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 until 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 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

© StephanieFrey | stockfresh.comfresh eggs. Araucanas are also known as the Easter Chicken for the blue or greenish colored eggs they lay.

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?

11/22/16

Antidepressant Misuse Disorder

54164089 - antidepressant pills 3d rendering isolated on white background

© Olekii Mach | 123rf.com

Chances are you know someone who is using an antidepressant. But that doesn’t necessarily mean the person you know has a problem with depression. In 2015, Takayanagi et al. published a study in The Journal of Clinical Psychiatry found that: “Among antidepressant users, 69% never met criteria for major depressive disorder (MDD); and 38% never met criteria for MDD, obsessive-compulsive disorder, panic disorder, social phobia, or generalized anxiety disorder in their lifetime.” Their data indicate that antidepressants were commonly used in the absence of “clear evidence-based indications.”

Writing for Mad in America, Justin Karter noted that previous studies revealed antidepressants were being over-prescribed and prescribed off-label. But others countered that these studies underestimated the lifetime prevalence of so-called mental disorders. The Takayanagi et al. study sought to address this criticism by conducting in-depth interviews to estimate whether participants met criteria for “mental disorders” over their lifetime. The study also indicated an individual was more likely to be prescribed an antidepressant if they were a woman, white, reported physical pain or discomfort to their doctor, or had recently visited a mental health care facility.

Another 2015 report by Kanton et al. published in JAMA found that the percentage of Americans on antidepressants increased from 6.8% to 14% between 1999 and 2012. The report’s authors speculated that the increase could in part reflect shifting attitudes regarding depression. Commenting on this report, Justin Karter pointed out how the increase likely includes a large proportion of off-label use of antidepressants. As was noted above, 69% of antidepressant users did not meet the criteria for major depression.

A JAMA study published in May of 2016 by Wong et al. found that 45% of the prescriptions given for antidepressants were to treat anxiety disorders, pain, insomnia and various other conditions. The study, which was done in Quebec Canada, looked at all adult prescriptions written for antidepressants (100,000 patients) between January 1, 2006 and September 30, 2015. Prescriptions for monoamine oxidase inhibitors were excluded. Prescriptions were classified as on or off label depending upon whether the drug was approved by Health Care of Canada or the FDA for the indication noted by September 0f 2015. Physicians prescribed antidepressant off-label for anxiety disorders (18.5%), insomnia (10.2%), pain (6.1%) and panic disorders (4.1%).

An online survey of long-term antidepressant patients by Cartwright et al., published in Patient Preference and Adherence, found that almost 90% reported some degree of improvement, with 30% also saying they had moderate to severe bouts of depression during treatment.  Ten different adverse effects were reported by over 50% of the participants. The five most common were: withdrawal effects (73.5%), sexual dysfunction (71.8%), weight gain (65.3%), feeling emotionally numb (64.5%), and failure to reach orgasm (64.5%). “Between 36% and 57% of respondents experienced these adverse affects at either a moderate or severe level.” Additional adverse effects reported included: agitation (55.1%), feeling not like myself (54.4%), reduced positive feelings (45.6%), caring less about others (36.4%), suicidality (36.0%), and feeling aggressive (31.6%).

Some patients in this study were particularly concerned about severe withdrawal symptoms that undermined their confidence to discontinue should they wish to and therefore limited their choices. In line with this, 45% patients also believed that they had some level of addiction to the antidepressant. Some patients were also critical of the lack of information given by prescribers with regard to adverse effects, including withdrawal symptoms. Some also expressed disappointment or frustration with the perceived lack of support available to them in managing withdrawal.

Limitations of the study include the fact that the data were self-reported and that the study was not a randomized control study—the gold standard methodology for evidence-based medicine. However, there are relatively few long-term outcome studies of antidepressant use.

A 2009 systematic review published in the Journal of Affective Disorders, concluded that long-term outcomes in depression were poor, with no clear relationship between drug treatment and positive outcomes.  The outcomes for non-antidepressant treatment were no worse than those for antidepressant treatment.

Overall 40% to 85% of patients experienced a recurrence during follow-up. Average time to recurrence was around 3.2 years across eight studies that provided data on this outcome. Around 25% of patients achieved a global rating of well or improved at the end of the study and a similar number had a poor outcome marked by multiple recurrences or continuous impairment. Most participants recovered from the index episode, but experienced multiple recurrences.

The August 2016 issue of Psychotherapy and Psychosomatics published a literature review of long-term use of newer generation antidepressants (i.e., SSRIs and SNRIs and others) by Carvalho et al. While many side effects were transient, disappearing after a few weeks, other potentially serious adverse events may persist or occur later. The main adverse events related to using newer antidepressant drugs included the following:

  • Gastrointestinal issues
  • Weight gain and metabolic disturbances
  • Genitourinary issues (issues related to the genital or urinary organs)
  • Sexual dysfunction
  • Hyponatremia (low sodium level in the blood)
  • Osteoporosis and risk of fractures
  • Bleeding
  • Central nervous system issues
  • Sweating
  • Sleep disturbances
  • Affective disturbances
  • Suicidality
  • Discontinuation syndromes

You can read more information on the above adverse effects and others in the Carvalho et al. review. What follows is a brief discussion of their findings for weight gain and diabetes, bleeding, sleep disturbances, affective disturbances, suicidality, and discontinuation syndromes.

Several studies have shown that long-term use of antidepressants (more than 6 months) is associated with weight gain. Paroxetine (Paxil) may be the worst offender. A population-based study indicated the use of antidepressants could be associated with a higher risk of obesity. The association between antidepressants and diabetes mellitus is inconclusive. Some reports indicate a higher risk; others do not. But a recent review and meta-analysis found that SSRIs were associated with an increased risk of diabetes mellitus.

All SSRIs have been associated with an increased risk of bleeding. “The most likely mechanism responsible for these adverse reactions is a reduction of serotonin reuptake by platelets.” Fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) have a higher risk of platelet dysfunction than other SSRIs. Veniafaxine (Effexor) and mirtazapine (Remeron) have been associated with an increased risk of bleeding. SSRIs have been associated with a higher risk of bleeding during operations.

Sleep disturbances are one of the hallmark symptoms of depression. However,  studies have shown that SSRIs and Effexor are associated with increased REM sleep latency and an overall reduction in the time spent in REM sleep. These effects are usually associated with the initial period of treatment and may return to baseline after 8 weeks. Remeron and trazodone have been associated with improving sleep. In my clinical experience, trazadone is regularly used off-label to help promote sleep.

