10/15/24

Is There a Better Way to Prevent Overdose Deaths?

The CDC released provisional data suggesting opioid overdose deaths dropped to the lowest level in three years. The newest CDC update indicated the provisional decline reflects data through April of 2024. An Associated Press report said experts reacted cautiously to the reported drop. It was only the second annual decline in more than 30 years, and it was also relatively small. One expert thought it should be understood more as a leveling off; another observed the previous decrease in 2018 was followed by an increase afterwards.

Nevertheless, the CDC Chief Medical Officer thought the dip was “heartening news,” but “there are still families and friends losing their loved ones to drug overdoses at staggering numbers.” A study reported in May of 2024 in JAMA Psychiatry found that an estimated 321,566 children lost a parent to drug overdose in the US from 2011 to 2021. The rate of children who lost a parent to drug overdose per 100,000 children increased from 27.0 per 100,000 to 63.1 per 100,000 in 2021. There were significant differences across racial and ethnic groups, with the highest rates among children of non-Hispanic American Indian or Alaska Native individuals, who had a rate of 187.1 per 100,000 in 2021. This was more than double the rate among children of non-Hispanic White individuals (76.5 per 100,000) and non-Hispanic Black individuals (73.2 per 100,000).

Given the potential short- and long-term negative impact of parental loss, program and policy planning should ensure that responses to the overdose crisis account for the full burden of drug overdose on families and children, including addressing the economic, social, educational, and health care needs of children who have lost parents to overdose.

According to the CDC, around 107,500 people died of overdoses in the U.S. in 2023, which was down 3% from 2022 when there were an estimated 111,000 such deaths. There have been more than 1 million drug overdose deaths since 1999. An August 14^th CDC update of that data had a graph that showed the 2018 leveling off was followed by a dramatic increase after the COVID-19 pandemic began in March 2020. See the following figure taken from the CDC update.

The update reported the overall decrease of overdose deaths in the U.S. was 12.2%. Yet the interactive maps indicated several Western states had overdose rates that were as high or higher than reported previously. Alaska (41.82%), Oregon (15.11%), Nevada (13.33%), and Washington (10.03%) all reported double digit increases. Utah, Wyoming, Colorado, Hawaii, and Iowa also reported increases. Nebraska (29.95%) and North Carolina (41.81%) had significant decreases. However, the “reported provisional counts may not include all deaths that occurred during a given time period.” These delays are because they require lengthy investigation, including toxicology testing.

Commenting on the same CDC update, CBS News reported at its peak last summer, the U.S. had more than 86,000 estimated deaths. This compared to the CDC estimate of 75,091 opioid overdose deaths for the year ending in April 2024. “The pace of opioid overdose deaths still remains far worse than before the pandemic, when there were fewer than 50,000 fatal overdoses a year.” Fatal overdoses from drugs other than opioids have been decreasing as well. But the individuals who overdosed aren’t the only victims.

Campaigning on Overdoses

Not surprisingly, CBS News noted how overdose deaths became part of the 2024 presidential campaign rhetoric. Former president Trump said overdoses were lower during his term. Technically, he was correct. The figures were lower during his tenure as the 45^th president of the United States from January 2017 to January 2021 than they are currently. But according to CDC data, the overdose increases began around March of 2019. During the Trump presidency, overdose deaths grew from 66,571 in the twelve months before January 2017 to 94,788 in the twelve months before January 2021, an increase of 29.8%.

The former president said he wanted to work with states to force homeless addicts into treatment and punish drug dealers with the death penalty. Both Trump and Harris have tied curbing drug overdoses to immigration and border issues. But Trump incorrectly claimed overdose deaths were up 18% “under Kamala.” Assuming he meant during the tenure for Joe Biden who became president in January of 2021, overdose deaths were reported to be 94,778 in January of 2021, and 97,309 in April of 2024, a 2.6% increase.

Notice that there was an effect of when the reported CDC data on overdose deaths was collected after the COVID-19 pandemic began. For example, at the time the WHO reported the beginning of the COVID-19 pandemic in March of 2020, there had been 74,679 overdose deaths in the previous 12 months. In March of 2021, there were 98,211 reported overdose deaths, an increase of 24% in the first year of the pandemic. This dramatic increase of overdose deaths in the first year of the pandemic occurred during the last year of Trump’s presidency.

The FDA first granted emergency use authorization to the Pfizer-BioNTech COVID vaccine on December 10, 2020, followed by the Moderna vaccine on December 17, 2020, and the Janssen vaccine on February 27, 2021. By April 19, 2021 all U.S. states had opened vaccine eligibility to residents 16 and over. By March of 2022, reported overdose deaths were 108,604 in the 12 previous months, an increase of 9.6%. By March of 2023, the previous 12 months of reported overdose deaths were 110,082, an increase of 1.4%. By March of 2024, reported overdose deaths were 100,518 for the previous 12 months, a decrease of 8.7%.

The variance of the increase in overdose deaths dropped from a high of 24% in the first year of the pandemic, to an increase of only 1.4% in 2023, and was followed by an 8.7% decrease in March of 2024, three years after the availability of the COVID vaccines in the U.S. This suggests it had nothing to do with who was president or vice president; or which political party was in power.

As noted above, there have been over a million overdose deaths since 1999. CDC data indicated there were 47,523 overdose deaths in the 12 months before January 2015, and 72,124 overdose deaths in the 12 months before January 2020, an increase of 34%. So, overdose deaths were a public health problem independent of the pandemic.

Preventing Overdose Deaths Through a Drug-Centered Model of MAT

In order to address this public health problem, the National Institutes of Health launched the HEALing Communities Study (HCS) in 2019. “It was the largest addiction prevention and treatment implementation study ever conducted.” It targeted 67 communities in four states (Kentucky, Massachusetts, New York and Ohio) that had been hit hard by the opioid crisis. The goal was to test the impact of an integrated set of evidence-based interventions for preventing overdose and treating opioid misuse in communities that were highly impacted by the opioid crisis.

