01/5/18

In the Dark About Antidepressants

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In 2011, antidepressants were the third most commonly prescribed medication class in the U.S. Mojtabai and Olfson noted in their 2011 article for the journal Health Affairs that much of the growth in the use of antidepressants was driven by a “substantial increase in antidepressant prescriptions by nonpsychiatric providers without an accompanying psychiatric diagnosis.” They added how the growing use of antidepressants in primary care raised questions “about the appropriateness of their use.” Despite this concern, antidepressant prescriptions continued to rise. By 2016, they were the second most prescribed class of medications, according to data from IMS Health.

A CDC Data Brief from August of 2017 reported on the National Health and Nutrition Examination Survey. The Data Brief provided the most recent estimates of antidepressant use in the U.S. for noninstitutionalized individuals over the age of 12. As indicated above, there was clear evidence of increased antidepressants use from 1999 to 2014. 12.7% of persons 12 and over (one out of eight) reported using antidepressant medication in the past month. “One-fourth of persons who took antidepressant medication had done so for 10 years or more.”

Women were twice as likely to take antidepressants. And use increased with age, from 3.4% among persons aged 12-19 to 19.1% among persons 60 and over. See the following figures from the CDC Data Brief. The first figure notes the increased use of antidepressants among persons aged 12 and over between 1999 and 2014. You can see where women were twice as likely to take antidepressants as men.

Figure 1

The second figure shows the percent of individuals aged 12 and over who took antidepressant medication in the past month between 2011 and 2014. Note how the percentages increase by age groups for both men and women, with the highest percentages of past month use for adults 60 and over for both men and women.

Figure 2

The third figure shows the length of antidepressant use among persons aged 12 and over. Note that while 27.2% reported using them 10 years or more, 68% reported using antidepressants for 2 years or more. “Long-term antidepressant use was common.” Over the fifteen-year time frame of the data, antidepressant use increased 65%.

Figure 3

The widespread use of antidepressants documented above is troubling when additional information about antidepressants is considered. A February 2017 meta-analysis done by Jakobsen et al., and published in the journal BMC Psychiatry, found all 131 randomised placebo-controlled trials “had a high risk of bias.” There was a statistically significant decrease of depressive symptoms as measured by the Hamilton Depression Rating Scale (HDRS), but the effect was below the predefined threshold for clinical significance of 3 HDRS points. Other studies have indicated that differences of less than 3 points on the HDRS are not clinically observable. See “Antidepressant Scapegoat” for more information on the HDRS. Jakobsen et al. concluded:

SSRIs might have statistically significant effects on depressive symptoms, but all trials were at high risk of bias and the clinical significance seems questionable. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial effects seem to be outweighed by harmful effects.

In his review of the Jakobsen et al. study for Mad in America, Peter Simons noted where these results add to a growing body of literature “questioning the efficacy of antidepressant medications.” He pointed to additional studies noting the minimal or nonexistent benefit in patients with mild or moderate depression; the adverse effects of antidepressant medications; the potential for antidepressant treatment to potentially worsen outcomes. He concluded:

Even in the best-case scenario, the evidence suggests that improvements in depression due to SSRI use are not detectable in the real world. Given the high risk of biased study design, publication bias, and concerns about the validity of the rating scales, the evidence suggests that the effects of SSRIs are even more limited. According to this growing body of research, antidepressant medications may be no better than sugar pills—and they have far more dangerous side effects.

Peter Gøtzsche, a Danish physician and medical researcher who co-founded the Cochrane Collaboration, wrote an article describing how “Antidepressants Increase the Risk of Suicide and Violence at All Ages.” He said that while drug companies warn that antidepressants can increase the risk of suicide in children and adolescents, it is more difficult to know what that risk is for adults. That is because there has been repeated underreporting and even fraud in reporting suicides, suicide attempts and suicidal thoughts in placebo-controlled trials. He added that the FDA has contributed to the problem by downplaying the concerns, choosing to trust the drug companies and suppressing important information.

He pointed out a meta-analysis of placebo-controlled trials from 2006 where the FDA reported five suicides in 52,960 patients (one per 10,000).  See Table 9 of the 2006 report. Yet the individual responsible for the FDA’s meta-analysis had published a paper five years earlier using FDA data where he reported 22 suicides in 22,062 patients (which is 10 per 10,000). Additionally, Gøtzsche found there were four times as many suicides on antidepressants as on placebo in the 2001 study.

In “Precursors to Suicidality and Violence in Antidepressants” Gøtzsche co-authored a systematic review of placebo-controlled trials in healthy adults. The study showed that “antidepressants double the occurrence of events that can lead to suicide and violence.” Maund et al. (where he was again a co-author) demonstrated that the risk of suicide and violence was 4 to 5 times greater in women with stress incontinence who were treated with duloxetine (Cymbalta).