Many individuals taking SSRIs report they experience emotional blunting. They say their emotions have been “toned down.” Others say they just don’t care about issues that were significant to them before. “Evidence indicates that these adverse affective manifestations may persist even after the symptoms of depression have improved and can occur in patients of all ages.” Mania or agitation can occur. These response have been said to unveil unrecognized bipolar disorder. But since this can also occur in previously unipolar patients, the mania could be drug-induced. An activation syndrome, where patients experience anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness and impulsivity can occur.

Carvalho et al. limited the occurrence of these adverse effects to the first three months of treatment. However, psychiatrist Peter Breggin has documented the emergence of agitation and activation with antidepressants in Medication Madness and other writings. Carvalho et al. said using antidepressants could also be associated with the return of depressive symptoms during baseline treatment, and the appearance of new symptoms or paradoxically, exacerbate the baseline clinical picture. The occurrence of paradoxical effects was reported in random control trials with Prozac and Zoloft.

The emergence of suicidality and self-injurious behavior with antidepressant treatment is one of the most debated and controversial risks. Nevertheless, the FDA has required a black box warning regarding the risk of suicidality for children and adolescents using antidepressants since 2014. The incidence of successful and attempted suicide has been frequently underreported in antidepressant RCTs. Carvalho et al. said:

Two recent meta-analyses have not identified a clear increased risk of treatment-emergent suicidality in adult individuals treated with antidepressants in RCTs. Notwithstanding that the use of antidepressants is efficacious for the treatment of MDD in adults, there is no clear evidence for either specific protective effects or increased risk related to suicidality.

Often underappreciated, is the emergence of withdrawal symptoms of varying degrees with treatment discontinuation and/or interruption with almost all SSRIs and SNRIs. These reactions have been described as “discontinuation syndromes” in an attempt to avoid the suggestion of dependence that could effect marketing. A review suggested the dependence and withdrawal with newer antidepressants was comparable to those experienced with benzodiazepines. “Due to the severity and unpredictability of these manifestations, it has been recently suggested that the term ‘discontinuation syndrome’ should be replaced by ‘withdrawal syndrome.’” These symptoms can include:

flu-like symptoms, tremors, tachycardia, shock-like sensations, paresthesia, myalgia, tinnitus, neuralgia, ataxia, vertigo, sexual dysfunction, sleep disturbances, vivid dreams, nausea vomiting, diarrhea, worsening anxiety and mood instability.

In their conclusion, Carvalho et al. said the common belief of fewer side effects with the newer generation antidepressants (especially the SSRIs) only pertains to their safety in overdose. “On the contrary, the long-term use of SSRIs and SNRIs is likely to yield important side effects.” The likelihood of treatment-emergent adverse effects is related to the duration of antidepressant treatment—particularly with weight gain, diabetes, and osteoporsis. Some adverse side effects may persist long after discontinuation of the drug. Particularly following long-term use, antidepressants,

 … may increase the risk of experiencing additional psychopathological (e.g. treatment emergent affective switches and paradoxical symptoms), or medical (e.g. obesity and bleeding) problems that do not necessarily subside after discontinuation of the drug.

This leads to their conclusion that: “The findings of this review suggest that long-term treatment with new generation ADs should be avoided if alternative treatments are available.”

11/11/16

Help the Medicated Military

© Oleg Dudko | 123rf.com

© Oleg Dudko | 123rf.com

A U.S. Air force pilot was assigned to transport a B-1 bomber from near the Persian Gulf to South Dakota. The trip took nineteen hours and crossed nine time zones. Every four hours, he took a “go pill”—a tablet of Dexedrine. After landing, he went out for dinner and drinks with a friend from the base. When they were driving back to the base, he began hitting his friend, saying that “Jack Bauer” had told him they were going to try and kidnap him. He was eventually charged with auto theft, drunk driving and two counts of assault.  But a court martial judge found him not guilty “by reason of mental responsibility.”

 

 

Four military psychiatrists concluded that Burke suffered from “polysubstance-induced delirium” brought on by alcohol, lack of sleep and the 40 milligrams of Dexedrine he was issued by the Air Force.

In her article for the LA Times, Kim Murphy went on to say a growing number of lawyers are blaming the U.S. military’s heavy use of psychotropics for their client’s aberrant behavior and the related health problems. In 2012 the U.S. Army surgeon general indicated there were almost 8% of active duty Army on sedatives and more than 6% using antidepressants. This was an eightfold increase since 2005.

A former military psychologist said: “We have never medicated our troops to the extent we are doing now … And I don’t believe the current increase in suicides and homicides in the military is a coincidence.” An Army pharmacy consultant said the military’s use of prescription drugs is comparable to the civilian world. “It’s not that we’re using them more frequently or any differently.” Grace Jackson, a former Navy staff, psychiatrist said: “The big difference is these are people who have access to loaded weapons, or have responsibility for protecting other individuals who are in harm’s way.”

According to a 2007 review in Military Medicine, the modern Army psychiatrist’s deployment kit will likely contain “nine kinds of antidepressants, benzodiazepines for anxiety, four antipsychotics, two kinds of sleep aids, and drugs for attention-deficit hyperactivity disorder.” Military doctors believe it would be a mistake to send battalions into combat without these medications, which they see as helping to prevent suicides, calm shattered nerves and help soldiers rest.

Psychiatrist Peter Breggin said that before the Iraq war, soldiers couldn’t go into combat if they were using psychiatric drugs. “You couldn’t even go into the armed services if you used any of these drugs, particularly stimulants,” just 10 or 12 years ago. Now some people are saying psychiatrists won’t approve their deployment unless they take psychiatric drugs.

An Army Pfc. Pleaded guilty to murdering a Taliban commander in Afghanistan. After the death of a good friend, he began hearing a harsh female voice. He was also depressed. He didn’t tell doctors about the voice—only that he was depressed and thinking of suicide. He was prescribed Zoloft for depression and trazodone for sleep. The voices became worse and he began seeing hallucinations of his dead friend. Eventually he walked into the cell of the Taliban commander and shot him in the face. He was eventually sentenced to a ten-year prison term.

Both the American Psychological Association and the American Psychiatric Association in a 2010 hearing urged the Army to stay the course on psychotropic drugs.

Military Times reported that many troops are mixing several different kinds of pills—an antidepressant and an antipsychotic to prevent nightmares, an anticonvulsant or anti-epileptic to prevent headaches. And these medications are being prescribed, consumed and swapped in combat zones. Dr. Grace Jackson said: “It’s really a large-scale experiment. We are experimenting with changing people’s cognition and behavior.”