The findings of the HCS study were published in the New England Journal of Medicine. The Communities That HEAL (CTH) intervention focused on a harm reduction approach, with education about overdose prevention and naloxone distribution, the use of methadone and buprenorphine to treat opioid use disorder, and safer opioid prescribing, dispensing and disposal practices. Yet, “despite the breadth and depth of the intervention, the risk of opioid-related overdose death was similar in the intervention group and the control group.” In other words, there were no statistically significant differences.

The researchers first said the time frame to implement the various strategies was insufficient. Secondly, they thought the COVID-19 pandemic reduced the capacity of communities to implement the Communities That HEAL (CTH) intervention. Thirdly, changes in the illicit drug market occurred with fentanyl becoming more prevalent, indications that it was used as an adulterant with stimulants and it also began appearing in counterfeit pills. Additionally, there were challenges from the growing use of xylazine in illicit opioids. For more information on xylazine, see “Tranq Dope and Its Consequences” and “Flesh Eating Tranq Dope.”

Attempting to put a positive spin on the disappointing results, a NIH news release from the National Institute on Drug Abuse (NIDA) in June of 2024 said that despite “unforeseen challenges,” the HCS successfully engaged communities to implement hundreds of evidence-based strategies, “demonstrating how leveraging community partnerships and using data to inform public health decisions can effectively support the uptake of evidence-based strategies at the local level.” The NIDA director, Nora Volkow said:

Yet, particularly in the era of fentanyl and its increased mixture with psychostimulant drugs, it’s clear we need to continue developing new tools and approaches for addressing the overdose crisis. Ongoing analyses of the rich data from this study will be critical to guiding our efforts in the future.

Then the leader of SAMHSA (Substance Abuse and Mental Health Services Administration) said:

This study recognizes there is no quick fix to reduce opioid overdose deaths. Saving lives requires ongoing commitment to evidence-based strategies. The HEALing Communities Study facilitated the implementation of 615 evidence-based practice strategies, with the potential to yield lifesaving results in coming years.

However, I believe an additional problem with the results of the HCS study was the various intervention strategies were based on a disease-centered model of drug action. NIDA and SAMHSA need to view MAT and opioid use disorder through the lens of a drug-centered model of medication action and adjust their intervention strategies accordingly.

Joanna Moncrieff describes two different types of drug action, the disease-centered model and the drug-centered model. The disease-centered model underlies the psychopharmacology presumed in current MAT. Its theoretical assumptions about how psychotropic drugs work are rarely discussed explicitly. This assumes psychotropic medications like buprenorphine help to correct a biochemical abnormality. For more on Moncreiff’s models of drug action, see “Rethinking Models of Psychotropic Drug Action.”

William White has tried for years to build bridges between the two philosophically-opposed positions on the use of MAT. In “From Bias to Balance,” he described them as “medication haters” and “medication advocates.” White said medications can play a valuable role in harm reduction, but we do addiction treatment a disservice if we portray medication alone as a panacea for the cure of opioid addiction, which seems to be what the HCS study did. He added:

Medications are best viewed as an integral component of the recovery support menu rather than being THE menu, and their value will depend as much on the quality of the milieus in which they are delivered as any innate healing properties that they possess. If the effectiveness of medication-assisted treatment (MAT) programs is compromised by low retention rates, low rates of post-med. recovery support services, and high rates of post-medication addiction recurrence, as this review suggests, then why are we as recovery advocates not collaborating with MAT patients, their families, and MAT clinicians and program administrators to change these conditions?

According to White, the addiction treatment field has yet to reach consensus on what is the optimal duration of medical support in the treatment of opioid use disorder. I think this impasse partly reflects the unacknowledged presumption of Moncrieff’s disease-centered model of drug action among medication advocates. The disease-centered model is itself a product of what is called the medical model, which sees psychopathology as the result of biology; a physical/organic problem in brain structures, neurotransmitters, etc. The over reliance on the medical model perspective (and the disease-centered model of drug action) in addiction treatment leads to an imperfect conception of substance use and a distorted understanding of the risks and benefits of buprenorphine and methadone when they are used to treat opioid use disorder.

There is no pharmacological difference between drugs used for psychiatric purposes and other recreational or psychoactive drugs. They all act on the nervous system to produce a state of altered consciousness, a state that is distinct from the normal undrugged state; a drug is a drug, is a drug. We need to develop a better way to prevent overdose deaths. The evidence-based interventions of HCS need to see their prevention attempts with MAT through the lens of a drug-centered model of drug action.

For more information on William White and the disease-centered versus the drug-centered models of drug action, see: “The Complexities and Limitations of Buprenorphine” Parts 1 and 2.

07/12/22

Tranq Dope and Its Consequences

A church friend of mine was lamenting his recent visit to Philadelphia. He said that for a city with so many different historic sites, he thought the officials there should have done a better job keeping the sites cleaned up. One of the noticeable parts of the debris were used needles and syringes. This led to us exchanging comments on the opioid epidemic, and how fentanyl had made the situation even worse. What neither of us realized at the time was that our assessment wasn’t quite accurate. We had never heard of “tranq dope.”

Although fentanyl has been replacing the heroin in the Philadelphia drug market, increasingly a substance known as xylazine has been found combined with fentanyl. It is a non-opioid veterinary tranquilizer that is not approved for human use. A brief report by Johnson et al, published in the journal Injury Prevention, reported that xylazine was detected in merely 2% of the unintentional overdose deaths in Philadelphia between 2010 and 2015. That rose to 11% in 2016; 18% in 2018 and 31% in 2019. See the chart below taken from the brief report.

