08/18/17

Public Health Time Bomb

May came and went with the vast majority of people in the U.S.—including me—being totally unaware that it was Hepatitis Awareness month. May 19^th was National Hepatitis Testing Day. Hepatitis-C (HCV) is the most common form of viral hepatitis in the U.S. The number of new HVC infections almost tripled between 2010 (850) and 2015 (2,436). We need to be more aware of this disease and its treatment because it kills more Americans than any other infectious disease, including HIV. Yes, more people than HIV. CDC data indicated nearly 20,000 Americans died from hepatitis-C-related causes in 2015; and the majority of those deaths were people 55 and older.

“Because hepatitis C has few symptoms, nearly half of people living with the virus don’t know they are infected and the vast majority of new infections go undiagnosed.” The highest rate of new infection occurs among 20- to 29-year-old injection drug users. But ¾ of the 3.5 million Americans living with hepatitis C are baby boomers born between 1945 and 1965. They are six times more likely to be infected with hepatitis C and are at much greater risk of dying from the virus. Around ½ of all the deaths from HCV in 2015 occurred within this age range. You can read the three CDC press releases this information was taken from here, here and here.

These press releases highlighted information in report, “A National Strategy for the Elimination of Hepatitis B and C” that suggested a strategy to eliminate both as public health problems by 2030. Immunization against hepatitis B (HBV) can prevent 95% of infections. There is no vaccine against HCV, but there are anti-viral drugs that can cure hepatitis C, but the costs are prohibitive. The introduction of the report said:

There is no longer any reason to disregard these diseases. There is an effective vaccine to prevent hepatitis B, advances in treatment can prevent most deaths in those chronically infected with HBV, and hepatitis C is now curable with a short course of easily tolerated treatment.

CDC data on HCV suggested that 75% to 85% of newly infected adults and adolescents develop chronic infections. From 2000 to 2002 incident rates for acute HCV decreased for all age groups except for persons aged 0-19. Then the rates remained fairly steady from 2002 through 2010. Between 2010 and 2015 rates increased for persons in all but the oldest (<60 years old) and youngest (0-19 years old) age categories. The largest increase was among persons between 20 and 29 years old. See the following graph of the reported CDC data.

The drug companies charge between $60,00 and #90,000 for a 12-week course of treatment. This is way out of proportion to the cost of treatment in third world countries. Eliminating HCV as a public health problem by 2030 would require mass treatment, but none of the direct-acting agents come off patent before 2029. In the long run, HCV treatment is cost-effective, but doesn’t address the upfront costs charged by pharmaceutical companies for their drugs. So the cost of antiviral that cure HCV is a major obstacle.

These drugs have strained the budgets of public and private payers alike. Faced with the unenviable task of allocating scarce treatment, payers gave first priority to the sickest patients, those at most immediate risk of death. Many also imposed sobriety restrictions, fearing the risk of re-infection in active drug users too great to justify the expense of treatment. Such restrictions have met with criticism. Overt drug rationing offends the American public, but it is difficult to know how else to act in the face of such high prices.

One of the recommendations of the report is for the federal government to purchase the rights to one of the direct-acting antiviral treatments for use with neglected populations such as individuals on Medicaid, in prisons and those treated through the Indian Health Services. This would be a voluntary transaction between the government and the pharmaceutical companies providing the antivirals. The company would be guaranteed reasonable compensation and the licensed drug would only be used in the limited markets (noted above) the companies aren’t now reaching.

Calculations show that the licensing rights should cost about $2 billion, after which states would pay about $140 million to treat 700,000 Medicaid beneficiaries and prisoners. By comparison, the status quo would cost about $10 billion over the next 12 years to treat only 240,000 similar patients.

Critics of the strategy suggest it sets a dangerous precedent by having the government negotiating a license for a costly medicine. Actually, it seems that the federal government’s reluctance to interfere with the pharmaceutical industry may have emboldened it to initially set the extremely high prices foe HCV drugs.

The Senate Finance Committee’s 2014 investigation into the pricing of sofosbuvir [Solvadi] concluded that Gilead had deliberately elevated the price in an effort to raise the market floor, ensuring continued high prices for all future hepatitis C treatments. Action now might discourage other companies from pursuing this strategy in the future.

A CNN article on the report by Susan Scutti noted the hardest hit areas of the U.S. in terms of new HCV infections are parts of Appalachia and rural areas of the Midwest and New England. Several states, Indiana, Kentucky, Maine, Massachusetts, New Mexico, Tennessee and West Virginia have infection rates that are two times or more than the national average. Ten other states have rates above the national average: Alabama, Montana, New Jersey, Noth Carolina, Ohio, Oklahoma, Pennsylvania, Utah, Washington and Winconsin.

There is a website, HepVu, presented by the Rollins School of Public Health at Emory University, which partnered with Gilead Sciences, the original price gauging pharmaceutical company with its antivirals, Solvadi and Harvoni. The original drug development research into Solvadi was done at Emory. Despite the Gilead partnership, HepVu has some helpful information, including an interactive map by state in the U.S. The home page stated there are an estimated 3.9 million people in the U.S. living with past or current hepatitis C infection. You can look up each state’s individual profile.

For example, within my home state of Pennsylvania, there are an estimated 142,100 people living with Hepatitis C. The HCV mortality rate is 4.952 per 100,000 persons, with 629 hepatitis C deaths in 2014. In West Virginia, there are an estimated 24,400 people living with Hepatitis C. The HCV mortality rate is 5.9 per 100,000 persons, with 110 hepatitis C deaths in 2014. In Ohio, there are an estimated 119,100 people living with Hepatitis C. The HCV mortality rate is 4.9 per 100,000 persons, with 567 hepatitis C deaths in 2014. Go to the site and check out your own state’s data.

The outrageous price of medications to treat hepatitis C illustrates how pharmaceutical companies are feeding off of the problems they had a hand in creating. The rise in hepatitis C infections comes as a result of increased IV drug use, which resulted from the prescription opioid epidemic leading individuals to switch from prescription opioids to heroin. And the public health problems with hepatitis C will only get worse since it often goes undiagnosed for years. It’s a public health time bomb.

The above recommendation to have the federal government negotiate a license for one of the existing Hepatitis C treatments is a good one. It just might deter other companies from trying the same pricing trick in the future with other medications. But the cozy lobbying relationship between Pharma and Congress could prevent it.

For more on this issue, see: “Is There No Balm in Gilead?,” “I Guess I’m a Little Bit Socialist,” “Riding the Hep C Gray Train,” “Impeccable Timing” and “Hepatitis Hostages.” Also see “Pharma Companies Hunt in Packs” for more information on the issues of the high cost of prescription drugs.

11/18/16

National ADHD Epidemic

The CDC published a study that found 11% of school-aged children in the U.S. between 2003 and 2011 had received an ADHD diagnosis. This statistic meant that 6.4 million children, 1 in 5 boys and 1 in 11 girls, were said to have ADHD. A different CDC report indicated the American Psychiatric Association (APA) estimated in their 2013 edition of the DSM, the DSM-5, that only 5% of children have ADHD. The rates of ADHD diagnosis are increasing over time, from an average of 3% per year between 1997 and 2006, to 5% between 2003 and 2011. The prevalence of children between the ages of 4 and 17 diagnosed with ADHD varied widely by state. In 2011, the lowest reported rates were in Nevada (5.6%); the highest rates were in Kentucky (18.7%). In contrast, the percentage of children diagnosed and medicated for ADHD in France is less than half of one percent—.5%!

You can see the CDC reports cited above here, here and here.

Writing for Psychology Today in 2012, Marilyn Wedge noted in “Why French Kids Don’t Have ADHD,” how the difference seemed to turn on how ADHD was conceived. In the U.S. ADHD is seen as a biological disorder with biological causes. So the go-to treatment method is stimulant medications. Dr. Wedge also pointed that French psychiatrists did not use the DSM system to diagnose childhood emotional problems. Instead they used an alternative classification system that focuses on the underlying psychosocial causes of a child’s symptoms.

French child psychiatrists, on the other hand, view ADHD as a medical condition that has psycho-social and situational causes. Instead of treating a child’s focusing and behavioral problems with drugs, French doctors prefer to look for the underlying issue that is causing the child distress—not in the child’s brain but in the child’s social context. They then choose to treat the underlying social context problem with psychotherapy or family counseling. This is a very different way of seeing things from the American tendency to attribute all symptoms to a biological dysfunction such as a chemical imbalance in the child’s brain.

