Category: Meta-analysis

Why most opioid risk tools fail?

ruler

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.

The Problem

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 Study

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).

Take home?

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

Diagnosing opioid addiction in people with chronic pain

As good as methadone if not better

equal

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

How can we do better job in studying Topiramate?

Will this patient go into severe alcohol withdrawal?

bottle in bag

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):

Research sheds light on how to improve diagnosis and treatment of severe alcohol withdrawal syndrome
The treatment of alcohol withdrawal urgently needs to be modernized in order to improve patient outcomes and safety and reduce health care cost, according to new research from the BC Centre on Substance Use (BCCSU).
The study, published today in the Journal of the American Medical Association, involved a multi-year systematic review involving more than 71,000 patients and sought to determine how best to identify the risks of developing severe, complicated alcohol withdrawal – a potentially life-threatening emergency. Those who consume alcohol in quantities above low-risk recommendations may develop this syndrome when they abruptly stop or substantially reduce their alcohol consumption.
Researchers found that patients are commonly over-admitted into inpatient alcohol withdrawal management care, resulting in a poor patient experience and unnecessary health care resource consumption. The review identified highly valid and easily administered screening tools to properly assess symptoms and risks before recommending acute treatment such as withdrawal management, and to look at outpatient care to improve patient outcomes and reduce the burden on the health system.
“Alcohol addiction is not only the most common substance use disorder, it’s among the most devastating in terms of both health impacts and the costs to our health system,” said Dr. Evan Wood, executive director of the BCCSU and lead author of the study. “This study demonstrates that there are more sophisticated tools that the health system should be employing to provide more appropriate care for patients, which will result not only in better outcomes but also free-up resources for high-priority needs.”
According to a study released by the University of Victoria’s Canadian Institute for Substance Use Research (CISUR) and the Canadian Centre on Substance Use and Addiction (CCSA), alcohol use costs Canadians $14.6 billion per year in health care, lost production, criminal justice, and other direct costs – higher than all other substances combined.
B.C. has the highest rate in the country of hospitalizations entirely caused by alcohol, and consumption is rising faster in the province than elsewhere in Canada. Research from the Canadian Institute for Health Information published last year found that British Columbians who use alcohol consume, on average, 9.4 litres of pure alcohol each year —  the equivalent of roughly 14 bottles of beer or two-and-half bottles of wine each week.
“Hospital wards are often filled with individuals suffering the consequences alcohol addiction,” said Dr. Keith Ahamad, a co-author on the study and Medical Director at Vancouver Coastal Health’s Regional Addiction Program. “This study helps identify those who truly need admission and demonstrates that many patients can be better treated as outpatients, even in primary care.”
The BCCSU is funded by the provincial government and is currently developing provincial guidelines for treating alcohol use disorder, expected to be released later this. They will be the first evidence-based guidelines of their kind for the province.

(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
778-918-1537
khollett[at]cfenet.ubc.ca

Systematic reviews enhance drugs conference

conference meeting

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.

Overdose

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;

Gender

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;

Services

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

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;

Other topics

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:

 

2017: Dr Wood tells the forum recipe for research-centre success

2016: Changing the ways of CPDD – College on Problems of Drug Dependence – June 12-16, #CPDD2016

2015: Getting the most out of the Conference of the College on Problems of Drugs Dependence #CPDD2015

2014: 76th Annual Conference of College on Problems of Drug Dependence: Decide to be fearless& fabulous 

2013: My itinerary for the Conference – College on Problems of Drug Dependence, San Diego, June 15-20