01/31/17

Curiouser and Curiouser with Chantix

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In Lewis Carroll’s Alice in Wonderland, Alice famously said: “It would be so nice if something made sense for a change.” Since Carroll wrote this, many people have cited it to refer to one thing or another that puzzles them. I can now add my name to that list, as it does a spot-on job of expressing my thoughts on the recent FDA reversal in removing its black box warning for the smoking cessation drug Chantix.

On December 16, 2016, the FDA issued a drug safety announcement regaring Pfizer’s request that the black box warning be removed from Chantix. The FDA announcement said the decision was consistent with the recommendations of the September 2016 FDA Advisory Committee meeting. Essentially, their rationale was that the benefits of potential smoking cessation outweighed the health risks with Chantix. The conclusion of the committee was that an FDA ordered clinical trial (the EAGLES study) demonstrated “the risk of serious side effects on mood, behavior, or thinking [for Chantix] is lower than previously thought.” These side effects were what led to the black box warning (Given when there are serious or life-threatening risks when using the medication) on Chantix in the first place.

The risk of these mental health side effects is still present, especially in those currently being treated for mental illnesses such as depression, anxiety disorders, or schizophrenia, or who have been treated for mental illnesses in the past. However, most people who had these side effects did not have serious consequences such as hospitalization. The results of the trial confirm that the benefits of stopping smoking outweigh the risks of these medicines.

Notice the FDA is acknowledging the risks are still there and should be noted in the medication guide. However this assertion is debateable when evidence like that on the website RxISK in “Chantix and Violence” is considered. The cases there were originally reported in the FDA database for adverse drug events.

The results of the EAGLES study were published in the journal Lancet here. As Ed Silverman reported for STAT News, this action resulted in renewed efforts by Pfizer to have the black box warning removed. An earlier attempt in 2014 failed when an FDA panel voted to keep the warning intact. The chief medical officer for Pfizer thought removing the warning would more accurately reflect the neuropsychiatric safety profile for Chantix and allow patients and prescribers make informed decisions about treatment options. Despite the rhetoric here, the real reason was money:

The side effects have plagued the drug ever since it was approved a decade ago and endured horrendous publicity about violent or suicidal behavior. As a result, Pfizer spent hundreds of millions of dollars to settle numerous lawsuits and sales for the pill — once pegged to become a blockbuster — have plateaued, sliding from $846 million in 2008 to $671 million in 2015.

Alan Cassels, a pharmaceutical policy researcher at the University of Victoria, British Columbia, pointed out that the FDA action in December 2016 was unprecedented. Most of the drugs removed from the U.S. market over the past 20 years first carried a black box warning. Remember that according to the FDA, those risks ARE STILL PRESENT with Chantix, The EAGLES study concluded those risks are lower than previously reported and the FDA pragmatically agreed the potential benefit from Chantix outweighed the risks.

Not everyone on the FDA Advisory Committee that recommended the removal agreed. Of the 19 panel members, 10 voted to remove the black-box warning. Four wanted to see changes in the wording, while five others recommended the warning remain.

Thomas Moore, a senior scientist with the Institute for Safe Medication Practices, has also voiced concerns with the EAGLES trial itself, used by the FDA to justify removing the Chantix black-box warning. Critical of the study’s design, Moore and the ISMP thought the trial “was greatly underpowered, used a novel, unvalidated measurement scale, required subjective judgements from study investigators, and detected no meaningful differences among eight treatment arms because of a defective design.”

The ISMP letter to the FDA indicated Chantix (varenicline) was suspected to be the primary drug in 17,900 serious injuries from psychiatric adverse events reported to the FDA, 43% of which were done by health professionals. The cases described a series of behaviors ranging from suicidal and homicidal thoughts to delusions, suicidal behavior and bizarre and reckless aggression. These effects were documented in peer-reviewed studies. And Pfizer paid around $300 million in compensation—to over 2,500 varceline victims—for serious injuries that occurred BEFORE the boxed warning was required.

Moore and ISMP were not alone in expressing concern with the EAGLES trial.  Ed Silverman of STAT reported that Sammy Almashat of Public Citizen pointed out how the study had composite outcomes of both serious and milder symptoms, such as irritability and agitation, that normally occur when people are trying to quite smoking. Almashat was concerned with the precedent in this reversal; black box warnings are usually not reversed, especially on such equivocal evidence.

This could set an ominous precedent. If the FDA rescinds, a company can now go to the agency with a substandard post-marketing trial, point to Chantix and demand the same outcome. We’re worried that if the FDA follows through with the recommendation, that this will become a new standard for removing a black box.

The concluding statement from the ISMP letter may be a forewarning of what is to come:

An ambiguous warning can be worse than no warning at all because not only does it render the warning ineffective, it undermines the value of all warnings and the credibility of the FDA. A clear warning does not restrict the access of any patient or physician to this treatment.

“Curiouser and Curiouser,” as Alice would say if she heard about the back-and-forth actions by the FDA. There is more on this topic in another article, “Chantix Tug-of-War.”

01/27/17

Scientist, What Do You Believe?

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In 1997, Edward Larson and Larry Witham sought to replicate a famous early 20th century survey by James Leuba on what typical scientists affirmed regarding  two central beliefs of Christianity. These two dogmas were belief in a personal God, and belief in human immortality. Leuba found that 58.2% of US scientists expressed disbelief or doubt in the existence of God. Roughly 50% believed in human immortality. Larson and Witham’s replication eighty years later found little change among American scientists: 59.8% expressed doubt or disbelief in a personal God; 61.9% doubted or disbelieved in human immortality.

Comparison among “regular” scientists

1916

1996

Belief in a personal God

Personal belief

41.8%

39.3%

Personal disbelief

41.5%

45.3%

Doubt or agnosticism

16.7%

14.5%

Belief in human immortality

Personal belief

50.6%

38.0%

Personal disbelief

about 20%

46.9%

Doubt or agnosticism

about 30%

15.0%

Larson and Witham noted that Leuba’s finding of widespread disbelief among US scientists 100 years ago was shocking at that time. It became a central element in the anti-modernism speeches given by William Jennings Bryan and others. Yet the similarity to their 1996 findings among “regular” scientists is equally shocking. “Today, many people presume that scientists are far less likely to believe in the supernatural than the general population.”

Despite the stability in the overall proportion of believers and disbelievers, there has been a significant shift in views held by the three professions surveyed—mathematics, biology and physics/astronomy. The 1996 survey showed that mathematicians are most inclined to believe in God (44.6%). And although biologists showed the highest rates of disbelief or doubt in Leuba’s day (69.5%), that ranking is now given to physicists and astronomers (77.9%).

The interesting twist was when Larson and Witham repeated Leuba’s survey of leading or elite scientists. Within the circle of elite scientists, Leuba saw doubt or disbelief in God rise to 73.6%. Larson and Witham found disbelief or doubt in God among elite scientists to be 93%. Only 7.0% of modern elite US scientists affirmed a belief in God, while 27.7% did so in 1914. The following table compares the findings of Larson and Witham to Leuba among so-called “elite” scientists.

Leuba thought his findings demanded a revision of public opinion on the prevalence and future of these two “cardinal beliefs.” He said: “The essential problem facing organized Christianity is constituted by the wide-spread rejection of its two fundamental dogmas.” Leuba saw this rejection as growing parallel to—and not caused by—the diffusion of knowledge and intellectual qualities that come with eminence in scholarly pursuits.

I conclude, therefore, that the greater loss of belief suffered by the greater men is probably not to be ascribed to their greater knowledge, but rather to certain temperamental qualities or energies which make it relatively easy for them to rid themselves of much of the social pressure to which others yield.

According to Leuba, the elite scientist existed in a social environment where “intellectual freedom is honored far above orthodoxy.” This removed him from the “lower circles where tradition holds undisputed sway.” Therefore they were relieved of the pressures, which bear upon their less favored colleagues. If they were from eminent families, then they were doubly favored because from an early age they have been freer than lesser men from influence of “narrow traditional opinion” upon youth. See a copy of Leuba’s original 1916 work, The Belief in God and Immortality, here.

