pain trials, presumably because of their high-risk for more SUDs, this obstacle can be overcome by including a standardized measure of pain, like the VAS, into every pharmacotherapy trial of SUD treatment.
Which pain patient treated with opioids will develop opioid use disorder?
Secondly, we still don’t know which pain patient treated with opioids will develop opioid use disorder (OUD). Despite the typical occurrence of OUDs among approximately 5.5% of the study populations in pain trials, there is no evidence for a reliable predictor of who will develop OUD. We need to find valid risk indicators.
Finally, the current opioid overdose crisis in many countries is primarily driven by not-as-prescribed-use of fentanyl – an anesthetic used to tranquilize elephants. What if people with opioid use disorders self-medicated their pain with fentanyl (see Voon et al., 2015)? What if their pain, both emotional and physical, was as big as elephants and we had nothing for them? What we offer to them is suspicion, exclusion, denial and mistrust. We should offer compassion and fairness.
- Busse, J. W., et al. (2017). “Guideline for opioid therapy and chronic noncancer pain.” Canadian Medical Association Journal 189(18): E659-E666.
- Socias, M. E. and K. Ahamad (2016). “An urgent call to increase access to evidence-based opioid agonist therapy for prescription opioid use disorders.” Canadian Medical Association Journal 188(17/18): 1208.
- Ti, L., et al. (2015). “Denial of pain medication by health care providers predicts in-hospital illicit drug use among individuals who use illicit drugs.” Pain Research & Management 20(2): 84-88.
- Voon, P., et al. (2015). “Pain among high-risk patients on methadone maintenance treatment.” The journal of pain 16(9): 887-894.