Although the drug industry, our drug regulators and leading psychiatrists have done what they could to obscure these facts, it can no longer be doubted that antidepressants are dangerous and can cause suicide and homicide at any age. Antidepressants have many other important harms and their clinical benefit is doubtful. Therefore, my conclusion is that they shouldn’t be used at all. It is particularly absurd to use drugs for depression that increase the risk of suicide when we know that psychotherapy decreases the risk of suicide. . . . We should do our utmost to avoid putting people on antidepressant drugs and to help those who are already on them to stop by slowly tapering them off under close supervision. People with depression should get psychotherapy and psychosocial support, not drugs.

Peter Breggin described “How FDA Avoided Finding Adult Antidepressant Suicidality.” Quoting the FDA report of the 2006 hearings, he noted where the FDA permitted the drug companies to search their own data for “various suicide-related text strings.” Because of the large number of subjects in the adult analysis, the FDA did not—repeat, DID NOT—oversee or otherwise verify the process. “This is in contrast to the pediatric suicidality analysis in which the FDA was actively involved in the adjudication.” Breggin added that the FDA did not require a uniform method of analysis by each drug company and an independent evaluator as required with the pediatric sample.

Vera Sharav, “a fierce critic of medical establishment,” the founder and president of the Alliance for Human Research Protection (AHRP), testified at the 2006 hearing. She reminded the Advisory Committee that the FDA was repeating a mistake they had made in the past.  She said in the past the FDA withheld evidence of suicides from the Advisory Committee. German documents and the FDA’s own safety review showed an increased risk of suicides in Prozac. “Confirmatory evidence from Pfizer and Glaxo were withheld from the Committee.”  Agency officials “obscured the scientific evidence with assurances.”

What the FDA presented to you is a reassuring interpretation of selected data by the very officials who have dodged the issue for 15 years claiming it is the condition, not the drugs. What the FDA did not show you is evidence to support that SSRI safety for any age group or any indication. They are all at risk. They failed to provide you a complete SSRI data analysis. They failed to provide you peer-reviewed critical analyses by independent scientists who have been proven right. FDA was wrong then; it is wrong now. Don’t collaborate in this. [But they eventually did]

Breggin commented that the FDA controlled and monitored the original pediatric studies because the drug companies did not do so on their own and failed to find a risk of antidepressant-induced suicidality in any age group. “Why would the FDA assume these same self-serving drug companies, left on their own again, would spontaneously begin for the first time to conduct honest studies on the capacity of their products to cause adult suicidality?”

In a linked document of two memos written by an Eli Lilly employee in 1990, Dr. Breggin noted where the individual questioned the wisdom of recommendations from the Lilly Drug Epidemiology Unit to “change the identification of events as they are reported by the physicians.” The person went on to say: “I do not think I could explain to the RSA, to a judge, to a reporter or even to my family why we would do this especially to the sensitive issue of suicide and suicide ideation. At least not with the explanations that have been given to our staff so far.” Those suggestions included listing an overdose in a suicide attempt as an overdose, even though (here he seems to be quoting from a policy or procedural statement) “when tracking suicides, we always look at all overdose and suicide attempts.” Eli Lilly brought the first SSRI, Prozac, to market in 1986.

Next time you hear someone say that the FDA studies only showed increased suicidality in children and young adults as opposed to adults, remember that the adult studies, unlike the pediatric studies, were not controlled, monitored or validated by the FDA. This is one more example of the extremes the FDA will go to in order to protect drug companies and their often lethal products.

The problems with antidepressants, most of which are SSRIs—selective serotonin reuptake inhibitors—were at least partially known as Prozac and its cousins were being developed and brought to market in the early 1990s. As the above discussion indicated, there seems to have been a disregard of the potential for multiple negative side effects from their use, up to and including the various forms of suicidality. The sleight-of-hand done by the drug companies, and apparently the FDA, means that many individuals are in the dark about the adverse side effects stemming from their SSRI medications.

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?

06/10/16

Psych Drugs and Violence

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A man began taking Zoloft because of some anxiety over whether he could cope with high school students as a student teacher. By the second day on Zoloft, he was having delusions. By day three, he believed aliens were hiding in the normal bodies of people all around him. He thought the alien leader had taken over his wife’s body. On the seventh day of Zoloft, he became certain that he had to kill the alien inside his wife to save himself and the world. So he drove their car full speed into a road barrier, unbuckling her seatbelt just before the crash. Finding her lying on the ground and alive after the wreck, he began to bang her head against the concrete and choke her. His wife survived, but their marriage did not.

A psychiatrist with a successful practice was stressed because of difficulties that ended up with him taking another psychiatrist to court. She in turn sued his son, who was involved in the business.  He prescribed himself Prozac hoping to relieve some of his tension and raise his spirits, but that didn’t help. He sought out treatment from another psychiatrist who treated him with more antidepressants, which led to further deterioration. Eventually he was placed on Luvox—the same antidepressant one of the Columbine shooters was taking. He became increasingly incensed at the psychiatrist who countersued his son and attacked her with a tack hammer.

