10/28/16

Fluctuations in the Heroin Market

© 4designersart | stcokfresh.com

© 4designersart | stcokfresh.com

The 2016 World Drug Report (2016 WDR) is a good-news bad-news source of information on global opiate statistics. The good news is that global opium production fell by 38% in 2015. The decrease was primarily the result of a decline in opium production in Afghanistan, which fell 48% compared to 2014. This was mainly because of poor yields in the country’s southern provinces. Despite this, Afghanistan was still the world’s largest opium producer, accounting for 70% of global opium production.

The bad news is that despite the drop in production, the global number of opiate users has remained relatively stable. And opium production in Latin America, mostly in Mexico, Columbia and Guatemala, more than doubled from 1998-2014. Central and South American production accounts for 11% of the estimated global opium production. Also, in North America, heroin use and heroin-related deaths have continued to rise. In both cases, the increases were roughly three times the 1999 levels. See the following chart from the 2016 WDR.

heroin-deathsIn 2014, the largest seizures of opiates were in South-West Asia, with Europe next in line. The Islamic Republic of Iran reported the largest opiate seizures worldwide, accounting for 75% of global opium seizures and 17% of global heroin seizures. The next largest heroin seizures were from Turkey (16% of global heroin seizures), China (12%), Pakistan (9%), Kenya (7%), the U.S. (7%), Afghanistan (5%), and the Russian Federation (3%). Iran is the first stop on the so-called “Balkan route” of opiate distribution. From there the route travels into Turkey, and onto South-Eastern Europe, where it is distributed throughout Western and Central Europe. “Seizure data suggest that the Balkan route, which accounts for almost half of all heroin and morphine seizures worldwide, continues to be the world’s most important opiate trafficking route.”

The massive decline in opium production of almost 40 per cent in 2015 is unlikely, however, to result in a decline of the same magnitude within a year in either the global number of opiate users or the average per capita consumption of opiates. It seems more likely that inventories of opiates, built up in previous years, will be used to guarantee the manufacture of heroin (some 450 tons of heroin per year would be needed to cater for annual consumption) and that only a period of sustained decline in opium production could have any real effect on the global heroin market.

In 2015 Bloomberg published an article with three maps of global drug smuggling routes. The major opiate producers are: Afghanistan, Myanmar, Laos, Mexico and Columbia. The opiate map illustrates the vast reach of the so-called Balkan route. The Americas are primarily supplied with opiates grown in Mexico and Columbia. More than 70% of all heroin and morphine seizures in the Americas were in the U.S. between 2009 and 2014. Seizures more than doubled from around 2 tons per year from 1998-2008 to 5 tons per year from 2009-2014. Heroin trafficking and use was seen in 2015 as the main national drug-related threat in the US, according to the 2015 National Drug Threat Assessment (NDTA).

The 2015 NDTA reported that heroin was available in larger quantities, used by larger numbers of people, and caused more overdose deaths than 2007. The increased demand and use of heroin is driven by greater availability and controlled prescription drug (CPD) abusers switching to heroin. Cheaper prices for heroin contribute to the switch as well.

Increases in overdose deaths are driven by several factors. The purity of heroin has increased in some areas. New heroin users switching from prescription opioids are used to the set dosage amounts potency of prescription drugs. Illicitly–manufactured drugs can vary widely in their purity, dosage and adulterants. Over the past few years the use of highly toxic adulterants like fentanyl (20 to 40 times stronger than heroin) in certain markets has also added to the increase in overdose deaths. Then there are heroin users who stopped using for a while (from treatment or incarceration) whose tolerance has decreased because of their abstinence.

Most of the heroin in the US today comes from Mexico and Columbia. Columbian heroin is still the predominant type available in the Eastern US. While Southeast Asian heroin, largely from Afghanistan dominates the global market, very little makes its way to the US. Southeast Asian heroin was the dominant supplier of heroin in the US at one time. But it no longer can compete with the transportation and distribution networks of the Mexican and Columbian drug cartels. Se the following chart from the 2015 NDTA.

heroin-seizuresThe Mississippi River has been a dividing line in the US heroin market for the past 30 years, with Mexican black tar and brown powder heroin west of the Mississippi and white powder heroin from South America in the East. There is increasing evidence that Mexican drug cartels are processing their own white powder heroin and mixing white heroin with Mexican brown powder heroin to create a more appealing product to the Eastern US markets. See charts 12 and 13 in the 2015 NDTA for further information on the availability of heroin types purchased in Eastern and Western cities.

The suspected production of white powder heroin in Mexico is important because it indicates that Mexican traffickers are positioning themselves to take even greater control of the US heroin market. It also indicates that Mexican traffickers may rely less on relationships with South American heroin sources-of-supply, primarily in Colombia, in the future. If Mexican TCOs [transnational criminal organizations] can produce their own white powder heroin, there will be no need to purchase white powder heroin from South America to meet demand in the United States. This would also reinforce Mexican TCOs’ poly-drug trafficking model and ensure their domination of all major illicit drug markets (heroin, cocaine, methamphetamine, and marijuana) in the United States.

Mexican TCOs have been increasing their cultivation of opium poppies, to an estimated 17,000 hectares in 2014. This can potentially produce up to 42 metric tons of heroin. Switching to opium cultivation from marijuana cultivation may be at least partly due to the lowered demand for illicit marijuana in the US because of the legalization movement. See “The Economics of Heroin” for more information.

The number of heroin users reporting they used heroin over the past month increased 80% between 2007 and 2012. Of the total number of heroin-related treatment admissions in 2012, 67.4% reported daily use and 70.6% reported their preferred route of use was by injection. Heroin treatment admissions were consistently highest in the New England and Mid-Atlantic states. There are also high rates of repeated treatment among heroin users. Eighty percent of the primary heroin users admitted to treatment in 2012 reported previous treatment; 27% had been in treatment five or more times.

Most opioid users in the 1960s began by using heroin. But that steadily changed until 75% of heroin-users in the early 2000s reported they began by using prescription opioids. The number of people using illicit prescription opioids who switched to heroin was a relatively small percentage of the total number of prescription drug abusers at 3.6%. But it represented 79.5% of new heroin users. Heroin use was 19 times higher among individuals who had previously used pain relievers non-medically.

The reformulation of OxyContin in 2011 is seen as helping to curb the abuse of the drug. In 2011 emergency department visits involving oxycodone declined for the first time since 2004. Overdose deaths from opioid analgesics also began to decrease in 2011. But remember, CPD abusers have been switching to heroin and seem to be contributing to the dramatic increase in overdose deaths from heroin.

The number of heroin overdose deaths increased 244% between 2007 and 2013. Keep in mind that heroin deaths are undercounted. This occurs because of the differences in state reporting procedures for reporting drug-related deaths; and because heroin metabolizes very quickly into morphine. A metabolite unique to heroin, 6-monoaceytlmorphine (6-MAM), quickly metabolizes into morphine erasing the biochemical evidence for heroin use. So many heroin deaths get reported as morphine-related deaths. So what does the future hold for heroin use in the US? The 2015 NDTA concluded the current outlook for the near future is more of the same.

Heroin use and overdose deaths are likely to continue to increase in the near term. Mexican traffickers are making a concerted effort to increase heroin availability in the US market. The drug’s increased availability and relatively low cost make it attractive to the large number of opioid abusers (both prescription opioid and heroin) in the United States.

The United Nations Office on Drugs and Crime (UNODC) publishes a yearly report giving a global overview of the supply and demand of various drugs and their impact on health.

10/25/16

The Handiwork of God

© Andrey Armyagov | 123rf.com

© Andrey Armyagov | 123rf.com

The modern Christian, believing that the Bible is God’s inspired Word, His special revelation to us, will inevitably have to wrestle with whether or not the creation and flood accounts in Genesis are scientifically accurate. It can appear that they are being challenged to “choose whom they will serve”—the revealed God of Scripture or Science. But such an either-or presentation of the issue is a false dichotomy. And the first clue that this is so is found in Scripture itself. “The heavens declare the glory of God, and the sky above proclaims his handiwork.”

