11/9/21

The Unseen Surge of Alcohol Use

Although the increase in overdose deaths preceded the COVID pandemic, the pandemic seems to have accelerated the trend. In December of 2020, the CDC reported that drug overdose deaths in the U.S. rose 29.4% that year, mostly from illicitly manufactured fentanyl. Overdose deaths involving psychostimulants increased 10 times from 2009 to 2019. This increase was a mixture of opioids and psychostimulants as well as psychostimulants alone. But all the attention on these two drug classes seems to have overlooked the unseen surge of COVID-related increases with another drug—alcohol.

Using death certificate data from the National Center for Health Statistics, White et al found that almost 1 million people died from alcohol-related causes between 1999 and 2017. The number of death certificates mentioning alcohol more than doubled during that time frame. The Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), George Koob, said:

Alcohol is not a benign substance and there are many ways it can contribute to mortality. The current findings suggest that alcohol-related deaths involving injuries, overdoses, and chronic diseases are increasing across a wide swath of the population. The report is a wakeup call to the growing threat alcohol poses to public health.

The researchers found that nearly half of alcohol-related deaths were from liver disease (31%) or overdoses on alcohol alone or with other drugs (18%). By the end of the study, alcohol-related deaths were increasing among people in almost every age, racial and ethnic group. Death rates increased for women (85%) more than men (35%). Women also appeared to be at a greater risk for several alcohol-related consequences than men—including cardio-vascular disease, liver disease, alcohol use disorder. Dr. Koob said:

Taken together, the findings of this study and others suggests that alcohol-related harms are increasing at multiple levels – from ED visits and hospitalizations to deaths. We know that the contribution of alcohol often fails to make it onto death certificates. Better surveillance of alcohol involvement in mortality is essential in order to better understand and address the impact of alcohol on public health.

The researchers said alcohol-related deaths were highest among males, individuals between 45 and 74 years of age, and non-Hispanic American Indians or Alaska Natives. Rates increased for all age-groups except 16 to 20 and 75 and over. The largest increase was among non-Hispanic White females. These findings confirm the increasing burden of alcohol on public health.

On his blog, William White observed how the alarm over recent drug surges with opioids and methamphetamines could be obscuring surges in alcohol consumption and its related consequences. In addition to the White et al study, William White also referred to Sherk et al, whose researchers found that even light or moderate alcohol consumption increased the risk for a number of health consequences, including cancer, heart disease and traumatic injuries. More than one quarter (27%) of alcohol-related hospital stays were experienced by individuals who drank within the weekly guidelines.

The low-risk drinking guidelines for men were no more than 14 drinks per week and no more than 4 drinks per day. Low risk guidelines for women were no more than 7 drinks per week and no more than 3 drinks per day. Sherk et al concluded drinkers who followed weekly low-risk drinking guidelines were not immune from harm. They suggested guidelines of one drink per day for both sexes. The researchers clearly demonstrated that alcohol abuse and the related consequences were increasing before the COVID pandemic.

Alcohol Abuse and COVID

As stay-at-home orders began in some US states to lessen COVID-19 transmission in March of 2020, Nielsen reported a 54% increase in national sales of alcohol for the week ending Mach 21, 2020. The World Health Organization warned that alcohol use could potentially worsen health vulnerability, risk-taking behaviors, mental health issues and violence. The WHO suggested existing rules and regulations to protect health and reduce the harm caused by alcohol, such as restricting access, should be reinforced during the COVID-19 pandemic. “Any relaxation of regulations or their reinforcement should be avoided.”

Pollard, Tucker and Green looked at “Changes in Adult Alcohol Use and Consequences During the COVID-19 Pandemic in the US.” The data were collected using the RAND Corporation American Life Panel (ALP), a nationally representative, probability-sample panel of 6,000 participants. A sample of 2,615 ALP members ages, 30-to-80, were invited to participate in the baseline survey.

Comparisons before and during the COVID-19 pandemic were made on the number of days participants reported any alcohol use and heavy drinking, and the average number of drinks consumed over the previous 30 days. Heavy drinking was defined as 5 or more drinks for men and 4 or more drinks for women within a couple of hours. Adverse consequences were assessed by the 15-item Short Inventory of Problems associated with alcohol use in the previous 3 months. Comparisons were made overall, and across self-reported sex, age, and race/ethnicity.

These data provide evidence of changes in alcohol use and associated consequences during the COVID-19 pandemic. In addition to a range of negative physical health associations, excessive alcohol use may lead to or worsen existing mental health problems, such as anxiety or depression, which may themselves be increasing during COVID-19. The population level changes for women, younger, and non-Hispanic White individuals highlight that health systems may need to educate consumers through print or online media about increased alcohol use during the pandemic and identify factors associated with susceptibility and resilience to the impacts of COVID-19.

It does seem that concern with overdoses from opioids and methamphetamine in the midst of COVID overshadowed the growing problem with increasing alcohol consumption and its related consequences during the pandemic. William White observed that alcohol use is historically pervasive in the U.S. and “so infused into the cultural water in which we all swim that we fail to see it. That blindness has exacted, and continues to exact, an enormous toll on individuals, families, and communities.” The findings of the above discussed research studies reinforce the need for continued efforts with public and professional alcohol-related education, alcohol treatment resources, screening for alcohol problems and recovery support for individuals and families effected by alcohol use disorders. We cannot let concerns with the pandemic or opioid epidemic draw our attention away from the growing problem with alcohol-related deaths.

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.”

08/24/21

Homelessness and COVID-19

The findings for the 2020 Annual Homeless Assessment Report (AHAR) to Congress were published in January of 2021 and it contained some disturbing information. In a single night in 2020, approximately 580,000 people experienced homelessness in the U.S. Sixty-one percent stayed in sheltered locations, while 39% were “living rough” on the street, in abandoned buildings, or wherever they could pitch a tent. For the fourth year in a row, homelessness increased nationwide. The number of people who were homeless increased by 2% between 2019 and 2020. Almost 60% experienced homelessness in an urban area and 53% of all unsheltered people were counted in the nation’s 50 largest cities.