Data obtained from the Defense Logistics Agency (DLA) showed the DLA spent $1.1 billion on psychiatric and pain medications from 2001 to 2009. The use of psychiatric medication has increased by 76%, with the use of some drug classes more than doubling. Orders for antipsychotic medications were up over 200%; annual spending more than quadrupled from $4 million to $16 million. Anticonvulsant use increased 70%; spending more than doubled from $16 million to $35 million. Spending on antidepressants decreased from $49 million in 2001 to $41 million in 2009, a drop attributed to cheaper generic versions hitting the market during that same time period.

The Army’s highest-ranking psychiatrist told Congress that 17% of the active-duty troops and as much as 6% of deployed troops are on antidepressants. Doctors and lawmakers are questioning whether the drugs are responsible for the spike in suicides within the military—trend that parallels the increase in psychiatric drug use. Dr. Peter Breggin said there was overwhelming evidence that the newer antidepressants commonly prescribed can cause or worsen suicidality, aggression, and other dangerous mental states. “Imagine causing that in men and women who are heavily armed and under a great deal of stress.” But many military doctors believe the risks are overstated and not fully treating depressed troops would be the greater risk.

Military Times said the Defense Department repeatedly denied its requests for copies of autopsy reports that would show the prevalence of these drugs.

From 2001 to 2009, the Army’s suicide rate increased more than 150 percent, from 9 per 100,000 soldiers to 23 per 100,000. The Marine Corps suicide rate is up about 50 percent, from 16.7 per 100,000 Marines in 2001 to 24 per 100,000 last year. Orders for psychiatric drugs in the analysis rose 76 percent over the same period. Other side effects can include increased irritability, aggressiveness and hostility.

Dr. Peter Breggin published an article in Ethical Human Psychology and Psychiatry, “Antidepressant-Induced Suicide, Violence, and Mania: Risks for Military Personnel.”  He noted where the activation side effects of newer antidepressant mimicked the symptoms of PTSD, increasing the hazard when they are prescribed to military personnel. He recommended that the military study the relationship between psychiatric drug treatment and suicide as well as random or personal violence. He also recommended that antidepressant be avoided when treating military personnel. See his website for more information on the relationship between antidepressants, suicide and violence in soldiers.

There is a strong probability that the increasing suicide rates among active-duty soldiers are in part caused or exacerbated by the widespread prescription of antidepressant medication. By themselves, these drugs cause a dangerous stimulant-like profile of adverse reactions. These symptoms of activation can combine adversely with similar PTSD symptoms found so commonly in soldiers during and after combat.

In September 28, 2016, US Senator John McCain introduced the Veteran Overmedication Prevention Act (S. 3410), a companion bill to HR 4640, the Veteran Suicide Prevention Act. Psychologist Philip Hickey reported the bills seek to fight against suicide deaths in military personnel by ensuring that accurate information is available on the relationship between suicides and prescription medication. If passed, these bills would bring information currently being withheld from the public on these relationships. A press release from Senator McCain said:

This legislation would authorize an independent review of veterans who died of suicide or a drug overdose over the last five years to ensure doctors develop safe and effective treatment plans for their veteran patients. We have a long way to go to eradicate veteran suicide, but this legislation builds on important efforts to end the tragedy that continues to claim far too many lives far too soon.

“Data suggests that every 65 minutes a veteran takes his or her own life.” One way to address this is by determining if there is any association between suicide and the medical treatments being received by veterans for service-related conditions. Congressman David Jolly said the following in a press release about his sponsorship of the Veteran Suicide Prevention Act:

Specifically, the Veteran Suicide Prevention Act would require the VA to record the total number of veterans who have died by suicide during the past five years, compile a comprehensive list of the medications prescribed to and found in the systems of such veterans at the time of their deaths, and report which Veterans Health Administration facilities have disproportionately high rates of psychiatric drug prescription and suicide among veterans treated at those facilities.  The VA would then be required to submit to Congress a publicly available report on the results of their review, along with their plan of action for improving the safety and well-being of veterans.

As suggested by Philip Hickey, honor the veterans who have served our country by writing your legislators in the Senate and the House in support of these bills:

Senate: S 3410 – Veteran Overmedication Prevention Act

House: HR 4640 – Veteran Suicide Prevention Act

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.”

06/14/16

Descent into Hell

© LoraLiu | stockfresh.com

© LoraLiu | stockfresh.com

I confess, I am not much of a listener of Contemporary Christian Music (CCM). So I had never heard of the CCM artist Kari Jobe or her music until someone asked me about a theological controversy that is making the rounds online about one of her songs, titled Forever. Apparently, the dispute is over a reference in her song to Jesus as the Son of God descending into hell where He defeated the enemy. The person was asking me to see whether I thought that lyric was heretical, and whether Jobe was spreading heresy. My initial reaction was to recall that some versions of the Apostles’ Creed made a similar claim and say that those who are critical of Jobe and her song seemed to be majoring on minor points.

Here is a description of one view of the controversy written by Jeff Maples on his blog, Pulpit & Pen: “Popular Charismatic Worship Artist, Kari Jobe, Teaching Dangerous Heresy.” Maples began by criticizing the Outcry 2016 music festival that will be held in several U.S. cities this year. Kari Jobe is part of the tour. He said: “Now, I’m not exactly sure who these people are worshiping, but it isn’t Jesus. Yet, thousands of Christians are blindly sending their children to partake in this evil.” This is provocative stuff to be saying about the participants of the Outcry 2016 and those who attend it.

His beef seemed to be focused primarily on something called the New Apostolic Reformation (NAR), which he said is a movement that elevates experience above doctrinal truth. Whether NAR is or is not heretical is not the focus here. Someone who wants more information on the movement or its beliefs can easily find discussions online. To get you started, try a Fresh Air podcast in 2011, “The Evangelicals Engaged in Spiritual Warfare”; or a Charisma News response to the NPR interview and article: “The New Apostolic Reformation Is not a Cult” by C. Peter Wagner. Also try “New Apostolic Reformation” on Wikipedia.

In his article, Maples quoted the lyric from Jobe’s song that he saw as offensive:

One final breath He gave
As heaven looked away
The Son of God was laid in darkness
A battle in the grave
The war on death was waged
The power of hell forever broken

Also there is a YouTube clip embedded on the page where Jobe said her favorite part of the song was the part that talks about the time in between the cross and the resurrection when “Jesus was in hell … defeating the enemy … taking those keys to death and hell and the grave to be victorious over that when he rose from the dead.”  Maples then equated this with an old heresy he said is found in the Word of Faith circles, that Jesus died spiritually and was “born again” after defeating Satan in hell. Personally, I’m not a fan of the teachings of Joyce Meyer or Kenneth Copeland, who Meyers quotes as promoting this heresy. But it seems to me the “culprit” behind Jobe’s lyric is the Apostle’s Creed rather than the Word of Faith movement.