These are just two of the case studies described by psychiatrist Peter Breggin in his book, Medication Madness. However, you don’t have to read it to find further examples. Read about the speculation after the Sandy Hook shootings about Adam Lanza. Or read this 2010 article by Moore, Glenmullen and Furberg, “Prescription Drugs Associated with Reports of Violence Toward Others.” Thirty-one different drugs met the study’s criteria for a disproportionate association with violence. The drugs included 11 antidepressants, 5 hypnotic/sedatives, 3 ADHD drugs and varenicline (Chantix). “SSRI Stories” describes over 6,000 stories where it seems prescription drugs  (primarily SSRIs) were linked to adverse outcomes, including violence. Also look at “Drugs, Violence and Revolution” or “Smoke and Mirrors” on this website.

These data provide new evidence that acts of violence towards others are a genuine and serious adverse drug event that is associated with a relatively small group of drugs. Varenicline, which increases the availability of dopamine, and serotonin reuptake inhibitors were the most strongly and consistently implicated drugs. Prospective studies to evaluate systematically this side effect are needed to establish the incidence, confirm differences among drugs and identify additional common features.

Several years ago I attended a conference and heard a presentation by Yolande Lucire on her research into the association of violence and psychiatric medications.  At the time I found her presentation both fascinating and concerning in that she thought she had identified a biomedical association between antidepressant medications and some perpetrators of violence. Could there actually be medical evidence of an association between antidepressants and violence? But I didn’t hear anything more about this finding, despite the parade of case studies and anecdotes like those above that did suggest a connection. Then I saw where she was the coauthor of an article in the April 2016 issue of Forensic and Legal Medicine, describing a forensic investigation of three individuals who committed homicide, two of which also intended suicide while taking antidepressants.

The article by Eikelenboom-Schieveld, Lucire and Fogleman was a forensic investigation of three cases they believed to be instances of antidepressant-induced akathisia-related homicide. They suggested that mutations in the CYP450-encoding genes of these individuals contributed to problems metabolizing psychiatric medications and were thus contributing factors to their homicides. The cytochrome P450 family of enzymes is responsible for metabolizing most of the drugs used in psychiatry. “These individuals 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 individuals knew they were supposed to take their medication regularly or how to stop taking it safely; and none of them improved on the medications. In addition, none of the prescribers recognized their complaints as adverse drug reactions. Nor were they aware of any impending danger from their patients. Interviews with the individuals indicated they had struggled with akathisia (agitation or distress), confusion, delirium, euphoria, extreme anxiety, obsessive preoccupation with aggression, and an incomplete recall of events. Impulses to kill were acted on without warning. Upon recovery, they all saw their actions as out of character. Their beliefs and behaviors horrified them.

They were all prescribed medications that interacted with one another and one person combined these with alcohol. The drug-to-drug interactions further decreased their metabolizing capacity and increased their risk for adverse events by prolonging the half-life of the medications and raising their blood levels.

Fast-changing levels of psychotropic substances, up or down, can cause behavioural changes, as the neurotransmitters in the brain react to reach some equilibrium. This phenomenon makes starting and stopping medication the most dangerous times for suicide and violence, but both can happen at any time, with stress, provocation, dose change, addition or subtraction of a medication. These toxic responses to antidepressants may occur early or later in treatment.

When reading this paper, I saw that Dr. Lucire had previously published an article in 2011 on anti-depressant-induced akathisia-related homicide and the CYP450 genes. In Lucire and Crotty they found that CYP450 allele frequencies were higher in those individuals who had experienced akathisia/serotonin toxicity after taking psychiatric medications. They presented ten cases whose the use of antidepressants had not mitigated their distress. Every person’s emotional reaction worsened while their treating physician attempted a “trial and error” method of increasing doses and then changing to another antidepressant when the previous one did not work.

The symptoms of antidepressant drug toxicity were not recognized as such by the subjects or their physicians. In many cases, the dosage of the antidepressant was increased while other medications were given to address the side effects Frequently the adverse effects were compounded.

In some cases the violence ensued from changes occasioned by withdrawal and polypharmacy. In all of these cases, the subjects were put into a state of drug-induced toxicity manifesting as akathisia, which resolved only upon discontinuation of the antidepressant drugs.

This paper has detailed and substantiated in specific terms how the metabolism of each of the antidepressant drugs used by the subjects would have been seriously impaired both before and at the time they committed or attempted homicide. They were experiencing severe reported side effects, adverse drug reactions due to impaired metabolism complicated by drug–drug interactions against a background of variant CYP450 alleles.

Eikelenboom-Schieveld, Lucire and Fogleman concluded that CYP450 was an important factor for determining who could tolerate a drug or combination of drugs from who could not. “Testing for cytochrome P450 identifies those at risk for such adverse drug reactions.” They hoped that as awareness of the biological causes of these disastrous side effects became more known, justice would be better served for both the victims and perpetrators of akathisia-related violence. “The medicalization of common human distress has resulted in a very large population getting medication that may do more harm than good by causing suicides, homicides and the mental states that lead up to them.”