NIDA (National Institute on Drug Abuse) said most overdose deaths linked to xylazine and fentanyl also involved other substances, including cocaine, heroin, benzodiazepines, alcohol, gabapentin, methadone and prescription opioids. When xylazine is taken in combination with other central nervous system depressants, it increases the risk of overdose.

Focus groups in Philadelphia said xylazine added to fentanyl gives the ‘nod’ that heroin provided before fentanyl took over the drug market. It “makes you feel like you’re doing dope (heroin) in the old days.” STAT News reported on paper published in the journal Drug and Alcohol Dependence that said while fentanyl produces a powerful high, its euphoria is short-lived when compared to other opioids like heroin. Adding xylazine gives fentanyl “legs,” meaning it extends the high.

The newer study by Friedman et al noted xylazine use is spreading beyond the Philadelphia area. It was found increasingly present in overdose deaths in all four US Census Regions. The highest prevalence data was still in the North East, in Philadelphia (25.8% of deaths), followed by Maryland (19.3%), and Connecticut (10.2%). Disturbingly, xylazine-involved overdoses may resist naloxone since it isn’t an opioid. That’s not all. “People who used drugs with xylazine seem to be more susceptible to wounds and infections on their skin and other tissues.”

The arrival of xylazine is “when we started to see way more people coming in with necrotizing skin and soft tissue issues. The amount of medical complaints related to xylazine was pretty astounding and terrifying. Xylazine wounds are a whole other kind of … just horror.”

The term “opioid crisis” doesn’t really capture what is developing with overdoses in the U.S. over the past two years. It’s an overdose crisis of polysubstance use—opioids, stimulants, and benzodiazepines; often used in combination. Friedman was quoted by STAT News as saying xylazine was an “especially noxious contaminant that is spreading through the drug supply.” A CDC MMWR Report said during January-December of 2019, xylazine was found in the overdoses reported in 23 states. It was listed as the cause of death in 64.3% of deaths in which it was reported.

Xylazine, or “tranq dope” as it’s known on the streets in Philadelphia, is an analogue of clonidine, and is used for sedation, anesthesia, muscle relaxation and analgesia in animals. It seems to reduce sensitivity to insulin and glucose levels in humans. It can lead to diabetes mellitus and hyperglycemia. Its side effects include bradycardia (a slow, resting heart rate), respiratory depression, blurred vision, disorientation, drowsiness, fainting, slurred speech, staggering, and shallow breathing. Chronic use is associated with physical deterioration, abscesses and skin ulceration.

Since xylazine is FDA approved for veterinary use only, it is not a controlled substance by the DEA. It is available in liquid form and is structurally similar to phenothiazines (first generation antipsychotics).

Its human use in Puerto Rico was reported by Rafael Torruella in a short report for Substance Abuse Treatment, Prevention, and Policy in 2011. He said Puerto Rican injecting users had been using it since the early 2000s. There, it is called Anestesia de Caballo (Horse Anesthetic). The report contained descriptions of how xylazine was viewed from a drug user’s perspective. One individual said the following about the first time he used xylazine and his later physical dependence on both heroin and xylazine:

I shot the anestesia […] and I felt asleep face first and when I opened my eyes five hours had gone by and I was laying on the floor. […] I don’t remember anything. I don’t remember anything! I fell down and I was gone. And I said: What the hell is this?! Oh, and I woke up sick [withdrawing]!I get there and don’t cop just heroin. I cop anestesia. Because that it what is going to get me high and what is going to get me straight [and reverse withdrawal symptoms]. I am not going to waste my money in just heroin because I’m going to stay the same. Do you understand? I’m going to stay the same.

Torruella said abscesses or ulcers were a serious health concern for several reasons. First, they are very painful. This encourages further injections in the abscess site with xylazine functioning as a sedative/anesthetic. This creates a need for medical attention and treatment.

Second, these open skin ulcers ooze and emit a strong odor. In severe cases, the mobility of the extremities where they appear is limited. Sometimes, amputations have been performed on the affected limbs. Third, when xylazine users asked for help in Puerto Rico, they were denied services because of their ulcers. The drug user quoted above said he was lucky because by the time his abscesses developed, he had relocated to the states and could access medical services:

[T]he times when the abscesses […] started to appear, I would come here, to the United States. […] [When the abscesses began to appear] I already knew. […] I had seen them [before]. […] [T]here are people that take a longer time in blowing up [with abscesses] than others. […] I am one in which it took a while. But when I saw that people were rotting I would get scared because I always have said that I am a junky with style.

Without basic healthcare needs, like medical/wound care, syringe exchanges and education, these open sores look terrible to both the medically trained and the untrained-eye. When a colleague saw the ulcers and their effects on non-users, she said: “Injecting drug users are being treated as if they were lepers.”

According to NIDA, the full scope of overdose deaths involving xylazine is unknown. But research shows they have spread westward across the U.S. NIDA-supported research is underway to illuminate emerging drug use patterns and changes to the illicit drug supply across the U.S. with xylazine, opioids and the evolving pattern of polydrug use, abuse and overdose. Stay tuned for the next sea change.

06/7/22

A Coming Opioid Storm?

When Rahul Gupta was sworn in as the Director of the Office of National Drug Policy (ONDCP) on November 18, 2021, he said on Twitter that the overdose epidemic would be his top priority. He is the first physician to lead the ONDCP. President Biden made it clear to him that addressing the overdose epidemic was an urgent priority. “As director, I will diligently work to advance high-quality, data-driven strategies to make our communities healthier and safer.” Tellingly, the day before Gupta was sworn in, the CDC reported on November 17^th that there were an estimated 100,306 drug overdose deaths in the U.S. during the 12-month period ending in April of 2021, an increase of 28.5% from the same time period the year before.