The Apostles’ Creed has been a confessional element of orthodox Christian belief since the times of the early church. Ambrose and Augustine suggested repeating it in daily devotions. Luther saw it as one of three binding summaries of belief. Calvin divided his Institutes into four parts that corresponded to the Apostles’ Creed. See “Christian, What Do You Believe?” for more background on the Apostles’ Creed.

J. N. D. Kelly, in Early Christian Creeds, pointed out that the first appearance of saying that Jesus “descended to hell” appeared in the Aquleian version of the creed referred to by Rufinus, a fourth century monk and theologian, in his Commentary of the Apostles’ Creed. There he noted the phrase “He descended into hell” was not part of the Roman Creed (See “The Old Roman Creed”) or those of the Eastern (Oriental) churches. Nevertheless, it seemed to be implied in saying that Jesus was buried. Kelly said the clause was also present in some Spanish creeds of the sixth century and Gallican creeds of the seventh and eighth centuries.

Rufinus remarked in his commentary that Jesus descending into hell was foretold in the Psalm 22, classically seen as intimately associated with the passion of Christ. The first words of the Psalm, “My God, my God, why have you forsaken me?” are cried out by Jesus as he was dying (Matthew 27:46; Mark 15:34). Psalm 22:7-8 is alluded to in Matthew 27:39, 43, “All who see me mock me; they make mouths at me; they wag their heads; He trusts in the Lord; let him deliver him!” The final words of the Psalm, “he has done it” were said in Hard Sayings of the Bible to have been alluded to by Jesus in John 19:30 as he bowed his head and died: “It is finished.” Rufinus saw similar references to a descent into hell in Psalm 22:15, “you lay me in the dust of death”; Psalm 30:3, “O Lord, you have brought up my soul from Sheol; you restored me to life from among those who go down to the pit”; and Psalm 30:9, “What profit is there in my death, if I go down to the pit?”

Tom Macy also expressed concern with Jobe’s reference to Jesus descending into hell in his article, “Did Jesus Go to Hell?” Macy said it was bad theology that taught an error striking at the heart of understanding the death and resurrection of Jesus. He said it taught the battle was not won on the cross. Rather, the real battle took place in hell between the death and resurrection of Jesus. “That is what seriously distorts the truth and why this song must not be used.”

A further example of the confusion arising from this reference to a descent into hell in the Apostles’ Creed is in this short video by Garrett Kell from Capitol Hill Baptist Church. I don’t concur with his explanation, but it does show how wild speculation creeps in to explain difficult passages of the Bible. Macy attributed the root of this confusion to Roman Catholic teaching. He then referenced Wayne Grudem’s Systematic Theology to explain passages that have been used to support Jesus’ decent into hell.

Fanciful interpretations of difficult passages must not override the declarations from the cross definitively showing that Jesus did NOT spend Saturday in hell, was NOT fighting Satan to finish the work of salvation, was NOT preaching a second chance salvation or simply condemning to those in hell. Jesus was with the repentant thief in Paradise in the presence of the Father.

And yet, the descent into the underworld was specifically mentioned by: Ignatius, Polycarp, Irenaeus, Tertullian and others, according to Kelly. “The belief that Christ spent the interval between His expiry on the cross and His resurrection in the underworld was a commonplace of Christian teaching from the earliest times.” One strand of patristic teaching thought Jesus himself hinted at it when he said in Matthew 12:40 that the scribes and Pharisees seeking a sign would get only the sign of the prophet Jonah: “For just as Jonah was three days and three nights in the belly of the great fish, so will the Son of Man be three days and three nights in the heart of the earth.”

Attempts to explain where Jesus was when his body was in the tomb ask space and time-oriented questions about something that occurred beyond the space and time of the created universe. The answer can’t fit within the cosmos in which we live and move and have our being. And yet, we still wonder where Jesus was when he wasn’t with his body in the tomb. The question says more about us, and our view of the cosmos, than it does about what actually happened to Jesus between about 3 pm Friday afternoon and early Sunday morning.  In a similar way, the addition to the Apostles’ Creed of Jesus descending into hell, and the Old and New Testament passages supposedly referencing the same, tell us more about how the people of Biblical times viewed the cosmos than where Jesus was between his death and resurrection.

In his book, Scripture and Cosmology, Kyle Greenwood described how ancient Hebrew cosmology of a three-tiered universe of the heavens, earth and sea had a place for the underworld or the abode of the dead—Sheol. “When people died, they were buried in the ground, and their bodies remained in Sheol, the abode of the dead.”  This three-tiered cosmology was shared by other Near Eastern cultures. “It was the abode of the dead, the final resting place beneath the earth for all who once lived.”

OT cosmos

 On the BioLogos website is a series of blog articles on a scholarly paper by Brian Godawa, “Mesopotamian Cosmic Geography in the Bible.” Here is a link to Part 4 of that series where there is a discussion of Sheol; here is a link to Godawa’s entire paper. The following quotation can be found under either link.

Sheol was the Hebrew word for the underworld. Though the Bible does not contain any narratives of experiences in Sheol, it was nevertheless described as the abode of the dead that was below the earth. Though Sheol was sometimes used interchangeably with “Abaddon” as the place of destruction of the body (Prov. 15:11; 27:20),and “the grave” (qibrah) as a reference to the state of being dead and buried in the earth (Psa. 88:11; Isa. 14:9-11) it was also considered to be physically located beneath the earth in the same way as other ANE worldviews.

The New Testament was written during a time of transition to an Aristotelean cosmology of spheres within rotating spheres.  “In time Aristotelean cosmology and biblical faith became inseparable, not because Aristotle was a Christian, but because his system was easily reconciled with biblical anthropology and monotheism.” While the idea of Sheol or the grave underwent some major changes in the Christian era, Aristotelean cosmology didn’t require an abandonment of the idea that beneath the surface of the earth was a region where the dead went. Greenwood added this shows up conspicuously within the Apostles’ Creed.

The added phrase of “descended to hell” to the Apostles’ Creed is then simply making clear that Jesus truly died. Like all people, the humanity of the Son of God died. Not only was he crucified and buried, as it was said within the Roman Creed; Jesus was crucified [dead] and buried [He descended into Hell]. So on the third day, He would arise from the dead; the grave; Sheol. In other words, he would live again. This is the promise of faith in Christ. He reversed the irreversible, according to the ancient thinking about death. I think Kari Jobe can sing about it Forever, if she likes.