This is the first verse of Psalm 19, which goes on to assert that this declaration is throughout all the earth. Day and night the creation pours out this knowledge, this general revelation. It comes to all human beings simply because they are alive. The Reformation Study Bible said: “God has revealed Himself this way from the start of human history.” Then there is a shift to declare the perfection of God’s word, His special revelation starting with verse seven: “The law of the Lord is perfect, reviving the soul; the testimony of the Lord is sure, making wise the simple; the precepts of the Lord are right, rejoicing the heart.”

So there is no dichotomy between God’s two books of revelation. Abraham Kuyper asserted this truth when he said: “God is honored not by those who close the second book of nature to ponder Scripture alone, but by those who in quiet obedience zealously study the two books of Scripture and nature.” And if there is no dichotomy between God’s Word and his creation, the problem must exist in how we have interpreted Scripture.

An American scientist and Christian named Richard Bube observed in his 1963 essay, “A Perspective on Scriptural Inerrancy,” that orthodox Christians have been so intent on defending the divine origin of Scripture, that they tended to overlook its relationship to those for whom it was intended. He said we tend the treat the Bible as if it was “dropped down from heaven in one piece, transcribed by the finger of God.” He suggested that a view of Scripture that he called “arbitrary inerrancy” was at fault for this problem. By arbitrary inerrancy, he meant that: “the Scriptures must be inerrant with respect to any criterion applied to them to test their inerrancy.”

Oftentimes conservative theologians have spoken out in defense of Scriptural inerrancy as if there were only one kind of inerrancy imaginable-a kind of all or nothing inerrancy. They argue that the Scriptures are either completely inerrant in every way and with respect to every criterion for inerrancy which may be applied, or they are not inerrant at all. This is the viewpoint of “arbitrary inerrancy.” The term “arbitrary” does not imply that the motives of those who hold to this point of view are arbitrary, but rather that inerrancy must be maintained and defended against arbitrary criteria.

He said there exists a fear that we subtract from God and from His glory when we ascribe His operations in creation to natural mechanisms. There has been a human tendency “to ascribe to the direct and supernatural intervention of God” all those things for which we have no natural or rational explanation. Unfortunately, as time passes and scientific knowledge increases, the unexplained in nature decreases. So there is a tendency to marginalize the relevance of God and His work. “As we find out more and more about His creation, we see less and less evidence of the Creator!”

The problem identified here by Bube is particularly evident when Christians seek to faithfully understand the creation and flood accounts in Genesis. His sense of arbitrary inerrancy would apply to questions raised by science about the age of the earth and process of creation, as well as the reality of a global flood. The relatively recent creation of the earth in six twenty-four hour days, and its later destruction by a worldwide flood was unchallenged for centuries. Then modern geology and Darwin happened.

Christians attempted to harmonize the biblical teaching in Genesis to the developing scientific theories, in a process called concordism. An example of this given by C. John Collins in his book, Did Adam and Eve Really Exist?, was how in the nineteenth century the days of Genesis 1 were said to have anticipated findings of modern science in the geological ages of the earth, “even down to details of sequence and timing.”

An obvious problem with this approach is that geologists today do not describe the earth’s history the way they did in 1871. So does that mean “we should reject contemporary geology in favor of 1871 geology, or that the Bible was wrong?” Collins went on to say:

More significantly from an exegetical standpoint, the kind of concordism on display in nineteenth century studies of Genesis assumes that the Bible writer’s purpose was to describe the same sorts of things as the contemporary scientist does. This is a highly problematic assumption, when one considers the audience for whom Genesis was written—Old Testament Israel, whose main concerns were dominated by subsistence agriculture. Further, it assumes that truth and scientific detail are the same thing, which is absurd.

Another sense of concordism is held by Denis Lamoureux. He separates concordism into theological and scientific concordism. By theological concordism, he means “there is an indispensible correspondence between the theological truths of Scripture and spiritual reality,” which he affirmed. On the other hand, scientific concordism referred to the belief there is “an alignment between the assertions about nature in the Bible and the physical world.”

Lamoureux agreed it is reasonable to believe there is agreement or accord between science and Scripture.  That is what the sense of the two books of revelation means—the book of God’s works (nature) and the Book of God’s Word (the Bible). But he has something else in mind. By the term scientific concordism, Lamoureux means the belief that through the Holy Spirit, God revealed modern scientific facts to the biblical writers. Therefore, the statements about the physical world in the Bible are themselves inerrant—without error. So questioning these statements is seen as an attack on the belief in biblical inerrancy. This sense of scientific concordism does appear to underlie young earth creationism.

So when an orthodox, Bible-believing Christian seeks to understand Genesis 1, what are they to do? Are they required to take up the arbitrary inerrancy position or the scientific concordist approach of young earth creation and thus defend a strict literalist understanding of the text? Can they have a more relaxed understanding of concordism that seeks to harmonize Genesis 1 with the science of origins, recognizing that their harmonization may change as science develops? Or can they avoid the dilemmas of concordism entirely by approaching Genesis 1 as an ancient text devoid of specifics on how God created the universe? R. K. Harrison, an Old Testament professor at Wycliffe College, University of Toronto said this in his textbook, Introduction to the Old Testament:

Since the first chapter of Genesis is clearly not intended to comprise a scientific document—if only because of its sheer untechnical language—it is obviously undesirable to posit concordist theories of the relationship between the creation narratives and the findings of modern descriptive science. Having said this, however, it is necessary to remind the reader that the phases of development recorded in Genesis 1 are by no means as unaligned with the findings of modern science as was supposed by earlier writers on the subject. What is of primary importance for the Biblical student as well as for the scientist is to realize that the Genesis narrative must be interpreted from the standpoint of its anonymous author before pontifications are made as to when it is and is not “scientific.”

For more articles on creation in the Bible, see the link “Genesis & Creation.”

10/21/16

Pharma Companies Hunt in Packs

© Michael Wick | 123rf.com

© Michael Wick | 123rf.com

Turing Pharmaceuticals and its former CEO Martin Shkreli unwittingly shined a spotlight into the dark corner where the high cost of prescription drugs had been growing for years. As Dylan Scott reported for STAT News, Turing acquired an anti-parasitic drug called Daraprim in August of 2015 and promptly raised its price from $13.50 per pill to $750 per pill, a 5,000% increase. Eventually Shkreli resigned as Turing’s CEO, and the $750 pill price changed. GoodRx lists the cost now at over $46,000 for 60 tablets of Daraprim 25mg tablets; $767 per pill. By the way, it still costs $1 or $2 per pill outside the U.S.

But Turing is not a lone wolf pharmaceutical company ravaging the defenseless sheep of American healthcare consumers. Like wolves, pharmaceutical companies hunt in packs. EpiPens cost $100 for a standard two-pack in 2009. Now they cost $600. Valeant Pharmaceuticals came under fire for raising the prices of its 147 drugs by an average of 76% in 2014 and 2015. The average price of a Valeant drug was 33 times higher than comparable generics, according to STAT News. Many of the price increases went unnoticed until Valeant raised the prices on two life-saving heart medications by 525% and 212% on the same day.

Then there is Gilead Sciences and its line of hepatitis C drugs, priced at $1,000 per pill or more. Their aggressive pricing boosted Gilead from the 21st ranked pharmaceutical company by sales in 2013 to the 9th ranked company in 2014. At one time, Gilead had a 95% share of the U.S. treatment market for hepatitis C. With market competition, Gilead prices have come down, but not to the rate they negotiated with seven Indian drug companies in 2014 at around $100 per pill. The cost of Solvadi, the first Gilead hepatitis C drug to hit the market, costs $130 to $150 per pill to produce.

The New York Times reported in April of 2016 that Johnson & Johnson raised prices on several of its top-selling drugs, including a leukemia drug, a diabetes treatment, and an anti-clotting medication. Makers were raising prices on brand-name drugs by double-digit percentages since the start of the year, according to two major drug-benefit managers, Express Scripts and CVS Caremark. The chief medical officer at Express Scripts said: “It used to be the drug companies only took one price increase a year. . . . Now what they’re doing is taking multiple price increases multiple times a year.”