Overdose deaths from opioids increased to 75,673 in the year prior to April 2021, an increase of 35% from the same time period the year before. Nearly 500,000 people died from overdoses involving any opioid from 1999-2019. The CDC said this took place in three distinct waves, with commonly prescription opioids (1990s), heroin (2010) and synthetic opioids (2013). See the graph below, which shows the three categories as well as opioids overall.

The Stanford-Lancet Commission was formed in response to the rising opioid-related morbidity and mortality rates in the USA and Canada over the past 25 years. An article by Humphreys et al in The Lancet in February of 2022, “Responding to the opioid crisis in North America,” noted that in the past 25 years, more people died of overdoses in the USA and Canada than World War 1 and World War 2 combined. Following the above-noted waves, the article made the following observations.

Humphreys et al said the approval of Purdue Pharma’s opioid medication OxyContin in 1995 marked the beginning of the first wave. Purdue fraudulently marketed it as less addictive than other opioids and thus more acceptable for a broad range of indications at high doses. See “Giving an Opioid Devil Its Due,” “The Tale of the OxyContin Lie,” and “Doublespeak in the Opioid Crisis, Part 2” for more on Purdue Pharma and OxyContin.

Backed by the most aggressive marketing campaign in the history of the pharmaceutical industry, OxyContin became the best known of a number of opioid medications (both extended-release and immediate-release formulations) whose prescription rate exploded in the USA and Canada.

There was a departure from decades of medical practice where opioids were used mainly for cancer, surgery and palliative care (people living with a serious illness like cancer). US and Canadian medical practitioners expanded opioid prescribing to include a broad range of non-cancer pain conditions that included lower back pain, headaches and sprained ankles. Per-person opioid prescribing roughly quadrupled between 1999 and 2011. There were 275 million opioid prescriptions written—approximately equal to the population of the two nations. The following graph shows UN data on international per-person consumption of opioids in 2010-12.

The political and cultural environment at the time the crisis emerged was not conducive to an early response; indeed, complacency allowed it to worsen. To attain respectability, trust, and influence throughout the world, opioid manufacturers strategically donated a small share of their profits to prominent institutions, including hospitals, medical and dental schools, universities, museums, art galleries, and sporting events. These donations secured goodwill and increased the credibility of the industry’s message that it was a selfless healer, pushing back against cruel anti-opioid prejudices.

The second wave began around 2010, as drug traffickers realized individuals addicted to prescription opioids were an untapped potential market for heroin. People were drawn in by the comparatively lower price of heroin. Before controls on prescribing were introduced, an analysis of national data suggested that 79.5% of Americans using heroin started with prescription opioids. When efforts began to stop the increase in prescriptions and reduce diversion of prescription opioids, addicted people began turning to heroin more rapidly than they otherwise might have.

The third wave of the opioid crisis began around 2014, as illicit drug producers began adding extraordinarily powerful synthetic opioids, such as fentanyl, to counterfeit pharmaceutical pills, heroin, and stimulants. This wave brought unprecedented lethality in addition to—rather than instead of—the previous waves, both of which continue today. Large numbers of US and Canadian people are still becoming addicted to prescription opioids each year, and most of those who die from heroin and fentanyl overdoses are previous or current users of prescription opioids.

An anonymous editorial in The Lancet accompanied the report of the Stanford-Lancet Commission, Managing the opioid crisis in North America and beyond.” It said the COVID-19 pandemic may have contributed to the number of overdose deaths by disrupting treatment programs and access to medications like naloxone, as well as disrupting support networks. The Commission called for characterizing opioid use disorder (OUD) as a chronic condition, requiring “innovation in treatment of OUD and in the treatment of pain. However, this innovation “must be met with reinforced regulation.”

A Mental Elf article commenting on the Stanford-Lancet Report, said it was an important and authoritative summary of the development of the opioid crisis in North America. It was called an invaluable resource for anyone interested in the problems associated with opioids. But the author, Ron Poole, thought it has a number of weaknesses. He said in his opinion, “at the heart of the international opioid problem is a false belief that pain can be eliminated pharmaceutically.” If we are to move forward, we need to embrace a rehabilitation approach to chronic pain “where opioids play a small and specific role,” rather than continuing to search for an “analgesic magic bullet.”

The pain-elimination myth is not soley the creation of the pharmaceutical industry; it has deep-seated roots in medical socio-cultural beliefs.”In the UK, gabapentinoids are frequently used alongside heroin, and the combination is a potent cause of respiratory depression and death. Gabapentinoids have a limited role in pain management, but they are widely prescribed. They are dependency forming in much the same way as benzodiazepines. Gabapentinoids are not mentioned in the Report.

Poole is right to point to these weaknesses with the Stanford-Lancet Report, especially the failure to mention that gabapentin, which is the sixth-most prescribed medication in the U.S. It has an addictive potential, but is not yet a scheduled substance by the DEA. Other researchers have referred to concomitant use of gabapentinoids and heroin as an emerging public health problem. See “The Truth About Gabapentin.”

Hopefully, we will have time to implement the recommendations in the Stanford-Lancet Report. Humphreys et al said it took more than a generation of mistakes to create the opioid crisis in North America and might take a generation of wiser policies to resolve it. Let’s hope the three “waves” of the opioid crisis, illustrated in the above CDC graph, aren’t signaling a coming storm surge of the opioid epidemic before that time.