She commented that the holistic, psychosocial approach of the French allowed for the possibility there could be nutritional factors that worsen ADHD symptoms. “In the U.S., the strict focus on pharmaceutical treatment of ADHD, however, encourages clinicians to ignore the influence of dietary factors on children’s behavior.”

Psychiatrist Robert Berezin commented on Wedge’s report saying that it seemed American boys had contracted some contagion that spread ADHD exponentially. More seriously, he went right to the heart of the problem: if ADHD rates are so drastically different between the U.S. and France, how can ADHD be a brain disease? “Yes there can be symptoms of hyperactivity and concentration. But it is created by psychosocial causes, not biological ones. And the treatments should be appropriate to the cause.” He concluded that the French situation showed that so-called ADHD was a psychosocial problem, not a brain disease.

So if we accept this conclusion, where does this leave us in America with regard to ADHD and the aftermath of decades of conceiving and treating it as a brain disease? A recent investigative report by the Milwaukee Journal Sentinel and MedPage Today pointed out several areas of concern. First is the increase in the diagnosis of Adult ADHD. Twenty years ago ADHD was rarely diagnosed in adult Americans. Now, 1 in 23 adult Americans, around 10 million people, are said to have ADHD. And there has been a fourfold increase among adults 26 and older who use Adderall recreationally.

The reporters cited a 2010 study where 22% of the adults tested for ADHD had exaggerated their symptoms. This finding underscores how college-aged adults increasingly use ADHD medications as “study aides.” A 2013 study found wastewater samples collected near college dormitories in Tacoma Washington were eight times higher for amphetamines during final exams week than during the first week of classes. Although FDA adverse events indicated there were more reports for children, the adults were reporting more serious adverse events. “Adults accounted for just over one-third of reports, but made up more than half of all hospitalizations and 85% of deaths.”

Experts question whether adult ADHD is truly a widespread condition that needs treatment with the array of FDA-approved prescription medications. A medical historian, Nicolas Rasmussen, was quoted as saying that amphetamines are grossly overused; and that “the streets are awash with Adderall.”

Drug companies counter that ADHD is a real and treatable medical condition that effects millions of Americans. Charles Catalano, a spokesperson for Shire, which manufactures two ADHD medications, Vyvanse and Adderall, said the drugs have been approved by regulators around the world and are safe to use. “Our medications are proven to be effective when used according to prescribing practices of a licensed, trained health care professional.” A spokesperson for Novartis, the manufacturer of Ritalin, said it has been used safely and effectively for more than 60 years. “If used inappropriately, the results could be serious, just like with the misuse of any other medication.”

The DSM-5, published in 2013 by the APA, relaxed the criteria for diagnosing adult ADHD. Previously adults needed to have six of nine possible symptoms. Now they only need five of nine symptoms. Seventy-eight percent of the panel of experts who approved the changes had financial ties to drug companies. The APA minimized the potential conflicts of interest by stating no panel member had made more than $10,000 a year working as industry speakers and consultants.

Moffitt et al. published the results of a forty-year study of individuals in New Zealand in The American Journal of Psychiatry. The study found that found 90% of adult ADHD cases did not have a history of childhood ADHD. “The findings raise the possibility that adults presenting with the ADHD symptom picture may not have a childhood-onset neurodevelopmental disorder.” The authors added that if the findings were replicated, adult ADHD’s place in the DSM should be reconsidered and that research needs to investigate the etiology of adult ADHD.

It also appears that using ADHD medication leads to addiction and abuse problems with some individuals. Some of this is simple common sense. All ADHD stimulant medications are Schedule II controlled substances, meaning that the DEA considers them to have the same addictive potential as cocaine. Yet the research literature presents conflicting accounts. Some studies report that untreated ADHD is a significant risk factor in developing substance use disorders. Others suggest there is no compelling evidence that treating children with ADHD medication leads to an increased risk of later substance use problems.

A Medscape article concluded that the bulk of evidence suggested that treating ADHD with stimulant medication did not increase the risk for developing a substance use disorder, nor did it decrease to risk. At the very end of the article this comment appeared: “This activity is supported by an independent educational grant from Shire.” The author of the article had also received grants and served as a paid consultant for Shire.

On the other hand, Peter Breggin and others have noted there is a high abuse liability with stimulant medications. A 1995 DEA report indicated there was an abundance of scientific literature on the abuse potential of Ritalin and other Schedule II stimulants. A 1998 NIH conference on the “Diagnosis and Treatment of ADHD” stated: “An extensive scientific literature spanning more than 30 years of research unequivocally indicates that MPH [Ritalin] has a high abuse liability.” A 1995 study by Nora Volkow and others found that cocaine and MPH had similar effects on the brain when given intravenously. Breggin commented in his discussion of the study in his book, The Ritalin Fact Book, that the main difference was the longer lasting effect of Ritalin. This was speculated to be why Ritalin was less subject to abuse than cocaine. Breggin said:

What does all of this mean in plain English? Ritalin’s biochemical mechanism of action is essentially the same as that of cocaine, and therefore Ritalin produces similar effects to cocaine. In fact, all of the stimulants, including Ritalin and cocaine, jack up dopamine, serotonin, and norepinephrine chemical messengers in the brain, producing a variety of similar mental abnormalities. If given intravenously, the “high” is the same for all of them.

A study by Schrantee et al. published in the September issue of JAMA Psychiatry found there was a distinct effect of methylphenidate (Ritalin) on the brains of children and young adults. A discussion of this study in an article on Mad in America indicated the lead researcher of the study’s team, Liesbeth Reneman, said given that maturation of several brain regions are not complete until adolescence, drugs given during the sensitive, early phases of life could effect “neurodevelopmental trajectories” and have profound effects later in life.

The adolescent brain is a rapidly developing system that maintains high levels of plasticity. As such, the brain may be particularly vulnerable to drugs that interfere with these processes or modify the specific transmitter systems involved.

The mesolimbic dopamine system (MDS), the reward pathway of the brain, is one of those later maturing brain regions. Incidentally, the MDS is probably the region of the brain where drugs produce dependence. In his book, The Science of Addiction, Carleton Erickson said neuroscientists believe that when the functioning of certain MDS neurotransmitter systems are disrupted from genetic “miswiring” and/or long-term exposure to a drug, “chemical dependence as a brain disease” can develop.

The Schrantee et al. study is the first evidence that using ADHD medications can alter brain development. So studies of the long-term consequences need to be completed. But one of the questions that should be investigated is does the long-term use of stimulant medications effect changes to the MDS of the brains of adolescents and young adults and are those changes related to a greater risk of substance abuse. Hopefully we’ll have some answers before prescription stimulant drugs compete with opioids as a national drug epidemic.

09/27/16

The Secret of Kratom

36473493 - tablet with the chemical formula of kratom (mitragyna speciosa) mitragynine. drugs and narcotics — © Vitally Vodolazskyy | 123rf.com

So you’ve never heard of kratom? A CDC study of kratom exposures reported to poison centers showed a tenfold increase from 26 in 2010 to 263 in 2015. If kratom becomes more widely known and used, those figures will be increasing. The CDC published a report on kratom on June 29, 2016, citing its potential as an “emerging drug of abuse.” The cited NIDA document, “Drug Facts: Kratom,” does not refer to it as an emerging drug of abuse as claimed, but it does say, “Like other drugs with opioid-like effects, kratom might cause dependence, which means users will feel physical withdrawal symptoms when they stop taking the drug.” The CDC report itself suggested it was an emerging public health threat.

Kratom use appears to be increasing in the United States, and the reported medical outcomes and health effects suggest an emerging public health threat. Members of the public and health care providers should be aware that the use of kratom can lead to severe adverse effects, especially when consumed in combination with alcohol or other drugs.

Kratom is a tropical tree-like plant native to Thailand, Malaysia, Myanmar and other countries in Southeast Asia. It has a long history of use as a stimulant in low doses. Kratom is often brewed as a tea, but it can also be smoked or swallowed in capsules. Southeast Asian laborers and farmers chew the leaves for energy to work harder and to relieve muscle strains. It has been used as a substitute for opium when opium is not available. And it’s used to manage opioid withdrawal symptoms. Long-term kratom use has produced anorexia, weight loss, insomnia, skin darkening, dry mouth, frequent urination and constipation.

