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 We included previously unpublished data obtained from primary trials.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
New research from the BC Centre on Substance Use (BCCSU) suggests applying easy and effective tool to identify patients at high risk of going into withdrawal, in efforts to modernize alcohol detox. In a study published in the August issue of the peer-reviewed Journal of American Medical Association, BCCSU researchers used data from approximately 71,295 persons taking part in 14 scientific studies to predict which patient will develop serious complications, including seizures and delirium.
Which patient will go into severe alcohol withdrawal?
From the press release by British Columbia Centre on Substance Use (Aug 28, 2018):
(Text taken from http://www.bccsu.ca/news-releases/)
From: Will This Hospitalized Patient develop Severe Alcohol Withdrawal Syndrome?: The Rational Clinical Examination Systematic Review. JAMA (In Press) JAMA Network: jama.jamanetwork.com
If you’re interested in alcohol, read more about my alcohol research here.
For more information about the study or to schedule an interview, please contact:
Kevin Hollett, BC Centre on Substance Use
Systematic reviews are the cream of the research crop. Those who understand their value thrive at an opportunity to meet the review authors at scientific conferences. This year, the annual meeting of the College on Problems of Drug Dependence (CPDD) in San Diego featured several important reviews. Here’s a listing of all the posters presenting reviews from the session on Wednesday, June 13th, 2018.
Non-fatal overdose prevalence among people who inject drugs Samantha Colledge (June 11, 2018);
Prescription drug monitoring programs on nonfatal and fatal drug overdoses David Fink;
Limited inclusion of women in functional neuroimaging studies of opioid-use disorder Hestia Moningka;
Women’s prescription drug misuse Bridgette Peteet;
Gender differences in HIV, anti-HCV and HBsAg prevalence among people who inject Janni Leung;
Case for hospital teams in treatment of opioid use disorders Kelsey Priest;
Addiction-related characteristics of substances users in harm reduction settings Charlotte Kervran;
STDs and injecting
Extremely low HIV incidence among PWID: Terminology, high/middle income settings, methodology, and addressing new outbreaks Don Des Jarlais;
Use of opioids and stimulants by people who inject drugs Amy Peacock;
Factors associated with uptake or willingness to use pre-exposure prophylaxis (PrEP) among people who inject drugs Yohansa Fernández;
Pre-exposure prophylaxis (PrEP) for people who inject drugs? Angela Bazzi;
Cannabis and cannabinoids for the treatment of people with chronic non-cancer pain conditions Emily Stockings;
Medical marijuana laws and adolescent marijuana use in the US Aaron Sarvet;
Does liberalization of cannabis policy influence adolescents’ levels of use? Maria Melchior;
Clinical and toxicological profile of NBOMESs Nino Marchi;
Sensation-seeking personality trait and its association to drug seeking behavior in adolescents Thiago Fidalgo.
Systematic reviews cream of the crop from Brazil through Egypt
NIDA International poster session on Monday, June 11, 2018
Three Australians, two North Americans; an Egyptian, African and Brazilian had one poster on systematic review each. Five were meta-analyses.
The Australian reviews dealt with overdose, STDs and injecting:
Nonfatal overdose prevalence among people who inject drugs S. Colledge, (UK, Australia);
Gender differences in HIV, anti-hepatitis C virus, and hepatitis B virus surface antigen prevalence among people who inject drugs J. Leung, (Australia, UK, Portugal);
Use of opioids and stimulants by people who inject drugs: A. Peacock, (Australia);
The North-Americans reviewed drug monitoring programmes:
Global review of drug-checking services 2017 L.J. Maier, (California);
Urinalysis frequency and health outcomes for persons on opioid agonist therapy: J. McEachern, (Canada);
Anger, brain stimulation and antipsychotics were reviewed too:
Anger in users of psychoactive substances H.V. Laitano, (Brazil);
Noninvasive brain stimulation in addiction medicine A. Elaghoury.(Egypt);
Atypical versus typical antipsychotics for the treatment of addiction: S. Hanu. (Ghana).
With the increasing demands on scientists’ workloads, systematic reviews are an effective way of staying up to date with the most recent developments in the field. See also my previous blog posts about CPDD from the previous years:
What is the state of the art in addiction research? How do we measure recovery? These, and other questions dominated presentations on systematic reviews of literature at the 2nd European conference on addictive behaviours and dependencies on October 24-26th, 2017, in Lisbon.
This post outlines the many presentations.
Systematic reviews at Lisbon 2017:
– Which individual, social and environmental influences shape different pathways of amphetamine type stimulant use over the life course? A systematic review and thematic synthesis of the qualitative literature. Amy O´Donnell and Michelle Addison, United Kingdom
– Determining the efficacy of an intervention to reduce IPV perpetration by men who misuse substances: a systematic review and meta-analysis. Gail Gilchrist, United Kingdom
– Drug use and infectious diseases: reviewing the evidence; Sarah Larney, Australia
Paper session 16
− Injecting and sexual risk-taking amongst people who inject drugs: a global review. Amy Peacock, Australia
− Needle syringe programmes and opioid substitution therapy for prevention HCV transmission among people who inject drugs: Cochrane systematic review. Matthew Hickman, United Kingdom
− Recent incarceration and risk of hepatitis C and HIV transmission amongst people who inject drugs: a systematic review and meta-analysis. Jack Stone, United Kingdom
− A systematic review and meta-analysis of psychosocial interventions to reduce drug and sexual blood borne virus risk behaviours among people who inject drugs. Gail Gilchrist, United Kingdom
− HIV prevention, treatment and care for people who inject drugs: a systematic review of coverage of interventions. Sarah Larney, Australia
– Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. Marica Ferri, EMCDDA
– What is the base for evidence-based treatment of opioid dependence? A systematic review of outcomes from longitudinal observational studies. Lucas Wiessing, EMCDDA
– Health outcomes for clients of needle and syringe programs in prisons: a systematic review. Heino Stöver, Germany
− Worldwide drug use decriminalization practices: a scoping review. Marta Pinto, Portugal
− Review of the effectiveness of treatment alternatives to incarceration for drug-involved persons. Roger Peters, United States
− Factors related to binge drinking in adolescence: integrative literature review. Tereza Barroso, Portugal
Systematic reviews posters at Lisbon 2017:
October 24th: 13:15 – 14:15 POSTER SESSIONS:
– Alcohol use disorders identification test (audit) and mortality risk in US Veterans and international population: a systematic review and meta-analysis. Sören Kuitunen-Paul, Germany
– Contingency management for drug use in treatment for opiate addiction: a systematic review and meta-analysis. Tom Ainscogh, United Kingdom
24th: 14:30 – 16:00 POSTER SESSIONS:
– A systematic review of internet addiction prevention interventions. Roman Gabrhelík, Czech Republic
October 25th: 11:00 – 12:30 POSTER SESSIONS:
– Prevalence and psychosocial predictors of performance enhancing substances use in physical activity settings: a systematic review. Ana Tavares, Portugal
October 25th: 14:30 – 16:00 POSTER SESSIONS:
– What works in the treatment of women with alcohol-use problems? Systematic review of evidence-based studies. Eva Hoch, Germany
Thank you all presenters for your reviews and conference presentations.
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.