10/12/21

Unintended Consequences of COVID-19

On December 17, 2020, while the country’s attention was focused on the just-approved COVID vaccines, the CDC released a health advisory that noted substantial increases in drug overdose deaths across the U.S. Then, the report estimated that there were 81,230 drug overdose deaths in the 12-months ending in May 2020. This represented a worsening of the drug overdose epidemic in the U.S. and was the largest number of drug overdoses ever recorded for a 12-month time period. The CDC report said it appeared that drug overdose deaths accelerated during the COVID-19 pandemic. But then a new CDC report released in July of 2021 reported the number of overdose deaths had increased to 92,183 in December of 2020.

The July 2021 CDC report contains interactive figures showing the month-ending counts of overdose deaths by drug class and by states. From December of 2019 until December of 2020 California overdose deaths increased 45.9%; New York State, 37.3%; New York City, 36.6%. The states with the highest increases of overdose deaths were: Vermont, 57.6%; West Virginia, 55.6%; Kentucky, 53.7%; and South Carolina, 52.8%. The overall increase for the U.S. was 29.6%. See the July 2021 CDC report for more information.

A public health researcher for Brown University said to AP News this was a “staggering loss of human life.” While the nation was already struggling with a serious overdose epidemic, “COVID has greatly exacerbated the crisis.” Lockdowns and other restrictions during the pandemic made treatment harder to get. The increased deaths are most likely from people who were already struggling with addiction. Suspensions of evictions and extended unemployment benefits meant there was more money than usual to spend on drugs.

According to Shannon Monnat, a sociology professor at Syracuse University, what is really driving the surge in overdoses is an increasingly poisoned drug supply. “Nearly all of this increase is fentanyl contamination in some way. Heroin is contaminated. Cocaine is contaminated. Methamphetamine is contaminated.”

Reuters reported that during the pandemic, many drug programs were not able to operate. Restrictions meant therapy sessions were done by Zoom, which are not as impactful as in person face-to-face contact. Indirectly, pandemic lockdowns likely contributed to the increase in overdose deaths. The lockdowns intensified feelings of isolation, which is a factor in anxiety and depression, which leads to drug abuse. A health policy expert at John Hopkins Bloomberg School of Public Health estimated on a day-to-day basis, the U.S. is now seeing more overdose deaths than COVID-19 deaths.

In “Drug overdose deaths accelerating due to the pandemic,” the director of the CDC said the disruption of daily life from COVID-19 hit those with substance use disorder hard. “As we continue the fight to end this pandemic, it’s important to not lose sight of different groups being affected in other ways. We need to take care of people suffering from unintended consequences.” Again, we see the problems from fentanyl contamination. Opioids, primarily illegally manufactured fentanyl, were largely responsible for most of the overdose deaths. Synthetic opioid fatalities rose 38.4% from 2019 to 2020.

Recently, the American Medical Association noted a similar spike in overdose deaths driven by opioid deaths. The past president of the American Medical Association, Patrice Harris, warned of the necessity to continue to pay attention to health issues other than COVID. She said:

It is imperative that we continue to talk about other health issues that are impacting our nation . . . We are appropriately focused on COVID, it is still top of mind for most people, and it’s understandable that we can lose focus on other issues … but we still have to make sure we are focused on the overdose epidemic that we continue to experience in this country.

There was a study in in JAMA Network Open, “Trends in Drug Overdose Mortality in Ohio,” that looked at the overdose deaths in Ohio during the first seven months of the pandemic. Fatal overdoses rose sharply from the declaration of the pandemic on March 11^th 2020 to the week of May 31^st 2020, an increase of 70.6%. The initial spike in deaths was most pronounced for the youngest adults, those up to and including the age of 24. However, fatal overdoses followed a similar pattern in all age groups, including those 65 years and older. See the follow chart from the JAMA article.

Another study published in the Journal of Drug Issues assessed the relationships between COVID-19 stay-at-home orders and opioid overdoses in Pennsylvania. The authors said in an article for the Fix that Pennsylvania was one of the hardest hit states by the opioid epidemic. They found statistically significant increases in overdoses with heroin, fentanyl, fentanyl analogs or other synthetic opioids, pharmaceutical opioids and carfentanil. The researchers suggested in the Journal of Drug Issues that the observed increases were likely to be underestimates because of undercounts of monthly overdose incidents. They recommended these drug clsses be continuously monitored for changing patterns of use to help guide the most effective treatment interventions.

This analysis suggests that the onset of COVID-19 in the state of Pennsylvania, and resulting policy responses to mitigate infection, created unintended consequences for opioid overdose. These unforeseen outcomes obligate attention to how economic effects of the pandemic, coupled with mental health stress and other triggers for addiction, complicate and undermine patterns of opioid use and misuse, and emphasize the need for opioid use to be addressed alongside efforts to mitigate and manage COVID-19 infection.

It was pointed out how the economic recession associated with the pandemic undermined housing policy and access, “which will have lingering effects for social cohesion, access to medical care, and consistent routines critical for addiction management.” Percentages of fatal versus nonfatal overdoses remained relatively constant throughout the study at 16-17%. Heroin accounted for the largest percent (65%) of the total reported opioid-related overdose cases, followed by fentanyl (14%) and the unknown drug class (14%). “Increased mental health stress, social isolation, and economic uncertainty will likely continue to affect those most vulnerable to addiction and relapse.”

The double impact of COVID-19 and drug overdoses induced a drop in life expectancy for 2020. The CDC reported that life expectancy at birth for 2020 was 77.3 years, a decrease of 1.5 years from 78.8 in 2019. This was the lowest it has been since 2003. The decline in life expectancy was primarily due to COVID-19 (73.8% of the negative effect), unintentional injuries (11.2%), and homicide (3.1%). “Increases in unintentional injury deaths in 2020 were largely driven by drug overdose deaths.”