10/21/15

Dirty Little Secret

© ia_64 | stockfresh.com

© ia_64 | stockfresh.com

Quoting Steven Hollon, in his book The Emperor’s New Drugs, Irving Kirsch said it was a “dirty little secret” that there was only a small difference between the experimental and control groups for the patients who participated in the randomized clinical trials (RCTs) used to approve SSRIs. Be sure to get this: the pharmaceutical companies that produced the drugs AND the regulatory agencies that approved them, knew there was essentially no difference between the effects of the drug and the placebo. Yet the drugs were approved for use with humans. “Many have long been unimpressed by the magnitude of the differences observed between treatments and controls, what some of our colleagues refer to as the ‘dirty little secret’ in the pharmaceutical literature.”

Kirsch was originally interested in studying the placebo effect, and not the antidepressant drug effect. “How is it, I wondered, that the belief that one has taken a medication can produce some of the effects of that medication?” He was not surprised to find a substantial placebo effect of the medications on depression. But he was surprised to see how small the drug effect was. “Seventy-five percent of the improvement in the drug group also occurred when people were give dummy pills with no active ingredient in them.”

You can read an article by Kirsch describing the research process described here in: “Antidepressants and the Placebo Effect.”

He replicated the findings in another study published in 2002, using the data submitted to the FDA by the pharmaceutical companies in their process of obtaining approval for six new generation antidepressants. There were some advantages to using the FDA data set. First, they received data on the published and unpublished clinical trials conducted by the pharmaceutical companies. What was particularly important here was that: “The results of the unpublished trials were known only to the drug companies and the FDA, and most of them failed to find a significant benefit of drug over placebo.”

A second advantage was that the FDA trials all used the same primary measure of depression—the Hamilton depression scale (HAM-D). The third advantage was that the FDA data was the same data used for the approval of the medications. So if there had been anything wrong with the trials, one would think, the medications would not have been approved.

In the data sent to us by the FDA, only 43% of the trials showed a statistically significant benefit of drug over placebo. The remaining 57% were failed or negative trials. . . . The results of our analysis indicated that the placebo response was 82% of the response to these antidepressants.

One explanation for Kirsch’s results could be that the replication done in 2002 contained both the published and unpublished clinical trials. The inclusion of failed and negative trials would have lowered the positive results required by the FDA for approval of a medication. So the placebo response was greater in this replication than it was in their original study because of including the unpublished trials. Nevertheless, the majority of the trials failed to show positive results. Remember that the pharmaceutical companies themselves conducted these studies; and that they were the trials done in the process of gaining approval for their medications.

Getting approval of a drug by the FDA requires the submission of two studies showing the new drug is better than a placebo. It doesn’t matter if it takes you ten studies to get those two; only the two positive ones count for approval. The requirement is that two trials have to demonstrate the drug is more effective than a placebo, and that measurement has to be statistically significant. Kirsch’s analysis found just a 1.8-point difference on the HAM-D scale between drug and placebo—a difference that is not clinically significant, even though it may be statistically significant. The National Institute for Health and Clinical Excellence (NICE) has set the criterion for a clinically significant difference between drug and placebo to be at least three points on the HAM-D scale.

A criticism of Kirsch’s 2002 study was that the results were based on clinical trials conducted on subjects who were not very depressed. So Kirsch et al. (2008) reanalyzed the data in: “Initial Severity and Antidepressant Benefits.” They found that “the overall effect of new-generation antidepressant medications is below recommended criteria for clinical significance.” Only for the most extremely depressed patients was there evidence for clinical significance, according to the HAM-D scale. Yet they also concluded this difference was “due to a decrease in the response to placebo rather than an increase in the response to medication.”

So the question becomes, what do all these drugs have in common that gives them a slight, but statistically significant effect on depression over placebo? The answer is that they all produce side effects.

Clinical trials are all double-blind studies, meaning that neither the patient nor the doctor is supposed to know whether the patient is given the active drug or the placebo. Yet in one study, 80% of patients guessed correctly whether or not they were on the drug or placebo; and 87% of doctors also guessed correctly. So most patients and most doctors could break the blind by guessing according to the presence or absence of side effects to the medications. Additionally, “89% of the patients in the drug group correctly ‘guessed’ that they had been given the real antidepressant, a result that is very unlikely to be due to chance.”

So clinical trials are not really double blind studies if most patients can guess whether or not they have been given the real drug rather than the placebo. This ability to “break blind” has been known in the research literature since 1986 when Rabkin et al. published their study, “How Blind is Blind” in the September issue of Psychiatry Research. Yet drug trials continue to use inert placebos.

But what would happen if an active placebo were used in clinical trials? Active placebos have been used with antidepressants in other studies. See “Active Placebos Versus Antidepressants for Depression.”  Moncrieff et al. reported that: “differences between antidepressants and active placebos were small.” Kirsch noted that in the nine clinical trials discussed by Moncrieff et al. where an active placebo (atropine) was used, there was only a significant difference in two of the studies.

In the vast majority (78 percent) of the clinical trials in which active placebos were used, no significant differences were found between the drug and the placebo. So comparisons with inactive placebos are much more likely to show drug-placebo differences than comparisons with active placebos. This suggests that at least part of the difference that has been found between antidepressant and placebo may be due to the experience of more side effects on the active drug than on the placebo.

It’s good this dirty little secret is becoming more widely known. But unfortunately the horse has already left the barn. Too bad it wasn’t getting press fifteen years ago before the SSRIs started going off-patent. The pharmaceutical companies have already gouged the public with their SSRI profits and their drugs have gone generic.

Eli Liliy’s Prozac went off patent in 2001. GlaxoSmithKline’s Paxil has been off-patent since 2003. Forest Labs’ Celexa patent expired in 2003. Pfizer’s Zoloft patent expired in 2006. Wyeth’s Effexor (now marketed by Pfizer) went off-patent in 2006. Wellbutrin, developed by Burroughs Wellcome and later acquired by GlaxoSmithKline, lost its patent in 2006. Lexapro was developed by Forest Laboratories in conjunction with Lundbeck and they won two patent extensions. But it lost exclusivity in 2012.

07/27/15

Clearing Away the Medical Marijuana Smoke

© lunamarina | stockfresh.com

© lunamarina | stockfresh.com

There have been some studies that demonstrate potential medicinal benefits of marijuana use, but they often don’t meet the clinical trial standards used by the FDA to approve medications for human consumption. With the state-by-state movement to legalize marijuana progressing, there is a need for quality scientific research into the potential medical benefits of marijuana. Although marijuana has been used recreationally and medicinally for centuries, the mechanics of how it works are not clearly understood. This is partly because there are over 400 different chemicals in cannabis. THC, the psychoactive ingredient in cannabis, was just isolated in the 1960s. What follows are reviews of some articles that look at the benefits and the concerns with medical marijuana.