Larson and Witham pointed out that given the ongoing persistence of the belief in God (about 90% of Americans believe in God), Leuba seems to have either misjudged the human mind or the ability of science to satisfy all human needs. Nevertheless, their own study indicated: “among the top natural scientists, disbelief is greater than ever — almost total.”

Leuba wrongly assumed that the rationalism and secularity of science would eventually overtake and replace the truth claims of religion within American culture. Ecklund and Scheitle noted how Leuba concluded from his research that in order for religion to continue to have an influence on American society, it should capitulate to science. They quoted the following from a 1934 article by Leuba:

In order to be again a vitalizing and controlling power in society, the religions will have to organize themselves about ultimate conceptions that are not in contradiction with the insight of the time. They will have to replace their specific method of seeking the welfare of humanity to appeal to, and reliance upon divine Beings, by methods free from a discredited supernaturalism.

While American society did not fall victim to Leuba’s prediction of a widespread decline in traditional forms of religiosity, his finding about the differences between scientists and the general population was supported. This corroborated the perception of a conflict between the principles of religion and those of science. It also seemed to confirm that individuals who pursued science tended to abandon religion—whether that abandonment was due to an inherent conflict between the knowledge claims of religion and science or because of the secularization of scientific education.

In 2007 Ecklund and Scheitle examined the religiosity of faculty members from randomly selected institutions in the University of Florida’s annual report, “Top American Research Universities.” Respondents were asked about their religious identity, beliefs and practices. This included questions about their view of God, religion and church attendance. A comparison of current religious affiliation and affiliation as a child was done between the responding scientists and the U.S. population. The following is an edited discussion of their findings. See the above link for a fuller discussion.

While nearly 14 percent of the U.S. population self-describe as “evangelicals” or “fundamentalists,” only 1.5% of the scientists from elite universities did. Almost 52% of the scientists said they had not current religious affiliation, compared to 14.2% of the general population. Ecklund and Scheitle’s findings did not report data on evangelical/fundamentalist affiliation as a child. However, there were noticeable differences in the religious affiliation of scientists now and when they were children. Scientists who affiliated as Protestant and Catholic as children decreased significantly as they grew older and were educated.  See the chart below.

Scientists

U.S. Population

Current affiliation

Evangelical/fundamentalist

1.5

13.6

Other Protestant

15.2

40.8

Catholic

8.7

18.3

Jewish

15.3

1.8

Other

7.3

4.5

None

51.8

14.2

Affiliation as a child

Protestant

39.0

54

Catholic

22.6

31

Jewish

18.5

2.2

Other

6.5

4.6

None

13.4

8.3

Ecklund and Scheitle did find that academics at elite research universities were less religious than the public. But assuming that becoming a scientist necessarily leads to losing religious commitments was untenable. “Our results indicate that people from certain backgrounds (the non-religious, for example) disproportionately self-select into scientific professions.” However, being raised in a home where religion was very important meant it was more likely that “a scientist would remain relatively more religious.” Scientists who said religion was important in their family when growing up were more likely to see truth in religion, to believe in God, and to attend religious services.

Finding that the strongest predictor of religious adherence among this group was childhood religiosity recasts previous theories about lack of religiosity among academic scientists in a new light. The idea that scientists simply drop their religious identities upon professional training, whether due to an inherent conflict between science and faith or institutional pressure, is not strongly supported by these data. If this was the case, then religious upbringing would have little effect on religion among scientists, with even those scientists who were raised in religious homes losing religion once they entered the academy or received scientific training. Instead … religious socialization and heritage remains the strongest predictor of present religiosity among this population of scientists.

So the assumed power of scientific rationalism and secularity has not been able to overtake and replace the religiosity of the general American population, as Leuba predicted. And although elite American scientists are less religious than the general public, it seems that demographic factors such as age, marital status and children in the home are stronger predictors of religiosity than their scientific training. “In particular, religiosity in the home as a child is the most important predictor of present religiosity.”

But I would think that it is the rich, fully embraced religiosity practiced in a home that has staying power as the child grows into adulthood. A shallow, conduct-oriented religiosity will fall away. When religion is a do-and-don’t-do system of regulation, it tends to fall away. But if a child is trained in a way that enables him to see and internalize the heart of his childhood religion, then when he grows old, he will not turn from it (Proverbs 22:6). Even if he is an elite scientist.

01/24/17

Herding Pharma “Cats”

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The Chinese government released a report in September of 2016 by the State Food and Drug Administration (SFDA) that found fraudulent clinical trial practices on a massive scale. The SFDA concluded that over 80% of clinical trial data was fabricated. The scandal was the result of a “breach of duty by supervision departments and malpractice by pharmaceutical companies, intermediary agents and medical staff.” More than 80% of the applications for the mass production of new medications have been cancelled, with warnings by the SFDA that further evidence of malpractice might still emerge.

Radio Free Asia also reported the SFDA indicated much of the clinical trail data was incomplete at best. But it also failed to meet basic analysis requirements or was untraceable. “Some companies were suspected of deliberately hiding or deleting records of adverse effects, and tampering with data that did not meet expectations.” Apparently, this came as no surprise to industry insiders. “Clinical data fabrication was an open secret even before the inspection.”

Many of the new drugs were combinations of existing ones. Clinical trial outcomes were written beforehand, and their data presented so it agreed with the fabricated outcomes. A doctor at a top Chinese hospital said the problem lay with the failure to implement regulations governing clinical trial data. “Guangdong-based rights activist Mai Ke said there is an all-pervasive culture of fakery across all products made in the country.” Reporting for Pharmafile, Ben Hargreaves said:

The root of the issue is then not regulation, with regulation for clinical trials running on similar lines to Western practises, but in the lack of adherence to them. China’s generic drug industry has struggled with quality problems and therefore there is a temptation for companies to manipulate data to meet standards. The report found that many of the new drugs were found to be a combination of existing drugs, with clinical trials outcomes written beforehand and the data tweaked to fit in with the desire outcomes.

Sadly, clinical trial problems are not unique to China. An editorial published in the British journal The Lancet Psychiatry described multiple issues beginning with how subjects are recruited, moving on to determining what the control group should be, and ultimately defining meaningful outcome measures. Sometimes, trial recruits receive “care” they didn’t agree to. “Researchers and ethics review boards need to examine the ethical arguments and practical procedures from other areas of medicine where consent is problematic.” If such trials are done, regular and rigorous monitoring is essential. Patient safety and autonomy needs to be a priority.

In his discussion of the editorial, Justin Carter elaborated on one of the problems with recruiting subjects. An individual was recruited into a study on three antipsychotics while under a forced commitment order from a judge. “The psychiatrist who recruited him was in charge of the study and was his treatment provider and was also empowered to report on the patient’s progress to the judge.” The individual died by suicide during the drug trial.

The work of Irving Kirsch and others has shown the problem with inert placebos (sugar pills). The side effects from medication make it easy for participants to guess which study group they are in.

And when the trial is over and the data in, do the outcome measures really provide something meaningful for people’s lives? If the ultimate goal is for people to fell better and resume their prior level of functioning, should outcome measures by primarily patient self-reports, clinical assessment, or differences shown by imaging or the as-yet-to-be-clearly-identified biomarkers?

Given the problems running and interpreting psychiatry trials, it is essential to learn how even the most successfully tested interventions work in real clinics with the broad patient population. Implementation, uptake, and effectiveness in real-life settings must be analysed, and delivery of new innovations modified accordingly. Future research should be thought of not as a plain linear process from innovation to trial to implementation, but as a virtuous circle where research feeds into the clinic and vice versa.

Another issue pointed to by Carter was the validity and reliability of the diagnosis or classification system used to determine who to include and who to exclude from the trials. The DSM system, now in its fifth edition (DSM-5), is the current “bible” for assessing and diagnosing problems the psychiatric medications in clinical trials are supposed to “treat” in the U.S. Yet there have been questions about the reliability and validity of the DSM dating from an argument raised by Robert Spitzer and others in the 1970s that ushered in changes still embedded in the DSM-5. Rachel Cooper gave a brief history of the reliability questions with the DSM in “How Reliable is the DSM-5?” You can also refer to “Psychiatry Has No Clothes,” “Where There’s Smoke …”, and  “The Quest for Psychiatric Dragons,” Parts 1 and 2.