These are but a few examples of the actions by the Pharma wolves. And they aren’t all getting away with these tactics. Valeant has paid a heavy price for its actions. It became the target of congressional probes. Two top executives of the company resigned or were pushed out. Valeant’s stock price dropped from a high of $250 per share to less than $50. At the hearing, an influential board member expressed regret over the steep price increases, “it’s horrible. It’s wrong.” He pledged to have Valeant examine its price structure for the two heart medications, Isuprel and Nitropress. “You can expect from us within weeks and hopefully sooner a response to where we’re going to price these drugs and it will be significantly lower than where they’re priced now.” But even a 30% price cut meant they would be significantly higher than when Valeant acquired the drugs.

In response to the growing pressure over drug prices, Allergan promised not to raise prices by more than single-digit percentage points. In addition, the Allergan CEO pledged to not raise prices more than once per year. In his blog, he stated: “The health care industry has had a longstanding unwritten social contract with patients, physicians, policy makers, and the public at large.” He said that Allergan must keep this social contract in mind as they make business decisions that will ultimately improve wellbeing. “Those who have taken aggressive or predatory price increases have violated this social contract!”

Valeant’s response to this pledge by Allergan was to raise the prices of its drugs by 9.9% soon afterwards in September of 2016. A Wells Fargo analyst called the 9.9% increase “very odd,” and thought it may be an attempt to stay under the radar of managed care plans and states looking for double-digit price increases. STAT News asked Valeant why it chose the 9.9% and not a 10% increase, but didn’t get a reply.

The outrage has led to yet another Congressional attempt to regulate drug prices. The Fair Drug Pricing Act, cosponsored by Senator John McCain and US Representative Jan Schakowsky, would require drug makers to notify the US Department of Health and Human Services and submit a justification report 30 days before a price increase of certain drugs if the increase was more than 10%. The report would also require the companies to provide manufacturing and R&D costs for those drugs, along with net profits and marketing and advertising spending on the drugs. The hope, according to STAT News, is to bring greater transparency to the prescription drug market. Senator Tammy Baldwin said: “Drug corporations are sticking it to American taxpayers with soaring prescription drug prices.”

They are doing so because they received permission to do it from Congress when the Medicare Part D prescription drug legislation was approved ten years ago. Families USA reported that when Medicare Part D became law in 2006, it prohibited the Medicare program from bargaining with pharmaceutical companies to secure lower drug prices. It placed the responsibility in the hands of private drug plans. The failure of to deliver lowers prices with the implementation of Part D was evident within a year. Their analysis of the prices for the top 20 most frequently prescribed drugs to seniors showed that prices through the Veterans Administration, which can negotiate drug prices, were substantially lower than the lowest price charged by the largest Part D insurers. “The median difference was 58 percent.” For half of the 20 drugs, the lowest price charged by Part D insurers was ay least 58% higher than the VA cost.

Science Daily reported on a study published in the August 23/30 2016 issue of JAMA. Per capita spending on prescription drugs was higher in the U.S. than all other countries. Unlike these nations, the U.S. healthcare system permits manufacturers to set their own price for drugs. In countries with national healthcare insurance systems, drug prices are negotiated and sometimes rejected if the asking price is excessive in light of the benefit provided. The most important factor that drives high drug prices is market exclusivity, as was seen with Gilead Sciences and its ability to bring its hepatitis C drug Solvadi to market ahead of its competitors. The availability of generic drugs after patents run out is the primary means of reducing prices in the U.S. However, this can be delayed by a series of business and legal strategies by the drug companies.

In 2013, per capita spending on prescription drugs was $858 compared with an average of $400 for 19 other industrialized nations. In the United States, prescription medications now comprise an estimated 17 percent of overall personal health care services.

The JAMA study, “The High Cost of Prescription Drugs in the United States,” related the standard Pharma justification for high drug prices—the research and development costs incurred by a company to develop new drugs. Their mantra is that if drug prices are regulated, the pipeline for developing new medications will dry up. Economic analyses favored by Pharma assert that it costs $2.6 billion in 2013 dollars to develop a new drug that makes it to the market. But the reality of this figure has been disputed.

First, innovations leading to new drug products are often done in academic institutions and supported by public funding of research grants from sources like the National Institutes of Health. “A recent analysis of the most transformative drugs of the last 25 years found that more than half of the 26 products or product classes identified had their origins in publicly funded research in such nonprofit centers.” Other analyses have pointed to the importance of smaller companies, which are often funded by venture capitalists.

Just one example of this would be the Gilead Science purchase of sofosbuvir (Solvadi) from Pharmasset, a small biotech company, for $11 billion. The drug development was based in part on federally funded research at Emory University. Gilead almost recouped the entire purchase price in 2014 with Solvadi, making $10.3 billion in the first full year it was on the market. In December of 2015, the US Senate Committee on Finance released a detailed report (United States Senate Committee on Finance. The price of Sovaldi and its impact on the US health care system) based upon its access to internal company documents that indicated Gilead’s intent was to maximize the prices it could charge for Solvadi and Harvoni. Senator Wyden said:

Gilead pursued a calculated scheme for pricing and marketing its Hepatitis C drug based on one primary goal, maximizing revenue, regardless of the human consequences. There was no concrete evidence in emails, meeting minutes or presentations that basic financial matters such as R&D costs or the multi-billion dollar acquisition of Pharmasset, the drug’s first developer, factored into how Gilead set the price. Gilead knew these prices would put treatment out of the reach of millions and cause extraordinary problems for Medicare and Medicaid, but still the company went ahead. If Gilead’s approach to pricing is the future of how blockbuster drugs are launched, it will cost billions and billions of dollars to treat just a fraction of patients.

Senator Wyden went on to say that if the cures for diseases such as cancer, Alzheimer’s diabetes and HIV are unaffordable to millions of people who need them, Congress will not have met its responsibilities to the American people. “I reject the idea that America has to choose between soaring, out-of-reach drug prices and one-size-fits-all government policies. Solving this challenge will take fresh, bipartisan thinking and political independence to bring people together.”

Returning to the JAMA study, the authors noted that most effective way to reduce prices would be to set them for the entire marketplace, like the approach of Sweden. Incidentally, Sweden’s per capita spending on prescription drugs was around $350 in comparison to the $858 per capita expenditure in the U.S. Another option would be to engage in international reference pricing, setting prices at levels found in other countries. “Taking such a step in the United States would have major marketplace ramifications and is not at present politically feasible, in part because of the power of the pharmaceutical lobby in Washington, DC.” The conclusion of the study said:

High drug prices are the result of the increasing cost and complexity of drug development but also arise in large part from the approach the United States has taken to the granting of government-protected monopolies to drug manufacturers, combined with restriction of price negotiation at a level not observed in other industrialized nations. Opportunities to address these problems include paying greater attention to potentially unjustified granting and extension of patent exclusivity, enhancing com- petition by ensuring timely generic drug availability, providing greater opportunities for price negotiation by governmental payers, generating more evidence about comparative cost- effectiveness of therapeutic alternatives, and actively educating physicians and patients about such choices to promote more value-based decision making. There is little evidence that such policies would hamper innovation, and they could even drive the development of more valuable new therapies rather than rewarding the persistence of older ones. Medications are the most common health care intervention and can have a major benefit on the health of individuals, as well as of populations, but unnecessarily high prices limit the ability of patients and health care systems to benefit fully from these vital products.

So the wolves are circling, waiting to see whether or not they can get away with continuing to raise their prices on prescription drugs. What needs to happen is action by Congress to drive back the Pharma wolves. But that may be difficult to attain. They will have to fight through a pack of Pharma lobbyists more numerous than the combined membership of the Senate and House of Representatives. And more daunting, then they have to turn away from the campaign contributions amounting to $272,000 per member of Congress in 2015. But there is some good news about patients needing Daraprim. Imprius Pharmaceuticals now sells an alternative compound with the main ingredient in Daraprim for $1 a pill.

10/18/16

Dancing with the Devil

© choreograph | stockfresh.com

© choreograph | stockfresh.com

I once knew a woman who had an anxiety disorder. She also abused benzodiazepines. She was able to conjure up a panic attack in a doctor’s office and walk out with a prescription for the benzo of her choice. At one time, she had four concurrent prescriptions for these anti-anxiety medications. Another person I know of has a ten-year history of using benzodiazepines at close to the maximum recommended dose. When he had an unexpected short-term hospital stay, the treating physicians were reluctant to continue prescribing benodiazepines at such a high level while he was in the hospital. When he returned home, in case his medical issue resulted in another unexpected stay, he put together an emergency hospital kit with various things—including extra benzodiazepines.