The 2020 AHAR count reflects a 7% increase of individuals staying outdoors with the number of sheltered individuals remained largely unchanged, with a 0.6% decline. “Increases in the unsheltered population occurred across all geographic categories.” The key factor was a sizeable increase (21%) in the number of unsheltered people with chronic patterns of homelessness. This means being homeless for more four times in the past 3 years, or continuously homeless for at least one year.

Unsheltered families with children also increased for the first time since data collection began. In 2020, just under 172,000 people in families with children were homeless. While most of these homeless families (90%) were in sheltered locations, there was an increase of unsheltered families by 13%.

People identifying as black or African American accounted for 39 percent of all people experiencing homelessness and 53 percent of people experiencing homelessness as members of families with children but are 12 percent of the total U.S. population. Together, American Indian, Alaska Native, Pacific Islander and Native Hawaiian populations account for one percent of the U.S. population, but five percent of the homeless population and seven percent of the unsheltered population. In contrast, 48 percent of all people experiencing homelessness were white compared with 74 percent of the U.S. population. People identifying as Hispanic or Latino (who can be of any race) are about 23 percent of the homeless population but only 16 percent of the population overall. [See the following graphic]

Psychological Services published a special issue on homelessness in 2017, “Homelessness as a Public Mental Health and Social Problem.” The authors said after deinstitutionalization in the 1960s, thousands of patients moved out of mental institutions into community-based care became homeless. Under the Bush administration, the federal government began requiring communities to conduct and report annual point-in-time counts of homeless individuals to track the scope of the problem. An epidemiological study found that 4.2% of Americans have experienced homelessness for over one month sometime in their lives and 1.5% experienced homelessness in the past year. “From both epidemiological studies and PIT counts, it is clear that homelessness remains a major problem in the country.”

Risk factors that are strongly associated with homelessness include adverse childhood experiences, mental illness and substance abuse. Most research on homelessness has focused on homeless, single, middle-aged men. “But there is increasing study on the growing number of homeless women and families who may have different needs.”

While there have been efforts to provide housing for the homeless or those at risk of homelessness, such as the HUD Exchange, many people who enter supported housing return to homelessness. Comprehensive primary care and behavioral health services have been intentionally integrated into many homeless organizations. Unfortunately, there continues to be limited access to mental health and substance use services available for many in supportive housing.

Nan Roman, the President and CEO of the National Alliance to End Homelessness, said the 2020 report gave a deeply troubling picture of homelessness in the U.S. on the eve of the COVID-19 pandemic. She said these results show an under-resourced system supposed to meet the needs of people at risk of and experiencing homelessness. While the Alliance was encouraged by the investments federal leaders have made in homelessness and housing resources during the pandemic, “the numbers make it clear that these investments are tragically overdue.”

COVID-19 and Homelessness

The pandemic was a major disruption for homeless system operations. The yearly Point-in-Time (PIT) survey for 2021 of persons who are homeless received new guidance that allowed for flexibility when counting people who were unsheltered. There were allowances made for observation-only counts, samplings, abbreviated surveys, and longer times permitted for the process. There was even a report published to guide those conducting a street-based PIT count that maintained the health and safety of those performing the count as well as those individuals who were homeless during the COVID-19 pandemic. See the National Alliance to End Homelessness for a webinar on “Conducting the 2021 PIT in the Age of COVID-19” and other resources.

In “COVID-19 and the State of Homelessness,” the National Alliance to End Homelessness reported how the pandemic significantly complicated efforts to end homelessness. One expert predicted there would be an increase of 250,000 new people homeless over the course of the year. Consider that before the pandemic, systems were not able to serve everyone experiencing homelessness. “Providers only had capacity to offer an emergency shelter bed to 1 in 2 individuals experiencing homelessness in 2019.” Limited resources resulted in overcrowded shelters and social distancing was difficult, if not impossible. “Unsheltered people lack consistent access to water, soap, and hand sanitizers that help prevent the spread of the virus.”

In “People experiencing homelessness: Their potential exposure to COVID-19,” Lima et al noted how many homeless people already have a diminished health condition, higher rates of chronic illnesses or compromised immune systems, “all of which are risk factors for developing a more serious manifestation of the coronavirus infection.” Those suffering from mental illness potentially struggle recognizing and responding to threats of infection. They also have less access to health care providers who could order diagnostic testing, and if confirmed, isolate them from others in coordination with local. Health departments.

In “Data for: People experiencing homelessness: Their potential exposure to COVID-19,” Neto et al said homeless organizations warned the coronavirus could cause catastrophic harm to unhoused communities. People who sleep in shelters or on the streets already have a lower life expectancy, as well as struggles with addiction and underlying health conditions that put them at greater risk should they develop the virus. Experts say the chronically ill homeless have a unique vulnerability to the coronavirus. “If exposed, people experiencing homelessness might be more susceptible to illness or death due to the prevalence of underlying physical and mental medical conditions and a lack of reliable and affordable health care.”

People experiencing homelessness are increasingly older and sicker. Many have underlying health conditions but lack access to primary-care physicians or preventive health screenings. They struggle to find public bathrooms to maintain their basic hygiene. Those who live in tent encampments or crowded shelters might be unable to keep their distance from others or self-isolate if they show symptoms.

A CDC Morbidity and Mortality Weekly Report (MMWR) for May 1, 2020 assessed the infection prevalence of COVID in five homeless shelters for residents and staff members in four U.S. cities—Boston, San Francisco, Seattle and Atlanta. They found that when COVID clusters (two or more cases in the preceding two weeks) occurred, “high proportions of residents and staff members had positive test results for SARS-CoV-2.” Community incidence (the average number of reported cases in the count per 100,000 persons per day during the testing period) varied, with Boston having the highest incidence and San Francisco the lowest.

To protect homeless shelter residents and staff members, CDC recommends that homeless service providers implement recommended infection control practices, apply social distancing measures including ensuring residents’ heads are at least 6 feet (2 meters) apart while sleeping, and promote use of cloth face coverings among all residents. These measures become especially important once ongoing COVID-19 transmission is identified within communities where shelters are located. Given the high proportion of positive tests in the shelters with identified clusters and evidence for presymptomatic and asymptomatic transmission of SARS-CoV-2, testing of all residents and staff members regardless of symptoms at shelters where clusters have been detected should be considered. If testing is easily accessible, regular testing in shelters before identifying clusters should also be considered. Testing all persons can facilitate isolation of those who are infected to minimize ongoing transmission in these settings.

