Tag: opioids

Electroacupuncture Spares Opioids for Knee Replacement Pain Relief

Source: Katherine Hanlon on Unsplash

Patients who have electroacupuncture during total knee replacement surgery report less pain and need far fewer opioids to manage their discomfort. In the study, 65% of patients who received acupuncture during surgery were able to have a low-dose or opioid-free postoperative experience, compared to 9% of patients outside of the study.

The results of the study were presented at the ANESTHESIOLOGY® 2021 annual meeting

“Total knee replacements are one of the most common operative procedures in the United States and often very painful, so there’s a great need to explore non-opioid pain relief techniques for this type of surgery,” said lead author Stephanie Cheng, MD, DABMA, assistant attending anaesthesiologist at the Hospital for Special Surgery and assistant professor of clinical anaesthesiology at Weill Cornell Medicine. “Acupuncture is extremely safe and can help reduce pain with few unwanted side effects, but it has not been well researched as part of surgical anesthesia.”

The study enrolled 41 patients who had primary total knee replacement, all of whom received the institution’s standard opioid-sparing multimodal analgesic protocol, with the addition of electroacupuncture, which is a modified form of traditional acupuncture that applies a small electric current to thin needles that are inserted at known acupuncture points on the body. The acupuncture was administered during surgery by Dr Cheng, who is board-certified in medical acupuncture, to eight specific points in the ear to provide targeted pain relief in the knee.

With the addition of acupuncture, the majority of patients had reduced postoperative opioid use, compared to historical controls, while 65% of patients either maintained a low-dose opioid regimen of 15 oxycodone pills or less (57.5%) or remained completely opioid-free (7.5%) from induction of anaesthesia to 30 days post-surgery. Historically, only 9% of patients outside of the study were able to maintain a low-dose or opioid-free regimen post-surgery. Thirty days after surgery, all patients discontinued opioid use.

“Our study shows that if a trained medical acupuncturist is available to perform acupuncture in the operating room, it can help patients with postoperative pain recovery,” said Dr Cheng. “Most studies fail to incorporate nontraditional techniques, such as acupuncture, to help decrease the dependence on opioid medications for postoperative pain control.”

Low-dose perioperative opioid consumption is key to mitigating the opioid epidemic and opioid misuse by patients. Dr Cheng pointed out that with acupuncture being commonly used outside of the hospital as an effective therapy for pain management and treatment for a range of health issues and symptoms, it’s time to consider its benefits inside the hospital as well. “Additional research is needed to further define acupuncture’s effects and encourage its use in all aspects of disease treatment.”

Source: American Society of Anesthesiologists

Breakthrough Could Lead to New Opioid Alternatives

Source: NCI on Unsplash

Monash University researchers have made a breakthrough discovery that might lead to new non-opioid analgesics to treat neuropathic pain safely and effectively, without the risk of opioid addictions.

Neuropathic pain occurs when nerves are damaged or dysfunctional, and can be caused by injury, virus infection or cancer treatment, or it can be a symptom or complication of conditions such as multiple sclerosis and diabetes.

The new study, published in Nature, has shown a new mode of targeting the adenosine A1 receptor protein, which had long been a promising therapeutic target for non-opioid painkillers to treat neuropathic pain. However, development of analgesics using it had failed due to a lack of sufficient on-target selectivity, as well as undesirable adverse effects.

In the study, Monash researchers used electrophysiology and preclinical pain models to show that a particular class of molecule, called a ‘positive allosteric modulator’ (PAM), can enhance the targeting of the A1 receptor by binding to a different region of the protein.

Another breakthrough in the study was observing the high-resolution structure of the A1 receptor bound to both its natural activator, adenosine, and an analgesic PAM, which was facilitated by the application of cryo electron microscopy (cryoEM), providing the first atomic level snapshot of the drug binding location.

Chronic pain remains a widespread global health burden. A lack of treatment options has led to over-reliance on opioid painkillers, which provide only limited relief in patients with chronic (particularly neuropathic) pain, while having severe adverse effects, such as respiratory depression and addiction. In 2016, 42 000 deaths related to opioid misuse were recorded in the US, while 25 million Americans suffer from chronic pain.

This new discovery opens the door to the development of non-opioid drugs that lack such side effects.

Co-corresponding author of the study and Dean of the Faculty of Pharmacy and Pharmaceutical Sciences, Professor Arthur Christopoulos said: “The world is in the grip of a global opioid crisis and there is an urgent need for non-opioid drugs that are both safe and effective.”