A study published in the American Journal of Public Health in April of 2016 found that benzodiazepines were the second most common drug in prescription overdose deaths for 2013. Given the common knowledge of the potential dangers of benzodiazepines and people becoming more aware of opioids, Marcus Bachhuber and a team of researchers thought that their study would show a steady of declining pattern for prescribing benzodiazepines. But they found exactly the opposite. Between 1999 and 2013 there was an increase of 30% among adult Americans who filled a benzodiazepine prescription. In addition, the amount of medication within a prescription doubled over the same time period.

Bachhuber was quoted by CNN as saying the study’s findings were very concerning. The risk of overdose and death from benzodiazepines alone is said to be generally lower in otherwise healthy adults. But in combination with other drugs like alcohol or opioids, they can be lethal.

Future research should examine the roles of these potential mechanisms to identify effective policy interventions to improve benzodiazepine safety. In particular, as underscored by several recent reports, interventions to reduce concurrent use of opioid analgesics or alcohol with benzodiazepines are needed.

The overdose problem with benzos has been overshadowed by the problems with prescription opioids. Writing for CNN, Carina Storrs said: “The current study could help shine a light on the problem of benzodiazepine abuse and overdose.” Dr. Gary Reisfield, a professor of psychiatry at the University of Florida, referred to the problem with benozdiazepines as a “shadow epidemic”:

Much attention has been paid to the explosion of prescription opioid prescribing and the associated morbidity and mortality. Much less attention has been paid to the shadow epidemic of benzodiazepine prescribing and its consequences.

A 2015 study by Jones and McAninch found that emergency department visits and overdose deaths involving opioids and benzodiazepines increased significantly between 2004 and 2011. Overdose deaths from combining the two classes of drugs rose each year from 18% in 2004 to 31% in 2011. This rate increased faster than the percentages of people filling prescriptions and the quantity of pills in the prescriptions.

As Dr. Indra Cidambi wrote in “Are We Ignoring an Escalating Benzodiazepine Epidemic?”,  she observed with increasing alarm the rising rate of concurrent use/abuse of benzos among opiate users. She pointed to two possible factors driving this trend. First, some opiate abusers use benzos to “spike” the euphoria from their opiates. Second, patients often receive their prescriptions from two different physicians. She said that it is “notoriously difficult” for doctors to refuse to prescribe these two medications.

Unfortunately, and ironically, pain and anxiety are neither verifiable nor quantifiable through medical testing! Consequently, self-reported symptoms by patients are the sole basis on which prescriptions for these medications are written, enabling individuals addicted to these medications to obtain them fairly easily.

Dr. Cidambi recommended the establishment of a national database for physicians to verify whether or not a patient has been prescribed one of these medications before prescribing or filling a prescription for the other. Second, she said physicians should develop limited, short-term treatment plans from the beginning to treat noncancerous pain with opiates and anxiety with benzodiazepines.

Studies have shown the decreasing efficacy of long-term treatment for pain with opioid medications, and evidence-based treatment protocols for benzodiazepines clearly indicate that long-term use of benzodiazepines is not recommended.

In “Benzos: A Dance with the Devil,” Psychiatrist Kelly Brogan described some of her work helping patients taper off of benzodiazepines. A woman who had been placed on Remeron (an antidepressant) and Klonopin (a benzodiazepine) for eight years said of her original prescriber: “He never once told me there might be an issue with taking these meds long-term. In fact, he told me I probably needed them after I tried stopping them cold turkey and felt so sick I thought I was dying.” Brogan said no one ever discussed with this woman or her patients the true risks, benefits and alternatives to psychiatric medications like benzodiazepines, “perhaps because we as clinicians are not told the full story in our training.”

She went on to quote from a paper by another psychiatrist, Peter Breggin, on the risks of benzodiazepines, which include: cognitive dysfunction that can range from short-term memory impairment and confusion to delirium; “disinhibition or loss of impulse control, with violence toward self or others, as well as agitation, psychosis, paranoia and depression.” There can also be severe withdrawal symptoms, ranging from anxiety and insomnia to psychosis and seizures after abruptly stopping long-term larger doses. The person can re-experience their pre-drug symptoms as they taper. These so-called rebound symptoms of anxiety, insomnia and others serious emotional reactions can be more intense than they were before drug treatment began. And don’t forget dependency or abuse.

Psychiatrist Allen Frances, the former chair of the DSM-IV, recently wrote: “Yes, Benzos Are Bad for You.” He introduced his article by saying that he was going to say some very negative things about benzodiazepines in the hope that doctors think twice before prescribing them and patients are discouraged from taking them. Benzos were wonder drugs in the 1960s. Anyone remember the 1966 song, “Mother’s Little Helper,” by the Rolling Stones? These drugs were reputed to be safe, and so were used for a variety of “ills,” such as anxiety, alcohol use disorders (yes, really), to take the edge off of agitation in dementia, and to help people sleep. “Initially we were pretty oblivious to the risk of addiction.” So benzodiazepines quickly became the most prescribed medications in America.

A second craze began in the 1980s with the release of Xanax. Frances said the dose to treat panic disorder was “dangerously close” to the dose leading to addiction. “This should have scared off everyone from using Xanax, but it didn’t.” It remains a best seller, with its own “brand” that now leads to fentanyl be pressed into counterfeit Xanax pills. See “Buyer Beware Drugs” and Paul Gaita’s article on fake Xanax laced with fentanyl.

The real wonder of the benzos is that sales continue to boom, despite their having so little utility and no push from pharma marketeering (because patents have run out – thereby decreasing costs and profits.) Between 1996 and 2013, the percentage of people in the U.S. using benzos jumped more than one-third from an already remarkable 4.1 to 5.6 percent. Especially troubling is that benzo use is ridiculously high (nearly one out of ten) in the elderly, the group most likely to be harmed by them.

Frances said the beneficial uses of benzodiazepines can be counted on the fingers of one hand: short-term agitation in psychosis, mania and depression; catatonia; “as needed” use for times of special stress, like fear of flying, or for sleep. While they should be used very short term, in real life most people take them long term—“in doses high enough to be addicting, and for the wrong reasons. . . . Benzos are very easy to get on, almost impossible to get off.”

In addition to the harm from overdoses, Frances described the painful and dangerous withdrawal symptoms, which he said are a “beast.” Common symptoms are irritability, insomnia, tremors, distractibility, sweating and confusion. “The anxiety and panic experienced by people stopping benzos is usually much worse than the anxiety and panic that initially led to their use.”  Concurrent use or abuse of alcohol or other drugs, like opioids, complicates withdrawal even further.

The most insidious issues with benzos for Frances, is how they effect brain functioning. Especially with the elderly, ongoing benzo use can be devastating. Many elderly begin their downward spiral to death and disability from falls—that happen from their benzo use! He said: “If you meet an elderly patient who seems dopey, confused, has memory loss, slurred speech, and poor balance, your first thought should be benzo side effects — not Alzheimer’s disease or dementia.” See “Sedating Seniors” for more information on this topic. It’s been over 30 years since he last prescribed a benzo for anxiety.

The tough question is what to recommend for those many unfortunates already suffering the tyranny of benzo addiction. Should they stay the course to avoid the rigors and risks of withdrawal or should they make the great effort to detox? This is an individual decision that can’t be forced on someone. But the longer you are on them, the harder it gets to stop, and the cognitive side effects of benzos create more and more dysfunction as your brain ages. The best bet is to stick with a determined effort to detox, however long and difficult, under close medical supervision. On a hopeful note, some of the happiest people I have known are those who have overcome their dependence on benzos.

So it was encouraging to see that the FDA will require class-wide changes in drug labeling to bring attention to the dangers of combining opioids and benzodiazepines. The changes will include boxed warnings on nearly 400 products with information on the risks of combining these medications. The FDA Commissioner, Robert Califf said: “It is nothing short of a public health crisis when you see a substantial increase of avoidable overdose and death related to two widely used drug classes being taken together.” He implored health care professionals to carefully and thoroughly evaluate on a patient-by-patient basis whether the benefits outweigh the risks when using these drug classes together.