In the Journal of Internal Medicine, “Addressing the COVID-19 Pandemic Among Persons Experiencing Homelessness,” Barocas et al noted that at least 1 in 5 of 13.8 million adults in rental housing say they are behind in rent. Coupled with an end to the federal eviction moratorium, this could mean an increase of more than 2.7 million newly homeless or unstably housed people in the U.S. Medical conditions such as heart and lung disease disproportionately effect the unsheltered and place them at risk for high morbidity and mortality from COVID-19. “A sudden increase in the number of people without housing or infections in the existing homeless population combined with COVID-19’s current strain on our health care system will greatly reduce our ability to care for this vulnerable population.”

Barocas et al recommended four changes. First, immediate improvements to and expansion of the national shelter system are needed. They believe the situation will become more dire if the federal eviction moratorium is not extended. Federal and state relief plans need to allocate funds for more shelters that are properly staffed and resourced.

Second, there needs to be an improvement with ongoing surveillance to prevent outbreaks among homeless individuals. One of the suggestions was to increase the use of waste water-based epidemiology, the practice measuring biomarkers in wastewater. “Active surveillance of municipal wastewater mapped to homeless shelters could be used to identify insipient outbreaks.” This seems to be a potentially low-cost COVID-19 surveillance method that could be used in low-resource settings such as shelters.

The third recommendation is to develop a universal approach to testing and contact tracing. A lack of testing supplies has led to a disproportionate allocation of tests across society, with more socially disadvantaged individuals encountering challenges when accessing tests. New methods of contact tracing rely on the assumption of stable housing, secure internet, or cell phones with application abilities. While most homeless people own or have access to a mobile phone, they often do not have smartphones that support app-based programs. “We need a dedicated investment in contact tracing in this population; otherwise, expanded testing will be for naught.”

The fourth and final recommendation is to provide places for persons with inadequate housing and without a permanent home to isolate once they are diagnosed with COVID-19 and do not meet criteria for skilled nursing care. Shelters are usually not equipped to convert entire floors into quarantine units. Innovative approaches to help this vulnerable population attain a space to recuperate and limit the spread of COVID-19, such as using hotels or college dormitories for temporary housing, were suggested.

As a nation, we have, thus far, done little to protect persons experiencing homelessness from COVID-19 disease. In the short term, we need funding for the expansion and improvement of our shelter systems, development and implementation of innovative strategies for active surveillance of outbreaks, rapid deployment of more COVID-19 tests coupled with a comprehensive contact tracing strategy, and expanded space for recuperation for this population. For a long-term effect, we need to extend the eviction moratoria and to use the pandemic as an opportunity to expand affordable and low-income housing and establish pathways to regain housing. Continued neglect of this vulnerable population will most certainly lead to considerable strain on the already stretched healthcare system during times of SARS-CoV-2 surge, increased transmission and mortality from SARS-CoV-2, and a widening health disparity gap.

The 2021 Annual Homeless Assessment Report will not be completed and published until 2022. The 2020 AHAR was published in March of 2021 and already showed a 2% increase from 2019 to 2020. What will the 2021 AHAR reveal?

03/23/21

The Trickery of Drug Approval

From all that the public is hearing and seeing about the COVID vaccines, both the pharmaceutical companies and the FDA have done an amazing job bringing the first two vaccines to market. In order to alleviate public mistrust of the “warp speed” development process, Dr. Anthony Fauci and NIH director Francis Collins publicly received their first dose of the Moderna vaccine. Dr Fauci said it was remarkable to be receiving it less than a year after the virus it treated was discovered. “What we’re seeing now is the culmination of years of research which have led to a phenomenon that has truly been unprecedented.” But will the pharmaceutical companies continue this standard of fast, safe and effective drug development?

In January 2020, just before the emergence of the pandemic, Harvard Medical School researchers published a study in JAMA that found the FDA is approving new drugs more quickly than ever before and using less stringent standards to determine if the drugs actually work. The lead author of the study told NPR “There has been a gradual erosion of the evidence that’s required for FDA approval.” As a result, patients and doctors “should not expect the new drugs will be dramatically better than older ones.” The use of expedited programs (Accelerated Approval, Fast-Track, and Priority Review) for new drugs increased over time, with 81% of new drugs benefiting from at least one such program in 2018. NPR reported the study found the median review time for standard drug applications was just over 10 months in 2018 compared to 2.8 years for standard and priority applications from 1986 through 1992.

The proportion of new approvals supported by at least 2 pivotal trials decreased from 80.6% in 1995-1997 to 52.8% in 2015-2017, based on 124 and 106 approvals, respectively, while the median number of patients studied did not change significantly (774 vs 816). FDA drug review times declined from more than 3 years in 1983 to less than 1 year in 2017. But total time from the authorization of clinical testing to approval has remained at approximately 8 years over that period.

Drug makers began to pay FDA fees to fund the review process as a result of AIDS activists protesting the slowness of the agency in the 1980s. In 1993, the first year after Congress passed the Prescription Drug User Fee Act, the FDA collected $29 million in fees. That amount rose to $908 million in 2018. The industry fees amounted to around 80% of the money spent on FDA employee salaries for drug reviews that year. The lead author of the JAMA study said: “There is some concern about the incentives that this created within the FDA … And whether it has created a culture in the FDA where the primary client is no longer viewed as the patient, but the industry.”

The Pharma Marketing Blog tracked the relationship of fees paid to the FDA by the pharmaceutical industry and the push for less rigorous scientific proof in clinical trials (and therefore faster drug approvals). He noted that there was a negative correlation between the rise in user fees and a drop in the number of warning letters sent out by the FDA to companies. There was also a positive correlation between drug user fees and adverse event reports, which track drug safety. See the following graphs taken from the Pharma Marketing Blog.