Source: Monash University

High-dose Buprenorphine in ED Could Improve Opioid Abuse Outcomes

Photo by Mat Napo on Unsplash
Photo by Mat Napo on Unsplash

High-dose buprenorphine therapy, provided under emergency department care, is safe and well tolerated in people with opioid use disorder experiencing opioid withdrawal symptoms, according to a study supported by the National Institutes of Health’s National Institute on Drug Abuse (NIDA).

Lower doses of buprenorphine, a medication approved by the US Food and Drug Administration to treat opioid use disorder, are the current standard of care. Higher doses, however, could extend the period of withdrawal relief for people after being discharged from the emergency department that could help them better seek care. 

“Emergency departments are at the front lines of treating people with opioid use disorder and helping them overcome barriers to recovery such as withdrawal,” said Nora D Volkow, MD, director of NIDA. “Providing buprenorphine in emergency departments presents an opportunity to expand access to treatment, especially for underserved populations, by supplementing urgent care with a bridge to outpatient services that may ultimately improve long-term outcomes.”

Presently, some emergency departments already administer higher buprenorphine doses to treat withdrawal and opioid use disorder. They do this as a response to the growing potency in illicit opioid drug supplies and delays in access to follow-up care, but this practice has not been evaluated previously.

Researchers used a retrospective chart review to analyse data from electronic health records documenting 579 emergency department visits at the Alameda Health System Highland Hospital in California, made by 391 adults with opioid use disorder in 2018. Many patients were from vulnerable populations, with 23% experiencing homelessness and 41% having a psychiatric disorder.

In 63% of cases, clinicians administered more than the standard upper limit of 12 mg of sublingual buprenorphine during emergency department induction, and in 23% of cases, patients were given 28 mg or more. Higher doses of buprenorphine were seen to be safe and tolerable, and there were no reports of respiratory problems or drowsiness among those given the higher doses. The few serious adverse events that occurred were determined to be unrelated to high-dose buprenorphine therapy.

Studies have shown that initiating buprenorphine in emergency departments improves engagement in treatment and is cost effective, but barriers to the medication’s use in the US persist, with restrictions on what training is required, how much can be administered and for how long. Recent changes to prescribing guidelines by the US Department of Health and Human Services now let some clinicians treating up to 30 patients to prescribe buprenorphine without the previous training and services criteria.

“Once discharged, many people have difficulty linking to follow-up medical care,” explained study leader Andrew A Herring, MD, of Highland Hospital Department of Emergency Medicine. “Adjusting the timing and dosage of buprenorphine in the emergency department, along with resources and counseling aimed at facilitating the transition to outpatient services, may provide the momentum needed to access continuing care.”

“This study enhances the evidence we know about emergency-department buprenorphine induction, and could be a gamechanger, particularly for vulnerable populations who would likely benefit from a rapid induction at the time of the visit,” said study author Gail D’Onofrio, MD, of Yale University. Dr D’Onofrio published the original studies on emergency department-initiated buprenorphine, as well as recent consensus recommendations on the emergency department treatment of opioid use disorder.
The researchers noted that their findings need confirmation in other emergency departments. Nevertheless, this study suggests that with proper support and training, emergency medicine providers may safely and effectively initiate high-dose buprenorphine therapy.

Source: NIH

Journal information: JAMA Network Open (2021). DOI: 10.1001/jamanetworkopen.2021.17128

Physician’s Personal Brush with Opioid Addiction

For Kevin Lamb, MD,  the opioid crisis became real to him in 2009. 

Once, he said, he had spoken at a leadership forum on opioid abuse, about the role of hospital systems in addressing it. Thinking over what to say, he “realized there was very little I could add. The crisis is epidemic, and hospitals are ill-prepared to do anything proactive. It is that overwhelming.” But leading medical missions made him realise that the rest of the world has overwhelming needs too, which only become real once they are experienced firsthand.

Since transparency is so important, he decided to share his own story.

“This is my story of how close I came to going down that perilous path that is opioid addiction (or any addiction for that matter). I was fortunate that I stopped before I went too far down that path. Unfortunately, too many are unable to stop and continue the downward spiral toward that deep, dark pit called despair and its brother hopelessness. If this could happen to me, it could happen to anyone. If my story prevents even one of you from experiencing this, then the trepidation I feel sharing this will be worth it.”