Used alone or in conjunction with opiates, benzodiazepines are potentially lethal and addictive. A too sudden withdrawal from benzodiazepines can be fatal, where the same is rarely true with opiates. They work quickly and effectively for anxiety and sleep problems and yet they can have a multitude of side effects, including addiction. Did I say they are addictive? Using benzodiazepines has become a dance with the devil for too many unsuspecting individuals … those that are still alive to regret it, that is.

This article previously appeared on the addiction and recovery website “The Fix” under the title of “Dangerous Dance.”

10/14/16

Diluted Evangelicalism

© MiroNovak | stockfresh.com

© MiroNovak | stockfresh.com

The last twelve months have brought home to me the incredibly diluted sense that the term “evangelical” now holds. The political Twilight Zone of our current presidential race played a central role in that realization. The confluence of presidential politics and evangelicalism led me to see that many so-called American evangelicals are what a CNN Religion Editor, Daniel Burke, labeled as “cultural evangelicals.”

Burke described seven types of evangelicals that ranged from the “old guard” of James Dobson, Tony Perkins and John Hagee, to the “entrepreneurial evangelicals” of Paula White, Kenneth Copeland and Jerry Falwell Jr; and of course the cultural evangelicals (CEs). This last category consists, according to Burke, of individuals raised as Christian, but who don’t attend church or consider religion to be important in their lives. Yet when pollsters ask about their faith, they say they are evangelical. Tellingly, Burke commented how CEs don’t seem dismayed with Trump referring to communion as “his little cracker” or when he could not name a favorite Scripture verse.

During a speech he made at Liberty University in January of 2016, Trump said “2 Corinthians” instead of “Second Corinthians.” He made his biblical ignorance worse by blaming his misstep on Tony Perkins. “Tony Perkins wrote that out for me — he actually wrote out 2, he wrote out the number 2 Corinthians. . . . I took exactly what Tony said, and I said, ‘Well Tony has to know better than anybody.’” Perkins admitted he did exactly as Trump said. Then he remarked how this showed Trump was not familiar with the Bible.

Not surprisingly, in a Pew Research poll on Faith and the 2016 Campaign done in January of 2016, Trump was seen as the least religious of all the candidates. Although conventional wisdom says someone who is not religious cannot be elected president of the United States, both Clinton and Trump were among the three presidential candidates seen as the least religious in the Pew poll. Bernie Sanders was the third least religious candidate. The number of Americans who say Hillary Clinton is not a religious person is sharply higher than when she was seeking the nomination in 2007.

The new survey confirms that being an atheist continues to be one of the biggest perceived shortcomings a hypothetical presidential candidate could have, with 51% of adults saying they would be less likely to vote for a presidential candidate who does not believe in God. Indeed, in the eyes of the public, being a nonbeliever remains a bigger drawback than having had an extramarital affair (37% say they would be less likely to support a candidate who had been unfaithful), having had personal financial troubles (41% say they would be less likely to support a candidate who had had financial struggles), or having used marijuana in the past (20% would be less likely to support a former pot smoker).

Another Pew Research poll (Evangelicals Rally to Trump) published in July of 2016, as Donald Trump became the Republican presidential candidate, indicated that 78% of white evangelicals would vote for Trump, including almost a third who strongly backed his campaign. And yet, many evangelical leaders such as Russell Moore, Max Lucado, and Erick Erickson, have said that supporting Trump for president in incompatible with evangelical principles and beliefs. Erickson said he would not vote for Trump. Ever. “Donald Trump has had no ‘road to Damascus’ conversion. He only wants to date the preachers’ daughter.”

There were no differences between evangelicals who say they attend religious services regularly (weekly or more) and those who attend less often. “Fully three-quarters of both groups say they would vote for Trump over Clinton.”

In his article for The Washington Post, Thomas Kidd suggested that what is going on is “a watering-down and politicization of the term ‘evangelical.’” He said that in American pop culture, evangelical now means “whites who consider themselves religious and who vote Republican.” Historically, early evangelical leaders like George Whitfield and Jonathan Edwards were fighting against the idea that Christianity was mostly cultural or political. “Swimming against the stream of culture, the evangelicals of the Great Awakening of the 18th century preached against the idea of an in-name-only affiliation, declaring you must be born again.”

He proposed three factors that have helped accelerate the corruption of the term evangelical since the 1980s. First was the success of the evangelical movement. In the 1800s, evangelicalism became the de facto religion in many parts of the South and Midwest. By the mid 1900s many Americans grew up supposing they were evangelicals, because the term seemed equivalent to that of Protestant and even “American.” This cultural environment meant people “were now born an evangelical, not born-again as one.”

Second, in the 1970s and 1980s, evangelicals began drifting away from candidates with personal evangelical backgrounds, like Jimmy Carter. This came to a head with the election of Ronald Reagan in 1980. “Reagan mastered the art of talking like evangelicals and promising progress on issues such as school prayer and abortion.” From that time on, self-identified white evangelicals seemed satisfied with candidates who learned the lingo and promised good Supreme Court appointments. “This meant that the public could disassociate evangelicals from theology, or affinity with other evangelicals, and link them inextricably with GOP politics.”

The third issue and the most serious one in understanding “evangelical” political behavior is in letting respondents define their own religious affiliation. One example he pointed to was the evidence suggesting that evangelicals who did not attend church were likely to support Trump. “For those who have a deeper understanding of the term’s historic meaning, there can be no such thing as a non-churchgoing evangelical.” African American, Hispanic and other evangelicals of color are often excluded because of how the term evangelical has been associated with being white and Republican.

These vague associations have turned “evangelical” into a term that luminaries like Edwards and Whitefield would not recognize. And, more problematically, they represent a faux gospel of moralism, nationalism and politicization. That is a gospel that certainly cannot save.

Cultural evangelicals are not true evangelicals. But then what is an evangelical? The Institute for the Study of American Evangelicals at Wheaton College observed how the term “evangelicalism” is a wide canopy that covers a diverse number of mostly Protestant traditions. Originally adapted by Martin Luther as the name of his movement, in the English-speaking world, it describes the religious movements that were associated with a series of revivals in America and England during the eighteenth and early nineteenth centuries.

By the 1820s, evangelical Protestantism was the dominant expression of Christianity in the U.S. Historian Martin Marty referred to a largely-evangelical “Benevolent Empire” that attempted the reshape American society in the decades before the Civil War. Cultural hegemony began to diminish after the war as American society changed from urbanization, industrialization and immigration. Millions of non-Protestant immigrants also came to America in the late 1800s and early 1900s.

Nonetheless, evangelical Protestantism remained a powerful presence within American culture (as evidenced by the success of evangelists like Dwight L. Moody and Billy Sunday). Going into the 20th century evangelicalism still held the status of a pervasive American “folk religion” in many sectors of the United States, particularly the South and certain areas of the Midwest.

Today, there are three ways in which the term evangelical is used. The first is to see evangelicals as all Christians who affirm a few key doctrines and practices. British historian David Bebbington identified four specific hallmarks of evangelical religion: 1) conversionism, 2) activism, 3) Biblicism and 4) crucicentrism. Conversionism means there has to be a change in how the person lives. Activism means effort is made to express the gospel. Biblicism has to do with a particular regard for the Bible. And crucicentrism means you stress the sacrifice of Christ on the cross.

Criticisms of Bebbington’s approach see his categories as too broad and inclusive. Yet it has become the baseline used by most scholars. Refer also to the work of the Barna Group or my discussion of it within “What is an Evangelical?

A second sense is to see evangelicalism as an organic group of movements and religious tradition. Here, evangelical denotes both a style and a set of beliefs; an attitude which insiders “know” and “feel” when they encounter it.

A third sense came from a coalition of individuals and organizations that arose during the Second World War. Individuals like Carl F.H. Henry, Billy Graham, and Harold Ockenga; and organizations like the National Association of Evangelicals played “a pivotal role in giving the aider movement a sense of cohesion” to the movement as a reaction against the fundamentalist movement of the 1920s and 1930s.