A few weeks before the release of the DSM-5, Thomas Insel, then the NIMH Director, announced the NIMH would be “reorienting” its research away from DSM categories. The agency’s new approach is called the Research Domain Criteria (RDoC) project. For now, RDoC is a research framework and not a clinical tool. But NIMH has high hopes for it: “RDoC is nothing less than a plan to transform clinical practice by bringing a new generation of research to inform how we diagnose and treat mental disorders.” While Tom Insel has moved on to work for Alphabet (Google), RDoC is alive and well within NIMH. You can keep up with news about RDoC on the “Science News About RDoC.”

The Science Update for February 16, 2106 noted the March 2016 issue of the journal Psychophysiology would be devoted to the RDoC initiative. Dr. Bruce Cuthbert said the special issue was a unique opportunity for researchers to engage with one another and reflect on work being done in various laboratories throughout the country. He thought it was encouraging to see many investigators already engaged in the kind of work RDoC advocates. “What this shows is that while the RDoC acronym may be new, the principles behind RDoC are certainly not new to psychiatric research.”

If the principles behind RDoC are not new to psychiatric research, how can it bring “a new generation of research to inform how we diagnose and treat mental disorders” in order to transform clinical practice? It sounds a lot like using the same deck of cards to just play a new card game. RDoC may not be the transformative framework it’s touted to become.

Added to these issues is the failure of pharmaceutical companies to publically report the results of clinical trials, as they are required by law to do. New reporting rules will take effect on January 18, 2017. But advocates for transparency in clinical research have cautioned the success of the new rules will depend upon the willingness and vigor of government enforcement of those rules. The failure to enforce the existing rules, which went into effect in 2008, led to widespread noncompliance with reporting requirements. If the FDA had fined the violators, they could have collected an estimated $25 billion.

Reporting for STAT News, Charles Piller said studies have indicated only a small fraction of trials will comply with the law. Yet there are no current plans to increase enforcement staffing at the FDA and NIH. That’s a big problem, according to Ben Goldacre, an advocate for full disclosure in clinical research. Francis Collins, the NIH director said they are serious about this and will withhold funds, if needed. “It’s hard to herd cats, but you can move their food, or take their food away.”

The legislation that created ClinicalTrials.gov emerged from numerous cases of drug manufacturers withholding negative trial results, making drugs look more effective and less harmful. Efforts to market the antidepressant Paxil for teenagers more than a decade ago stimulated the push for better reporting. A recent analysis in the journal BMJ found that GlaxoSmithKline, Paxil’s manufacturer, failed to disclose 2001 data showing the drug to be no more effective than a placebo, and was linked to increased suicide attempts by teens.

Writing for Time, Alexandra Sifferlin reported on a new study that suggested many of the medical reviewers for the FDA go to work for the drug companies they oversaw while working for the government. One of the study’s authors said: “I don’t think there is overt collusion going on, but if you know in the back of your mind that a major career opportunity after the FDA is going to work on the other side of the table, I worry it can make you less likely to put your foot down.”

Returning to the Francis Collins metaphor, it seems that the willingness to try and herd Pharma cats is dependent on whether or not you are afraid they will scratch you in the attempt.

01/20/17

Marijuana Use and the Heart

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Research was presented in November of 2016 at the American Heart Association’s Scientific Sessions that connected marijuana use and a heart muscle problem that can mimic the symptoms of a heart attack. “Stress cardiomyopathy is a sudden, usually temporary, weakening of the heart muscle that reduces the heart’s ability to pump, leading to chest pain, shortness of breath, dizziness and sometimes fainting.” Younger marijuana male users were twice as likely as non-users to experience this heart condition, which usually occurs in older women. They were also significantly more likely to go into cardiac arrest and need an implanted defibrillator to detect and correct the dangerously abnormal heart rhythms.

None of the people in the study who had used marijuana died after they were admitted to the hospital; so this study did not link marijuana use to sudden death. But some reports, discussed below, do report such a link. Nevertheless, one of the study’s co-authors said the link between smoking marijuana and stress cardiomyopathy in younger patients suggests the need for further investigation, especially with the growing legalization of recreational and medical marijuana in the U.S. “If you are using marijuana and develop symptoms such as chest pain and shortness of breath, you should be evaluated by a healthcare provider to make sure you aren’t having stress cardiomyopathy or another heart problem.” See the article on Live Science and the press release from the American Heart Association for more information.

The above heart condition is a rare occurrence, as is sudden cardiac death with marijuana use, but the incidence rate is not zero. Thomas, Kloner and Rezkalla published an article in the January 2014 issue of The American Journal of Cardiology describing a series of marijuana-related heart problems. Thomas et al. noted that published reports describe a temporal relationship between marijuana use and developing heart problems such as: acute myocardial infarction (a heart attack), cardiomyopathy, and sudden cardiac death. Careful evaluation of the cardiovascular effects of marijuana are complicated by the fact that it is often combined with other drugs, such as alcohol or tobacco.

The mechanism underlying the association between marijuana use and myocardial infarction is currently unknown. But it seems possible cannabis has a negative effect on coronary microcirculation. One reviewed report demonstrated how marijuana use made a 34-year-old man susceptible to ventricular tachycardia. After he stopped his marijuana use, his coronary flow returned to normal. A 2010 case study by Karabulut and Cakmak in Kardiologia Polska documented the existence of slow coronary flow in an individual who consumed marijuana regularly over a long period of time.

In “Triggering Myocardial Infarction by Marijuana,” Mittleman et al. interviewed 3,882 individuals an average of four days after the onset of myocardial infarction. The risk of myocardial infarction was 4.8 times higher in the sixty minutes after marijuana use. The risk rapidly decreased afterwards. They were less likely to have a history of angina or hypertension. Showing the presence of the above noted complicating factors, they also tended to be current cigarette smokers and obese.

Thomas, Kloner and Rezkalla noted where most case reports described relatively young patients in their 20s or 30s with normal coronary arteries or minimal atherosclerosis. This suggested that marijuana does not lead to or accelerate atherosclerotic damage in healthy adults and might explain the rarity of reports of marijuana-associated myocardial infarction despite the widespread use of the drug.

Marijuana use may also precipitate the development of myocardial infarction in patients with coronary artery disease. After myocardial infarction, mortality is signiifcantly higher in marijuana users than in the general population. In a study of 1,913 adults after hospitalization for myocardial infarction, Mukamal et al found a 4.2-fold increased risk for mortality in marijuana users who reported consuming the drug more than once per week before the onset of the infarction compared with nonusers.

Reports of marijuana use and sudden death are rarer than those of myocardial infarction, but nevertheless still evident. Most patients were abusing other drugs along with marijuana, precluding an accurate conclusion about the role played by marijuana in the cause of death. Yet there was a case report in the December 2001 issues of Forensic Science International by Bachs and Morland, “Acute cardiovascular fatalities following cannabis use,” of six possible cases of acute cardiovascular death in young adults, who had very recent cannabis use. This was confirmed by the presence of THC in post mortem blood samples; no other drugs were present. The article abstract noted where similar cases have been reported, but the toxicology reports were absent or limited to just urine samples.

The authors also speculated on the underlying mechanisms to these adverse effects. They acknowledged that currently relatively little is known about the underlying mechanisms at this point in time. Yet they noted several features of marijuana use that may explain the potential for an adverse effect on patients with known coronary artery disease. For example, marijuana is known to increase heart rate.

Supporting these findings, the American College of Cardiology described the following effects of marijuana on the cardiovascular system. In “Marijuana and Coronary Heart Disease,” the cardiovascular effects of marijuana included: elevated systolic and diastolic blood pressure, tachycardia,elevated sympathetic stimulation, decreased time to angina, increased risk of myocardial infarction for one hour after marijuana use.