This hasn’t been the only recent evidence of how the pharmaceutical industry seems to be replacing patients as the FDA’s primary clients. Researchers published a study of the “Association between FDA and EMA [European Medicines Agency] expedited approval programs and therapeutic value of new medicines” in the October 2020 issue of the BMJ. The study sought to characterize the therapeutic value of new drugs approved by the FDA and EMA and how these ratings were associated with the regulatory approval process of the expedited programs of the FDA and EMA.

Over the past few decades both agencies have established programs to expedite drug development for serious conditions. The four main expedited programs of the FDA are: fast track (introduced in 1987), accelerated approval (1992), priority review (1992), and breakthrough therapy (2012). Emergency use authorization, under which the COVID-19 vaccines have been expedited, technically isn’t an FDA approval of the drug, but it authorizes the FDA to facilitate an unapproved product during a declared state of emergency. Its latest update occurred in 2017. The EMA has two expedited programs, accelerated assessment (2005) and conditional marketing authorization (2006). The EMA instituted a third program, PRIME, the priority medicines scheme, in 2016.

These expedited programs were intended to prioritize the most important medicines for faster access to patients, and are increasingly the route by which new medicines are approved. For example, the FDA approved 60% of new drugs through at least one expedited program in 2019, while only 34% of drug approvals in 2000 were expedited. The FDA and EMA guidance indicated that an expedited program should be reserved for drugs that are expected to show an improvement over the available therapies. “However, neither the FDA nor the EMA specifically requires data on, or makes regulatory approval contingent on, comparative effectiveness; most new drugs are approved on the basis of placebo-controlled trials or single arm studies.”

This means the therapeutic value of medicines that benefitted from the FDA and EMA expedited programs is uncertain. Using ratings of therapeutic value published by health authorities in four countries and an independent non-profit organization, the researchers “evaluated the association between expedited programs and ratings of therapeutic value for all new drugs approved by the FDA and EMA from 2007 through 2017.”

We found that less than a third of all new drugs approved by the FDA and EMA were rated by any of five independent organizations as having high therapeutic value—that is, providing moderate or better improvement in clinical outcomes for patients. Most of the increase in the number of new drug approvals over the past decade was driven by drugs rated as having low therapeutic value, which calls into question the common practice of using simple counts of new drug approvals as a measure of innovation. Rather, a more nuanced view of innovation is needed that takes into account the clinical benefits and relevance to patients of new medicines.

The study’s findings suggest that after FDA regulatory approval, there is a widening gap between the drug’s approval and the clinical and public health priorities of health systems, payers and patients in drug safety and efficacy. Contributing to this gap is the varying quality of clinical evidence available at the time of approval. This leads to uncertainty around the extent of clinical benefit of the respective drug. The study’s data emphasizes the importance of robust post marketing evaluation for expedited drugs. “Such an evaluation would confirm early evidence of efficacy and help to elucidate findings from several previous studies suggesting that accelerated approval, priority review, and fast track drugs were associated with increased safety related reports or labeling changes.”

The researchers suggested one step leading to greater assurance of timely completion of post marketing study requirements for expedited drugs could be to require that certain mandated studies enroll patients before the FDA or EMA grants approval. They also suggested that regulatory agencies explore whether additional explanations were necessary. These explanations could include elaboration in product labeling, press releases, or approval documents. They could provide more realistic expectations of benefit for expedited drug approvals by patients and clinicians. Their findings also had implications for the controversy around drug prices.

In the US, the largest public payers are required by law to cover most (Medicaid) or a substantial number (Medicare) of drugs approved by the FDA, regardless of the quality of the evidence supporting their approval or their therapeutic value. Previous studies of cancer drugs have found no association between clinical benefit and drug prices and reimbursement.

In conclusion, the researchers said while the FDA and EMA are increasingly using expedited programs to facilitate drug development, the absolute value of highly rated drugs approved by the FDA and EMA over the past decade was low. Policy makers could explore implementing therapeutic value ratings more widely for new drug approvals. This would align the evidentiary needs of regulatory approval and reimbursement decisions with informing patients and doctors about the benefits and risks of new drugs, particularly those approved by expedited programs.

It’s not so surprising, then, that so many Americans are hesitant to say they plan to get a coronavirus vaccine. It seems that the above discussed results of research into new drug development by the pharmaceutical companies is at least partly to blame. Many people do not trust the claims drug companies make about their products.

The Pew Research Center conducted a survey of Americans at the end of November 2020. Sixty percent said they would definitely or probably get a vaccine for the coronavirus, which was up from 51% in September. Thirty-nine percent say they will definitely or probably not get a coronavirus vaccine. About half of this group, 18%, said it’s possible they would decide to get vaccinated once people start getting vaccinated and there is more information available. “Yet, 21% of U.S. adults do not intend to get vaccinated and are ‘pretty certain’ more information will not change their mind.”

While public intent to get a vaccine and confidence in the vaccine development process are up, there’s considerable wariness about being among the first to get a vaccine: 62% of the public says they would be uncomfortable doing this. Just 37% would be comfortable.

Public confidence has increased since September that the research and development process will yield a safe and effective vaccine for COVID-19. Seventy-five percent of individuals now have a great deal or fair amount of confidence in the R&D process. However, one of the factors influencing whether someone intends to get a vaccine for COVID-19 is mistrust of the vaccine development process. Sixteen percent of Americans do not have much confidence in the process; 8% have no confidence that the R&D process will produce a safe and effective vaccine for COVID-19. Confidence in scientists remains slightly higher than before the pandemic.

With scientists and their work in the spotlight, 39% of Americans say they have a great deal of confidence in scientists to act in the public’s best interest, an uptick from 35% who said this before the pandemic took hold. Most Americans have at least a fair amount of confidence in scientists. However, ratings of scientists are now more partisan than at any point since Pew Research Center first asked this question in 2016: 55% of Democrats now say they have a great deal of confidence in scientists, compared with just 22% of Republicans who say the same.

Pharmaceutical companies have an opportunity when they resume the research and development process for new drug applications after the pandemic. Will they continue to use external committees of scientists vetting the data for new drug applications and produce truly independent recommendations and rejections? If pharmaceutical companies can maintain an open and transparent R&D process and develop drugs with a truly high therapeutic value, the confidence level of patients and their doctors would be higher than ever. For more on COVID, see “Learning from COVID Drug Development.”