The National Association of Evangelicals (NAE) also reviewed Bebbington’s summary of evangelical distinctives. They indicated evangelicals were a diverse group that cut across denominations, churches and nations. “Our community brings together Reformed, Holiness, Anabaptist, Pentecostal, Charismatic and other traditions.” There is a link to the NAE Statement of Faith on their website linked above.

The NAE commented how evangelicals are often the target of research. But the outcomes vary because of the differences in how evangelicals are identified by the researchers. Along with LifeWay Research, the NAE developed a tool as a consistent standard for evangelical belief.  Respondents must strongly agree with the following four statements to be categorized as an evangelical:

  • The Bible is the highest authority for what I believe.
  • It is very important for me personally to encourage non-Christians to trust Jesus Christ as their Savior.
  • Jesus Christ’s death on the cross is the only sacrifice that could remove the penalty of my sin.
  • Only those who trust in Jesus Christ alone as their Savior receive God’s free gift of eternal salvation.

When evangelicals are self-described, then someone who would refer to Paul’s second epistle to the Corinthians as “2 Corinthians” could easily say he was an evangelical, and have his responses in the research codified as “evangelical.”  A true evangelical is something more than just a person who is considered to be an evangelical just because he or she says they are. Evangelicals need to self-consciously work against the watering-down and politicization of the term “evangelical.” We have to remember that the term comes originally from the Greek word euangelion, meaning “the good news” or the “gospel.” When we dilute the meaning of evangelicalism, aren’t we in danger of diluting the gospel itself? Remember that a faux gospel of moralism, nationalism and politicization does not save.

10/11/16

Stacking the Deck with Clinical Trials

© photosebia | stockfresh.com

© photosebia | stockfresh.com

In September of 2007 the “Food and Drug Administration Amendments Act of 2007” became law. This law requires that findings from human testing of drugs and medical devices be made publically available on the NIH website, ClinicalTrials.gov. But it seems that both drug companies and most research institutions—including leading universities and hospitals—routinely violate the law. An investigation by STAT News found that at least 95 percent of all disclosed research results were posted late or not at all.

Drug companies have long been castigated by lawmakers and advocacy groups for a lack of openness on research, and the investigation shows just how far individual firms have gone to skirt the disclosure law. But while the industry generally performed poorly, major medical schools, teaching hospitals, and nonprofit groups did worse overall — many of them far worse.

Four of the top ten recipients of federal medical research funding from the NIH were among the worst offenders. These four were: Stanford, the University of California, San Diego, the University of Pennsylvania, and the University of Pittsburgh. Researchers, university administrators and hospital executives interviewed by STAT News said they were not intentionally breaking the law. They were just too busy and lacked administrative funding to complete the required data entry on ClinicalTrials.gov. NIH estimated it takes, on average, around 40 hours to submit trials results.

Six organizations — Memorial Sloan Kettering, the University of Kansas, JDRF (formerly the Juvenile Diabetes Research Foundation), the University of Pittsburgh, the University of Cincinnati, and New York University — broke the law on 100 percent of their studies — reporting results late or not at all.

The Director of NIH, Francis Collins, said the findings were “very troubling.” He said pointing to the time demands on posting data to ClinicalTrials.gov was not an acceptable excuse for noncompliance. Beginning in the spring of 2016, after further refinement of the ClinicalTrials.gov rules, Collins said NIH and FDA will have “a firmer basis for taking enforcement actions.” The FDA is empowered to levy fines of up to $10,000 a day per trial for late reporting to ClinicalTrials.gov.

In theory, it could have collected $25 billion from drug companies since 2008 — enough to underwrite the agency’s annual budget five times over. But neither FDA nor NIH, the biggest single source of medical research funds in the United States, has ever penalized an institution or researcher for failing to post data.

When the “Food and Drug Administration Amendments Act of 2007” became law, Senator Charles Grassley said: “Mandatory posting of clinical trial information would help prevent companies from withholding clinically important information about their products. . . . To do less would deny the American people safer drugs when they reach into their medicine cabinets.” But the failure of drug companies and others to post clinical trial results, coupled with the failure of the FDA to hold them accountable via fines when they don’t, means the American people are being denied the ability to see for themselves if the drugs they take are safe and effective. Kathy Hudson, a deputy director for NIH, said:  “If no one ever knows about the knowledge gained from a study, then we have not been true to our word.”

The scarcity of clinical trial results posted to ClinicalTrails.gov is not the only issue with clinical trials and the NIH website. Drug companies and research facilities are also not prospectively registering clinical trials as they should. Scott, Rucklidge and Mulder found that “less than 15% of psychiatry trials were prospectively registered with no changes in POMs [primary outcome measures].” You can see Julia Rucklidge’s discussion of the study here. Also see “Clinical Trial Sleight-of-Hand” on this website.

Writing for Health Care Renewal, Bernard Carroll said there was a disconnection between the FDA’s drug approval process and what gets published in the medical journals. “Pharmaceutical corporations exploit this gap through adulterated, self-serving analyses, and the FDA sits on its hands.” He suggested that independent analyses of clinical trials be instituted, “because we cannot trust the corporate analyses.”

When corporations are involved, there is no point in prolonging the myth of noble and dispassionate clinical scientists searching for truth in clinical trials. It’s over. We would do better to stop pretending that corporate articles in medical journals are anything but marketing messages disguised with the fig leafs of co-opted academic authors and of so-called peer review.

Carroll proposed that Congress mandate the FDA to analyze all clinical trials data strictly according to the registered protocols and analysis plans. This should apply to new drugs as well as approved drugs being tested for new indications. And it should be applied to publications reporting new trials of approved drugs. “Corporations and investigators should be prohibited from publishing their own in-house statistical analyses unless verified by FDA oversight.” (emphasis in the original) Carroll quoted Eric Topol in a recent BMJ editorial as saying: “The disparity between what appears in peer reviewed journals and what has been filed with regulatory agencies is long standing and unacceptable.”

He gave three reasons for prohibiting in-house corporate analyses of clinical trials data. First, the inherent conflict of interest is too great to be ignored. Carroll described Forest Laboratories and citalopram as an example in his article to illustrate this point. Second, when corporate statisticians are encouraged to play around with the statistical analysis of the trial data (i.e., p-hacking), “they are no longer testing the defined study question with fidelity to the methods specified in the IND protocol.” Third, the FDA should monitor the publication of clinical trial reports in medical journals. The FDA inspects production facilities for evidence of physical adulteration, why not verify that what gets published in journals matches what they presented to the FDA for drug approval? “The harms of adulterated analyses can be just as serious as the harms of adulterated products.”

Pharmaceutical corporations are betting on huge profits with drug development. And allowing them to play fast and loose with clinical trial registration and the analysis of the trial data is akin to stacking the deck in their favor. It’s time to require pharmaceutical companies to stop trying to rig the clinical trial process in their favor.

10/7/16

Sure Cure for Drunkenness

© Volodymyr Baleha | 123rf.com

© Volodymyr Baleha | 123rf.com

Researchers at the University of North Carolina have identified a circuit between two regions of the brain that are thought to control binge drinking. The two areas—the extended amygdala and the ventral tegmental area (VTA)—have been implicated in past studies of alcohol binge drinking.  The results of this study provide the first direct evidence that inhibiting a circuit between two brain regions may protect against binge drinking. Todd Thiele, who directed the research, said: “If you can stop somebody from binge drinking, you might prevent them from ultimately becoming alcoholics. We know that people who binge drink, especially in their teenage years, are much more likely to become alcoholic-dependent later in life.” But so far, the research has only been demonstrated with mice.

Thiele and his team demonstrated that alcohol activates the CRF (corticotropin releasing factor) neurons in the extended amygdala, which in turn act on the ventral tegmental area. Applied to humans, these observations suggest that when someone drinks alcohol, CRF neurons in human brains are activated in a similar manner, promoting continued and excessive drinking. Thiele thought their findings could be relevant for future pharmacological treatments to help curb binge drinking. Although Thiele and his team didn’t connect their research to a particular pharmacological treatment for binge drinking, others did.