Marijuana has been used as a folk medicine as far back in time as five thousand years ago. The first medical use likely occurred in Central Asia and spread from there to China and India. The Chinese emperor Shen-Nung is known to have prescribed it in 2800 BC.  Between 2000 and 1400 BC it came to India, and from there to Egypt, Syria and Persia. The Greeks and Romans valued marijuana as hemp for ropes. Europeans ate its seeds and used its fibers to make paper. An urban legend falsely held that the U.S. Constitution, Declaration of Independence, and Bill of Rights were written on hemp paper. All three were actually written on parchment.

An Irish doctor, W. B. O’Shaughnessy, working in Calcutta in the 1830s, wrote a paper on the medical uses of cannabis, which were strikingly similar to those known today—vomiting, convulsions and spasticity. By 1854, the medical use of cannabis was listed in the US Dispensatory. Nineteenth-century physicians had cannabis tinctures and extracts for ailments from insomnia and headaches to anorexia and sexual dysfunction. “Cannabis-containing remedies were also used for pain, whooping cough, asthma, and insomnia and were compounded into extracts, tinctures, cigarettes, and plasters.”

The above short history on the history of medical marijuana was taken from an article by J. Michael Bostwick, “Blurred Boundaries: The Therapeutics and Politics of Medical Marijuana.” He noted how the term medical marijuana refers to botanical cannabis, which contains hundreds of compounds—including the two most often used medicinally, THC and cannabidiol. Synthetic cannabinoids are produced in a laboratory. Botanical cannabis attracts the notoriety and controversy—because it is the same substance used recreationally by “stoners” to get high.

Bostwick noted how the recreational and medical marijuana use of marijuana is not always distinct, which has medical implications for both seasoned and naïve users. For example, naïve users may decide to stop using medical marijuana because of the psychoactive effects of the THC. Although most users will experience a mild euphoria, a few experience dysphoria, anxiety and even paranoia.

As cannabis strains are bred that amplify THC content and diminish counteracting cannabidiol, highs become more intense but so do degrees of anxiety that can rise to the level of panic and psychosis, particularly in naive users and unfamiliar stressful situations.

The Bostwick article reviewed the often-blurred relationship between medical and recreational users. He discussed a Canadian study that found medical cannabis use often followed recreational use; and that most medical users continued using marijuana recreationally.  Another study of 4100 Californians found that medical users preferred inhaling their medication. Smoked cannabis has a more rapid response and is easier to titrate so that users get the analgesic effects without the higher levels favored by recreational users seeking the high. Given some of the medical problems from smoking marijuana, using vaporizers or nasal sprays may be an effective alternative delivery system.

Doctor Robert DuPont, in his book The Selfish Brain: Learning from Addiction, referred to marijuana as “a crude drug, a complex chemical slush.” Marijuana and hashish contain over 420 different chemicals, falling into 18 different chemical families. THC and cannabidiol (CBD), are only two of sixty-one cannabinoids, chemicals found only in the marijuana plant. THC is highly soluble in fats, and this quickly passes the blood-brain barrier. The factor, plus the fact that it is insoluble in water, means that it is trapped in bodily organs like the brain and reproductive glands, remaining there of days or even weeks afterwards.

Grant et al. reviewed evidence on the medicinal usefulness of marijuana in “Medical Marijuana: Clearing Away the Smoke.” They noted that most of the studies on the efficacy and safety of cannabinoids for pain and spasticity have occurred since the year 2000. A series of randomized studies at the University of California Center for Medicinal Cannabis Research (CMCR) found that cannabis significantly reduced pain intensity. A significantly greater proportion of individuals reported at least 30% reduction in pain on cannabis; the threshold of decreased pain intensity generally associated with improved quality of life. Medium doses of 3.5% THC cannabis cigarettes were as effective as higher dose (7% THC).

Oral preparations of synthetic THC (dronabinol, Marinol) and a synthetic THC analogue (nabilone, Cesamet) are legally available. Studies suggest that dronabinol significantly reduces pain. The effects on spasticity are mixed: “there may be no observable change in examiner-rated muscle tone, but patients report significant relief.” There has been less research done with nabilone, but there have been reports of modest analgesia. Dronabinol and nabilone are FDA-approved for control of acute and delayed nausea and vomiting from cancer chemotherapy.

Alternative delivery systems for cannabis include vape-pens, sublingual devices, and others that use a metered spray device. The advantages to such systems seem to be the use of known cannabinoid concentrations, predetermined dosing portions, and time-out systems that may help prevent overuse.

There are side effects, which are dose-related in terms of severity. Grant et al. reported that they seem to decline over time and are of mild to moderate severity. “Reviews suggest the most frequent side effects are dizziness or lightheadedness (30%-60%), dry mouth (10%-25%), fatigue (5%-40%), muscle weakness (10%-25%), myalgia [muscle pain] (25%), and palpitations (20%).” There is little data on a timeline of adverse or therapeutic effects. There have been concerns that rapid tolerance to adverse effects may indicate a corresponding tolerance to beneficial effects. But studies of oral sprays in multiple sclerosis report that you can reduce the incidence and severity of adverse effects by downward self-titration without loss of analgesia.

There are additional adverse effects, including some psychiatric side effects, especially with cannabis having high concentration of THC. See the original article for more specifics. The longer-term health risks of medicinal cannabis are unclear; most of the current evidence is based upon non-medical use. Some medical professionals indicate that effective medicinal use of cannabis requires significantly less marijuana than is typically consumed by recreational users.

In “The Current Status of Medical Marijuana in the United States,” Doctor Gerald McKenna noted how the majority of medical marijuana users in Hawaii claim they have chronic pain. He said a main problem in getting the medical profession to support the use of medical marijuana is that it is not widely used medicinally in a non-smoking form. “Authorizing use by inhalation of a drug with an unknown number of co-drugs contained in the same raw form is not supportable.” He said that supporting the use of medical marijuana by inhalation because users prefer it is akin to supporting the inhalation of any other drug taken orally. His impression is that medical marijuana laws have been passed “to bypass the illegality of marijuana.”

He did recommend removing marijuana from Schedule I controlled substance so research could be done more easily. “Until that research is done, stating that marijuana is useful for treating chronic pain, anxiety, post-traumatic stress disorder, depression, and other health conditions remains anecdotal and conjectural.”

It has become clear that the federal government needs to modify its resistance to reclassifying marijuana’s Schedule I Controlled Substance status to allow more quality research into its use and to fund that research. Otherwise, the current circus of inconsistent regulations from state to state, and unverified claims about the medicinal benefits of marijuana will have us back in the days of patent medicines, as far as marijuana is concerned. Further reflections on medical marijuana can be found in: “Let’s not Get Ahead of Ourselves,” “Is the Cart Before the Horse?” and “Marijuana Peek-a-Boo.”