01/26/21

Learning from COVID Drug Development

On December 11, 2020 the FDA issued an emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 Vaccine. Then on December 18^th, the FDA issued an EUA for the Moderna COVID-19 Vaccine. The FDA News Releases for both drugs said the data provided clear evidence both vaccines may be effective in preventing COVID-19. The known and potential benefits for both drugs were said to outweigh the known and potential risks. “In making this determination, the FDA can assure the public and medical community that it has conducted a thorough evaluation of the available safety, effectiveness and manufacturing quality information.”

In December of 2019, no one knew COVID-19 existed and now there are two vaccines being distributed in the US that are both around 95% effective in preventing the novel coronavirus. Despite the unprecedented speed of their development, there were not any compromises with the safety or the scientific integrity of the process. According to Dr. Anthony Fauci, the speed was “a reflection of the extraordinary scientific advances in these types of vaccines which allowed us to do things in months that actually took years before.” He wanted to settle the concerns some people have about the rush of development and approval. Despite the politicization of the process, there was an independent body of people with no allegiance to the administration or to the pharmaceutical companies who were the first ones to review and then approve the data from the companies’ late-stage clinical trials. “We need to put to rest any concept that this was rushed in an inappropriate way . . . Help is on the way.”

The FDA requires that a vaccine be at least 50% effective, according to the latest guidance. By comparison, two doses of the measles vaccine is about 97% effective, and flu vaccines range from about 40% to 60% effective, according to the Centers for Disease Control and Prevention (CDC).

The FDA just finalized the guidance for EUAs in January of 2017. The purpose of this guidance was to explain the FDA’s current thinking on the authorization of the emergency use of certain medical products under certain sections of the Federal Food, Drug and Cosmetic Act, as it was amended or added to by the Pandemic Reauthorization Act of 2013 (PAHPRA).

The provisions in PAHPRA include key legal authorities to sustain and strengthen national preparedness for public health, military, and domestic emergencies involving chemical, biological, radiological, and nuclear (CBRN) agents, including emerging infectious disease threats.

The Washington Post published an article that addressed common concerns about the COVID-19 vaccines. First, it is not just the vulnerable who should get the vaccine. Vaccines protect more than just the person who is inoculated. The more people who are vaccinated means there are fewer people the virus can infect, “lowering the infection rate and the risk for us all.” Another reason is to protect those who cannot get it. The first two approved vaccines were only approved for individuals over the ages of sixteen for the Pfizer-BioNTech COVID-19 Vaccine and 18 for the Moderna COVID-19 Vaccine.

Your decision not to get vaccinated could affect other people around you. Individuals with a weakened immune system may need to rely on the immunity of others to keep them healthy. Not getting a vaccine would be like refusing to wear a mask. We will likely have to wear masks through 2021. In fact, vaccinated people should wear masks and follow social distance guidelines. While the vaccine is effective at reducing symptomatic illness, it is not yet known whether it reduces the likelihood of contracting the coronavirus and being an asymptomatic carrier.

As more people get vaccinated and the US gets to community or herd immunity, there will come a point when we can do away with the masks. “In the meantime, vaccination is a crucial tool. It doesn’t replace other tools but is a powerful measure that can help save lives and help the economy recover.” Allergic reactions can be treated without lasting consequences, but the same is not true for COVID-19. At this time, it is not known what component of the vaccine triggers allergic reactions, but there is not reason for people with food or medication allergies to avoid the vaccine as long as they are monitored in a health-care setting.

All viruses mutate and it may turn out that people will have to receive regular booster shots, like with tetanus or the flu shot. Enough mutations could eventually reduce the potency of existing vaccines. A study of the Moderna vaccine found it was effective for at least 119 days. But some experts believe immunity should last at least a year. “The theoretical necessity of future vaccinations doesn’t override the urgency of getting one now.”

For those worried about political interference in expediting approval, it’s critical to emphasize that no shortcuts were taken in research or the approval process. Vaccine safety was tested in phase 3 trials involving tens of thousands of participants. External committees of scientists vetted the data and produced independent recommendations to support vaccine authorization.

The Allegheny Health Network (AHN) posted a series of frequently asked questions (FAQs) and answers that addressed further questions about the COVID-19 vaccines. The further information there included that no doctor’s order will be necessary to get the vaccine, but you will have to schedule an appointment. AHN said the vaccine is free to all Americans and will be available at retail pharmacies. “Remember, some vaccines require two doses to be effective. It’s extremely important you get both and follow the suggested timeline.”

Who knows where we’ll be with COVID in another twelve months! But there are some things we’ve learned through this pandemic about drug companies and hopefully will continue to insist on. Drug development can be done quickly and safely. Pharmaceutical companies can be open and transparent about their research and allow truly independent, external committees to verify their findings. People can trust the results of drug development when the clinical trial process is not statistically or methodologically manipulated to show what the researchers want to find.

The widespread mistrust of science that became evident during the pandemic seems partly due to the previous manipulation of drug development by the pharmaceutical companies. Like good illusionists, they directed our attention to what they wanted us to see and away from what they wanted to hide. Going forward, open, transparent drug development can restore the trust that is now lacking for the COVID vaccine. During the pandemic drug companies showed they could do COVID Drug Development quickly and safely. We need to remember these things and hold the drug companies accountable to these standards.

01/19/21

Co-Occurring COVID Surges

We’re now all getting ready to queue up for one of the COVID vaccines. But while our attention was on COVID surges and the political circus, there were also a surge of drug overdose deaths. The CDC reported in the twelve months ending in May 2020, there were over 81,000 drug overdose deaths in the US, the largest number of drug overdoses ever for a 12-month period. After declining 4.1% from 2017 to 2018, the number of overdose deaths increased 18.2% from June 2019 to May 2020. The increases appear to have accelerated during the COVID-19 pandemic.