Writing for the Telegraph last year, Laura Donnelly connected the dots between the UNC team of researchers and a drug called Selincro (nalmefene).  Selincro was approved by the National Health Service (NHS) in Britain to help individuals cut back on their alcohol intake. It costs £3 ($3.96) and is to be taken as needed to stave off the desire to drink. Writing for the Mirror, Paul Christian’s headline was designed more to catch your attention than communicate truth: “New £3 pill to ‘cure’ alcoholism can stop binge boozing.”

Paul Fuhr was more cautious in his article for After Party Magazine, “Pill Could Cure Alcoholism, Binge Drinking.” His review accurately pointed out that Selincro is recommended for heavy drinkers. “In targeting weekend warriors rather than career alcoholics, the drug becomes less a cure-all than a solid first step toward sobriety.” He thought the implication of using Selincro to treat binge drinking was more intriguing than the reported effectiveness of the pill.

The prospect of a $4 pill that helps binge drinkers from falling down the alcoholic rabbit hole is an intriguing one but, in my opinion, could cause more damage than good. The pill’s very existence would feed the very problem it’s trying to combat, serving as something of a security blanket for people who know they can take a pill. It’s more important that researchers have uncovered the link between brain areas than designing a drug to flip the switch.

I think Fuhr is exactly right in his assessment that uncovering the link between brain areas is more important than a drug designed to “flip the switch.” I also agree that any drug used to turn this neurochemical circuit off and on will likely do more harm than good, aggravating the problem it is supposed to relieve. Its effectiveness is contingent upon the person actually taking the Selincro. And since it will also limit the euphoric effects of the alcohol as well as the cravings, if you don’t want to limit the euphoria, you won’t take it.

It may disrupt cravings and limit the euphoria from drinking, and this could limit how much you drink; but it won’t neutralize the other physiological effects of the alcohol you do drink. Physiological conditions from heavy drinking (anemia, cancer, cardiovascular disease, cirrhosis, gout, high blood pressure, pancreatitis, to name a few) may not improve—and could even progress—with continued drinking. It also won’t limit you blood alcohol level (BAL), so alcohol can still effect your judgment and decision making. Your self-control will still be blunted.

And this isn’t a new drug or a new treatment method, as some of the media seems to imply. The Sinclair Method actually recommends intentionally drinking after taking naltrexone. It conceives alcoholism to be a learned disorder. Limiting the euphoric reward of drinking is alleged to “cure” your alcoholism by systematically extinguishing the high. They should have remembered from behaviorism 101 that intermittent reinforcement (flicking the alcohol euphoria switch off-and-on) makes it more difficult to extinguish a behavior. See “A ‘Cure’ for Alcoholism.”

Another issue lies with the mixed results of research studies done with nalfmefene on humans.

Two French researchers published “Nalmefene: a new approach to the treatment of alcohol dependence” in the journal Substance Abuse and Rehabilitation. They reviewed the recent scientific literature on nalmefene that described its value in reducing alcohol consumption in alcohol-dependent patients. They noted where nalmefene was well tolerated. Its most common side effects were nausea, dizziness, insomnia and headache—which were mild or moderate and of short duration. Now the adverse effects disclaimer:

Selincro® must not be used in people who are hypersensitive (allergic) to nalmefene or any of its other ingredients. It must not be used in patients taking opioid medicines, in patients who have current or recent opioid addiction, patients with acute symptoms of opioid withdrawal, or patients in whom recent use of opioids is suspected. It must also not be used in patients with severe liver or kidney impairment or a recent history of acute alcohol withdrawal syndrome (including hallucinations, seizures, and tremors).

Paille and Martini said the available studies on nalmefene showed it to be more effective than placebo in reducing the number of heavy drinking days and total alcohol consumption. They lamented that the reduction of alcohol consumption in alcohol-dependent patients is not more widely recognized as a treatment objective. They pointed to the February 2013 approval of nalmefene by the European Medicines Agency with the following indications:

Selincro is indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking risk level, without physical withdrawal symptoms and who do not require immediate detoxification.

Selincro should only be prescribed in conjunction with continuous psychosocial support focused on treatment adherence and reducing alcohol consumption.

Selincro should be initiated only in patients who continue to have a high drinking risk level two weeks after initial assessment.

The European Medicines Agency limits the use of Selincro (nalmefene) in patients with a high drinking risk level that continues two weeks after an initial assessment. These patients should not exhibit physical withdrawal symptoms upon decreased alcohol consumption; and should not be in need of detoxification. And it should only be initiated in patients who remained in “continuous psychosocial support” that focused on treatment adherence and reducing alcohol consumption. In others words, use nalmefene as a method to reduce alcohol consumption and not as a method to more effectively control the negative consequences of drinking large amounts of alcohol. Paille and Martini concluded:

Nalmefene appears to be an effective treatment to reduce alcohol consumption in alcohol-dependent patients not wanting to become totally abstinent. It differs from other drug therapies essentially by replacing systematic dosing by “as-needed” dosing adapted to the patient’s clinical situation on a day-to-day basis. Patients therefore take nalmefene when they feel that alcohol consumption is imminent.

This is not the final word in nalmefene as a harm reduction tool with alcohol dependence. Palpacuer et al. published a literature review and meta-analysis of published and unpublished double-blind randomized controlled trials of nalmefene: “Risks and Benefits of Nalmefene in the Treatment of Adult Alcohol Dependence.” Significantly, they used the Cochrane Collaboration tool for assessing the risk of bias in their screening of nalmefene trials for their methodological quality. Five randomized control studies with a total of 2,567 randomized participants were included in the main analysis. So what did the researchers find?

The researchers identified five RCTs that met the criteria for inclusion in their study. All five RCTs (which involved 2,567 participants) compared the effects of nalmefene with a placebo (dummy drug); none was undertaken in the population specified by the European Medicines Agency approval. Among the health outcomes examined in the meta-analysis, there were no differences between participants taking nalmefene and those taking placebo in mortality (death) after six months or one year of treatment, in the quality of life at six months, or in a summary score indicating mental health at six months. The RCTs included in the meta-analysis did not report other health outcomes such as accidents. Participants taking nalmefene had fewer heavy drinking days per month at six months and one year of treatment than participants taking placebo, and their total alcohol consumption was lower. However, more people withdrew from the nalmefene groups than from the placebo groups, often for safety reasons. Thus, attrition bias—selection bias caused by systematic differences between groups in withdrawals from a study that can affect the accuracy of the study’s findings—cannot be excluded. Indeed, when the researchers undertook an analysis in which they allowed for withdrawals, the alcohol consumption outcomes did not differ between the treatment groups.

What do these findings mean?

These findings show that there is no high-grade evidence currently available from RCTs to support the use of nalmefene for harm reduction among people being treated for alcohol dependency. In addition, they provide little evidence to support the use of nalmefene to reduce alcohol consumption among this population. Thus, the value of nalmefene for the treatment of alcohol addiction is not established. Importantly, these findings reveal a lack of information on clinically relevant outcomes in the evidence that led to nalmefene approval by the European Medicines Agency. Thus, these findings also call into question the decisions of this and other regulatory and advisory bodies that have approved nalmefene on the basis of the available evidence from RCTs, and highlight the need for further RCTs of nalmefene compared to placebo and naltrexone for the indication specified in the market approval.

germanPaul Fuhr observed how the idea of miracle cures was as old as time itself, reminiscent of the days of patent medicines, like the German liquor cure sold at one time by Sears Roebuck and company for a buck.

Culturally, we want to believe there is a “cure” for drunkenness in pill form that doesn’t require us to do the hard work of establishing and maintaining abstinence.  My suggestion is to do the hard work.

10/4/16

Political Pot Stirring

© Hofmeester | stockfresh.com

© Hofmeester | stockfresh.com

The account of David and Bathsheba is one of the better-known stories in the Bible. And like a modern soap opera, it tells of adultery, deception and cover up, murder and exposure. Ultimately, there were ripple effects from it that would tear David’s family and even the nation of Israel apart. The Ewing family from the TV show Dallas comes to mind when I think about the schemes, plots and counter plots that occurred. And when you look closely, there’s even a character who could go toe-to-toe with J.R Ewing in terms of his cunning and deviousness—Jonadab.