The DEA included kratom on its Drugs of Concern list and recently announced its intention classify kratom and two of its psychoactive chemicals temporarily as a Schedule I controlled substances. “The two chemicals are called mitragynine and 7-hydroxymitragynine. By banning the active chemicals, the DEA is making sure that both the plant and any synthetic versions of it are included in the new regulation.” STAT reported the DEA is authorized to temporarily place substances in Schedule I for up to two years when it believes they are a potential public health threat. If their studies demonstrate there is a threat, the ban will remain. If not, it will revert to being legal.

Like marijuana, it contains multiple alkaloids, but mitragynine and 7-hydroxymitragynine are the primary active ones in the plant. At lower doses, it produces stimulant effects. Users report increased alertness, physical energy, talkativeness and sociable behavior. At higher doses, opiate effects, including sedation and euphoria occur. “Effects occur within 5 to 10 minutes of ingestion and last 2 to 5 hours.” The DEA announcement described the following health risks from kratom in some detail.

Several deaths associated with kratom have been reported, often when it is mixed with other substances. There are also reports of drug-induced liver damage, psychosis, seizures, weight loss, insomnia, tachycardia, vomiting, poor concentration and hallucinations. Fifteen of the reported deaths occurred between 2014 and 2016. There was a cluster of nine deaths reported in Sweden from a kratom product called “krypton.” See “Krypton Can Kill You.”

The CDC kratom study said 24.5% of the reports on adverse events were for minor complications; 41.7% required some treatment and were considered to be moderate complications. There were major complications—meaning life-threatening signs or symptoms, with some residual disability—for 7.4% of the kratom exposures. The adverse effects included: tachycardia [abnormally rapid heart beat] in 25% of the reported cases, agitation or irritability in 23.8%, drowsiness in 19.4%, nausea in 14.7% and hypertension in 11.7%.

A recent article in the International Journal of Legal Medicine by Warner, Kaufman and Grundmann reported the death of a young adult who had mixed kratom with prescribed medications—Prozac and Lamictal. Another article, “A Drug Fatality Involving Kratom,” noted a 17-year-old male with a history of heroin abuse and chronic back pain who died from a “possible Kratom toxicity.” He had mixed kratom, benzodiazepines and over-the-counter cold medications (containing DXM?).

In “Pharmacology of Kratom,” Prozialeck et al. found there was an increasing level of kratom use, especially among college students. They also noted a large number of online vendors and general information websites for kratom. An Internet search they did with Google had more than 2 million hits in February of 2012. When I repeated the search in August of 2016, I had over 6.36 million hits. Prozialeck et al. said their search of websites indicated kratom was being used for pain management as well as a recreational drug.

Kratom is regulated as an herbal product in the U.S. and is currently considered a legal substance, despite the CDC concern for its abuse potential. Along with the DEA declaration that there isn’t a legitimate medical use for kratom, this meant: “it cannot legally be advertised as a remedy for any medical reason.”

Pharmacologically, the mitragynine in kratom activates the μ, δ, and κ opioid receptors. Its main activity is on the μ receptor, the one that produces the analgesic and euphoric effects with opioids; and of course results in physical dependency. Despite kratom’s reputation as a “legal opioid,” there have been few scientific studies that addressed its psychoactive properties. Most of the available information is in anecdotal reports, like those on the website, Erowid.

Erowid has a plethora of Kratom reports categorized in groups such as: First Times, Combinations, Preparation/Recipes, Difficult Experiences, Health Problems, Addiction & Habituation, Mystical Experiences and Medical Use. A nondrinking male reported it caused liver toxicity in “Killing My Liver.” A more serious reaction resulted in a hospital stay for a drug–induced hepatic injury in “”Almost Destroyed My Liver.” Then there was a disturbing report under Addiction & Habituation called “This Thing Is a Secret.”

A man with a history of drug and alcohol addiction hadn’t used any “hard stuff” like heroin, alcohol, amphetamines or cocaine in five years. He was active in Alcoholic Anonymous. Then in January of 2005, he decided to order some kratom on a whim from an online vendor. When it kicked in, it had a “Definite opiate effect.” Nine months later, when he wrote his report for Erowid, he said he was using it daily. If he forgets to place his order in time, he’ll have to go a day without it. It was just like the withdrawals from his hydrocodone/Ambien habit.

His wife doesn’t know. No one knows, except the people he orders kratom from. He said he felt guilty spending family money of the stuff, but not guilty enough to stop. “Maybe I’ll quit some time, but for now, things are maintaining. It’s better than shooting heroin or oxycontin or any stuff like that…”

Naturally, I don’t go around blabbing to my AA associates about how I am using this plant every day. They are some of the best people I have ever met and cherish their friendship. We have a saying in AA, ‘your secrets keep you sick.’ This Kratom thing is a secret.

Prozialeck et al. reported that as kratom use has expanded to Europe and the U.S., there have been increasing reports of individuals becoming physically dependent or addicted to kratom. Most of the published studies, like this one by McWhirter and Morris were case reports. They described a case of kratom dependence in a 44-year-old man with a history of alcohol dependence and anxiety disorder. His withdrawal symptoms were consistent with mild opioid withdrawal: anxiety, restlessness, tremors, sweating and cravings.

Evidence suggests that kratom is being used extensively for both medical and nonmedical purposes. Recent studies have shown that kratom contains a variety of active compounds that produce major pharmacologic effects at opioid and other receptors. Kratom and kratom-derived drugs may potentially be used for the management of pain, opioid withdrawal symptoms, and other clinical problems. At the same time, serious questions remain regarding the potential toxic effects and the abuse and addiction potential of kratom. This issue is further confounded by the lack of quality control and standardization in the production and sale of kratom products. The possibilities of kratom products being adulterated or interacting with other drugs are also serious concerns. Until these issues are resolved, it would not be appropriate for physicians to recommend kratom for the treatment of patients. Nevertheless, physicians need to be aware that patients may use kratom or kratom-based products on their own. Further studies to clarify the efficacy, safety, and addiction potential of kratom are needed.

Regulating kratom presents issues similar to what we are now facing with marijuana. Both plants contain dozens of compounds with some potential medical use. Both are currently not viewed by the U.S. government as having any medical use. Where marijuana’s classification as a Scheduled I controlled substance makes scientific research into its potential medical uses difficult, the limited use and knowledge of kratom contributes to it being understudied. Each also has one or two dominant psychoactive ingredients.

There is also a lack of quality control with both. The strength of THC or CBD in marijuana and mitragynine or 7-hydroxymitragynine in kratom can vary widely. Products containing these herbal substances cannot be guaranteed to carry similar doses of the active ingredients. And they are likely to have contaminants, such as pesticides, if grown commercially. The limited, scientifically reliable knowledge of their medical usefulness, and the lack of regulation with regard to that knowledge, results in a wide variety of anecdotal claims similar to past the age of patent medicines.

What is to be done? Federal funding of research into kratom’s potential medical uses needs to occur. The two-year temporary classification as Schedule I can be extended another year if more time is needed while the studies of it medical uses are completed. A permanent classification of kratom as a Schedule I Controlled substance seems inadvisable. Remember that hasn’t worked very well with marijuana. Future classification as a controlled substance seems reasonable, given its activation of the μ, δ, and κ opioid receptors. But let’s base it upon reliable scientific information.

07/1/16

Misleading Info on ADHD

Three Swedish researchers did a study on the information published online by the National Institute of Mental Health (NIMH) on ADHD. What is intriguing about their study is that they were looking at how the NIMH document sought to persuade its readers to take action to address their child’s ADHD problem. They suggested there was a circular argument wherein ADHD was defined according to the presence of certain behaviors, which the diagnostic label of ADHD was said to explain. They also pointed out how ADHD is presented as legitimate medical disorder, despite the fact that “diagnostic criteria are subjectively interpreted from the behavior of the child.”