“The Leading Causes of Death in the US for 2020,” published in JAMA, found that COVID-19 was the third leading cause-of-death after heart disease and cancer. There were substantial increases from 2019 to 2020 for several leading causes. Heart disease deaths increased by 4.8%; unintentional injury by 11.1%; Alzheimer disease by 9.8%; and diabetes by 15.4%. Early estimates of life expectancy at birth for January 2020 to June 2020 showed declines not seen since World War II. See the following table taken from “The Leading Causes of Death in the US for 2020.”

The influence of the pandemic on the opioid epidemic has not gone unnoticed by the White House. In March of 2021, President Biden released a Statement of Drug Policy Priorities that said illicitly manufactured fentanyl and synthetic opioids other than methadone (SOOTM) have been the main influence behind the increase. However, overdose deaths from cocaine and other psychostimulants like methamphetamine have also risen. “New data suggest that COVID-19 has exacerbated the epidemic.” The American Rescue Plan, signed into law in March of 2021, set the following drug policy priorities for the administration:

Expanding access to evidence-based treatment;
Advancing racial equity issues in our approach to drug policy;
Enhancing evidence-based harm reduction efforts;
Supporting evidence-based prevention efforts to reduce youth substance use;
Reducing the supply of illicit substances; Advancing recovery-ready workplaces and expanding the addiction workforce; and
Expanding access to recovery support services.

Concern over the entwined consequences of the COVID-19 pandemic and the opioid epidemic exist beyond the US. In an opinion article for the BMJ, Ian Hamilton noted how the COVID-19 pandemic has amplified inequalities such as poverty, unemployment, poor housing and homelessness in the UK. He said these inequalities have been felt most acutely felt by those from the lowest socioeconomic groups. “Until effective ways of reducing social inequality are implemented, the best that we can hope for is timely specialist support for those developing drug related problems, such as dependency.” He concluded that problem drug use is an issue that will be with us for years and we need to build a workforce to meet the demand and ensure that these avoidable fatalities “are just that—avoided.”

07/21/20

Drug Overdose Deaths: In the Shadow of COVID-19

Over the last several months news of the COVID-19 pandemic has flooded the U.S. news media. Fears of a resurgence of positive cases and deaths from the virus are the new concern as states relax social distancing guidelines. When you look at the CDC website tracking total cases and deaths due to COVID-19, a clear geographic pattern is evident. California, Illinois, Michigan, Pennsylvania, New York, New Jersey and Rhode Island all have reported 40,000 or more cases, while Alaska, Hawaii, Montana, Wyoming and Vermont have reported less than 1,000 cases. Unfortunately, worry over COVID-19 has driven concern over drug overdose deaths as a public health concern from the consciousness of most people.

The CDC also reported a pattern to its data on overdose deaths in a “National Vital Statistics Report,” that illustrated the most lethal drug by geographic region. Overall, the drug most frequently involved in overdose deaths in the U.S, was no surprise; it was fentanyl. It accounted for approximately 39% of all drug overdose deaths. When the data is grouped regionally, fentanyl was the drug most frequently involved in overdose deaths east of the Mississippi and methamphetamine was the drug most frequently involved west of the Mississippi. Region 7, consisting of Nebraska, Iowa, Missouri and Kansas broke this pattern in reporting fentanyl as the drug most frequently involved in overdose deaths. See the following map for fentanyl taken from the October 2019 edition of the “National Vital Statistics Reports.”

The top 15 drugs belonged to several drug classes: opioids (fentanyl, heroin, hydrocodone, methadone, morphine, oxycodone, and tramadol), benzodiazepines (alprazolam, clonazepam, and diazepam), stimulants (amphetamine, cocaine, and methamphetamine), an antihistamine (diphenhydramine) and an anticonvulsant (gabapentin). Nationally, 38.9% of drug overdose deaths involved fentanyl (including fentanyl metabolites, precursors, and analogs), 22.8% involved heroin, 21.3% involved cocaine, and 13.3% involved methamphetamine. Alprazolam, oxycodone, and morphine were each involved in 6.9%–9.5% of the drug overdose deaths in 2017, while methadone, hydrocodone, diphenhydramine, clonazepam, diazepam, gabapentin, amphetamine, and tramadol were each involved in less than 5.0%.

Among the opioids, fentanyl, heroin, hydrocodone (Vicodin) and oxycodone (OxyContin) have been getting the lion’s share of the overdose press. But notice that methadone, used as an opioid maintenance drug, and tramadol also made the list. Benzodiazepines like alprazolam (Xanax), clonazepam (Klonopin) and diazepam (Valium) have been a growing, and hidden misuse and overdose problem, overshadowed by opioids like heroin and fentanyl. Gabapentin (Neurontin) likely became an overdose drug because of its use as a cheap way to potentiate an opioid high.Six drugs were found among the top ten most frequently involved drugs in all 10 of the Department of Health and Human Services (HHS( public health regions: alprazolam, cocaine, fentanyl, heroin, methadone and oxycodone. See the following table listing the top fifteen drugs most frequently involved in overdose deaths.

Commenting on the CDC data in the “National Vital Statistics Report” for ABC News, Holly Hedegaard, an epidemiologist and co-author of the report, noted how the drug problem was not the same across the country. “What’s interesting is that the patterns are different across the U.S.”

Zachery Dezman, an assistant professor of emergency medicine, thought the regional variations were the end product of cultural influences. Methamphetamine use beginning in California could account for the drug’s strong regional presence. “Like all culture, it varies from region to region and is a result of history, demand, law enforcement.” Although methamphetamine can be made cheaply, using material found on most farms, it produces a large amount of toxic waste. “So methamphetamines are more often produced in rural or isolated areas where it is easier to hide from the authorities.”