06/17/15

The Coming Depression Apocalypse

© 3quarks | 123RF.com

© 3quarks | 123RF.com

According to the Motley Fool, the pharmaceutical company Alkermes has a potential blockbuster drug for treating major depression in its pipeline. Currently in Phase 3 clinical trials, ALKS-5461 is one step away from Alkermes filing for approval by the FDA. Mental Health Daily reported that ALKS-5461 was given fast track approval by the FDA and is expected to be available in 2016. Its projected use is as a supplementary treatment to current antidepressant drugs. But once approved, the “supplementary” element will likely stop because it’s new and fast acting. The problem is, the drug in ALKS-5461 that is supposed to treat depression is an opioid with addictive potential.

Before going further on this issue, we need to take a short trip into pharmacology and neurotransmitter function in order to understand what’s going on. There are proteins embedded within the membrane of a cell called receptors. These receptors receive chemical signals from outside the cell, and in turn produce a biochemical reaction inside the cell. The chemicals that bind and activate a specific receptor are called agonists. While an agonist causes a reaction, an antagonist blocks that reaction from occurring within the cell. It turns the cell off from the influence of the agonist.

Receptors are activated by either endogenous agonists (hormones or neurotransmitters), or exogenous agonists (drugs). Endogenous agonists are produced by the body. The endogenous opioid agonists include dynorphins, and the more widely known endorphins. If you want more information on biochemistry and neurotransmitter activity, try these Wikipedia pages for starters: opioid receptor, mu-opioid receptor, and agonist.

Opioids are known to have energizing and mood enhancing effects with some users. This effect seems to be associated with dynorphin, which is elevated in depression. Dynorphin is a full agonist for the kappa opioid receptor (KOR). Studies like that done by Knoll and Carlezon, “Dynorphin, Stress and Depression,” suggest that KOR antagonists may have a potential therapeutic potential in treating anxiety and depression. While this biochemical hypothesis makes sense to psychiatrist Daniel Carlat, in The Carlat Psychiatry Report, he was more reserved on the treatment potential of ALKS-5461 than Mental Health Daily and the Motley Fool.

The efficacy of ALKS-5461 for depression remains to be seen. Some trials of ALKS-33 alone have already been performed, particularly in the areas of alcohol dependence and binge-eating disorder. These have been negative.

Now let’s look at my concern with ALKS-5461. First, it is a combination of buprenorphine, and samidorphan, or ALKS-33. Buprenorphine is used in addiction treatment as a detoxification drug and in opioid maintenance therapy, where its brand names are Suboxone (buprenorphine with naloxone) and Subutex (buprenorphine without naloxone). Suboxone and Subutex are classified as Schedule III controlled substances, meaning they have a moderate to low potential for physical and psychological withdrawal. Other Schedule III drugs include ketamine and anabolic steroids.

Buprenorphine is a partial mu opioid agonist, meaning it displaces morphine, methadone, and other full opioid agonists from activating the mu opioid receptor (MOR). But it does not provide the same degree of receptor activation as the full agonists (It doesn’t get you as high), resulting in a net decrease of agonist effect and the onset of withdrawal if it used soon after a full agonist like heroin. Patients planning to begin Suboxone maintenance therapy are told to abstain from opioids for twenty-four hours before their first dose of Suboxone.

At lower doses and with individuals who are not dependent on opioids, both full agonists like heroin and partial agonists like buprenorphine will produce identical euphoric effects. Partial agonists like buprenorphine also have a ceiling effect, meaning that past a certain point, typically 12 to 16 mg, no difference in analgesia, euphoria and respiratory depression will be felt.

Buprenorphine does produce physical dependence. Reportedly, this is to a lesser degree than full opioid agonists; and it is supposed to be easier to discontinue at the end of medication treatment. While this is the received wisdom on websites like NAABT, The National Alliance of Advocates for Buprenorphine Treatment, that has not been the case for what I’ve observed clinically with individuals who have tried buprenorphine. Generally I’ve heard that buprenorphine is harder to kick than heroin. So ALKS-5461 will be treating depression with a drug that may be harder to kick than heroin.

Buprenorphine is also a full antagonist of the kappa opioid receptor (KOR), which underlies its use in ALKS-5461 as an antidepressant. If the production of dynorphine by KOR receptors increases with depression, theoretically then buprenorphine would block these receptors and limit the release of dynorphine—elevating the individual’s mood. Peter Tenore, in “Psychotherapeutic Benefits of Opioid Agonist Therapy,” said that opioids like buprenorphine could be “effective, durable and rapid therapeutic agents for anxiety and depression.”  The problem is with the partial agonist effect that buprenorphine has on mu opioid receptors (MOR) you can still use buprenorphine to get high.

That was the rationale for combining naloxone with buprenorphine in Suboxone. Naloxone is an opioid antagonist that counters the effects of opioids at the mu receptor, but doesn’t trigger a euphoric effect. Marketed under the brand name of Narcan, naloxone is used to counter the effects of opioids in overdose situations. The death of Phillip Seymour Hoffman led to calls for greater availability of naloxone (see “The Opioid-Heroin Cycle”) for individuals to use in overdose situations.

While naloxone is still the standard medication for emergency reversal of opioid overdose, its clinical use in long-term opioid addiction treatment is being superseded by naltrexone. Naltrexone (C20H23NO4) is structurally similar to naloxone (C19H21NO4), and samidorphan (C21H26N2O4). But it has a slightly increased affinity for κ-opioid receptors (KOR) and has a longer duration of action than naloxone. Naltrexone is used as a preventative medication for opioid use disorder in Vivitrol, whose marketing rights are owned by Askemet.

Samidorphan (ALKS-33) is also a full opioid antagonist, acting on the MOR receptor with mixed agonist-antagonist activity at the KOR receptor. Combining samidorphan with buprenorphine is supposed to block the agonist effect of buprenorphine on the MOR receptor, while not inhibiting the buprenorphine antagonist effect on the KOR receptor.  A study by Shram et al. comparing samidorphan to naltrexone was published online ahead of the June 2015 issue of the Journal of Clinical Psychopharmacology. Samidorphin was found to have greater binding affinity than naltrexone to mu receptors and a longer half-life. This was suggestive of prolonged opioid receptor antagonism at lower doses of samidorphin. The study, though, was funded by Askemet.

Suboxone (buprenorphine and naloxone) and ALKS-5461 (buprenorphine and samidorphin) appear to be biochemical twins. And it does not seem to me that the addictive potential of buprenorphine has been entirely neutralized by its combination with samidorphin as claimed. The history of abuse and diversion with Suboxone supports this concern. If my fear is true, then in the name of treating depression, ALKS-5461 will create a huge population of individuals who become dependent upon buprenorphine.