The authors, Erlandsson, Lundun and Punzi, linked this Easy-to-Read NIMH document on ADHD in their study. However, their citations appear to be from this NIMH document, “What is Attention Deficit Hyperactivity Disorder (ADHD, ADD)?” They noted where the image of ADHD as a legitimate medical disorder was established by the first sentence of the article, “ADHD is one of the most common childhood disorders [and can continue through adolescence and adulthood].” This is word-for-word in the latter article, where the Easy-to-Read one is slightly different: “ADHD is a common mental disorder that begins in childhood and can continue through adolescence and adulthood.” The bracketed phrase was not quoted by Erlandsson, Lundun and Punzi, possibly because they were looking at ADHD in children; or when they examined the document in October of 2015, it wasn’t there.

Erlandsson et al. noted how the repeated use of the term “disorder” (at least 15 times) and a number of references to brain imaging and brain chemicals gave the impression of a chronic, long-term disability. The rhetoric is clearly suggestive that ADHD is a brain disorder. And yet, because symptoms vary from person to person, the ‘disorder’ can be difficult to diagnose. The so-called ‘key behaviors of ADHD’ are also found in all children—inattention, hyperactivity, and impulsivity. “But for children with ADHD, these behaviors are more severe and occur more often.” They have to be present for at least six months, and be present to a degree “that is greater than other children of the same age.” Erlandsson et al. said:

In fact, as shown in the document, there are no biological markers, environmentally defined categories, or objective tests to distinguish “ADHD” as a discrete condition. Rather, diagnostic criteria are subjectively interpreted from the behavior of the child: “No single test can diagnose a child having ADHD. Instead, a licensed health professional needs to gather information about the child, and his or her behavior and environment.” Professionals as well as teachers and parents are involved in the evaluation and examination process, and subsequently in the diagnostic process.

There is a clear bias in presenting ADHD as a biomedical problem. While saying scientists aren’t sure what causes ADHD, NIMH then said many studies suggest genes play a large role. Twin studies show ADHD runs in families. “Children with ADHD who carry a particular version of a certain gene have thinner brain tissue in the areas of the brain associated with attention.” But the differences were not permanent and as the children with this gene grew up, the brain developed to a normal level of thickness and the ADHD symptoms improved. As Erlandsson et al. commented: “The biomedical discourse assumes that there is a consensus among professionals on how to interpret the behaviors of the child, which means that pharmacological treatment is the preferred intervention.” But this is not the case.

In “ADHD: an Imbalance of Fire over Water or a Case of the Fidgets?” I reviewed several different sources questioning whether ADHD was a biochemical disorder. Psychiatrist Peter Breggin said the search for a genetic and biological cause for ADHD would never succeed because the researchers are looking in the wrong place. Neurologist Fred Baughman said:

Despite regular pronouncements that its biologic roots have been discovered, no proof of a definite physical or chemical abnormality is ever found. All such research and all such claims … have been a sham, meant to create illusions of science and disease while proving nothing.

The NIMH material also did not mention there was a lack of consensus on the safety of using medication to treat children. Rather, medication is said to be a safe treatment: “Under medical supervision, stimulant medications are considered safe.” The potential for substance abuse or dependence is downplayed, saying: “there is little evidence of this.” ADHD stimulants are classified as Schedule II controlled substances, which have “a high potential for abuse, with use potentially leading to severe psychological or physical dependence.” See “ADHD: an Imbalance of Fire over Water or a Case of the Fidgets?” for more information on ADHD medications and addiction.

The consequences of a biomedical view of ADHD were addressed in a recent study by the CDC of ADHD treatment among children between 2 and 5 years of age. While the American Academy of Pediatrics and other organizations recommend behavior therapy ahead of stimulant medication for children under 5, only 53% of children had received behavior therapy in the year prior to the survey, while 47% had received stimulant medication during the previous week. Between 75% and 78.5% of children aged 2-5 with ADHD received one or more ADHD medications.

ADHD is a highly prevalent condition that can lead to poor health and social outcomes. Despite 2007 and 2011 guidelines recommending behavior therapy as first-line treatment for children aged <6 years with ADHD, during 2008–2014 only about half of children aged 2–5 years with ADHD received psychological services. To effectively mitigate impairments associated with ADHD and minimize risks associated with ADHD medications, it is important to increase the percentage of young children with ADHD who receive evidence-based psychological services, especially parent training in behavior therapy.

Around 30% of children aged 3-5 experienced adverse effects from ADHD medications. The most common ones were appetite suppression and sleep problems. But other commonly reported side effects were: abdominal pain, emotional outbursts, irritability, lack of alertness, repetitive behaviors and thoughts, social withdrawal, and irritability when the medication wears off. In one large study, of methylphenidate (Ritalin or Concerta) over 10% of children 3-5 had to stop treatment because of adverse effects. They were also 20% lower for height and 55% lower for weight. Anne Schuchat, the CDC’s Principle Deputy Director, said:

We are still learning about potential side effects of long-term use of ADHD medicine on young children. Until we know more, the recommendation is to refer parents for training in behavior therapy for children under 6 years of age with ADHD.

We recognize that these are not easy treatment decisions for parents to make. We know that behavior therapy is effective, and the skills they learn through behavior therapy can help the whole family be successful. Building these skills in parents and children both empowers families and helps young children with ADHD live up to their full potential.

An article in The Washington Post, “CDC Warns that Americans May Be Overmedicating Youngest Children with ADHD,” addressed this concern as well. The long-term effects of the drugs of choice for treating ADHD, Adderall and Ritalin, were not well studied. An estimated 2 million of the 6 million children diagnosed with ADHD were so labeled between the ages of 2 and 5. While ADHD medications don’t work for everyone, in many cases they take effect almost immediately. In contrast, behavior therapy can take several months to have an impact. However, it can be long lasting; and has no side effects.

06/17/16

Impeccable Timing

Timing is everything—even with medications coming to market. In the last few years new, effective treatments for the Hepatitis C Virus (HCV) have come to market as the death rates steadily climbed. Solvadi (12/2013) and Harvoni (10/2014) by Gilead Sciences; Viekira Pak (12/2014) by AbbVie and Zepatier (01/2016) by Merck are the main ones. They have cure rates over 90% in many cases. Although their prices have been sky high, according to the WHO, the production costs of these drugs are quite low. Harvoni prices were expected to drop, but I haven’t anything much cheaper than $94,500 for 12 weeks of medication. Viekira Pak lists at $83,300 for 12 weeks; Zepatier is the bargain at $54,600.

New CDC data in May of 2016 indicated that HCV deaths for 2014 reached an all-time high of 19,659. The rates have been steadily rising since 2010 when the total was 16,627. The CDC also stated their numbers were most likely a fraction of the deaths attributable in whole or in part to chronic hepatitis C. There are an estimated 2.7 to 3.9 million chronic cases of HCV in the U.S. New acute cases of HCV have also been steadily increasing. In 2014 there were 2,194 new cases of HCV reported, a 300% increase since 2005. The CDC suggested that actual cases are estimated to be 13.9 times higher than the number of reported cases in any year. The following chart was compiled from the CDC data.

	2010	2011	2012	2013	2014
Actual New HCV	853	1,230	1,778	2,138	2,194
Estimated New HCV	11,800	16,500	24,700	29,700	30,500
Cause of Death as HCV	16,627	17,721	18,650	19,368	19,659

A study done on the CDC HCV data found that from 2003-2013 the number of deaths from HCV surpassed the combined total of 60 other infectious conditions. This was despite the improving therapies now available. The HCV death statistics could begin decreasing in the next few years, as the impact of the new drugs is felt in treatment. But the high cost of medications has resulted in health insurance companies prioritizing treatment for the worst HCV cases. So as the heroin and prescription pain medication epidemic rages on, new HCV patients have to wait their turn until their HCV gets serious enough for their health insurance to approve treatment.

Despite enthusiasm for the new curative, brief (12-week), all-oral antiviral treatments for hepatitis C virus (HCV) infection, the continued health burden and increased mortality for HCV-infected patients in the United States remain underappreciated.

A CDC press release indicated the greatest HCV burden falls on baby boomers, born between 1945 and 1965. A study published in The Lancet Infectious Diseases in 2016 suggested injection and blood transfusion technologies were not as safe as they are today, so many boomers may have been unknowingly living with HCV for many years. Jonathan Mermin of the CDC said: “Why are so many Americans dying of this preventable disease? Once hepatitis C testing and treatment are as routine as they are for high cholesterol and colon cancer, we will see people living the long, healthy lives they deserve.” The outrageous price for HCV medications may be part of your answer, Dr. Mermin.