The recent increase in drug overdose deaths began in 2019 and continued into 2020, before the declaration of the COVID-19 National Emergency in March. However, provisional overdose death estimates indicate that from the end of February 2020 to the end of March 2020 there was an increase of 1,511 deaths. From the end of March 2020 to the end of April 2020 there was an increase of 2,146 deaths. And from the end of April 2020 to the end of May 2020 there was an increase of 3,388 deaths. These totals were the largest monthly increases since provisional 12-month estimates began to be calculated in January 2015. See the figure below taken from the CDC Health Alert Network report.

Not surprisingly, synthetic opioids were the main driver of the increases in overdose deaths. “State and local health department reports indicate that the increase in synthetic opioid-involved overdoses is primarily linked to illicitly manufactured fentanyl.” Not all of the reporting jurisdictions (the fifty states plus the District of Columbia and New York City) had available data on synthetic opioids. Of the 38 jurisdictions with available synthetic opioid data, 37 reported increases in synthetic opioid overdose deaths for the time period (June 2019 to May 2020); 18 increases were greater than 50% and 11 increases were between 25% and 49%. See Figure 3 in the above linked CDC report for information on which jurisdictions were not included.

Historically, deaths involving illicitly manufactured fentanyl have been concentrated in the 28 states east of the Mississippi River, where the heroin market has primarily been dominated by white powder heroin. In contrast, the largest increases in synthetic opioid deaths from the 12-months ending in June 2019 to the 12-months ending in May 2020 occurred in 10 western states (98.0% increase). This is consistent with large increases in illicitly manufactured fentanyl availability in western states and increases in fentanyl positivity in clinical toxicology drugs tests in the West after the COVID-19 pandemic. Increases in synthetic opioid overdose deaths were also substantial in other regions: 12 southern states and the District of Columbia (35.4%), 6 midwestern states (32.1%), and 8 northeastern states and New York City (21.1%) (Figure 3).

Overdose deaths from cocaine increased by 26.5% from June 2019 to May 2020. The recent deaths are due primarily to overdose deaths involving both cocaine and synthetic opioids. In contrast, overdose deaths from psychostimulants like methamphetamine have been increasing without synthetic opioid co-use. The rate of increase was faster than overdose deaths involving cocaine and is now greater than the number of cocaine-involved deaths. There was a projected increase of 34.8% of overdose deaths from psychostimulants from June of 2019 to May of 2020.

During a recent webinar, “COVID-19 and Its Impacts on Substance Abuse,” a past president of the American Medical Association (AMA) said it was imperative that we continue to talk about health issues other than COVID 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.” The AMA said that science, evidence and compassion must continue to guide patient care and policy change as the nation’s opioid epidemic develops into a more alarming and convoluted drug overdose epidemic.

The federal government has eased regulations that make it easier for doctors to treat patients with substance use disorder during the pandemic. But it is not clear that all states will take advantage of these relaxed policies. The DEA has issued guidance that allows practitioners to prescribe buprenorphine to new patients with opioid use disorder after a telephone evaluation. A SAMHSA (Substance Abuse and Mental Health Services) policy allows stable methadone patients to obtain up to 28 days of take-home medication. “With social distancing recommendations and inconsistent public transportation availability, this policy assists patients that might not be able to visit an opioid treatment program on a daily basis.”

In the midst of COVID surges and the steady rise of drug overdose deaths, there is another COVID-related escalation happening with mental health symptoms in the U.S. and around the world. The 2020 Commonwealth International Health Policy Survey found that one-third of U.S. adults reported experiencing stress, anxiety and great sadness that was difficult to cope with since the COVID outbreak started. Americans were more likely than people in other countries to report mental health concern. Past research showed that Americans were already more likely to experience emotional distress, yet it seems the pandemic has contributed to higher rates of emotional distress in several countries. “The negative impact of COVID-19 on mental health has been immediate, and the pandemic is certain to have long-term effects in every country it has touched.”

Fifty-six percent of U.S. adults who reported experiencing any negative economic consequences of the pandemic also reported having mental health distress. The pandemic’s economic toll has contributed to higher levels of mental distress in other places as well. In all five countries for which reliable estimates could be calculated, people who said they experienced any type of economic insecurity since the start of the outbreak were several times more likely to also report stress, anxiety, and great sadness that was difficult to cope with alone.

The New York Times reported there is growing evidence that a small number of COVID patients with no history of mental health problems are developing severe psychotic symptoms weeks after contracting the virus. A British study published in The Lancet found 10 individuals out of 153 patients hospitalized with COVID-19 had new-onset psychosis. A Spanish study published in the journal Psychiatry Research also found ten individuals with new-onset psychotic episodes in COVID-19 patients. In COVID-related social media groups, medical professionals discussed seeing patients with similar symptoms in the Midwest, Great Plains and other places in the U.S. Neurological, cognitive and psychological symptoms could emerge even in patients who did not have serious lung, heart or circulatory problems.

A 36-year-old nursing home employee in North Carolina who became so paranoid that she believed her three children would be kidnapped and, to save them, tried to pass them through a fast-food restaurant’s drive-through window.A 30-year-old construction worker in New York City who became so delusional that he imagined his cousin was going to murder him, and, to protect himself, he tried to strangle his cousin in bed.A 55-year-old woman in Britain had hallucinations of monkeys and a lion and became convinced a family member had been replaced by an impostor.

Experts speculate that these brain-related effects may be linked to either vascular problems or surges of inflammation caused by the disease process; Another possibility is the body’s immune system response to the coronavirus. Persistent immune activation is a leading explanation for memory problems and what has become known as “COVID brain fog.” Some post-COVID psychosis patients needed weeks of hospitalization while doctors tried different medications. There have been past reports of post-infectious psychosis and mania with other viruses, including the 1918 flu, SARS and MERS.

We don’t know what the natural course of this is . . . Does this eventually go away? Do people get better? How long does that normally take? And are you then more prone to have other psychiatric issues as a result? There are just so many unanswered questions.

While we appropriately focus our attention on COVID, let’s not forget about the growing problem with drug overdoses and not neglect the emergence of post-COVID psychosis. As the AMA exhorted, science, evidence and compassion must guide us in addressing the COVID pandemic, the overdose epidemic and the concurrent rise of mental health concerns.

For other articles on drug overdoses or anxiety in the midst of COVID, see “Drug Overdose Deaths: In the Shadow of COVID-19” and “An Epidemic Emerging from the Pandemic?”