Dezman’s assessment may have been true in the 1990s, but there seem to be other factors influencing the geographic divide noted above. Writing for The Fix, Seth Ferranti indicated that 90% of the methamphetamine in the U.S. comes from Mexico, primarily manufactured in super labs by drug cartels. The Mexican labs, like the TV show Breaking Bad, are making a very pure, relatively cheap meth. Local suppliers then “cut” the meth with cheaply produced fentanyl in order to sell more of it at a lower expense. Brandon Costerison, a project manager for the National Council on Alcoholism and Drug Abuse said: “It’s a lot stronger, so we’re seeing a lot more psychosis, but we’re also seeing it being tainted with fentanyl, which is leading to more deaths.”

According to the 2018 National Drug Threat Assessment, the methamphetamine sampled in the second half of 2017 averaged 96.9% pure. The price per gram of meth was $70. The purity had increased 6%, while the price decreased 13.6%. Most of the Mexican transnational criminal organizations (TCOs) or drug cartels are involved in trafficking methamphetamine, which has led to increased competition between the cartels. The authors of the 2018 National Drug Threat Assessment speculated this competition led the Mexican TCOs to try moving into new territories and experiment with novel smuggling methods, such as the use of drones, in attempts to increase their methamphetamine customer base.

Though not favored by traffickers due to their noise, short battery life, and limited payload, advances in technology may make this method more feasible. As the technology advances and addresses these shortcomings, drones may prove more attractive to smugglers, which in turn may increase their prevalence as a smuggling technique across the border.

Currently methamphetamine laboratory seizures in the U.S. are at the lowest level in 15 years and domestic production is at its lowest point since 2000. From a high of 23,703 in 2004, there were 3,036 seizures in 2017. Between 2012 and 2017, the number of seized domestic meth laboratories decreased by almost 78%. This can be attributed, at least partly, to the Combat Methamphetamine Epidemic Act (CMEA), which was signed into law on March 9, 2006 to regulate over-the-counter sales of methamphetamine precursors like ephedrine and pseudoephedrine. But it left a supply hole the Mexican cartels were happy to fill.

The number of deaths due to psychostimulants continues to increase dramatically. According to the CDC, methamphetamine drug poisoning deaths are included under the broader category of psychostimulants, which include MDMA, amphetamine and caffeine. While the value changes yearly, recently 85 to 90% of the drug poisoning deaths reported under psychostimulants mentioned methamphetamine on the death certificate. “According to the CDC, in 2016 there were 7,542 psychostimulant drug poisoning deaths in the United States, representing a 32 percent increase from 2015, and a 387 percent increase since 2005.” See the following figure from the 2018 National Drug Threat Assessment.

Despite the growth of methamphetamine use, for people who use the drug, treatment options are slim. Currently there is no FDA-approved medication for methamphetamine use disorder, but there seems to be some promising results with naltrexone. Available as a pill or an extended release injection (Vivitrol), naltrexone is used to prevent a relapse with opioid use and it suppresses the euphoria and pleasurable sensations from drinking alcohol. There have been some studies of naltrexone as a treatment for methamphetamine use disorder.

Ray et al published a double blind, placebo-controlled study of naltrexone with individuals meeting DSM criteria for methamphetamine abuse or dependence. The results indicated that naltrexone reduced the pleasurable effects of the drug as well as cravings. The lead author of the study, Lara Ray told ScienceDaily: “The results were about as good as you could hope for.” She has done several studies on the effectiveness of naltrexone for methamphetamine addiction, including one on how executive function moderated naltrexone effects on methamphetamine-induced craving.

Naltrexone significantly reduced the subjects’ craving for methamphetamine, and made them less aroused by methamphetamine: Subjects’ heart rates and pulse readings both were significantly higher when they were given the placebo than when they took Naltrexone. In addition, participants taking Naltrexone had lower heart rates and pulses when they were presented with their drug paraphernalia than those who were given placebos.

NPR published an article noting how a woman successfully used naltrexone to help her stop using methamphetamine. She had used drugs like cocaine for years, since she was a teenager. But when she tried crystal meth, she said she was hooked from the first hit. “It was an explosion of the senses. It was the biggest high I’d ever experienced.” She went from 240 pounds to 110. She also lost custody of her children. She said three to four hours after she took the first naltrexone pill, she felt better. After taking the second pill, her withdrawal symptoms lessened.

Nancy Beste, the certified addiction counselor and physician’s assistant who treated the woman, has tried naltrexone with about 16 patients who use methamphetamine. It appeared to help reduce cravings in about half of them. She also treats individuals with opioid addiction and all her patients do counseling in conjunction with medication-assisted treatment. Her treatment goal is to eventually wean them off the medications. Unlike buprenorphine and methadone, naltrexone is not a controlled substance with its own addiction potential. In my opinion, that makes it a promising medication assisted treatment (MAT) for methamphetamine.

Drug overdose deaths did not just disappear when COVID-19 arose. The CDC reported 128 people die every day from an opioid overdose. Although the number of drug overdose deaths decreased by 4% from 2017 to 2018, it was still four times higher than in 1999. Prescription-involved deaths had increased by 13.5% while heroin-involved deaths decreased by 4%. Synthetic opioid-involved deaths, excluding methadone, increased by 10%. Methamphetamine-involved deaths accounted for approximately 11% of the of the number of drug overdose deaths in 2018. The COVID-19 pandemic may have overshadowed the opioid epidemic, but it didn’t stop it.

I’ve written about all these drug classes and the potential they have for abuse. For starters, see “Through the Fentanyl Looking Glass,” “Doubling the Risk of Overdose,” and others on opioids. Also see “Global Trouble with Tramadol”, “Gabapentinoids Perpetuate Addiction” and “The Evolution of Neurontin Abuse” for more on the problems with gabapentin or tramadol. See “Are Benzos Worth It?” “It Takes Away Your Soul” and “Dancing with the Devil” on concerns with benzodiazepines. Search on the website for the drug you are interested in reading more about in other articles.