A Live Science article on the CDC study noted that HCV is primarily spread today through people sharing needles, syringes or other equipment used when injecting drugs. “But before 1992, when the U.S. began screening the blood supply for the virus hepatitis C was also commonly spread through blood transfusions and organ transplants.” The following chart from Wikimedia Commons, composed by Opigan13, was compiled from CDC figures. It shows data on hepatitis C infection by source.

HCV can be a “silent illness,” with people having no symptoms for decades. This allows the disease to progress unnoticed. Hepatitis C is “a different beast” from other liver infections that have more symptoms or are shorter in duration, according to Dr. Raymond Chung, director of hepatology and the Liver Center at Massachusetts General Hospital. Dr. Chung thought the increase in HCV deaths could continue for five more years or longer.

Amy Nunn, an associate professor of behavioral and social sciences at the Brown University School of Public Health said the rise in HCV deaths was alarming. About 85 percent of individuals who are infected with HCV don’t know they have it. Most people are not routinely screened for the virus. Nunn also pointed to the high cost of the new hepatitis C drugs as one reason that some people are having trouble getting access to them in the early stages of the disease.

A report by IMS Health for 2015 indicated that nearly 250,000 new patients received treatment for HCV in 2015. Added to the 170,000 new patients in 2014, the past two years have seen 5 times the number of patients than the previous three years combined. The majority of patients were treated by Medicare (50%); followed by commercial insurance (28%) and Medicaid (19%); 3% paid cash. Non-discounted spending over the past two years for the newer HCV drugs was $31.0 billion. “The discussion continues over the price of these medicines and the criteria for determining patient access and insurance coverage.” See chart 10 in the report for this data.

Spending on HCV went from so small an amount in 2013 that a figure couldn’t be shown in chart 8, to 12.2 billion in 2014 and 18.8 billion in 2015. Looking at the top medicines by spending in 2015, Harvoni was #1 with $14.3 billion. Solvadi dropped to 19th with $3.0 billion spent. In 2014 Solvadi had been tied for 1st with Humira at $7.8 billion in spending.

The World Health Organization (WHO) estimates that 130 to 150 million people globally have chronic hepatitis C infection. Around 500,000 people die yearly from HCV-related liver diseases. The most affected regions are Africa, Central Asia and East Asia. Populations at risk of HCV include: people who injects drugs, people who have used intranasal drugs, people who have tattoos or piercings, people with HIV, prisoners or previously incarcerated individuals, and children born to mothers with HCV.

The incubation period for hepatitis C ranges from 2 weeks to 6 months. After the initial infection, 80% of people do not show any symptoms. Individuals who are acutely symptomatic could exhibit “fever, fatigue, decreased appetite, nausea, vomiting, abdominal pain, dark urine, grey-coloured faeces, joint pain and jaundice (yellowing of skin and the whites of the eyes).” The WHO said:

Recently, new antiviral drugs have been developed. These medicines, called direct antiviral agents (DAA) are much more effective, safer and better-tolerated than the older therapies. Therapy with DAAs result can cure most persons with HCV infection and treatment is shorter (usually 12 weeks) and safer. Although the production cost of DAAs is low, the initial prices are very high and likely to make access to these drugs difficult even in high-income countries.

So pharmaceutical companies like Gilead Sciences, AbbVie and Merck are making enormous profits from their HCV treatments and will continue to do so for many years (see “Riding the Hep C Gravy Train”). The low production cost for HCV drugs is also an explanation for why Gilead Sciences was so willing to offer steep discounts to countries like Egypt (See “Is There No Balm in Gilead?” and “Hepatitis Hostages”)—it’s good PR and they either still make a profit or buy a lot of goodwill for a nominal cost. As Amy Nunn said, “This is an epidemic of enormous magnitude.” And it looks like it will be around for awhile longer. Gilead, Merck and AbbVie, your timing for drug development was impeccable.

05/17/16

Overdosing

Melanie (not her real name) was one of the first persons I counseled at White Deer Run in the late 1980s. She was 18 at the time, and a heroin addict before it was being called a national epidemic. She completed treatment; relapsed and returned about a year later as an adult patient. I think she even completed treatment that time as well. I can’t tell you much more about her, except that she was from Philly; and she is the first person I worked with who became an overdose statistic. There have been many more since then.

Most of the places I’ve worked as a drug and alcohol counselor have been within Pennsylvania. So when I heard of the study done by Balmert et al. on the accidental poisoning deaths in Pennsylvania from 1979 to 2014, I was interested in reading it. There aren’t too many ways that statistics, especially death statistics, can be interesting reading. But buried within those tables and figures are people I knew.

Within a data set attached to the study, I found the reported deaths by accidental drug poisoning for the years 1987 through 1989. In 1987, there were 41 individuals between the ages of 15 and 24 who died from accidental poisoning, 6 of whom were female; in 1988 there were 39, 12 of whom were female; in 1989 there were 54, 9 of whom were female. Somewhere in those statistics is Melanie’s overdose.

When I compared those deaths with the last three in the data set, 2012, 2013 and 2014, the stats grew exponentially. In 2012, there were 224 individuals between the ages of 15 and 24 who died from accidental poisoning, 63 of whom were female; in 2013 there were 203, 47 of whom were female; in 2014 there were 277; 70 of whom were female. That’s a lot of Melanie’s.

The CDC published a data brief indicating drug poisoning became the leading cause of injury-related death in 2008, surpassing deaths from motor vehicle accidents. 90% of those deaths were from drug poisoning. From 1999 to 2008 the number of drug poisoning deaths from opioid analgesics more than tripled. “Of the 36,500 drug poisoning deaths in 2008, more than 40% (14,800) involved opioid analgesics.”

Most of those 14,800 deaths involved natural and semi-synthetic opioid analgesics such as morphine, hydrocodone and oxycodone. The number of drug poisoning deaths from methadone, a synthetic opioid, increased sevenfold from 1999 to 2007. Then it decreased between 2007 and 2008. The age group with the highest death rate from opioid poisonings was between 45 and 54 years of age.

In 2007-2008 48% of Americans reported the use of at least one prescription drug in the past month. Not surprisingly, this was related to increases in drug use, misuse and nonfatal health outcomes. Over 5 million reported using prescription pain relievers nonmedically in the previous month.

In 2012 the CDC looked specifically at drug-poisoning deaths from opioid analgesics and heroin. Their report in Health E-Stats noted that from 1999 to 2012 the drug poisoning deaths from opioid analgesics increased from 1.4 per 100,000 in 1999 to 5.1 in 2012. The death rates from heroin overdoses nearly tripled from .7 per 100,000 in 1999 to 1.9 in 2012. The states with death rates significantly higher than the overall U.S. rate of 13.1 per 100,000 included Pennsylvania, Ohio and West Virginia, which had the highest overall rate at 32.0 per 100,000. See the linked CDC reports for more detailed information.

Returning to the Balmert et al. study on accidental poisoning deaths in Pennsylvania, we can see how the Pennsylvania rates compare to those just reviewed. Table 1 in Balmert et al. indicated the overall death rate for Pennsylvania in 2014 was 29.16 per 100,000. The death rate was highest for the 25-34 age group (39.87), and lowest among the 15-24 age group (16.25). See Table 1 in the Balmert et al. article.

Examining the mortality patterns by county showed that the highest rates for males from 2010 to 2014 were in the counties of southwestern PA (the Pittsburgh metro area), the counties surrounding Philadelphia and those near Scranton in the Northeast part of the state. The highest rates for females were in the same areas.

The county level findings provide possible avenues for targeting interventions to areas with the highest mortality from accidental poisoning. Counties with the highest 2010–2014 rates in females are primarily in suburban southwest PA. In males, the highest prevalence rates are more widespread and include both southwest and southeast PA, plus the northeast area including Carbon and Susquehanna. These patterns emphasize that, currently, accidental poisoning deaths especially among white females are occurring in suburban and rural areas. Other area-specific analyses should focus on non-urban mortality patterns.

