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 We included previously unpublished data obtained from primary trials.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
Updating Cochrane systematic reviews makes them most useful and fresh for readers. We updated our review on concurrent alcohol and drug problems again.
Which new studies we found?
We found seven studies that examined 825 people with drug problems. Six of the studies were funded by the National Institutes for Health or by the Health Research Board; one study did not report its funding source.
One study focused on the way people think and act versus an approach based on Alcoholics Anonymous. It aimed to motivate the person to develop a desire to stop using drugs or alcohol.
Three studies looked at a counselling style for helping people to explore and resolve doubts about changing their behaviour (group, individual and intensive formats). Their controls were education, or less intensive counselling, or assessment-only.
Two Irish studies and one Swiss study looked at practices that aimed to identify an alcohol problem and motivate the person to do something about it versus usual treatment.
This study has been made into a podcast available at Cochrane.org news item at https://www.cochrane.org/news/podcast-which-talking-therapies-work-people-who-use-drugs-and-also-have-alcohol-problems
and a Network news item https://mhn.cochrane.org/news/podcast-which-talking-therapies-work-people-who-use-drugs-and-also-have-alcohol-problems Listen to the podcast below:
Updating Cochrane Review – Key results
The Swiss and Irish studies were directly compared. They took place in general practices (one trial) or methadone clinics (two trials). They included 170 participants with a mean age of 37 years. All participants had positive alcohol screening test upon entry to the trial. At the end, the scores between groups were similar (average difference in scores: -0.6, 1.7 and -2, respectively).
One study found that a brief motivational intervention led to a reduction of alcohol use (by seven or more days in the past month at 6 months).
It remains uncertain whether talking therapies affect drinking and drug-using in people who have problems with both alcohol and other drugs. We lack high quality studies.
Cited cochrane review: Klimas J, Fairgrieve C, Tobin H, Field C-A, O’Gorman CSM, Glynn LG, Keenan E, Saunders J, Bury G, Dunne C, Cullen W. Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users. Cochrane Database of Systematic Reviews 2018, Issue 11
Read a summary of the previous version of this review here
Diagnosing opioid addiction in people with chronic pain requires a fully validated alternative to DSM-5.
Over the past two decades, a steep rise in the number of opioids dispensed for pain treatment has been accompanied by a dramatic rise in overdose deaths in the United States. In 2016, up to 32 000 deaths reportedly involved prescription opioids. Besides that, the economic burden of prescription opioid overdose exceeds $78bn (£59bn; €67bn) annually.
Despite all the evidence of harm, it remains unclear exactly how to determine if a patient with chronic pain has opioid addiction. What criteria should serve as a gold standard in making a diagnosis of opioid use disorder (OUD) in this context? This is an important gap in the literature. It hinders both evidence based care and research on the links between prescription opioids and OUD. Therefore, we discuss the limitations of diagnosing OUD in people with chronic pain, and make several recommendations for further research.
Diagnosing opioid addiction in people with chronic pain
The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) provides a widely used set of diagnostic criteria for OUD. But these criteria do not always apply to patients who are prescribed opioids for chronic pain. According to DSM-5, if a patient presents with 2 out of 9 specific symptoms, it may indicate …
Diagnosing opioid addiction in people with chronic pain
Will an increasing pressure on prescribers curb the rising opioid overdose rates?
With only 0.5% of patients prescribed opioids reportedly developing addictions, there must be something else going on that’s making people overdose. A mismatch. Research on this topic is messy and patchy–– simply put, the large correlational research and incidence studies of addiction do not match up. In a recent commentary, we outline how prescription opioids might indirectly influence the rising overdose and addiction rates.
Mismatch: Why Correlation and Incidence Might Not Match Up
First, diversion gets medically prescribed opioids (MPOs) to those who are not prescribed the medication. Diverted MPOs can be sold, gifted (mostly to family members or friends), stolen, or sometimes obtained through “doctor shopping”, where patients get the same prescription from multiple physicians. But we don’t know how much diversion is due to sold, gifted or stolen medicines. How much do the different diversion types contribute to addiction and overdose? And for that matter, how much is diversion occurring, and to what extent is it contributing to national opioid crises?
Second, because overdose is often preceded by addiction, many researchers have focused on the persons who develop an addiction when prescribed opioids. However, if addiction doesn’t come before overdose, some high-risk patients go unstudied, and thus unreported. This has been shown in some states, such as West Virginia, where prescription opioids contributed to 93% of overdose deaths and very few of the deceased had iatrogenic addiction. So, some people might be at risk of sudden overdose but are missed in research studies that focus on medical diagnoses of addiction. This gap in the research is likely due the difficulty of studying overdose risk without the presence of addiction.
Polydrug use and overdose
Third, polydrug use may lead to overdose in people who use prescription opioids but do not specifically have addiction to their MPO. Here benzodiazepines are a big issue. It is important to note that many studies of addiction to MPOs do account for polydrug use by incorporating urine drug screens; however, positive results are often lumped together with other “aberrant” behaviours such as failed pill counts or requesting opioids from multiple doctors. Ultimately, we can’t tell how much polydrug use is really leading to addiction or overdose in this context.
Finally, it is possible that incidence studies to date could be misrepresenting the true risk of addiction to MPOs. Studies of OUD incidence in pain care use definitions of addiction that range from very broad to highly specific, mixing up terms like “dependence”, “abuse”, “misuse”, or “problematic use”. This could make it so our guesses about the risk of addiction to MPOs are muddled, leading to skewed results.
We need to understand better if reduced opioid prescriptions can reduce the opioid crisis. Then we can make the change happen.
To read the whole commentary, please visit the journal website www.canadianjournalofaddiction.org or lookup the paper using the following citation:
Gorfinkel, L., Wood, E., Klimas, J. (In Press) Prescription opioids, opioid use disorder, and Overdose Crisis: Current Dilemmas and Remaining Questions. (Published ahead of Print, June 4th) Canadian Journal on Addiction
I thank Lauren Gorfinkel for feedback on this post.
If you enjoyed reading this post, you may also like my poem about pain. See link below:
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.