A 2006 study based on data from The Coronary Artery Risk Development in Young Adults (CARDIA) study showed that marijuana use was associated with increased appetite, high caloric diet, and acute increase in blood pressure. “Although marijuana was not independently associated with cardiovascular risk factors, it was associated with other unhealthy behaviors … which all have long-term detrimental effects on health.”

There seems to be a consensus with the following remarks by Thomas, Kloner and Rezkalla to cardiologists and their patients alike:

In conclusion, the potential for increased use of marijuana in the changing legal landscape suggests the need for the community to intensify research regarding the safety of marijuana use and for cardiologists to maintain an awareness of the potential for adverse effects.

01/17/17

Reinhold Niebuhr and the Serenity Prayer

Heath Union Church, Heath MA

In May of 1943 Reinhold Niebuhr completed teaching his classes at Union Theological Seminary and left for a two-month series of meetings, conferences and lectures in England and Scotland. The German Axis forces in North Africa surrendered on May 12, 1943. Four days later, German troops crushed the last resistance in the Warsaw Ghetto Uprising, killing thousands of Jews. The rest were sent to Treblinka. Soon after Niebuhr returned to his family in Heath Massachusetts, Allied troops landed in Sicily on July 10th. On July 24th, the Allies began bombing the German city of Hamburg. By July 25th, Mussolini was overthrown and the new Italian government began peace talks. Somewhere in the midst of these earth-shaking events, Niebuhr preached a sermon at the Heath Union Church and uttered what would become known as the Serenity Prayer for the first time.

The above-described origins of the Serenity Prayer were given by Elisabeth Sifton, the daughter of Reinhold Niebuhr, in her book: The Serenity Prayer. Sifton deftly placed its origins in the midst of the work and ministry of her father during WW II. She said at some point in late 1943 or early 1944, a friend of her father’s, Howard Robbins suggested this little prayer about “grace, courage and wisdom” would be appropriate for inclusion in material he was preparing for army chaplains in the field. Niebuhr gave Robbins a copy of the prayer, and in 1944 it was included in the Book of Prayers and Services for the Armed Forces.

This was its first publication in any form and in any language, and its because of this little booklet that eventually it became famous. . . . A short while later Alcoholics Anonymous, then a fledgling small organization scarcely a decade old, with my father’s permission, also started to use the prayer in their regular meetings.

Sifton said she doesn’t know when or how AA simplified the text of her father’s original version of the Serenity Prayer. And although he let it happen “and didn’t fuss when the wordings were altered,” he did mind the changes. But Niebuhr never copyrighted his prayer. Sifton said it was inconceivable to him to construe prayers as a source of revenue. So he could not and did not control its misquotation, misattribution or embellishment.  The original text for Niebuhr’s Serenity Prayer is followed by the shortened AA version, and one of the longer versions.

Niebuhr’s 1943 version: “God give us grace to accept with serenity the things that cannot be changed, courage to change the things that should be changed, and the wisdom to distinguish the one from the other.”

The AA version appears in the Third Step essay of the AA book, The Twelve Steps and Twelve Traditions: “God grant me the serenity to accept the things I cannot change, courage to change the things I can, and the wisdom to know the difference.”

One version of the so-called “Complete” Serenity Prayer is in the linked article below by Nell Wing, an A.A. archivist. It is as follows:

God, grant me the Serenity to accept the things I cannot change; Courage to change the things I can, and the Wisdom to know the difference. 

Living one day at a time; enjoying one moment at a time; accepting hardship as the pathway to peace. Taking, as He did, this sinful world as it is, not as I would have it. Trusting that He will make all things right; if I surrender to his Will; that I may be reasonably happy in this life, and supremely happy with Him forever in the next. Amen. 

Elisabeth Sifton said she has no idea where the additional clauses of the “complete” version came from. But their message and tone were not in any way “Niebuhrian.” She noted how the A.A. version simplified the opening and framed the prayer in the first person singular, rather than the first person plural of her father’s original text. It also omitted the spiritually correct, but difficult idea of praying for “grace to accept with serenity that which we cannot change.” Instead, it focused on the simpler idea of obtaining “serenity to accept what cannot be changed.”

Nell Wing, an A.A. Archivist, wrote a paper in 1981: “Origin of the Serenity Prayer.” There she described several different purported “origins” for the Serenity Prayer that A.A. was told over the years. Bill W. and A.A. have attributed their initial discovery of the Serenity Prayer to Niebuhr, but still seem to repeat information about it that conflicts with Sifton’s above-described version—which she was told to her by her parents. For example, A.A. attributes their initial discovery of the (then) anonymous prayer to an obituary found by an early A.A. member in a New York paper in June of 1941. The connection to Dr. Niebuhr didn’t come to A.A.’s attention in the late 1940s.

Wing said an A.A. member reported seeing the prayer in Reinhold Niebuhr’s writings, “as if it were original to him.” She also quoted from a 1951 letter by an A.A.  member to Bill W. The man who had been in contact with Dr. Niebuhr, who confirmed that he did write the prayer and that it had been distributed to soldiers during WWII. Bill W. responded by saying that it was probable the Serenity Prayer existed in some form or other before Dr. Niebuhr. “Now it is pretty certain that Dr. Niebuhr did write the prayer in its present form and we also have on file a letter from him to that effect.” Bill then referenced a September 1950 article by Jack Alexander, which Wing quoted:

 Originally thought in Alcoholics Anonymous to have been written by St. Francis of Assisi, it turned out on recent research to have been the work of another eminent nonalcoholic, Dr. Reinhold Niebuhr, of Union Theological Seminary. Dr.Niebuhr was amused on being told of the use to which his prayer was being put. Asked if it was original with him, he said he thought it was, but added, “Of course, it may have been spooking around for centuries.”Alcoholics Anonymous seized upon it in 1940 [actually1941], after it has been used as a quotation in the New York Herald Tribune. The fellowship was late in catching up with it; and it will probably spook around a good deal longer before the rest of the world catches up with it.”

Wing also referred to several other “origins” of the payer that have been sent to A.A. at one time or another. There was even the reprint of a letter written by Ursula Niebuhr, Reinhold’s wife, which briefly reviewed the background to the Serenity Prayer given above by her daughter.

In the January 1950 issue of the AA Grapevine, there appeared an article entitled: “The Serenity Prayer,” that attributed the prayer to Niebuhr, and even gave what they said his original text. The prayer attributed to Niebuhr in the Grapevine article was not the version quoted above as the Niebuhrian 1943 version. The A.A. article also dated the origin of the Serenity Prayer to 1932. Howard Robbins is said to have received permission to place it in a compilation of prayers he then published in 1934. An A.A. member saw the prayer in an obituary in 1939, and brought it to the attention of Bill W. and others in A.A. The history described here seems to contradict that given above by Sifton. For more on the A.A. understanding of the origins of the Serenity Prayer, see: “The Serenity Prayer and A.A.”

Elisabeth Sifton, her mother and father all seem to have a similar sense of the Niebuhrian version of the Serenity Prayer coming from a sermon that he preached at Heath during WWII. Nell Wing reviewed several other possibilities, some of which were shown to be false. Yet the consensus from A.A. seems to believe the 1943 Niebuhrian version wasn’t the first. Writing for the Yale Alumni Magazine in 2008, Fred Shapiro wrote of his own investigations into the origins of the Serenity Prayer, “Who Wrote the Serenity Prayer?”

Shapiro noted that Niebuhr’s version of the Serenity Prayer was selected by the editor’s of the World Almanac as one of the ten most memorable quotes of the last 100 years. In English and German-speaking countries, he thought it was probably the only prayer to rival the Lord’s Prayer in popularity. Shapiro said Niebuhr himself said it was possible he assimilated its concept from some earlier, forgotten source. Nevertheless, Niebuhr made it clear that he believed the prayer originated with him.

Shapiro’s research found versions of the Serenity Prayer in newspaper databases before 1943. He stated how the evidence was by no means, conclusive; and it is entirely possible Niebuhr composed the prayer much earlier than he himself remembered. When he found at least eight versions of the prayer in newspapers before 1943, he contacted Elisabeth Sifton with his evidence. In response, Sifton commented that prayers evolve, are borrowed, transmuted and revised—by their original writers and others.