In September of 2014 legislation went into effect allowing first responders to carry naloxone for reversing the effects of an overdose. As of September 1, 2015, 302 overdoses had been reversed with naloxone. The following graphic represents the drug-related overdose deaths by county in Pennsylvania for 2014. See the original here.

In September of 2015, Tom Wolf, the governor of Pennsylvania, announced that the CDC had granted the Pennsylvania Department of Health $900,000 to prevent overdose deaths related to prescription opioids. Governor Wolf said: “Too many citizens of our commonwealth are dying from drug overdose, and Pennsylvania families in hardworking communities are impacted by prescription drug addiction every day.” The “Prevention for States” grant will support 16 states with annual awards between $750,000 and $1 million over the next four years. The goal is to hopefully turn the tide on the prescription drug overdose epidemic by implementing prevention strategies and improving safe prescribing practices.

On March 18, 2016, the CDC published revised guidelines for primary care physicians when prescribing pain medication. Nearly half of all opioid prescriptions are dispensed by primary care clinicians. An estimated 20% of patients with noncancer pain symptoms or pain-related diagnoses receive an opioid prescription. While evidence supports the short-term efficacy of opioids for reducing pain, few studies have assessed the long-term benefits of opioids for chronic pain. An estimated 9.6 to 11.5 million adults (3% to 4% of the adult U.S. population) were prescribed long-term opioid therapy in 2005.

This guideline is intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death.

The guidelines are not mandatory, but if they are followed, maybe the opioid-related overdose deaths will start to decrease and people like Melanie will live instead of die.

02/23/16

Emerging Public Health Threat

I’m almost positive that a guy I saw was high on Flakka. I’d been to Fort Lauderdale Florida for a training conference on relapse prevention. The conference finished early on Friday, so my friend and I decided to catch lunch down by the beach. We were getting a recommendation for lunch from a woman renting Segways, when a man walked by. He was barefoot, shirtless and wearing sweat pants cut off at the knees. He was also busy arguing with someone who wasn’t there. He walked right by us, caught up in his own world.

The reason I suspected he was high on Flakka, was because Fort Lauderdale is in Broward County Florida, which has been ground zero for Flakka. After I commented that I thought the guy was on Flakka, the woman told us that Clearwater was where most of the Flakka problems were at the time. She added that people high on Flakka usually kept to themselves and weren’t violent or aggressive. Then she added that Flakka caused problems because it opened (or activated) the third eye and users were then able to see into the future. We thanked her for her lunch recommendation and left. The guy on Flakka had moved on as well.

We are entering a brave new world of mind-altering substances with NPS—new psychoactive substances—coming to market faster than governments around the world can ban them. See “The New Frontier of Synthetic Drugs” and the “2014 Global Synthetic Drugs Assessment” for more information on the growing problem with NPS. Synthetic cannabinoids (synthetic marijuana), with names like K2 and Spice, are available everywhere. Sold online or in small retail outlets like convenience stores (I’ve heard there’s one that sells it within a mile of my home), synthetic marijuana is popular among younger drug users. After cannabis, synthetic marijuana was the most frequently reported illicit substance used by teenagers in 2012. No longer is finding a pipe in a teenager’s jeans an automatic indication that they are smoking cannabis, the marijuana of their parents’ generation.

The Synthetic Drug Abuse Prevention Act (SDAPT) was signed into law in 2012, but keeping up with the ever-changing chemical formulas used in the manufacturing process is difficult. “The chemical compositions of synthetic drugs are frequently altered in an attempt to avoid government bans.” SDAPT permanently placed 26 types of synthetic cannabinoids and cathinones into Schedule 1. The total number of NPS identified in 2012 was 158.

A CDC report in 2012 said that multiple states found there was an association between synthetic marijuana and unexplained acute kidney injury that was diagnosed after severe nausea, vomiting and flank or abdominal pain brought them to emergency departments. Additional side effects can include tachycardia (faster than normal heart rate) and hypertension.

Synthetic cannabinoid compounds originally were developed to facilitate study of cannabinoid receptor pharmacology, but in recent years have emerged as drugs of abuse. In 2005, SC products marketed as “Spice” first emerged in European countries, before appearing in the United States in 2009, where they were marketed initially as “K2.” Today, SC products are distributed worldwide under countless trade names and packaged in colorful wrappers designed to appeal to teens, young adults, and first-time drug users. Products often are packaged with disingenuous labels such as “not for human consumption” or “incense,” but health professionals and legal authorities are keenly aware that these products are smoked like marijuana. Despite federal and state regulations to prohibit SC sale and distribution, illicit use continues, and reports of illness are increasing.

A 2015 CDC report indicated that poison control centers had 3,572 calls related to synthetic cannabinoid use, which was a 299% increase over the same January-May period in 2014. The number of calls spiked in mid-April before decreasing to 2014 levels by the end of May. The number of reported calls stayed under 100 all throughout 2014. They rapidly increased to 500 calls by April 16th and did not decrease to near 100 until May 28th. See the figure in the 2015 CDC report.

The most commonly reported adverse health effects were: agitation (35.3%), tachycardia (29.0%), drowsiness or lethargy (26.3%), vomiting (16.4%), and confusion (4.2%). Eighty-three percent of the poison center calls had a medical outcome and 11.3% of those had a major adverse event—signs or symptoms that were life threatening or that could in substantial disability or disfigurement. There were 1,407 (47.5%) with a moderate effect—signs or symptoms were not life threatening, and no threat of disability or disfigurement, but did require some form of treatment. “A total of 1,095 (37.0%) had a minor effect (signs or symptoms that are minimally bothersome and generally resolve rapidly with no residual disability or disfigurement).” Fifteen deaths were reported.

This is a fast growing problem and we can’t afford to see it get out of hand. Synthetic cannabinoids were first reported to be in the US in December of 2008 when a shipment of “Spice” was seized by U.S. Customs and Border Protection in Dayton, Ohio. And now, the CDC is saying: “The increasing number of synthetic cannabinoid variants available, higher toxicity of new variants, and the potentially increased use as indicated by calls to poison centers might suggest that synthetic cannabinoids pose an emerging public health threat.”

01/29/16

High on Overdoses

A recent CDC Morbidity and Mortality Weekly Report indicated that in 2014 more people in the U.S. died from drug overdoses than any other year on record. There were approximately one and a half times more deaths from drug overdoses than from motor vehicle accidents. Sixty-one percent (28,647) of all drug overdose deaths were from opioids; the rate has tripled since 2000. Drug overdose deaths from heroin have more than tripled in 4 years. The overdose death rate involving synthetic opioids almost doubled between 2013 and 2014.

Drug overdose deaths are up for both men and women; in adults of nearly all age groups. The following table presents data for all overdose deaths in 2013 and 2014; by sex; and by age group. The death rates per 100,000 are given, as is the percentage increase from 2013 to 2014.

	2013	2014	% change 2013-2014
	#	Rate	#	Rate
All	43,982	13.8	47,055	14.7	6.5%
Male	26,799	17.0	28,812	18.3	7.6%
Female	17,183	10.6	18,243	11.1	4.7%
Age Group (yrs)
0-14	105	0.2	109	0.2	0.0%
15-24	3,664	8.3	3,798	8.6	3.6%
25-34	8,947	20.9	10,055	23.1	10.5%
35-44	9,320	23.0	10,134	25.0	8.7%
45-54	12,045	27.5	12,263	28.2	2.5%
55-64	7,551	19.2	8,122	20.3	5.7%
≥65	2,344	5.2	2,568	5.6	7.7%

The authors of the Report said these figures indicate the opioid overdose epidemic is worsening. That almost seems to be an understatement. In a CDC Press Release Tom Frieden, the Director of the CDC, said the increased number of overdose deaths was alarming. “The opioid epidemic is devastating American families and communities. To curb these trends and save lives, we must help prevent addiction and provide support and treatment to those who suffer from opioid use disorders.” He added how important it was for law enforcement to intensify its efforts to reduce the availability of heroin, illegal fentanyl and other illegal opioids.

The 2014 data on overdose deaths showed there were two interrelated trends driving the increase: “a 15-year increase in overdose deaths involving prescription opioid pain relievers and a recent surge in illicit opioid overdose deaths, driven largely by heroin.” Natural and semisynthetic opioids, which include oxycodone and hydrocodone, continued to be the most common type of opioid involved in overdose deaths.

