01/26/18

Violence and the Brain

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Reporting for the Las Vegas Review-Journal, Jessie Bekker said Stanford University would begin a targeted autopsy investigation on the brain of Las Vegas mass shooter Stephen Paddock. Experts have already expressed doubt that an autopsy alone will uncover clues as to why Paddock did what he did. A University of Utah neuropathologist said a pathologist could look for evidence of something like dementia or CTE—chronic traumatic encephalopathy. I wonder if they will look for a possible connection between his violence and a diminished metabolic capability with his cytochrome P450 gene family.

Yolande Lucire, a forensic psychiatrist with fifty years of experience, has been investigating this possibility for a number of years. I first heard of her and her work at a conference presentation she made in March of 2012 on “Akathisia Homicides.” You can watch a video of her 35-minute presentation at the conference here on YouTube. She’s not anti-drug, but believes a disregulation with the cytochrome P450 gene family, which produces drug-metabolizing enzymes, could be a factor in akathisia-related violence and suicide. In other words, there can be an adverse reaction to psychiatric medications when the cytochrome P450 family of enzymes fail to metabolize those psychiatric medications.

This adverse reaction could lead to akathisia, a state of “increased tenseness, restlessness and a feeling of being very uncomfortable.” There can also be irritability and/or insomnia. An estimated 20% of people on an antidepressant will have significant symptoms of akathisia and at least 50% of individuals on an antipsychotic with symptoms of akathisia. On higher doses of antipsychotics, that percentage can increase to 80% or more.

In an open access journal, Epidemiology, Dr. Lucire published an article titled “Phramacological Istrogenesis: Substance/Medication-Induced Disorders That Masquerade as Mental Illness.” She described how information on the safety and efficacy of psychiatric medications has been manipulated to favor the “pseudo-scientific ideology of the pharmaceutical industry.” Adverse side effects from the medication becomes misinterpreted to justify ongoing treatment with the very medications causing the problems; or to justify treatment of the adverse events with another medication. “There was a pill for every ill and another for each side effect.”

Misinformation has resulted in prescribing practices that produced an epidemic of akathisia-related suicide and homicide as well as substance/medication-induced conditions mimicking the mental illnesses that the drugs were supposed to cure or prevent.

Lucire said the dominant view of how to practice psychiatry has come from the pharmaceutical industry and its agents. Regulatory bodies reinforce this view when they recommend the continued use of antidepressant medications in cases where individuals only became suicidal or psychotic after taking their medication. “Their members have no comprehension of Cytochrome P450-based interactions described in product information and refuse to countenance drug company fraud.” She further observed:

A Medical Board has determined that medications and doses that had caused people to commit suicide and homicides were ‘standard psychiatric treatment’ even when the consequence had been fatal. Akathisia cases were not investigated or given any credit. Coroners sitting on five cases of antidepressant-akathisia-related suicides brought before them refused to hear this evidence.

She co-authored another article that described three cases of what authors believed were instances of antidepressant-induced akathisia-related suicide: “The relevance of cytochrome P450 polymorphism in forensic medicine and akathisia-related violence and suicide.” They also had “diminishing mutations in the CYP450 family of metabolizing enzymes and all were taking medicines that further decreased metabolism by inhibition.” None of the three knew they were supposed to take their medications regularly or how to stop taking them safely. None of them improved on the medications and none of their prescribers recognized their complaints as adverse drug reactions. See: “Psych Drugs and Violence” for more on this article. You can also explore more on Dr. Lucire’s work on her website.

Dr. Lucire’s work is not without its detractors. An earlier 2011 article she co-authored, “Antidepressant-induced akathisia-related  homicides  associated  with  diminishing   mutations in metabolizing genes of the CYP450 family,” was critiqued by Loonen and Verkes in a letter to the editor of Pharmacogenomics and Personalized Medicine. They thought the population of that study was too heterogeneous and poorly characterized from a phenomenological perspective. They also suggested her use of the term “akathisia” was not defined well and could result in a false interpretation between aggression and akathisia. See a copy of their critique and Lucire’s reply here.

Yolande Lucire replied to the critique by noting how their paper pointed out how akathisia has been correlated with aggression, suicide and homicide as far back as the 1950s. In response to their curious criticism of her article not providing a definition for akathisia, she said akathisia could range in intensity from mild discomfort to “the most painful and dangerous mental state known to psychiatry.” She said the DSM-III defined akathisia as “a subjective desire to be in constant motion caused by drug sensitivity.” She also referred to the DSM-IV, which said the condition fluctuated with the subjects describing bouts of restless legs, twitching, toe turning, pacing and other activities, that occurred outside of the interview hours.

She then commented how the FDA’s restriction to indentify akathisia “only when its physical manifestations appeared in front of the interviewer” led to under diagnosis of the condition. Professor Loonen’s sense, that akathisia should be limited even further to what has been observed within a circumscribed timeframe, would result in even more cases being missed “with tragic consequences.”