Sifton herself noted in her own book where the ideas expressed in the Serenity Prayer existed in previous works by her father. She noted how the tone of the Serenity Prayer radiated throughout Niebuhr’s classic work, The Nature and Destiny of Man. Niebuhr gave a series lectures with the same name at the Gifford Lectures between 1938 and 1940 at the University of Edinburgh. She pointed out where the second volume ended with a consideration of the ideas he was to express in his little prayer just a year or so later:

Wisdom about our destiny is dependent upon a humble recognition of the limits of our knowledge and our power. Our most reliable understanding in the fruit of “grace,” in which faith completes our ignorance without pretending to possess its certainties as knowledge, and in which contrition mitigates our pride without destroying our hope.

The following are two examples of what Shapiro found. Follow the above link to his full article for more.

In the January 16, 1936 edition of the Syracuse Herald, the executive secretary for the Syracuse Y.W.C.A. quoted the following prayer in her annual report:

O God, give us courage to change what must be altered, serenity to accept what cannot be helped, and insight to know the one from the other.

In the February 19, 1939 edition of the Ada (Oklahoma) Herald the home counselor for Oklahoma City’s public schools prayer said the prayer for both parents should be:

Oh God, give me serenity to accept that which cannot be changed, give me courage to change that which can be changed and wisdom to tell the one from the other.

Shapiro said it was possible that Niebuhr introduced the prayer by the mid-1930s in an unpublished or private setting. It was then quickly disseminated with his identification largely forgotten. But he said it must be asked why Niebuhr himself never suggested he had used the prayer in the 1930s. However, he believes a second alternative is more likely. The prayer really was “spooking around for years” and Niebuhr unconsciously adapted it from some already-existing formulation.

Sifton responded to Shapiro’s conclusions in “It Takes A Master to Make A Masterpiece.” You can find her response at the end of the link for Shapiro’s article, “Who Wrote the Serenity Prayer?” She still affirmed her father as the essential author of the Serenity Prayer. Shapiro merely demonstrated that her father’s voice reached far more American churches and organizations than they had previously realized. Prayers are presented orally and become famous orally long before they are put on paper.

Yet the great masterpiece prayers don’t materialize in some random, bubble-up way, either: their power comes from a distillation of complex spiritual truths, and for this we need authors, we need the tradition’s most gifted practitioners. In my book, I quoted prayers from various sources that my father knew well and whose cadences and theology feed into the Serenity Prayer’s concise wisdoms, because I wanted to suggest how the rich texture of worship as experienced by generations of believers nourishes the creation of new prayers. To throw light on this long, often anonymous process was one purpose of my book.

Sifton commented that since the Serenity Prayer has become so associated with the 12 Steps of Alcoholics Anonymous, most people think of it as expressing what we must work on within our “personal self-improvement projects.” Yet it was composed in wartime. It addresses “the inconsolable pain, loss, and guilt that war inflicts on the communities that wage it.”

She said her father drafted his prayers rapidly, or composed them right on the spot, rewording them many times before he felt they were in final form. Most of the prayers she cited in her book were not published until after his death in 1971. But by then generations of student and worshipers had known them well and used them for decades. “The Serenity Prayer was unusual in his oeuvre [body of work], then, only in the odd circumstance of its wartime publication and subsequent diffusion.”

The Niebuhrian version of the Serenity Prayer seems to have clearly come from Reinhold Niebuhr’s 1943 sermon. It also seems likely that the concepts within the prayer had been part of his teaching, thinking and writing in the years prior to that fateful sermon. And yet, religious believers and philosophers for thousands of years have struggled to be at peace or in harmony with the things in life that cannot be changed; to find courage to change the things they can; and to know the one from the other. The dilemma of the Serenity Prayer strikes at the heart of all religious and philosophical quests to know the will of God. Lord, by your grace grant us the serenity, courage and wisdom to know and do your will.

01/13/17

Iatrogenic Gun Violence

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Whenever I read about horrific violence like the incident in the Fort Lauderdale airport, I wonder what role psychiatric medications played. I wonder if the violent behavior was iatrogenic—was it caused by psychiatric medications? This question will sound counter intuitive for many people. Surely the reverse is true. Psychiatric medication and proper diagnosis should have prevented it. Let’s see if it is.

Esteban Santiago was deployed to Iraq from April 2010 to February 2011 with the 130th Engineer Battalion, the 1013th Engineer Company of the Puerto Rico National Guard. After flying from Alaska to Fort Lauderdale Florida, he retrieved his baggage, which incidentally contained a semi-automatic handgun. Santiago had followed proper protocol, checking the weapon with TSA. He went into the men’s bathroom, loaded his weapon and opened fire in Terminal 2 of the airport, killing five people and wounding six others. A witness said he was just randomly shooting people, with no rhyme or reason to it.

Family members reported that he was a changed man when he returned from Iraq. His aunt said his mind was not right. At times he seemed normal, but other times he seemed lost. In Iraq, his unit cleared roads of improvised explosive devices and maintained bridges. Two people in his unit died while he was in Iraq. His aunt said: “He talked about all the destruction and the killing of children. He had visions all the time.” He had changed.

His brother Bryan confirmed that recently Esteban was hallucinating, but said he was receiving psychological treatment. Bryan said he believes the shooting rampage resulted from mental issues that surfaced after the Iraq tour. When Esteban’s tour ended, he was hospitalized for mental problems. Upon his release, he went to Puerto Rico where his father was ill and eventually died. While in Puerto Rico, he received mental health therapy. Esteban eventually moved to Alaska, where he joined the Alaska National Guard in November 2014. He was discharged in August of 2016.

Over the course of 2016, Santiago was repeatedly reported to Anchorage police for physical disturbances. In January of 2016 he was arrested and charged with assault and criminal mischief after an argument with his girlfriend. He allegedly yelled at her while she was in the bathroom and broke down the bathroom door. She told investigators that he tried to strangle her and struck her on the side of the head.

Santiago pleaded no contest to criminal mischief and assault charges. Under a deferred prosecution agreement, his charges would have been dismissed if he complied with the conditions. He was due back in court on March 28th, 2017 to assess his progress.

While living in Alaska, Esteban continued to receive psychological treatment, according to his brother. Although his girlfriend alerted the family to the situation in Alaska, Bryan said he did not know what mental health problem Esteban was being treated for; they never spoke about it by phone.

His son was born in September of 2016. In November of 2016, Esteban walked into an FBI office in Anchorage to report that his mind was being controlled by a U.S. intelligence agency. He told officials he had a firearm in his car, along with his newborn son. Santiago was checked into a mental health facility; his firearm was logged as evidence for safe keeping. The infant’s mother came for their child. FBI special agent Marlin Ritzman said:

During the interview, Mr. Santiago appeared agitated, incoherent and made disjointed statements. Although he stated he did not wish to harm anyone, as a result of his erratic behavior our agents contacted local authorities, who took custody of Mr. Santiago and transported him to the local medical facility for evaluation.

After conducting database reviews, interagency checks and interviews with his family members, the FBI closed its assessment of Santiago. Agents found no ties to terrorism during their investigation. A CNN senior law enforcement analyst and former FBI assistant director said Santiago hadn’t been adjudicated a felon and he hadn’t been adjudicated as mentally ill. So they couldn’t keep his weapon. The Walther 9-millimeter pistol was returned to him in the beginning of December. Authorities told CNN it was the pistol he used in the shooting incident in Fort Lauderdale.

Typically, Esteban was considered to be a calm young man who was never violent. Recently he began selling his possessions, including his car. Friends and associates noticed more erratic behavior. He bought a one-way ticket to Fort Lauderdale and packed his pistol and two magazines. His carryon bag with the pistol was his only luggage. He flew from Anchorage to Minneapolis to Fort Lauderdale. He retrieved his bag from the baggage claim area and went into a men’s room stall to load his pistol.