Drug overdose deaths involving heroin continued to climb sharply, with heroin overdoses more than tripling in 4 years. This increase mirrors large increases in heroin use across the country and has been shown to be closely tied to opioid pain reliever misuse and dependence. Past misuse of prescription opioids is the strongest risk factor for heroin initiation and use, specifically among persons who report past-year dependence or abuse. The increased availability of heroin, combined with its relatively low price (compared with diverted prescription opioids) and high purity appear to be major drivers of the upward trend in heroin use and overdose.

The 2014 rates were highest in these five states: West Virginia, New Mexico, New Hampshire, Kentucky and Ohio. There were statistically significant increases in overdose deaths for fourteen states: Alabama, Georgia, Illinois, Indiana, Maine, Maryland, Massachusetts, Michigan, New Hampshire, New Mexico, North Dakota, Ohio, Pennsylvania and Virginia. Here is an interactive CDC map with this data.

Supporting these findings by the CDC, the National Institute on Drug Abuse (NIDA) reported in “Overdose Death Rates” that there was a 3.4-fold increase in the total number of overdose deaths from opioid pain relievers and a six-fold increase in the total number of overdose deaths from heroin from 2001 to 2014. The following charts are from the NIDA report.

The CDC pointed to four ways to prevent overdose deaths:

Limit initiation into opioid misuse and addiction. Opioid pain reliever prescribing has quadrupled since 1999. Providing health care professionals with additional tools and information—including safer guidelines for prescribing these drugs—can help them make more informed prescribing decisions.
Expand access to evidence-based substance use disorder treatment—including Medication-Assisted Treatment—for people who suffer from opioid use disorder.
Protect people with opioid use disorder by expanding access and use of naloxone—a critical drug that can reverse the symptoms of an opioid overdose and save lives.
State and local public health agencies, medical examiners and coroners, and law enforcement agencies must work together to improve detection of and response to illicit opioid overdose outbreaks to address this emerging threat to public health and safety.

Overdoses are not just a U.S. problem. The World Health Organization (WHO) estimated that globally 69,000 people die from opioid overdose each year. The World Drug Report 2014 estimated thee were 183,000 drug-related deaths worldwide in 2012. The main type of drug implicated in those deaths is opioids.

International Overdose Awareness Day reported that like the U.S. both the UK and Australia have had more deaths due to overdose than road fatalities. Nearly four Australians die each day from overdoses. Ontario, Canada had a 242% increase in fatal opioid overdoses between 1991 and 2010. European Union nations reported 6,100 overdose deaths in 2012. “It is estimated that more than 70,000 lives were lost to drug overdoses in European union countries in the first decade of the 21st Century.”

The CDC recommendations, for the most part, are ones I’d endorse. But like riders attached to big spending bills that have to be passed by Congress, the little phrase in the second recommendation “including Medication-Assisted Treatment” isn’t necessary. Medications like naloxone and naltrexone have a place in the expansion of substance use disorder treatment. But the phrase “medication-assisted treatment” refers to these medications as well as two opioids—methadone and buprenorphine—used in opioid substitution therapy. There is proposed legislation to expand the availability of buprenorphine, the Recovery for Addiction Treatment Act, in committee.

My objection is simple. You don’t “treat” an opioid use disorder with another opioid. You simply substitute dependence on one opioid for another.

I’ve regularly voiced concern over the treatment of opioid dependency with methadone and buprenorphine. Stop and think for a minute. Isn’t it reasonable to find that an individual who was physically addicted to heroin or prescription opioids would improve when they substitute ingesting enough methadone (a Schedule II controlled substance) or buprenorphine (a Schedule III controlled substance) to neutralize their physical withdrawal symptoms? The positive evidence base for opioid substitution treatment is based upon medically assisting an addict to begin using another opioid.

The “evidence-based” effectiveness of opioid “maintenance” treatment involves using these acknowledged addictive substances (methadone and burprenorphine) for weeks and even years to manage or stabilize an addiction to other opioids. There is more information on this issue in other articles I’ve written: “The Seduction of Opioid Substitution,” “Another Head for the Hydra,” and “A Double-Edged Drug.”

Another one of the drug types showing an increase in overdose deaths since 2001 in NIDA’s “Overdose Death Rates” was benzodiazepines. There has been a five-fold increase in the total number of deaths related to benzodiazepines. “Benzos” combined with opioids like methadone and buprenorphine have a synergistic effect and will give the person a heroin-like euphoria with the right drug cocktail. They also contribute to the higher rates of accidental overdose deaths. Expect the opioid overdose death rates to continue to rise even if the expansion of opioid substitution curtails overdose deaths from heroin.

12/11/15

If I Get to Sixty Four

There is some surprising news going around about middle-aged white Americans and it has nothing to do about presidential politics and Donald Trump. Two Princeton economists published a report showing that the “all-cause” mortality rate for middle-aged whites (men and women) has dramatically increased between 1999 and 2013. This increase was largely driven by increased death rates from drug and alcohol poisonings, suicide, chronic live diseases and cirrhosis. While all education groups saw increases in mortality from suicide and poisonings, individuals with lower amounts of education had the most marked increases.

Self-reported declines in health, mental health, and ability to conduct activities of daily living, and increases in chronic pain and inability to work, as well as clinically measured deteriorations in liver function, all point to growing distress in this population.

Several news outlets have commented on this startling report, including The New York Times and NPR. Just a thought: I wonder how many of the reporters are white middle-aged Americans.

The Princeton economists are husband and wife: Dr. Angus Deaton and Dr. Anne Case. Deaton just won the 2015 Nobel Prize in Economics. They said they stumbled on their finding by accident. They were looking at health and mortality data from the Centers for Disease Control and Prevention (CDC) and other sources that asked people about their levels of pain, disability and general ill health. Deaton was looking at statistics on suicide and happiness. Case was investigating poor health, including chronic pain. She herself has suffered from chronic disabling lower back pain for 12 years.

Dr. Deaton noticed the high rates of suicide for middle-aged whites in national data sets, and that the all-cause mortality in this group was rising. He and Dr. Case realized suicides alone would not be enough to push up the overall death rates, so they began to look at other causes of death. “That led them to the discovery that deaths from drug and alcohol poisoning also increased in this group.” NPR quoted Deaton as saying: “Pretty quickly, we started falling off of our chairs because of what we found.”

There was this extraordinary turnaround, which is sort of something like – you would say the ship’s been going in this direction for a very long time, and then all of a sudden, it just reverses and goes the other way. And when we saw this, that was the thing that sort of really thought, oh, my goodness, we have something here that we really haven’t seen before.

In their report, Case and Deaton said this increased mortality is only partly understood. Increased availability of opioid painkillers began in the late 1990s. The tighter control on opioid prescriptions could have led to some substituting heroin. At the same time there was increased availability, falling prices and better quality with heroin. However, the prevalence of pain, which the opioids were ostensibly to treat, can’t be pointed to as either a cause or an effect for the increase of opioid use. “Both increased rapidly after the mid-1990s.”

Speaking to NPR, Deaton noted how declining mortality statistics were typically viewed as one of those that indicated how well a nation was doing. The following figure, taken from the Case-Deaton report, shows a reversal of the decline in midlife mortality for US whites after 1998. Before that time, the mortality rate had been falling by 2% per year on average. After 1998, while other countries’ mortality rates continued to decline, US rates started to rise. No other country had a similar turnaround.

They also looked at causes of death and found that three causes of death accounted for the reversal in mortality rates, namely suicide, drug and alcohol poisoning (accidental or intentional), and chronic liver diseases and cirrhosis. All three rose yearly after 1998. For comparison, they added mortality rates for lung cancer and diabetes. Notice how suicides are trending to surpass lung cancer as a cause of death in the near future. “Poisonings overtook lung cancer as a cause of death in 2011.” See the following figure, also taken from the Case-Deaton report.

Case and Deaton suggested their findings could help explain recent large increases in Americans on disability. In conclusion, they expressed concern that those now in midlife could age into Medicare with worse health issues than the current elderly. This won’t be automatic, especially if the noted trends are brought under control. “However, addictions are hard to treat … so those currently in midlife may be a ‘lost generation’ whose future is less bright than those who preceded it.”