Before we meet Jonadab, let me give a recap of the David and Bathsheba story from 2 Samuel 11 and 12. King David was walking on the roof of his house in the cool of the evening when he saw a beautiful woman bathing. He sent someone to find out who she was, and was told she was Bathsheba, the daughter of Eliam and the wife of Uriah the Hittite. She was the daughter of one of his best fighters (2 Samuel 23:34) and the wife of another man from his elite guard (2 Samuel 23:39). In addition, her grandfather, Ahithophel, was one of David’s respected advisors (1 Chronicles 27:34). Bathsheba was a woman of influence.

David stupidly slept with her, just after she had purified herself from her menstrual cycle (1 Samuel 11:4). This meant two things. She was not pregnant when David slept with her; and he did so when she was most likely to become pregnant. When Bathsheba discovered she was pregnant, she sent word to David.

His scheme to cover up their adultery was simple. He had Uriah sent to him as a messenger to report on the siege against the Ammonites in Rabbah. Afterwards he encouraged Uriah to go to his house and “wash his feet”, which is a polite way of suggesting that Uriah sleep with his wife. David even provided a present to help set the mood. But Uriah didn’t cooperate. Instead he slept at the door of the king’s house with the servants (2 Samuel 11:9).

When David heard this, he asked Uriah why he didn’t avail himself of the opportunity to be with his wife. Robert Bergen in his commentary suggested this could have been a thinly veiled attack on Uriah’s virility, something like this: “What’s wrong with you that you didn’t take advantage of the opportunity to sleep with your wife?” Bathsheba must have been really confused to have David’s present show up at her home, but not have Uriah come with it. But David had a “plan B.”

David invited Uriah to feast with him before returning to the battle. He encouraged Uriah’s drinking to the point of getting him drunk, but Uriah still would not go and sleep with his wife. So David gave him a sealed message to give to Joab, the commander of the army. The message Uriah carried was his death warrant. David ordered Joab to put Uriah at the head of a suicide attack on Rabbah. Then when the fighting was at its peak, withdraw and let Uriah be killed. Plan C worked.

When the time of mourning was complete for Uriah, David “generously” took Bathsheba as his wife. It would have looked like good PR. The king honored the wife of a fallen warrior by taking her into his household. Also recall her background. Bathsheba was not only beautiful, she was the daughter of one his elite warriors and granddaughter of his trusted advisor. “But the thing that David had done displeased the Lord” (2 Samuel 11:27).

The prophet Nathan told David a parable, and in his judgment of the rich man from the parable, David condemns himself. Nathan then publically declared David’s actions against Uriah and his adultery with Bathsheba. God’s judgment against David will be both the death of the illegitimate son by Bathsheba and that “the sword shall never depart from your house.” God will raise up evil against David out of his own house. What David did in secret, God will do before all of Israel in judgment against him (2 Samuel 12:11-12).

David is sincerely repentant for his sin, and God forgives him. Psalm 51 is a beautiful illustration of David’s repentance. There David acknowledged his sin against God, pleading that the Lord not cast him away from His presence. He asks God to create in him a clean heart; to renew a right spirit within him. But the child does die; and the sword and evil rose up against him out of his own house.

In chapter 13 of 2 Samuel, the story turns to David’s children, Amnon, his firstborn son, Absalom his third born son and Tamar Absalom’s beautiful sister. Amnon “loved” (had the hots for) Tamar, but despaired of being able to do anything about it. Jonabab, the cousin and friend of Amnon, suggested that Amnon pretend to be ill and ask David if Tamar could make some cakes, perhaps laced with herbs to heal his supposed sickness. When they are alone, Amnon forces himself onto Tamar and then forcibly has her sent away (2 Samuel 13:11, 15-17). In doing this, Amnon acted like the Caananite prince Shechem when he raped Dinah, the daughter of Jacob (Genesis 34:2-3). The reader is then set up to look for a similar outcome as the story progresses.

Absalom takes Tamar in after her humiliating rape and rejection. David is furious that Amnon, his heir apparent, brought such public shame and embarrassment to the royal family. Remember Nathan’s prophecy? Absalom said nothing publically about his brother’s behavior, but he hated Amnon for what he had done (2 Samuel 13:23). There is some speculation that Amnon’s actions were intended to help him assure his claim on the throne. Absalom and Tamar’s mother was herself the daughter of a king (2 Chronicles 3:2). Perhaps his lineage made him a better candidate for kingship than the apparently common ancestry of Amnon and Daniel who were older than Absalom.

Two years later, Absalom has a feast for all the sons of David. Amnon was the eldest son. Absalom was the third son, but seems to have had precedence over Daniel, David’s second eldest son. Third in line for the throne was Adonijah (1 Chronicles 3:1-9). Absalom had instructed his servants that when Amnon was good and drunk, they should kill him, which they did. Chaos broke out, and the sons of David fled.

The word that reached David was that Absalom had killed all of the king’s sons. Both David and his servants tore their clothes in mourning. But then Jonadab  (remember him?) corrected the false report, saying that only Amnon was killed. So the good news was that only the heir-apparent was killed—by the next son in line for the throne—in a very public way. Strangely, Jonadab seems to have known what happened at Absalom’s feast before any of them could reach David (2 Samuel 13:30, 32). Could he have known ahead of time what was going to happen? What was he plotting?

Jonadab is not mentioned again, but it does seem he assisted Amnon in an attempted plot to solidify his claim to the throne after David. But that failed, perhaps because of Amnon sending Tamar away after he had raped her. Tamar did try to change his mind, saying that the wrong in sending her away would be greater than what he had already done to her (2 Samuel 13:16). Jonadab saw the political winds changing and switched his allegiance to Absalom, whose killing of Amnon seems to have been as much politically motivated as it was by revenge. Could Amnon have been convinced to attend Absalom’s feast by Jonadab?

These are questions to which the Bible provides no answer. What we see is that David apparently didn’t have the heart to punish Amnon or Absalom for committing the same sins of adultery and murder that he himself did. His failure to reign in Absalom eventually led to Absalom’s attempt to take over the throne. He publically slept with David’s concubines, again as an apparent political maneuver (2 Samuel 16:20-23). Note that the person giving this advice to Absalom was Ahithophel, the grandfather of Bathsheba and the former advisor to David.

Robert Bergen suggested in his commentary that Ahithophel seems to have broken with David because of David having unlawful sexual relations with his granddaughter and then killing her husband. His plan would unambiguously demonstrate Absalom’s claim to Israel’s throne by exercising privileges reserved only for Israel’s king. Secondly, it would embolden those participating in the coup to also brazenly act in a way to become a stench in David’s nostrils.

For Ahithophel personally, the scheme must have seemed like a particularly satisfying application of the Torah’s lex talionis (“eye for eye, tooth for tooth …,” cf. Exod 21:24; Lev 24:20; Deut 19:21). David had had unlawful sexual relations with Ahithophel’s granddaughter at the royal palace in Jerusalem, though she was married to another; so now, unlawful sexual relations with David’s harem would take place at the same palace—only in this case the retributive act would be ten times greater than the original offense, and in public!

David still didn’t have the heart to do deal decisively with Absalom, ordering his military leaders Joab, Abishai and Ittai to deal gently with him. But Joab had Absalom killed. The circumstances of how Absalom was caught are symbolic, in that his head was caught up in a tree so that “he was suspended between heaven and earth” (2 Samuel 18:5-14). Deuteronomy 21:23 declared that anyone hung on a tree was cursed by God.

Modern political intrigue in the U.S. is starting to look downright peaceful and civil after studying this section of 2 Samuel. Character assassinations are rampant in the election, but at least there aren’t any coups or killings going on.

Jonadab played a key role in fanning the flames of ambition, lust, revenge and intrigue that led to the deaths of both Amnon and Absalom. He was never said to have taken an active role in what transpired, but he was clearly there stirring the pot. J. R. Ewing and he were cut from the same cloth. Some might find parallels to individuals who are “pot stirrers” in the ongoing presidential election. I don’t follow politics close enough to point to “Jonabad’s” behind Hilary Clinton or Donald Trump. But I can guess they are there. It’s a tradition that goes at least back to the time of King David.