His story began following his first back surgery in 2009 for an acutely herniated disc that occurred while leading a medical mission in Eastern Europe, which he said was the worst pain he had ever experienced, leaving him with a weak, numb right leg. Having to be carried to bed, living in very basic conditions, with no running water and power interruptions, he feared his condition would force him to be evacuated, although he was able to regain neurologic function for a short while, finishing the mission. 

He went in for surgery two days after getting home. He received Oxycontin with a refill, which at the time was common practice, and it eased the pain and had a calming effect, he said. Before the trip, he had experienced a lot of stress, and now being on medical leave he enjoyed the feeling of relief that it gave.

However, as the pills started to run out, he felt embarrassed at the thought of having to request a refill, at being thought of as an addict. But after he used the last pill, withdrawal symptoms kicked in — restlessness, abdominal cramping, diarrhea. “Though relatively mild, it frightened me. I never imagined I could become physically and mentally dependent. I thought this only happened to people who were ‘weak’ or lacked ‘self-discipline’. I was wrong,” he recalled.

He said that besides “scary and humbling”, it was also “surreal… “If it could happen to me, it could happen to anyone!” he warned. The reality is that many in the medical profession are at risk, the pressures of the profession can mean that substance abuse is an easy escape with devastating consequences.

He concluded, hoping that by sharing his story he could make a difference. “My fervent desire is that it will make this crisis more personal and thus more real to you. Only then can you better know the enemy you face and how best to defeat it.”

Source: KevinMD

Unique Genetic Basis for Chronic Pain in Women Discovered

A meta-analysis of UK genetic data has found a different genetic basis for chronic pain in women compared to men.

While the results are still preliminary, this is one of the largest genetic studies on chronic pain analysing by sexes.

“Our study highlights the importance of considering sex as a biological variable and showed subtle but interesting sex differences in the genetics of chronic pain,” said population geneticist Keira Johnston of the University of Glasgow in Scotland.

Chronic pain conditions are among the most prevalent, disabling, and expensive conditions in public health, and are frequently overlooked for research funding. With 100 million people in chronic pain in the US in 2016, overprescription of opioids for chronic pain has resulted in an epidemic of opioid misuse, with 66% of overdose cases being for opioids. Even very moderate opioid use carries the risk of addiction and abuse.

Even when studies are done, they often overlook underlying sex differences, and that’s a huge and detrimental oversight. Compared to men, women are far more likely to develop multiple chronic pain disorders, and yet historically, 80 percent of all pain studies have been conducted on male mice or male humans. This means we know very little about how and why females are suffering more and what treatments can help them best.

While there are probably multiple biological and psychosocial processes in this sex discrepancy, the current genome-wide study suggests there’s a genetic factor in the mix, too.

The researchers compared gene variants associated with chronic pain in 209 093 women and 178 556 men from the UK Biobank, and found 31 genes associated with chronic pain in women and 37 genes associated with chronic pain in men with barely any overlap. This might be due to the slightly smaller sample size of men but the results are nonetheless intriguing, the researchers maintained.

The vast majority of these genes were active in a cluster of nerves within the spinal cord, known as the dorsal root ganglion, which transmits messages from the body to the brain.
While several genes in the male-only or female-only list were linked with psychiatric disorders or immune function, only one, called DCC, was found in both lists.
DCC encodes for a receptor that binds with a protein crucial for the development of the nervous system, especially the dopaminergic system. The dopaminergic system is the ‘reward centre’ but also has been linked to pain.

DCC is also linked to depression, and DCC mutations appear in those with congenital mirror movement disorder, which results in movements on one side of the body being replicated on the other side.

It’s not how DCC is linked to chronic pain, but the researchers believe their results support several theories “of strong nervous system and immune involvement in chronic pain in both sexes”, which will, they hope, result in the development of better treatments.

Should chronic pain be more closely linked to immune function in women, immune-targeting drugs may have very different side-effects than in men. Opioids negatively impact immune function, indicating that they could in fact worsen the situation for women suffering chronic pain. However, more research is needed to strengthen these findings and understand their impacts.

“All of these lines of evidence, together, suggest putative central and peripheral neuronal roles for some of these genes, many of which have not been historically well studied in the field of chronic pain,” the authors concluded.

Source: Science Alert

Journal information: Johnston KJA, Ward J, Ray PR, Adams MJ, McIntosh AM, Smith BH, et al. (2021) Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank. PLoS Genet 17(3): e1009428. doi.org/10.1371/journal.pgen.1009428

A Public Archive for Opioid Lawsuit Information

In order to improve transparency about the opioid crisis,  the University of California San Francisco and Johns Hopkins University launched a digital public archive of documents from lawsuits against drug manufacturers.