Coming off of buprenorphine is not fun. Here is a personal testimony of someone tapering off of buprenorphine. Oh, and mood swings with bouts of anxiety or depression are common side effects with buprenorphine withdrawal.

Buprenorphine withdrawal symptoms last longer for those who use buprenorphine for longer periods of time or at higher doses. Additionally, those who use buprenorphine other than prescribed (snort, inject, chew) may experience more severe symptoms than someone taking buprenorphine as prescribed. In these cases, physical buprenorphine withdrawal symptoms can last weeks after stopping.However, psychological withdrawal symptoms can last for many months after cessation. It is recommended that you join a support group or see a psychologist who can help see you through the protracted or post acute withdrawal symptoms (PAWS). Many heavy buprenorphine users experience PAWS. With continued use of buprenorphine, there comes a point where the brain produces in an inadequate amount of neurotransmitters in the body. People going through buprenorphine PAWS manifest long lasting changes in the brain as a result of long term use.

The Substance Abuse and Mental Health Services Administration (SAMHSA) estimated that in 2013, 1.8 million people had an opioid use disorder; 517,000 of which had one related to heroin use. SAMHSA also estimated that each year, 9.1% of the adult population experience symptoms consistent with major depression. One 2012 study suggested that 10% to 30% of individuals with major depression suffer from treatment resistant depression. Using a U.S. population estimate of 320.94 million, with a median 20% for individuals with treatment resistant depression, that leaves a target population of over 5.84 million Americans with treatment resistant depression. God help us.

I don’t think it is too strong rhetorically to speak of a pending depression apocalypse. I hope I’m wrong. But widespread use of ALKS-5461 could instigate a huge population of individuals dependent upon buprenorphine. And the problems coming off of ALKS-5461 would eclipse what we now know happens with SSRI withdrawal. Within the biochemical worldview, these symptoms will be reinterpreted as evidence of the underlying depression and proof the individual needs to remain on ALKS-5461. Sound familiar?

12/8/14

The New Frontier of Synthetic Drugs

In 1988, Gary Henderson, a professor of pharmacology at the University of California-Davis Medical School, predicted the coming global problem with synthetic drugs. He wrote that the scientific literature was full of potential synthetic routes and pharmacological properties for a wide variety of drugs. He said that information was readily available for “clandestine chemists” to exploit. Restricting access was not feasible and controlling the chemicals needed to make these drugs would only have a minimal effect. Henderson prophetically said:

It is likely that the future drugs of abuse will be synthetics rather than plant products. They will be synthesized from readily available chemicals, may be derivatives of pharmaceuticals, will be very potent, and often very selective in their action. In addition, they will be marketed very cleverly.

Today, news about the problems with synthetic drugs or new psychoactive substances (NPS) is hard to avoid. The parents on a 19-year-old who died after smoking synthetic marijuana started a facebook page in his memory. The governor of New Hampshire declared a state of emergency because of the overdose deaths from “Smacked,” a synthetic marijuana sold in convenience stores.

A Minnesota teen pled guilty to third-degree murder when the N-Bomb, a synthetic form of LSD, he supplied to several other teens resulted in an overdose death. The DEA reported that N-Bomb was responsible for at least 19 deaths between March of 2012 and November of 2013. A survey of 15,000 high school students in Minnesota revealed that 12% had used synthetic drugs. Minnesota has responded by launching a synthetic drug awareness website, KnowTheDangers.com. Drug WarFacts.org has a page devoted to information on NPS.

The problem is truly a worldwide one. By 2013, NPS had been identified in every region of the world. The majority of NPS worldwide were in three basic groups: synthetic cathinones, synthetic cannabinoids and phenethylamines. Together they accounted for 70% of the total number of reported NPS. See the following chart found in the 2014 Global Synthetic Drugs Assessment:

UntitledJapan introduced new laws to combat its growing synthetic drug problems. “Speckled Cross” resulted in 20 deaths in Northern Ireland. Synthetic cannabis is a growing problem in UK prisons. One prison reported that 85% of its inmates were using or supplying Spice. The chief inspector of prisons in the UK said: “What we can say for definitive is that spice is a significant problem in a number of prisons and it is rising.” DrugScope put together a status report on NPS and ‘club drugs’ in the UK.

A DEA spokesperson, Rusty Payne, called synthetic drugs the new frontier: “As chemistry and science advances, we’re seeing more and more drugs, designer drugs, new derivatives, new compounds that are making their way into the Unites States and across the world.”

Effects and Risks Associated with Novel Psychoactive Substances” gathered together helpful information on the pharmacology, clinical effects and adverse effects of the more common classes of NPS. See the original article for more details than the following summary.

Synthetic cathinones or “bath salts” can have both stimulant and hallucinogenic effects. They can cause severs intoxication. Their adverse effects include cardiovascular problems such as tachycardia—a faster than normal heart rate (22-56%), arterial hypertension (4-25%), palpitations (11-28%), dyspnea—shortness of breath (8-11%), and others. Psychiatric adverse effects include: agitation (50-82%), aggression (57%), hallucinations (27-40%), confusion (14-34%), anxiety (15-17%), and others. The psychotic adverse effects often consist of paranoia and hallucination (auditory and visual) that can persist for up to four weeks.

“Spice” or synthetic cannabinoids are much more potent, longer-acting and have worse adverse effects than THC. These adverse effects include: cardiovascular problems such as tachycardia (36-76%), arterial hypertension (10-34%), ECG changes (2-14%), chest pain (7-10%) and others. Neurological effects are present and can include: dizziness (9-24%), loss of consciousness (2-17%), somnolence—sleepiness (17-19%) and others. Psychiatric adverse effects include: agitation (19-41%), hallucinations (11-38%), anxiety/panic attacks (21%), and others.

Effects and Risks” also had some information on a phenylethylamine first synthesized in 1998, “Bromo-dragonfly.” It has a LSD-like effect that could last up to six hours. The effect includes visual and auditory hallucinations and a feeling of well-being that could last up to three days. It is highly toxic and has been associated with a number of deaths from overdose (study abstract here). A pro-drug website, Erowid, has a page of information (positive and negative) on Bromo-Dragonfly that included difficult experiences, bad trips and health problems. One report was titled: “Thankful That I’m Alive.” Probably the most disturbing piece I saw was a YouTube video, “My Bromo-DragonFLY Trip” by a young woman who sounded like she was describing an exciting, unexpected encounter while on a road trip with friends.

The 2014 Global Synthetic Drugs Assessment said it was still not clear if NPS were replacing other controlled substances. Maybe they are simply supplements to the existing bevy of drugs under international control. Then again, maybe we ain’t seen nothing yet.