Tag: opioid overdose

Effectiveness of Common Treatments for Opioid Use Disorder in Mothers and Infants

Photo by Alina Matveycheva

Over the last 20 years, substance use-related deaths have more than doubled for women of reproductive age. Overdose deaths are now a leading cause of maternal mortality in the US, and in some states, the leading cause.

Still, substantial gaps remain in understanding how different treatment approaches influence the short- and long-term health of mothers and infants, as well as their broader economic impacts over time.  

New research published this month in the journal JAMA Pediatrics found that while established medications for opioid use disorder in mothers – buprenorphine and methadone – are both superior and cost saving compared to alternative treatment pathways (naltrexone, medication-assisted withdrawal or no treatment), buprenorphine produced the greatest health gains and cost savings for mothers and infants.

Using a mathematical simulation model, the study projected the health and cost outcomes for pregnant individuals with opioid use disorder and their infants over their lifetime. The economic model captured how treatment decisions during pregnancy can have lasting health and economic consequences, such as risks of preterm birth, that extend from infancy through adulthood and drive substantial downstream health effects and costs. Outpatient buprenorphine emerged as the optimal treatment in most scenarios tested (58%-100%) and in nearly every lifetime scenario that incorporated both mother and infant trajectories (99%). In other words, across thousands of simulations, buprenorphine consistently produced the best health outcomes and lower costs compared to alternative strategies. 

The study, led by Ashley Leech, PhD, assistant professor of Health Policy at Vanderbilt University Medical Center, and Stephen Patrick, MD, MPH, O. Wayne Rollins Distinguished Professor of Health Policy and chair of the Department of Health Policy and Management at Emory University, is among the first to compare the short- and long-term health benefits and costs of opioid use disorder treatment for mothers and infants, examining outcomes during pregnancy, postpartum and beyond the infant’s first year of life using simulation modeling.

Existing studies have not examined outcomes beyond the infant’s first year of life. The study used a hypothetical treatment group modeled on known demographic and other social factors to estimate differences in outcomes and cost savings over time for each treatment and population group. The paper found that, although neonatal opioid withdrawal syndrome (NOWS) has received much of the clinical attention as a marker of poor infant health after opioid exposure during pregnancy, preterm birth and low birth weight carry greater morbidity and mortality and played a more significant role in shaping long-term infant outcomes. Notably, buprenorphine, despite its direct association with NOWS, was protective against these critical outcomes. 

“Nationwide, we have seen a significant growth of pregnant women with opioid use disorder, but there have not been comprehensive models that evaluate trade-offs of different medications and strategies,” said Patrick. “This study evaluated the trade-offs we face as clinicians – How will medications affect moms and babies? With the evidence we have available, what can we expect years from now? Bottom line, we found that buprenorphine treatment in pregnancy was cost saving and improved outcomes for mothers with opioid use disorder and their babies.”

The researchers emphasised, however, that patient-centred care and patient choice remain essential to sustaining treatment. “While we found that buprenorphine yielded the greatest health gains and was cost saving across all model variations, methadone could still be a viable option for mothers, and at the individual level, it might work better for some,” said Leech, the lead author of the study. “Buprenorphine shows clear benefits for long-term infant outcomes, but it can be more difficult for patients to start and stay on this treatment because, as a partial agonist, it may not feel as strong to those dependent on drugs like heroin or fentanyl. Methadone, by contrast, is often easier for patients to initiate and sustain.

“This is an opportunity to make sure buprenorphine works as well as possible – by ensuring pregnant individuals receive effective doses across trimesters (since they often need higher and increasing amounts for effectiveness compared to nonpregnant patients) and by removing unnecessary Medicaid restrictions.”

The study estimated substantial cost savings to public insurance programmes like Medicaid, finding that treating pregnant individuals this year could save roughly $4 billion in infant-related lifetime costs alone.  

“Medicaid is the largest payer for pregnant individuals and those with substance use disorders. Our research shows that treatment is not only effective but also has the potential to generate significant savings for Medicaid, benefiting both mothers and their children’s long-term health,” Leech said.

Source: Vanderbilt University Medical Center

New Vaccine may Counter the ‘Zombie Drug’ Xylazine

Xylazine, only intended for animals, is being added to opioids and cocaine, with deadly effects. Photo by Colin Davis on Unsplash

Xylazine is an FDA-approved sedative and pain reliever for use in animals, but it has severe adverse effects when used in humans. Now, it is now being added illicitly to opioids, like fentanyl and heroin, as well as cocaine – leading to a sharp rise in overdose deaths.

Scripps Research chemical biologists have developed a vaccine to block the effects of xylazine’s toxicity. The vaccine works by training the immune system to attack the drug, which is described in a new paper published in Chemical Communications.