Ronald Lee, a professor of economics and demography and the director of the Center on Economics and Demography of Aging at the University of California, Berkley said: “Seldom have I felt as affected by a paper. It seems so sad.”

It seems quite apropos to whimsically close this article by listening to the Beatles song, “When I’m Sixty Four.” And who better to sing it given the above commentary than The Apollo Club, an all-white, mostly middle-aged choir.

10/12/15

“Shake and Bake” Meth Labs

The DEA posted maps of the total number of meth lab incidents from 2004 through 2014. There were 23,829 total incidents in 2004; 6,858 in 2007; 13,432 in 2012; and 9,306 in 2014. Missouri, Tennessee and Iowa were the state with the highest amounts of reported meth lab accidents in 2004; Indiana, Missouri, and Tennessee for 2014. Many states throughout the US had dramatic decreases in reported accidents. That’s the good news. The bad news is that a CDC study indicates injuries from methamphetamine-related incidents are on the rise in some parts of the country.

The CDC report noted there was an increase of reported incidents from 2001 through 2004; followed by decreases through 2007; with increases again through 2012. In 7% of the meth-related incidents, 162 people were injured, including 26 children (16%). Among the injured, 136 (84%) were treated at a hospital, including 19 of the injured children. There were also two reported deaths: one probable meth cook and one law enforcement official.

The percentage of incidents with injured persons increased from less than 5% during 2001-2004 and 2005-2007 to 10% during 2008-2012. Most of the injuries were to members of the general public (97) and law enforcement officials (42). The most frequently reported injuries overall were: respiratory irritation, burns and eye irritation. Burn injuries were almost exclusively experienced by the general public, with 42 of the 44 reported injuries.

The researchers speculated that the initial declines in injuries were related to state and federal restrictions on the retail sales of common meth precursor drugs, ephedrine and pseudoephedrine. This was reversed in 2008 when meth cooks adapted by buying permitted quantities from multiple locations, often with false identification. Additionally, a new method for making meth became popular, one called “shake-and-bake.” This involves shaking smaller amounts of the precursor chemicals in a 2 liter plastic bottle. Unfortunately, the bottles frequently burst, causing burns and environmental contamination. “Burn injuries increased during this time, particularly to members of the public, who might have been meth cooks or household residents.”

Children who are present during the production of meth face many hazards. The Horton et al. study cited below reported that half the events with injured children occurred between midnight and 6 am, when most children are asleep. The authors speculated that sleeping children have an even higher risk of acute injury during an emergency event. “This is particularly true if the parents/care givers are in another part of the house and/or are under the influence of meth.” Several states have enacted laws to protect children from meth-related injuries.

A 2003 study by Horton et al. examined data from Hazardous Substances Emergency Events Surveillance (HSEES Events) identified eight children injured in meth events. “Five of the meth events with children occurred in private residences: three of which occurred in houses, one in an apartment building, and one in a duplex.” One of the children injured was 8 years-old. They concluded:

The HSEES data appear to indicate that the numbers of meth labs and associated emergency events will continue to increase, putting more children and other unsuspecting individuals at risk for hazardous substance(s) exposure. More action is needed to remove children from these dangerous environments and to educate innocent bystanders, as well as the substance abusers themselves, about the risks involved with meth and its illicit production.

A 2009 study by Thrasher et al., using case reports from the Washington State Poison Control Center found that a large proportion of meth lab exposures occurred in private households. Of the 198 exposed persons, 10.6% were meth cooks, 15.7% were law enforcement personnel, 35.4% were residents and 38.3% were classified as other. Twenty-eight of the reported exposures (19.2%) were children. “A subject’s own residence was the predominant site of exposure for cooks (71%), other adults (41%), and children (66%).”

Although the CDC study indicated recent increases in an increase in meth-related injuries, there is distinct likelihood the true incidence is significantly under reported. One limitation of the CDC study was that only five states were included. Now this was because those five states (Louisiana, Oregon, Utah, New York, and Wisconsin) were the only ones with complete information available for the time period 2001-2012. Another limitation was that meth incidents in homes were not included in the original data from the National Toxic Substance Incidents Program (NTSIP) unless there was a public health action, such as an evacuation.

	Total Meth Incidents 2004	Total Meth Incidents 2014
Oregon	632	1
Utah	107	1
Wisconsin	109	14
Louisiana	176	11
New York	136	197
Missouri	2,913	1,034
Tennessee	2,341	958
Iowa; Ohio (2014)	1,666	919
Illinois; Michigan (2014)	1,576	750
Indiana	1,377	1,471

One illustration of this under reporting can be seen by examining the incidents reported in the DEA maps for those five states included in the CDC study to the incidents in the five states with the highest reported incidents in 2004 and 2014. The five states included in the CDC study were: Oregon, Utah, Wisconsin, Louisiana, and New York. The five states with the highest reported incidents in 2004 were: Missouri, Tennessee, Iowa, Illinois, and Indiana. The five states with the highest reported incidents in 2014 were: Missouri, Tennessee, Indiana, Michigan, and Ohio. The total meth incidents for the five states in the CDC study, for 2004 AND 2014 were less than the incidents for just one of the top five states—for both 2004 and 2012. Another readily noticeable fact is that the highest incident states for both 2004 and 2014 cluster in the Midwest, with the border states of Tennessee and Kentucky thrown in for good measure.

We can say there was an increase for the five states included in the CDC study, but can’t assume that increase holds throughout the US. It is likely the real total is much higher, especially in the selected states from the DEA map noted here.

The Department of Justice has produced a handy pamphlet of “Fast Facts” about meth labs. It described signs to look for if you suspect the presence of a meth lab. These signs include: unusual odors; excessive trash, especially chemical containers, coffee filters, red stained pieces of cloth, and duct tape rolls. Other indications are secretive, unfriendly occupants; frequent visitors, esp. at unusual hours; curtained or blackened windows; extensive security measures or attempts to ensure privacy, such as “no trespassing” or “beware of dog” signs.

Meth labs come in all sizes. Super labs produce 10 pounds or more of meth at a time; smaller “box” labs produce as little as an ounce and can fit in a box or backpack. They can be located almost anywhere: private homes, hotels and motels, automobiles, boats and luggage. They can also be found in commercial and industrial districts; or nestled away in a secluded rural area.

The chemical used to produce methamphetamine are extremely dangerous. Some are very volatile and could ignite if not handled properly, as apparently was the case in the motel video mentioned below. Even if there is not fire or explosion, meth production is dangerous. Exposure to the chemical can pose a series of health risks, including respiratory problems, severe chemical burns, pulmonary edema, and more. Look at a table in the pamphlet listing various chemicals used in meth labs and the hazards associated with them.

Health Research Funding posting some facts about meth lab explosions and also had two embedded videos of meth lab explosions. One video shows a mobile home in a rural setting going up in smoke. The other captured an explosion in a motel room on a security camera. Seven burn units have shut down over the last six years because of the unreimbursed costs of treating burn victims in meth lab explosions. One pound of meth results in six pounds of toxic waste. Eighty percent of the meth labs found and dismantled by authorities used the “shake and bake” method.

The simplified “shake and bake” method and smaller size of these labs means that rolling meth labs in cars, trailers or mobile homes can be easily moved to a secluded location where the manufacturing fumes can’t be detected and the toxic waste discarded. In 2002, Interstate 24 in southwest Kentucky was temporarily shut down when a car containing anhydrous ammonia exploded. It was a rolling meth lab. “Trucking down the highway allows them to disperse the rotten egg smell the labs produce and keep the waste out of their own homes.” Of the 2,000 chemicals that could be used to make meth, at least half are explosive.

Illustrating how meth labs can be found anywhere, here is an article about an explosion that occurred at a federal facility in Gaithersburg, MD. The explosion happened on the main campus of the National Institute of Standards and Technology (NIST) on June 19th, 2015. Federal law enforcement officials found pseudoephedrine, drain opener and a recipe for making methamphetamine in the lab. Representative Lamar Smith wrote in a letter to the Commerce Secretary said: “I am troubled by the allegations that such dangerous and illicit activity went undetected at a federal research facility.”

Faith Seeking Understanding

Charles Sigler, D.Phil.

Tag: CDC