11/5/19

Ticking Time Bomb of Speedballing

What do the following celebrities have in common: John Belushi, Chris Farley, Phillip Seymour Hoffman, and River Phoenix? Their deaths were attributed to speedball use, a combination of cocaine and heroin or morphine. Speedballs may also combine other pharmaceutical opioids, benzodiazepines or barbiturates along with stimulants, as it seems was the case with the death of Phillip Seymour Hoffman. The combination of stimulant and depressant drugs suppresses the usual negative side effects of each class of drugs, which can lead to misjudging the tolerance or intake of one or both drugs. “Due to the countering effect of the cocaine, a fatally high opioid dose can be unwittingly administered without immediate incapacitation, thus providing a false sense of tolerance until it is too late.”

Combining stimulants and opiates dates back at least to Sigmund Freud, who unsuccessfully attempted to counteract a friend’s morphine addiction with cocaine. Freud later acknowledged he may have hastened his friend’s death by “trying to cast out the devil with Beelzebub.” Nevertheless, Freud continued his personal use of cocaine despite his failed attempt to counter his friend’s morphine addiction. Several scholars have debated whether or not Freud’s use of cocaine influenced his developing theories, especially their emphasis on sex. For more information on Freud and his cocaine use, see “Sigmund Freud was a Cocaine Evangelist and Addict.”

The polysubstance misuse of stimulants and opioids has not received much media attention, but in the evolving nature of the opioid crisis that may be changing. The CDC recently published the results of an investigation of drug overdose deaths with cocaine and psychostimulants in the US between 2003 and 2017. In 2017 there were 70,237 drug overdose deaths, of which nearly a third (32.9%) involved cocaine, psychostimulants or both. Nearly three quarters of cocaine-involved deaths and about one half of the psychostimulant-involved deaths involved at least one opioid. Between 2006 and 2012 there was a decrease in overall cocaine-involved death rates that seems to have paralleled a decline in cocaine supply, but they began to increase again in 2012 (See the following figures).

Drug overdoses continue to evolve along with emerging threats, changes in the drug supply, mixing of substances with or without the user’s knowledge, and polysubstance use. In addition, the availability of psychostimulants, particularly methamphetamine, appears to be increasing across most regions. In 2017, among drug products obtained by law enforcement that were submitted for laboratory testing, methamphetamine and cocaine were the most and third most frequently identified drugs, respectively. Previous studies also found that heroin and synthetic opioids (e.g., illicitly-manufactured fentanyl) have contributed to increases in stimulant-involved deaths. Current findings further support that increases in stimulant-involved deaths are part of a growing polysubstance landscape. Although synthetic opioids appear to be driving much of the increase in cocaine-involved deaths, increases in psychostimulant-involved deaths have occurred largely without opioid co-involvement; however, recent data suggest increasing synthetic opioid involvement in these deaths.

Among the 70,237 overdose deaths in 2017, 13,942 (19.8%) involved cocaine and 10,333(14.7%) involved psychostimulants. Death rates increased from 2016 to 2017 in both drug categories across demographic categories such as sex and race. Male overdoses involving cocaine increased 31.9%. Male overdoses involving psychostimulants increased 32.4%. Female overdoses involving cocaine increased 38.9%. Female overdoses involving psychostimulants increased 35.7%.

White, non-Hispanic overdoses involving cocaine increased 35.3%. White, non-Hispanic overdoses involving psychostimulants increased 40.0%. Black, non-Hispanic overdoses involving cocaine increased 36.1%. Black, non-Hispanic overdoses involving psychostimulants increased 33.3%. Hispanic overdoses involving cocaine increased 25.0%. Hispanic overdoses involving psychostimulants increased 33.3%.

Preliminary data for 2018 suggests continuing increases in drug overdose deaths. Given the rise in deaths involving cocaine and psychostimulants “and the continuing evolution of the drug landscape,” the authors called for a rapid, multifaceted and broad approach that included both surveillance efforts and prevention and response strategies. The mixture of opioids in stimulant-involved overdoses underscored the importance of continued opioid overdose surveillance and prevention measures, including the expansion of naloxone availability. The CDC is expanding its drug overdose surveillance to include stimulants. And it is implementing evidence-based opioid prevention efforts such as improving the ability for users to access care and collaborations with public health and public safety organizations.

The increase of stimulant deaths without opioid involvement requires efforts to identify and improve access to care for persons who only use stimulants as well. The authors also suggested implementing upstream prevention efforts focusing on shared risk with both opioids and cocaine. The Fix cited comments by Hans Brieter, a psychiatry professor at Northwestern University, on how cocaine is thought of as a safer drug to use by many people today. “There’s been a lot of bad press about other drugs.” Younger people today didn’t see firsthand the 1970s dangers of cocaine, he said, so they mistakenly believe it to be the safer drug. Increased efforts towards protective factors that address substance use/misuse and improve risk reduction (“don’t use alone”) should be made as well.

The concluding sentence of the CDC Report called for collaboration between the community and public health and safety organizations, in order to understand the local drug scene and reduce its risks to users of both drugs. “Continued collaborations among public health, public safety, and community partners are critical to understanding the local illicit drug supply and reducing risk as well as linking persons to medication-assisted treatment [MAT] and risk-reduction services.” Here we may be seeing a peek under the hood at what the authors fear the most with their suggested linking to MAT, namely the increasing synthetic opioid involvement in cocaine-involved or psychostimulant overdose deaths. Remember that speedballing mixes a stimulant with a depressant. Due to the offsetting effects of the two drugs, a fatal amount of an opioid could be used without a realization of the danger until it’s too late.

Faith Seeking Understanding

Charles Sigler, D.Phil.

Tag: overdose deaths