Akathisia is rarely monocausal in clinical practice. It is dose related and cases formerly thought to be idiosyncratic are now known to be associated with diminished cytochrome metabolism, the co-prescription of cytochrome inhibitors, the removal of inducers, competition from polypharmacy for enzymatic substrate, diet and age of the patient, and their general and liver health.

Dr. Lucire’s work with diminished cytochrome metabolism isn’t the only voice raised in concern over a connection between antidepressants and violence or suicide. Dr. Peter Breggin has been warning of this issue since the first edition of his book, Toxic Psychiatry, in 1991. Dr. Breggin wrote of a February 7, 1991 New York Times article, “Suicidal Behavior Tied Again to Drug: Does Antidepressant Prompt Violence?” The article referred to cases of suicidal ideation that had been described in a letter in the New England Medical Journal. The individuals reportedly had not had previous signs of wanting to kill themselves. More than fifty lawsuits were filed against the manufacturer, Eli Lilly, at the time. “Other lawsuits blame Prozac for driving patients to mutilate themselves and even to commit murder.”

In the American Journal of Psychiatry, “Emergence of Intense Suicidal Preoccupation During Fluoxetine Treatment” reported how six depressed patients, “free of recent suicidal ideation, developed intense, violent suicidal preccupation after 2-7 weeks of fluoxetine treatment.” This persisted for a range of 3 days to three months after fluoxetine treatment was discontinued. Breggin added:

The report estimates that 3.5 percent of Prozac users were at risk. While denying the validity of the study, Dist Products, a division of Eli Lilly, put out a brochure for doctors dated August 31, 1990, stating that it was adding “suicidal ideation” to the adverse events section of its Prozac product information.

So what happened? According to David Healy in “Vampire Medicines,” the Teicher et al. article (“Emergence of Intense Suicidal Preoocupation During Fluoxetine Treatment”) offered undeniable evidence that SSRIs can cause suicide and hearing were convened to discuss the need for warnings.  “But coincident with these hearings, BMJ [British Medical Journal] published a meta-analysis of Prozac trials which Lilly claimed showed Prozac was not linked to suicidal events.”

The published data showed an increased risk on Prozac, which Lilly and BMJ ignored, claiming nothing was statistically significant.  Beyond this, Lilly played some of the tricks other companies later played – the small print shows the only placebo event hadn’t happened on placebo, so that technically there was a statistically significant  infinitely greater risk on Prozac.The way this played in public was that the stories of suicides on Prozac were tragic but anecdotal.  The scientific evidence demonstrated that patients and doctors just can’t believe the evidence of their own eyes and ears. They have to be told what’s what by experts.This dangerous and misguided message triumphed with regulators, and later in Courts.This message killed any interest journals like AJP and BMJ had in taking Case Reports. Besides companies didn’t buy reprints of these, whereas they handed over huge amounts of money for reprints of ghost-written fraudulent RCTs with zero access to data, and even more for the best science money could buy – meta-analyses of these trials. Evidence Based Marketing was here.

So what happens when there is a mass shooting like that in Las Vegas with Stephen Paddock, or with Devan Patrick Kelley in Sutherland Springs Texas? The possible connection between gun violence and psychiatric medications like antidepressants in the media is voiced by individuals like Kristie Alley (see here) and Pat Robertson (see here) who can be dismissed or marginalized by readers and viewers for their religious stands on Scientology and evangelical Christianity respectively. Additionally, they have no personal scientific or medical credibility. Individuals like Yolande Lucire, Peter Breggin or David Healy who do have medical and/or scientific credibility are not the go-to “talking heads” in main stream media outlets on the possible connection between psychiatric medications and violence, especially gun violence.

It’s not too late to prevent the trap on unsuspecting brains from being sprung. Yolande Lucire’s research findings and the critiques of Peter Breggin and David Healy should not be dismissed as fringe science. There have been reports of akathisia associated with aggression, violence and suicide from the 1950s. Peter Breggin was pointing out a similar connection from the honeymoon time with the first SSRI, Prozac. David Healy has been pointing out the connection between antidepressants and violence for years (See this link to a search on his website for “antidepressants violence”).

Not every instance of gun violence or mass shooting can be attributed to diminished cytochrome metabolism or akathisia-induced violence. But when the total number of incidents of gun violence in the US from January 1 to December 1 of 2017 was 56,355, and the number of mass shootings for the same time period was 324, there is a good chance an investigation would confirm an association in many of them. Below is a graphic taken from the website Gun Violence Archive that shows the geographic distribution of the 324 incidents of mass shooting. Also see: “Iatrogenic Gun Violence” on this website.

Post Script. The number of incidents of reported gun violence in the U.S. on Gun Violence Archive rose from 56,355 on December 1st, 2017 to 61,418 on December 31st, 2017. The number of mass shootings increased to 345. The 2018 totals were 2,628 incidents of gun violence and 12 mass shootings on January 20th, 2018. Go see where the totals are when you read this.

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?