The digital repository of publicly disclosed legal documents related to the crisis allows free, public access to anyone interested in the continuing litigation and uncovered evidence.

“All too often, the public never gets the benefit of seeing and learning from litigation that generally takes place behind closed doors,” said Caleb Alexander, MD, a professor of epidemiology and medicine at Johns Hopkins and the founding co-director of the Center for Drug Safety and Effectiveness, which will assist in maintaining the archive.

“Our focus is to be sure that the millions of pages of documents arising from opioid litigation ultimately see the light of day,” Alexander told MedPage Today. “We owe it to all those who have been impacted — especially patients and their loved ones — to see to it that these materials are placed in the public domain.”

The goal of the archive is to provide transparency into the methods used by drug companies to increase opioid sales, which led to the opioid epidemic in which, according to the CDC, over the past two decades, nearly 500 000 Americans died of overdoses involving an opioid. Additionally, the economic cost of the crisis in 2015-2018 was put at $2.5 trillion by the White House Council of Economic Advisers.

Most of the archive’s documents were released thanks to efforts by the Washington Post and the Charleston Gazette. Records include company emails, memos, presentations, sales reports, audit reports, budgets, Drug Enforcement Administration briefings, expert witness reports, and depositions of drug company executives.

The archive is located on a website called Drug Industry Archives, a UCSF project that houses documents illustrating how the pharmaceutical industry, academic institutions, continuing medical education organizers and regulatory agencies impact public health. (UCSF also maintains similar archives related to tobacco, food, chemicals, and fossil fuel industries.)

The  Opioid Industry Documents Archive presently holds over 3300 legal documents, much of it coming from litigation in Kentucky and Oklahoma, as well as documents from the Insys investigation, which sold an oral fentanyl spray called Subsys. This archive’s launch coincides with the university hosting over 250 000 documents produced during Insys’ bankruptcy proceedings that resulted from successful lawsuits and criminal prosecutions.

“We don’t really know what’s in these documents yet, but there is a wealth of information,” said Kate Tasker, an associate librarian at UCSF who helps manage the archive. “Our number one goal is to make this information accessible and useful.”

Alexander said the opioid crisis was “an epidemic of catastrophic public health proportions.” He said that placing legal documents in the public domain is a crucial step to ensure that lessons are learned from the crisis.

“The primary goal is to ensure that history never repeats itself,” Alexander said. “And we can’t learn from past mistakes without understanding what those mistakes have been.”

Source: MedPage Today

Opioid Overdoses in US Increasing due to COVID

The COVID pandemic has not seen a drop in the United States’ opioid crisis, rather there has been an exacerbation of the problem.

A study published in JAMA Psychiatry examined the impact that the COVID pandemic had on the US opioid crisis. 

Opioid misuse and addiction is an ongoing and increasing problem in the US, making up two thirds of overdoses. Some three million Americans have suffered opioid use disorder at some point. With approximately 100 million Americans living with chronic or acute pain, the situation is seemingly intractable. In 2019, there were 70 000 deaths from opioid overdoses, making it a top priority in public health, academic, and political debates. When the COVID pandemic hit, it did not displace the opioid crisis through distraction or somehow preventing access to opioids, it fanned the flames of it. 

Researchers analysed 190 million ED visits, and over March to October 2020. they observed an increase of  up to 45% in weekly opioid overdose admissions over the same period in 2019. Overall, ED visits for opioid overdoses had increased 28.8% compared to the previous year.

In September, the CDC warned that deaths from opioid overdoses were up by 38.4% in the first half of the year. The many stresses of the pandemic, such as its associated lockdowns and job losses and losing loved ones, has fuelled the opioid abuse. The same study also found that visits to the ED for mental health conditions, domestic violence, and child abuse and neglect increased over the same period of time, along with suicide attempts. 

Source: ABC News

Journal information: Holland KM, Jones C, Vivolo-Kantor AM, et al. Trends in US Emergency Department Visits for Mental Health, Overdose, and Violence Outcomes Before and During the COVID-19 Pandemic. JAMA Psychiatry. Published online February 03, 2021. doi:10.1001/jamapsychiatry.2020.4402

Misuse of Psychiatric Meds Common in Teens

A study into the use and misuse of psychoacttive drugs by US teens has found that about a fifth report misusing their prescribed medications.