He shot the first people he saw, going up and down the carousels of the baggage claim, shooting through luggage to get at people that were hiding. He thinks he fired 15 bullets, aiming at his victim’s heads. A witness said Esteban showed no remorse. He didn’t say anything. “No emotion, no nothing. About as straight-faced as you get.” Afterwards, he just lay face down, spread eagle, waiting for the deputies to come and get him.

The above report was pieced together from information contained in the following reports by The New York Times here,  NJ.com here, CNN here, and NPR here.

There was no explicit mention of Santiago’s repeated involvement in “psychological treatment” involving psychiatric medications, but it highly probable he was taking psychiatric medication of some sort. The lack of any mention of his being prescribed medication may simply be due to confidentiality regulations. Or this silence could be due to the chicken-and-egg argument often applied to incidents involving violence and individuals with known psychiatric problems. Their mental illness, not the drugs to treat it, caused their horrific behavior.

Several psychiatrists have voiced concerns with psychiatry, its over reliance upon medication and denial of serious adverse effects from medication, like violence and suicide. Joanna Moncrieff said she’s sad her profession has not taken the harms drug treatments can do more seriously. She said it has a long history of ignoring the adverse effects of drugs, or attributing them to the underlying disease—of blaming the patient instead of the drug. “Too many psychiatrists have just accepted that drug treatments are good, and have not wanted to contemplate that actually these treatments could be harmful.”

First and foremost, she said, psychiatry needs to adopt a drug-centered model for understanding its drug treatments and what they do to people. Psychiatrists need more information, knowledge and training on what the drugs do—what effects they produce in people; “how they change the way that people think and feel and what sort of impact those changes have on people’s lives.” Watch two brief videos of her expressing her concerns here. You can read more about her “drug-centered model” here on this website: “A Drug is a Drug is a Drug.”

Peter Breggin has raised concerns with the association of violence and antidepressants since the early days of Prozac. In his 1991 book, Toxic Psychiatry, Dr. Breggin related newspaper and scientific reports pointing to an association between Prozac and “compulsive, self-destructive and murderous activities.” He said then he was personally familiar with several cases of compulsive suicidal or violent feelings that developed after taking Prozac. Over the years, his familiarity grew.

In “Psychiatry Has No Answer to Gun Massacres,” Breggin described how the Columbine High School shooter, Eric Harris had a “therapeutic” level of Luvox (fluvoxamine) in his body at the time of the murders.  He had a dose increase in his medication 2 ½ months before the assault and showed signs of drug toxicity five weeks before the event. James Holmes, the Aurora Colorado theater shooter, was in psychiatric treatment with the medical director of student health services, who was considered an expert on campus violence. She was concerned enough about Holmes to report him to the campus police and the campus threat assessment team a few weeks before the assault. When the assessment team suggested putting him on a 72-hour involuntary hold, she rejected the idea. “When Holmes quit school, the school washed its hands of all responsibility for him.”

In a 2010 journal article, “Antidepressant-Induced Suicide, Violence, and Mania: Risks for Military Personnel,” Dr. Breggin related how the adverse effects described in the 2009 edition of the Physicians’ Desk Reference for Zoloft (sertaline) resembled the most frequent psychiatric disorder associated with combat—PTSD—with its hyperalert overstimulated symptoms. He said identical or nearly identical warnings can be found in all antidepressant labels. “All these potentially dangerous symptoms are also commonly seen in PTSD in military personnel, posing the risk of worsening this common military disorder.”

Looking at the revised 2016 medication guide for Zoloft, we see that nothing much has changed with regard to adverse effect warnings. It said Zoloft and other antidepressant medications could increase suicidal thoughts or actions. Symptoms needing immediate attention included: acting aggressively or violent, feeling agitated, restless angry or irritable, an increase in activity or talking more than what is normal, acting on dangerous impulses, trouble sleeping, new or worse anxiety or panic attacks, trouble sleeping, other unusual changes in behavior or mood.

A condition known as “serotonin syndrome” has symptoms such as: agitation, hallucinations, coma and other changes in mental status. Symptoms of potential manic episodes included: greatly increased energy, racing thoughts, unusually grand ideas, severe trouble sleeping’s, reckless behavior, excessive happiness, talking more or faster.

Dr. Breggin concluded his article with the following cautions and recommendations. He said there was a strong possibility the increased suicide rates among active-duty soldiers were in part caused or made worse by the widespread prescription of antidepressant medication. Alone, they can cause a stimulant-like series of adverse effects. “These symptoms of activation can combine adversely with similar PTSD symptoms found so commonly in soldiers during and after combat.” He recommended the military study the relationship between psychiatric drug treatment and suicide as well as random or personal violence. He also suggested that antidepressants should be avoided in the treatment of military personnel.

Another emerging concern of an association between antidepressants and violence is in the research done by Yolande Lucire. She suggested that mutations in CYP450-encoding genes contributed to problems metabolizing psychiatric drugs, and thus were contributing factors in three cases of antidepressant-induced akathisia-induced homicide. The cytochrome P450 family of enzymes is responsible for metabolizing most of the drugs used in psychiatry. You can read her article here. You can also find another article: “Psych Drugs and Violence” on this web site. Within that article you will find a link to another article by Lucire on antidepressant-induced akathisia-related homicide and the CYP450 genes.

Hasn’t there been enough evidence associating suicide and violence with psychiatric medications, especially antidepressants, for open dialogue and more comprehensive scientific research into this public health issue? How many more Columbines, Auroras and Fort Lauderdales need to happen before we begin to address the association of psychiatric drugs and violence?

01/10/17

Marijuana Makes You Nauseous?

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Live Science reported on a study published in the August 31, 2016 issue of The Lancet that found more people are using marijuana and they are using it more often.  In 2014, 13.4% of people said they had used marijuana in the previous year, an increase of 3% since 2002. The percentage of people who reported daily or near daily use rose from 1.9% to 3.5%. At the same time concerns about the risks associated with marijuana use dropped. In 2002, 50.4% of adults thought there was a great risk with marijuana use. That fell to 33.3% by 2014. But the perception of lowered risks may be premature.

The authors of the Compton et al. study thought the combination of increased marijuana use and a decreasing perception of the harm suggested there was a need for education regarding the risks of smoking marijuana. One of these health risks is for a medical condition called cannabinoid hyperemesis syndrome, or CHS. It is caused by heavy, long-term use of various forms of marijuana. Its symptoms include cyclic episodes of nausea and vomiting; some people have severe abdominal pain. A CBS Evening News report described a man who struggled with symptoms of CHS for two years before it was correctly diagnosed. Oddly, hot showers or baths seem to provide symptom relief.

CHS was first reported in 2004 by Allen et al. The ten patients were all cyclical vomiters and chronic marijuana users. Nine of the ten also had the abnormal bathing behavior of multiple hot showers or baths. The symptoms of nausea, vomiting and abdominal pain would all settle within minutes of taking a hot bath or shower. Symptoms resolved with abstaining from marijuana use in seven of the ten patients. Three of the abstaining patients resumed marijuana use and relapsed within months.

High Times described CHS as a rare form of cannabinoid toxicity that developed in chronic smokers. The author suggested with CHS, there was generally daily use in excess of three to fives times for several years. CHS is often mistaken for cyclic vomiting syndrome (CVS), because the symptoms are similar. But CVS is not caused by marijuana use. CHS is easily cured by abstaining from cannabis use.

This should not, by any means, hurt marijuana’s reputation for being the safest recreational drug around, but people need to be aware of the syndrome’s existence. If you know anyone with these symptoms tell him or her go to a doctor and stop smoking.

A 2011 review article by Galli et al., “Cannabinoid Hyperemesis Syndrome,” observed how the recognition of CHS coincided with the increased use of cannabis. Their review gave an overview of cannabinoid pharmacology that focused on the properties that seem to contributes to CHS. They also gave a clinical description of CHS and a proposed a method for clinical evaluation, which included differential diagnosis and treatment modalities.

Patients are typically young adults with a long history of cannabis use. They present with recurrent episodes of nausea, vomiting and dehydration with frequent visits to emergency departments. In almost all cases, there was a delay of several years between their chronic marijuana use and the onset of symptoms. One study reported an average duration of 16.3 years of cannabis use before the onset of symptoms. But there have been reports where the time lag was equal to or less than three years.