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.

06/9/20

An Epidemic Emerging from the Pandemic?

According to a report by Express Scripts, America’s State of Mind, the number of prescriptions filled per week for antidepressant, anti-anxiety and anti-insomnia medications increased 21% between February 16^th and March 15^th. COVID-19 was declared a pandemic on March 12^th. Prescriptions for anti-anxiety medications rose 34.1% during that four-week period, with an increase of almost 18% during the week ending March 15. “The number of prescriptions filled for antidepressants and sleep disorders increased 18.6% and 14.8%, respectively, from February 16 to March 15.”

More than three quarters (78%) of all antidepressant, antianxiety and anti-insomnia prescriptions filled during the week ending March 15^th (the peak week) were for new prescriptions.

Express Scripts is the largest pharmacy benefit management (PBM) company in the U.S., with $100.75 billion in revenues. The Express Scripts Drug Trend Report has been published annually since 1993 and provides a detailed analysis of prescription drug costs and utilization. Express Scripts said it was understandable that Americans have become more anxious as they’ve seen the COVID-19 global pandemic swiftly and dramatically upend their lives. “This analysis, showing that many Americans are turning to medications for relief, demonstrates the serious impact COVID-19 may be having on our nation’s mental health.”

The increase of anti-anxiety medications was particularly striking, given that Express Scripts’ research showed the use of these drugs had been declining over the past five years. Mental health medication trends from 2015 through 2019 recorded a decline of more than 12% in the use of anti-anxiety medications. This was among 21 million people with employer-funded insurance. There was a similar decline in the use of anti-insomnia medications, which were down 11.3%.

While the recent increased use of medications to treat anxiety, depression and sleep disorders is sudden, it is encouraging to see our members recognizing the need for help and seeking support from their physician. What’s crucial now is ensuring Americans who are experiencing symptoms of these mental health conditions have support and access to their physicians, therapists and educational resources, including digital tools and virtual care and counseling to help them cope during this time.

The rapid increase in anti-anxiety prescriptions is troubling, perhaps more troubling than the Express Scripts data indicates. Prolonged use of benzodiazepines is associated with tolerance and withdrawal symptoms, as well as misuse and substance use disorder. In older adults, benzodiazepines increase the risk of falls, hip fractures, cognitive impairment and drug-related hospital admissions. Contrary to what was reported by Express Scripts, the number of U.S. adults with a prescription for a benzodiazepine increased from 4.1% in 1996 to 5.6% in 2013, according to a report by the National Center for Health Studies released on January 17, 2020.

Overdose deaths that involved benzodiazepines increased from .58 per 100,000 in 1996 to 3.07 in 2010. “Data from the National Institute on Drug Abuse show that 11,537 overdose deaths involving benzodiazepines occurred in 2017.” About 85% of the 2017 overdose deaths involving benzodiazepines also involved an opioid, despite warnings that coprescribing benzos with opioids increases the risk of respiratory depression. The coprescription of benzodiazepines and opioids increased from .5% of doctor visits in 2003 to 2.0% in 2015; opioids were prescribed at 26.4% of the visits where there was also a prescription for benzodiazepines. In 2016, the FDA issued warnings on the concurrent use of opioid medications and benzodiazepines.

The data examined from the 2014-2016 National Ambulatory Medical Care Survey included office visits where opioids were coprescribed. “Among visits at which benzodiazepines were prescribed, approximately one-third involved an overlapping opioid prescription.” More women than men were prescribed benzodiazepines and this pattern went across all age groups. This was also true when benzodiazepines were prescribed with opioids for adult patients. See the chart below.

About one-half of the visits where a benzodiazepine was prescribed were with a primary care provider (48%) and one-half (50%) were with another type of provider. Among primary care providers, general or family practice (54%) and internal medicine (39%) were the most frequent specialties. Among nonprimary care providers, psychiatrists accounted for 28% of visits where benzodiazepines were prescribed. Patients who visited the doctor frequently, six or more times in the past 12 months, were more likely (40%) to receive a prescription for benzodiazepines.

Private insurance (39%) and Medicare (38%) were the primary sources of payment for office-based visits when benzodiazepines were prescribed, followed by Medicaid (9%) and no insurance (7%). One-half the visits by adults between 18 and 44 and 45 and 64 where benzodiazepines were prescribed used private insurance, whereas 79% of visits by adults 65 and over used Medicare as the primary source of payment. 88% of the visits where in which benzodiazepines were prescribed, benzos were a continued prescription. See the chart below for the data by age group and source of payment.

There were 23 million prescriptions of benzodiazepines, accounting for 35% of the doctors’ office visits at which benzos were prescribed. The percentage of visits having new prescriptions for a benzodiazepine and an opioid was significantly lower than the percentage of visits with continued prescriptions across all age groups. The percentage of visits with a new prescription for benzodiazepines decreased with age. But the percentage of visits with a continued prescription for benzos increased with age. See the chart below.

In “The Disturbing Rise in Benzodiazepine Prescriptions,” Christopher Lane reported for Psychology Today that the results of the National Center for Health Studies report were “discouraging and disappointing.” He thought we should be concerned with bringing these numbers down. “Between 2003 and 2015, the number of ambulatory visits with one or more prescriptions for a benzodiazepine increased sharply from 27.6 million to 62.6 million.” Keith Humphreys of Stanford, said “The enormous growth of benzodiazepine prescribing has flown under most policymakers’ and clinicians’ radar.” He speculated it may be because many people with a dependency on benzos are older; fewer are violent. “Or maybe people think that since they come from a doctor, they can’t be all that bad.”

While primary care physicians and psychiatrists may be prescribing in good faith for anxiety, pain, and insomnia, the concern is that they are not getting the message about the risks of overprescribing and are instead inadvertently helping to fuel the crisis.

Not only are benzodiazepines a concern in office-based visit Benzodiazepines were implicated in a high rate of ED visits in the U.S., according to Medscape. About a quarter of patients brought to an emergency department (ED) were unresponsive or in cardiopulmonary arrest. More than half (55.9%) of ED visits involving benzos were for the nonmedical use (recreational use or using someone else’s medication) or for self-harm (30.4%). Among visits involving the nonmedical use of benzodiazepines, 54.8% were made by patients between the ages of 15 and 34. About 20% of ED visits for the nonmedical use of benzos involved the concurrent use of other substances. “A quarter (24.9%) of visits involved prescription opioids, a quarter (26.4%) involved alcohol, and almost half (47.8%) involved illicit drugs.”