Israel Agaku, PhD, of Harvard School of Dental Medicine in Boston, and colleagues used data from a survey of adolescents aged 12-17 prescribed opioids, stimulants, tranquilizers, or sedatives, and found that 20.9% reported using them not as prescribed or directed. There has been considerable concern in recent years over whether adolescents in the United States were being overprescribed psychiatric medication, although a 2018 study concluded that they are not. However, as with adults, the prospect of misuse, possibly leading to substance use disorders is a concern.
Of these youths, 3.4% reported having substance misuse disorders, and this proportion increased to nearly half when youths were taking two or more prescribed medications.

Some 25% of 12-17 year olds reported receiving a psychiatric prescription in the past year. The most common psychoactive prescription in the past year was opioids in 19% of all youth, followed by stimulants (7.2%), tranquilisers (4.3%), and sedatives (2.2%). Tranquilisers were the most commonly misused (40.1%), with substance use disorder in 7%. Stimulants were misused by 24.2%, 3% having a substance use disorder.
Among adults aged 18-25, 41% had been prescribed and had used psychoactive medication, with a third saying they had used opioids in the past year, Similarly to the 12-17 age group, stimulants and tranquilisers were most likely to be misused. 

“The largely overlapping population profiles for medical use versus misuse indicates the high abuse liability of these prescription substances,” the researchers noted. “Having serious psychological distress was consistently associated with misuse of every assessed psychoactive prescription medication.”

The researchers suggested that an open-minded, collaborative approach by healthcare providers was the best approach to dealing with the situation.

“Rather than asking only about cigarette smoking, pediatric practitioners should screen for different commonly used substances, including ‘social use.’ Specifically asking youth and young adults if they have used certain substances, including occasional use, is important as those who use such substances infrequently or only occasionally may not self-identify as users if asked in generic terms,” the researchers explained.

Source: MedPage Today

Journal information: Agaku I, et al “Medical use and misuse of psychoactive prescription medications among US youth and young adults” Fam Med Com Health 2021; DOI: 10.1136/ fmch-2020-000374.

New Study Challenges the Need for Some Post-surgical Opioids

Doctors must carefully weigh the pain relief value of opioids for patients against their potential for misuse and inducing opioid addiction even in patients with no history of substance abuse. Now, a new study challenges current practice by showing the effectiveness of an approach that takes a middle way to giving opioids.

Some 16 million people around the world suffer from opioid use disorder, which can result from opioid administration from surgery and for chronic pain. Opioids are highly addictive, with tolerance reached in days and addiction can occur within a matter of weeks, so there is every incentive to minimise exposure of patients to these effective but potentially dangerous medications.

To investigate the effectiveness of minimising opioid use, a team from Michigan Medicine at the University of Michigan conducted a study with 620 patients who had surgery in hospitals across Michigan, had their anaesthetic usage tracked, and filled in surveys within one to three months following their surgeries. The patients were split equally into two groups.
The first group received pre-surgery counseling emphasising non-opioid pain treatment as their first option. Some patients in this group received small, “just in case” prescriptions, but a third of them didn’t receive any opioid prescription at all after surgery.

The patients in the other group received standard care, that is, receiving the usual amount of opioids prescribed after such operations. The prescriptions received in fact were larger than in the opioid sparing group. Most patients didn’t take all of the pills, which if left lying around could be used inappropriately.

Patients in the two groups had the same surgery: either gallbladder removal, full or partial thyroid removal or hernia repair. However, both groups reported equal levels of quality of life and satisfaction with care when followed-up. Most surprisingly, the opioid-sparing group reported less pain overall.

First author Maia Anderson, MD, a resident in the U-M Department of Surgery, said: “It’s so exciting to think about the potential for opioid sparing postoperative pathways to not only reduce the risk of opioids for our patients, but also to substantially decrease the risk of opioid diversion into our communities.”

Senior author Ryan Howard, MD, Surgical Resident, Michigan Medicine commented: “We know that opioids pose serious risks to patients after surgery. We can protect patients from those risks by reducing or eliminating opioids after surgery. But that idea always raises the concern that patients will have uncontrolled pain and feel miserable. This study suggests that’s not the case – patients who get small opioid prescriptions, or even no prescription, are just as satisfied with their recovery after surgery.”

Source: News-Medical.Net

Journal information: Anderson, M., et al. (2020) Patient-Reported Outcomes After Opioid-Sparing Surgery Compared With Standard of Care. JAMA Surgery. doi.org/10.1001/jamasurg.2020.5646.