CHS is a recurrent disorder, with symptom-free periods. There are three phases: pre-emetic, hyperemetic, and recovery. The pre-emetic phase can last for months or years. Patients have early morning nausea, a fear of vomiting and abdominal discomfort. They maintain normal eating patterns and may even increase their marijuana use because its reported relief of nausea.

The hyperemetic phase has spasms of intense and persistent nausea and vomiting, which has been described as “overwhelming and incapacitating.” Patients vomit profusely, often without warning—up to five times per hour.  There can be weight loss. Most patients have diffuse, but relatively mild abdominal pain. They are found to be dehydrated, but hemodynamically stable. The tests and work ups done at EDs are inconclusive in the majority of cases.

During this phase, patients take numerous hot showers throughout the day. As this seems to be the only measure that brings some symptom relief, it rapidly becomes a compulsive behavior. The precise mechanism for this relief is not known. It typically lasts for 24 to 48 hours, but the risk of relapse is high if the patient resumes cannabis use.

The recovery phase can last for days, weeks or months. It’s associated with relative wellness and eating patterns. “Weight is regained and bathing returns to regular frequency.”

Patients with CHS usually are misdiagnosed for a considerable length of time. One problem is that it is often confused with cyclic vomiting syndrome (CVS). “Confusion also exists in the medical literature secondary to a failure to recognize chronic marijuana use as a source of vomiting.” Although there is a close similarity of conditions, there are also significant differences.

A 2015 study by Kim et al. looked at the prevalence of patients presenting for cyclic vomiting in Colorado before and after the liberalization of medical marijuana in 2009. A secondary objective was to describe the odds of marijuana use among cyclic vomiting visits during these same time periods. The prevalence of CVS increased from 42 per 113,262 Ed visits to 87 per 125,095 ED visits after marijuana liberalization. Patients with CVS post liberalization were more likely to have documented marijuana use than patients in the pre liberalization period.

The prevalence of cyclic vomiting presentations nearly doubled after the liberalization of medical marijuana. Patients presenting with cyclic vomiting in the postliberalization period were more likely to endorse marijuana use, although it is unclear whether this was secondary to increased marijuana use, more accurate marijuana reporting, or both.

The study said it does not demonstrate causation of CHS. But it does demonstrate a preliminary association “and should serve as the foundation for future prospective studies on the association between marijuana and cyclic vomiting, the eventual establishment of formal diagnostic criteria for CHS.” Foremost among the interventions for symptomatic treatment should be counseling toward abstinence from marijuana use. The authors saw their study as a crucial first step towards establishing a formal diagnosis of cannabinoid hyperemesis syndrome.

High Times seemed to minimize the present concerns with CHS by referring to it as “a very rare syndrome” that is easily cured. CHS does not reverse marijuana’s reputation as “the safest recreational drug around” at this point. But remember that even High Times agreed the cure for CHS is to stop using cannabis. We are just entering into a time of not only increased marijuana use, but also increased daily or near daily marijuana use. As this trend grows into a population of chronic, heavy marijuana users, the safety profile for marijuana will likely change; and it seems that CHS will be part of that decreasing safety profile.

01/6/17

The Serenity Prayer and A.A.

Alcoholics Anonymous and the Serenity Prayer are forever bound together. The prayer originated with the American theologian, Reinhold Niebuhr, but its dissemination within the wider culture occurred through A.A. So there are two distinct historical threads that can be followed in tracing the history and use of the prayer. One thread follows its presence through A.A. itself and another traces its origins with Niebuhr. This article will concentrate on the A.A. connection, while another one, “Reinhold Niebuhr and the Serenity Prayer,” will trace its origins with Niebuhr.

Pass It On is the A.A. approved history of Bill W. and how the message of A.A. reached the world. It described how one of its members saw the prayer in an obituary of an early June 1941 edition of a New York paper, the Herald-Tribune. Pass It On quoted it as existing then in its commonly received form: “God grant me the serenity to accept the things I cannot change, courage to change the things I can, and the wisdom to know the difference.” An A.A. member had the idea to print the prayer on cards and paid for that first printing out of his own pocket.

It was initially referred to as: “the A.A. prayer” or “God grant us” by A.A. members. But by the late 1940s, it became known as the Serenity Prayer. Nell Wing, the first A.A. Archivist and a secretary to Bill W., wrote “Origin of the Serenity Prayer: A Historical Paper” in 1981. She quoted from a June 12, 1941 letter written by Ruth Hock, the A.A. secretary at that time, to an A.A. member and a printer by trade about getting the prayer printed on a wallet-sized card. He responded:

Your cards are on the way and my congratulations to the man who discovered that in the paper. I can’t recall any sentence that packs quite the wallop that that does and during the day shown it to the A.A.’s that dropped in and in each case have been asked for copies.

In the January 1950 edition of the AA Grapevine, an article appeared that “solved” the mystery of the origins of the Serenity Prayer. Although its origin had been previously attributed to several different sources, the article said it originated with Dr. Reinhold Niebuhr. He was said to have written it around 1932 as the ending of a longer prayer. In 1934 a friend asked Niebuhr’s permission to use the shorter section in a compilation of prayers he was making at the time. Niebuhr was quoted as saying: “Of course, it may have been spooking around for years, even centuries, but I don’t think so. I honestly do believe that I wrote it myself.”

According to the AA Grapevine article, the original form of the prayer, as written by Niebuhr was: “God give me the serenity to accept things which cannot be changed; Give me courage to change things which must be changed; And the wisdom to distinguish one from the other.” The article said Dr. Neibuhr didn’t mind the changes from his original rendering of the prayer, saying: “In some respects, I believe your way is better.”

Nell Wing’s article reviewed the variety of supposed original sources for the Serenity Prayer, which included: St. Francis of Assisi, the early Greeks or Aristotle, St. Thomas Aquinas, St. Augustine, the Dutch philosopher Baruch Spinoza, and even ancient Sanskrit writings. Research done by a German member of A.A. Peter T., attributed the first written form of the prayer to a Roman statesman and Christian philosopher named Boethius (480-524). Nell added in a footnote:

While this is a fascinating story in its own right and appears to correct a long-standing misconception, Boethius’ connection with the prayer remains unclear and haunting! What were his thoughts and ideas that so affected succeeding generations of religious dissidents?

Boethius was born in Rome and educated in Athens and Alexandria. In 510 he became a Consul under Emperor Theodoric. He was accused of treasonable dealings with the emperor in Constantinople, imprisoned and eventually beheaded. While in prison he wrote The Consolation of Philosophy, his most influential work and that from which Peter T. said the first form of the Serenity Prayer appeared. His commentaries on Aristotle became a major source of knowledge of Platonic and Aristotelian ideas in the Middle Ages. More information on Boethius can be found in: New Dictionary of Theology; and Classical Pastoral Care, Volume 4: Crisis Ministries. You can also read this article on him by Carl Trueman: “Boethius: The Philosopher Theologian.”

In Alcoholics Anonymous Comes of Age, Bill W. said when he first saw the Serenity Prayer on that day in June of 1941, “Never had we seen so much A.A. in so few words.” After the cards were printed up, A.A. included one in every piece of correspondence they sent out. This continued for several years, and the Serenity Prayer rapidly came into general use within A.A. After reiterating the possible origins of the prayer, Bill said: “Anyhow, we have the prayer and it is said thousands of times daily. We count its writer among our great benefactors.” Over 950 references have been made to the Serenity Prayer in the AA Grapevine since its first issue in 1944.

What is it about this prayer that gives it so much value for A.A.? Bill W. unpacked its usefulness in his article for the March 1962 issue of the AA Grapevine, “What is Acceptance?” This article is also available in the A.A. published selection of Bill W.’s Grapevine writings, The Language of the Heart. Bill said one of the ways to get at the meaning of the principle of acceptance is to meditate on it within the context of the Serenity Prayer. Essentially it is asking for the resources of grace by which we can make spiritual progress. Emphasized within the prayer is the need for wisdom that discriminates between the possible and the impossible.