The noted decrease in anti-anxiety medication prescriptions over the past five years by Express Scripts was likely due to its limited population sample—only those individuals with private insurance. If this assumption is correct, what is happening with benzodiazepines during the COVID-19 pandemic among patients with Medicaid and Medicare? And if benzodiazepine prescriptions tend to be renewed or continued as noted above, what does the future hold for the already problematic coprescription of benzos and other medications, especially opioids, according to the National Center for Health Studies report? It seems we may be facing an epidemic of benzodiazepine addiction emerging from the current pandemic of COVID-19. For more information on the problems with benzodiazepines, see “Doubling the Risk of Overdose,” “Are Benzos Worth It?,” “It Takes Away Your Soul” and “Dancing with the Devil.”

04/7/20

Serving Others During the Pandemic

Traditionally Christians celebrate Easter together in local church services, sometimes with pageantry composed specially for the occasion, but not this year. Following the recommendations of health officials against social gatherings, the COVID-19 pandemic has led to silent, empty buildings or a skeleton crew of individuals presenting a worship service to an empty church that congregants watch live on YouTube or some other media streaming service. There are some who are resistant to social distancing and stay at home orders, like the pastor of a megachurch in Tampa Florida who was arrested for holding public worship services. But is this really the best way to demonstrate your faith in the face of the COVID-19 pandemic? We can look to the past and gain insight from how the followers of Christ acted in times of plague.

In 166 AD triumphant Roman legions returned from their victory over the Parthians in Armenia, bringing with them an epidemic that would ravage the Roman Empire for the next twenty years. Known as the Antonine Plague, it would alter the landscape of the Roman world and kill at least 7 to 10 percent of the population. Lyman Stone said in “Christianity Has Been Handling Epidemics for 2000 Years,” some historians have also suggested it contributed to the spread of Christianity, as “Christians cared for the sick and offered a spiritual model whereby plagues were not the work of angry and capricious deities but the product of a broken Creation in revolt against a loving God.” But it was the Plague of Cyprian (250-270) that really triggered an explosive growth of Christianity.

That plague caused political, military, economic and religious upheaval within the Roman Empire. At its height, it claimed an estimated 5,000 deaths per day in Rome. The outbreak claimed the lives of two emperors: Hostilian (251 AD) and Claudius II Gothicus (270 AD). It also decimated the ranks of the military. Populations in the countryside fled to the cities. “The abandonment of the fields along with the deaths of farmers who remained caused the collapse of agriculture production.”

The illness claimed the lives of emperors and pagans who could offer no explanation for the cause of the plague or suggestions for how to prevent further illness much less actions for curing the sick and dying. Christians played an active role in caring for the ill as well as actively providing care in the burial of the dead. Those Christians who themselves perished from the illness claimed martyrdom while offering non-believers who would convert the possibility of rewards in the Christian afterlife.

Pagans believing the plague had a supernatural origin, believed the gods were punishing them. Dionysius, the bishop of Alexandria, said “the heathen” deserted those who began to be sick, and fled from their close friends. Not so the Christians:

Most of our brother Christians showed unbounded love and loyalty, never sparing themselves and thinking only of one another. Heedless of danger, they took charge of the sick, attending to their every need and ministering to them in Christ, and with them departed this life serenely happy; for they were infected by others with the disease, drawing on themselves the sickness of their neighbors and cheerfully accepting their pains. Many, in nursing and curing others, transferred their death to themselves and died in their stead.

Writing for The Gospel Coalition, Glen Scrivner said Christian death rates during the Plague of Cyprian were significantly lower than the general population. The mutual love and care meant those who provided care were at a higher risk of infection, but those who were infected had better survival rates. When the plague had swept through the Empire, Christians were stronger as a proportion of society since proportionally more of them survived. “They also had more resilience because they had a robust hope in the face of death.”

In 1527, Martin Luther refused calls to leave Wittenberg during an outbreak of the bubonic plague, staying rather to care for the sick. This refusal cost him the life of his daughter, Elizabeth. He wrote a tract reflecting on what a Christian should do, “Whether Christians Should Flee the Plague.” He called for Christian doctors to remain at their hospitals; Christians who hold public office should continue in their service. “Preachers and pastors should likewise remain steadfast before the peril of death.”

Where no such emergency exists and where enough people are available for nursing and taking care of the sick, and where, voluntarily or by orders, those who are weak in faith make provision so that there is no need for additional helpers, or where the sick do not want them and have refused their services, I judge that they have an equal choice either to flee or to remain.

Applying this stance to the current situation, Lyman Stone said it is better for Christians to die serving our neighbor than surrounded by a pile of masks we never had a chance to use. If we care for each other, if we share masks and hand soap and canned foods, if we truly are our brother’s keeper, we may actually help flatten the COVID-19 surge. “The Christian motive for hygiene and sanitation does not arise in self-preservation but in an ethic of service to our neighbor. We wish to care for the afflicted, which first and foremost means not infecting the healthy.”

And there are ways Christians can care, and are caring for the sick and loving their neighbor in this time. Christianity Today noted where churches are dropping off groceries or supplies to those in need. Another church in a farming community provides fresh eggs, fruit and vegetables for those in need. An unemployed young woman was given toilet paper purchased by a store employee when she discovered the store was out. Others provide care and meals for the medical workers and first responders. Another church recruited childcare workers for healthcare workers.

The concluding words of Ed Stetzer for Christianity Today exemplify the heart of those Christians who ministered during the Antoine Plague and the Plague of Cyprian. Martin Luther cries, “Amen!” to these words: “We don’t know a lot about the future. But we know the Lord does, and he cares. And in the meantime, we are called to glorify him by serving others.” So, what can you do during the COVID-19 pandemic?

Faith Seeking Understanding

Charles Sigler, D.Phil.

Tag: COVID-19