“We demonstrated that a vaccine can reverse the symptoms of a xylazine overdose in rodents,” says study senior author Kim D. Janda, PhD, professor of chemistry at Scripps Research. “There is currently no remedy for xylazine poisoning other than supportive care, thus, we believe our research efforts and the data we have provided will pave the way for an effective treatment in humans.”

The rapid increase in lethal drug overdoses attributed to xylazine combined with fentanyl prompted the White House Office of National Drug Control Policy to declare this combination an emerging threat to the United States. Xylazine intoxication presents similarly to opioid overdose, causing respiratory and central nervous system depression, and it can heighten the effects of opioids. However, naloxone – typically administered to reverse the effects of opioids – does not tackle the impact of xylazine, highlighting the need for effective measures to treat acute toxicity caused by xylazine.

Researchers suspect xylazine works by reducing blood flow to the brain, among other areas of the body. The drug also causes non-healing skin lesions and wounds, often located on the forearms and lower legs, that can require amputation in some cases – giving it the nickname “zombie drug.”

Although no treatment currently exists, targeted vaccines may offer a solution. Antibodies from vaccination can target toxins as well as viruses and bacteria. But sometimes molecules are too small to initiate an immune response, as is the case with xylazine. So, to circumvent this problem, the researchers created a vaccine using a design principle that Janda pioneered, which relies on pairing the drug molecule (called a hapten) with a larger carrier molecule (a protein) and an adjuvant.

In this study, the scientists combined a xylazine hapten with multiple different protein types, to see which combination would create a robust immune response against xylazine. The team tested three vaccine formulations (termed TT, KLH and CRM197, based on the protein involved) to see which vaccine cocktail could help rodents after being challenged with xylazine. One of the three vaccines (TT) significantly increased movement in mice given xylazine after 10 minutes, while two of the three vaccines (TT and KLH) led to an improvement in breathing.

The scientists also examined how these vaccines would limit xylazine blood brain barrier, (BBB) permeation, a filtering mechanism that scrutinizes drug penetration. When xylazine was injected, it immediately crossed into the brain to bind with receptors. Antibodies typically cannot navigate the BBB; however, two of the three vaccines (TT and KLH) showed a strong ability to stop xylazine from reaching its receptors in the brain, limiting its detrimental effects.

A provisional patent has been filed on the research. In the future, his team will build off this work to create a bifunctional antibody that will reverse both fentanyl and xylazine’s toxicity simultaneously, something that naloxone cannot do.

“A monoclonal antibody treatment could be given in tandem with the vaccine to provide both immediate and long-term protection from both opioid substance use disorders as well as opioid-xylazine overdoses,” says Janda. “This strategy could make a significant impact on the opioid epidemic.”  

Source: Scripps Research Institute

Opioid Respiratory Depression Reversed with Electrical Pulses

Source: Pixabay CC0

Opioid use is a significant cause of premature death, caused by supressing respiratory activity. New research, published in The Journal of Physiology, points to a novel treatment for respiratory depression associated with opioid use that administers electrical pulses to the back of the neck, helping patients regain respiratory control following high dosage opioid use.

Breathing problems can occur after opioid use or post-operative complications from anaesthesia because opioids desensitise the brain stem to rises in carbon dioxide. This can cause respiratory failure, which can be fatal. Current treatments, such as manual lung inflation and medication, can work in the short term to combat breathing problems following opioid use, but getting patients to breathe independently remains a challenge. Therefore, this new research, which administers epidural electrical stimulation (EES) offers an alternative, non-pharmacological treatment.

EES administered at the cervical spinal cord, which is located at the back of the neck, activates a network of neurons in the brainstem that stimulates and coordinates respiratory muscles and improves the rate and depth of breathing.

Researchers from the University of California, Los Angeles (UCLA), targeted sensory-motor circuits in the cervical spinal cord of 18 patients with degenerative spine diseases who were anaesthetised for surgical treatment. They delivered 30 Hertz of EES to the cervical spinal cord continuously for no longer than 90 seconds.

They found that short periods of continuous low-intensity EES not only increased the volume of breath but also actively controlled the frequency and rhythm during opioid-induced breathing problems. The rhythmic breathing pattern was sustained briefly after the EES stopped in the presence of high-dose opioids.

Senior author Dr Daniel Lu, UCLA professor and vice chair of neurosurgery, said: “Our results provide proof of principle that cervical EES could improve respiration following opioid use. We can compare the human body to a car, our goal is to jump start the body so it can run by itself without periodic pushes. We hope to use EES to provide novel approaches to restore breathing for healthcare providers as we are now using defibrillation devices for restoring cardiac activities.”

Future human trials with larger cohorts will be conducted to further assess the practical application and impact of EES to determine whether EES can alleviate or reduce the need for ventilator support in acute pathological conditions such as OIRD, stroke, and traumatic brain, brain stem or spinal cord injury. Experimental studies in mice will be carried out to further investigate the role specific neurons play in response to EES.

Source: Physiological Society