Sometimes we need the right kind of acceptance for each day. Other times we need to develop acceptance for what will come in the future. Yet again, we may have to accept a situation that will never change. Then there are misuses of acceptance. “It can be warped to justify nearly every brand of weakness, nonsense and folly.” We can “accept” failure as a chronic condition without failure or remedy. We can pridefully “accept” worldly success as something we did ourselves.

This is why we treasure our “Serenity Prayer” so much. It brings a new light to us that can dissipate our old-time and nearly fatal habit of fooling ourselves. In the radiance of this prayer we see that defeat, rightly accepted, need be no disaster. We now know that we do not have to run away, nor ought we again try to overcome adversity by still another bull-dozing power drive that can only push up obstacles before us faster than they can be taken down. . . .Therefore our very first problem is to accept our present circumstances as they are, ourselves as we are, and the people about us as they are. This is to adopt a realistic humility without which no genuine advance can even begin. Again and again, we shall need to return to that unflattering point of departure. This is an exercise in acceptance that we can profitably practice every day of our lives. Provided we strenuously avoid turning these realistic surveys of the facts of life into unrealistic alibis for apathy or defeatism, they can be the sure foundation upon which increased emotional health and therefore spiritual progress can be built. At least this seems to be my own experience.

I’ve read an article that sees the Serenity Prayer as creating an either/or, black-and-white dichotomy, “as if all of the situations and challenges that a person in recovery is confronted by can be neatly placed into one or the other bucket.” But I don’t see Bill W. using the Serenity Prayer as a black-and-white dichotomy. He said it emphasizes the need for wisdom to discriminate between the possible and impossible. He also said there can be misuses of acceptance—when it is used to justify “weakness, nonsense and folly.” The goal of acceptance in the Serenity Prayer, at least for Bill W. and A.A., is to have humility; to avoid turning a realistic assessment of the situation into an alibi or excuse for apathy or defeatism.

01/3/17

Like Footprints in the Sand

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An amazing letter was sent to the president of the American Psychiatric Association (APA) on August 1, 2016 by no less than sixteen well known medical and psychological professionals from around the globe. They are attempting to have an article published in a 2004 issue of the American Journal of Psychiatry retracted. Their concern was that a recent analysis of that study found “gross misrepresentations” made in the article with regard to use of citalopram (Celexa) in treating child and adolescent depression. As of the beginning of December of 2016, the original journal article is still available; nor does there seem to have been any response to the letter requesting the retraction. Perhaps the APA hopes that if they simply ignore the issue, it will just go away.

The article was ghostwritten by agents of the manufacturer and seriously misrepresented both the effectiveness and the safety of citalopram in treating child and adolescent depression.

The letter was addressed to Dr. Maria Oquendo, the 2016 President of the APA. The coauthors of the letter expressed concerns with the “gross misrepresentations” made within the 2004 article, “A Randomized, Placebo-Controlled Trial of Citalopram for the Treatment of Major Depression in Children and Adolescents.”

Since the publication of the analysis alleging the problems with the 2004 Celexa article, there were three different attempts to have it retracted. In response to a May 9, 2016 letter, the current editor for the American Journal of Psychiatry refused to retract the original study. Two other attempts, one to the former editor of the American Journal of Psychiatry who accepted the article, received no response. Given the failure of the American Journal of Psychiatry to retract the article, the letter’s authors are concerned that children and adolescents are put at risk of unnecessary harm because well-intentioned physicians who continue to prescribe citalopram to children and adolescents are being misled.

The 2004 citalopram study said it provided evidence that “citalopram produces a statistically and clinically significant reduction in depressive symptoms in children and adolescents.” It was said to be superior to placebo and the adverse events were mild.

In conclusion, citalopram treatment significantly improved depressive symptoms compared with placebo within 1 week in this population of children and adolescents. No serious adverse events were reported, and the rate of discontinuation due to adverse events among citalopram-treated patients was comparable to that of placebo. These findings further support the use of citalopram in children and adolescents suffering from major depression.

Yet there have been a series of lawsuits against Forest Laboratories, the manufacturer of Celexa, because of its serious side effects; and for Forrest’s failure to warn about the risks when using Celexa and other SSRIs. Drugwatch noted that Celexa is the best-selling antidepressant in 13 countries. Yet it has been linked to several congenital birth defects as well as autism. FindLaw noted evidence that Celexa and other antidepressants have been linked to an increased risk of suicidal behavior in patients under the age of 25.

Forest Laboratories also pleaded guilty in a 2010 criminal case for misbranding Celexa for a use not approved by the FDA. “According to the Department of Justice, Forest Pharmaceuticals had illegally promoted Celexa for the treatment of depression in children and adolescents. The company also pleaded guilty to obstructing justice and distributing an unapproved drug.” Forest Pharmaceuticals was fined $150 million.

A class action law suit, Celexa and Lexapro Marketing and Sales Practice Litigation, was brought by plaintiffs who alleged that Forest Laboratories misrepresented the safety and efficacy of Celexa and Lexapro when marketing the drugs for off-label pediatric use. Over 63,000 documents from Forest were deposited in a database maintained by the plaintiff’s attorneys. Jureidini, Amsterdam and McHenry reviewed 750 internal documents from this database in their 2016 article for the International Journal of Risk & Safety in Medicine.

They found that the published article, “A Randomized, Placebo-Controlled Trial of Citalopram for the Treatment of Major Depression in Children and Adolescents,” contained efficacy and safety data that was inconsistent with the protocol criteria. Although the published article concluded citalopram was safe and significantly more efficacious than placebo for children and adolescents, the outcome measures “showed no statistically significant differences between citalopram and placebo.”

Unreported procedural deviations contributed to the claimed statistical significance of the primary outcome and negative secondary outcomes were not reported. Moreover, post hoc measures were introduced; and adverse events were misleadingly analyzed. The Wagner et al. citalopram study failed to mention five citalopram-treated subjects who discontinued treatment due to hypomania, agitation, or akathisia. “None of these potentially dangerous states of over-arousal occurred with placebo.” There were also many more adverse gastrointestinal events for citalopram than placebo. Yet the final report grouped the data in a way that masked the evidence for potential gastrointestinal intolerance.

In conclusion, corporate mischaracterisation of clinical trial results is of concern in psychiatry where outcome measures are more subjective and easily manipulated. Because few industry-sponsored studies gain public scrutiny and even fewer are ever formally retracted, it is important to make these articles transparent to correct the scientific record. It is furthermore imperative to inform the medical community of mischaracterized data that could lead to potential harm to children and adolescents who are vulnerable to the effects of medication on the growing brain and may increase suicidal thinking and behaviour.

STAT News reported the retraction request comes after years of controversy over the extent to which some drug makers massaged clinical studies to broaden their medicines’ market. Four years ago, GlaxoSmithKline paid $3 billion to settle civil and criminal charges of “preparing, publishing, and distributing a misleading journal article” about the use Paxil with children and adolescents. “The pill had not been approved for that use and the study cited by federal authorities had been ghostwritten.” David Healy, John Nardo, and Jon Jureidini, three of the sixteen individuals who submitted the letter to the APA requesting that the 2004 citalopram study be retracted, have been actively involved in critiquing the misrepresentation of Study 329 and attempting to get it retracted as well. See a series of articles Healy has written on this issue here, in the Mad in America archives.

After a running a gauntlet of reviews, Le Noury et al. were able to successfully publish a reanalysis of Study 329 in the British Medical Journal. But getting there wasn’t easy, see: “Restoring Study 329: Letter to BMJ” and “The Troubled Life of Study 329: Consequences of Failure to Retract.” However, the original article, “Efficacy of Paroxetine in the Treatment of Adolescent Major Depression, A Randomized Controlled Trial,” was never retracted by Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP).

Hmmm. Perhaps my opening comment that the APA is hoping the request to withdraw the 2004 citlopram article, “A Randomized, Placebo-Controlled Trial of Citalopram for the Treatment of Major Depression in Children and Adolescents,” wasn’t all that smarmy. They could be hoping that it will just fade away like footprints in the sand.