Tag: David Healy

09/25/18

Rewiring the Adolescent Brain with Antidepressants

A depressed teenager walking towards the light

Research has shown that the earlier in life a person begins to use drugs, the more likely they are to develop serous problems as they mature. The interaction of early social and biological risk factors needs to be considered in assessing the developmental progression of later in life problems like addiction. “The fact remains that early use is a strong indicator of problems ahead, including addiction.”  While this is a noncontroversial perspective on how recreational drug use effects adolescent brain development, what about the effects of antidepressants and other psychiatric drugs on the developing brains of adolescents?

As our brains develop, our experiences reduce excess neural connections while simultaneously strengthening those that are used more often. The more we repeat any thinking or behavior pattern, the more it becomes habitually entrenched. If we repeatedly have a specific thinking pattern or do a particular behavior over and over again, the neurons in our brains strengthen that learning sequence, becoming what we refer to as a habit. “The more we actually do of whatever we do, the more ‘habitual’ that learning will become.” This is known as Hebbs Law, “Neurons that fire together, wire together.” When you combine Hebb’s Law with early drug use and the still maturing adolescent brain, you have a ready-made recipe for disaster.

image credit: NIDA

The above images of brain development are found in the NIDA (National Institute on Drug Abuse) discussion of “Drug Use and Addiction.” The images are for normal children and teens from the age of 5 to 20. Scientists think the process of brain maturation, depicted as the yellow to blue transition, corresponds to the steady reduction in gray matter volume seen during adolescence.  Note that the pre-frontal cortex is the last area of the developing brain to mature. Environmental forces, like drug use, help determine which connections wither and which are reinforced. This is a process that can “cut both ways” as not every habit reinforced by Hebb’s Law is desirable.

One of the brain areas still maturing during adolescence is the prefrontal cortex—the part of the brain that allows people to assess situations, make sound decisions, and keep emotions and desires under control. The fact that this critical part of a teen’s brain is still a work in progress puts them at increased risk for making poor decisions, such as trying drugs or continuing to take them. Introducing drugs during this period of development may cause brain changes that have profound and long-lasting consequences.

There is a euphoric effect from drugs that is still poorly understood, but it seems to be related to surges of neurotransmitters in parts of the brain’s reward circuit (i.e., the basal ganglia and amygdala). Some drugs cause a surge of neurotransmitters that are significantly greater than the normally occurring bursts produced naturally with healthy pleasurable activities such as eating, or social interaction. “Just as drugs produce intense euphoria, they also produce much larger surges of dopamine, powerfully reinforcing the connection between consumption of the drug, the resulting pleasure, and all the external cues linked to the experience.”  Simply put, surges of dopamine “teach” the brain to seek drugs at the expense of other goals and activities.

For the brain, the difference between normal rewards and drug rewards can be likened to the difference between someone whispering into your ear and someone shouting into a microphone. Just as we turn down the volume on a radio that is too loud, the brain of someone who misuses drugs adjusts by producing fewer neurotransmitters in the reward circuit, or by reducing the number of receptors that can receive signals. As a result, the person’s ability to experience pleasure from naturally rewarding (i.e., reinforcing) activities is also reduced.

One of the brain’s areas within its pleasure or reward center is the amygdala, which regulates emotions such as anxiety and depression, as well as having a role in the development of recreational drug addiction discussed above. While antidepressants won’t “shout” at the reward center in the same way cocaine or alcohol does, the individual who uses an antidepressant will experience a similar, if less radical, adjustment of their neurotransmitters and/or receptors. Consider what this could mean in the developing brain of an adolescent using an antidepressant that inhibits the uptake of serotonin (SSRI) or serotonin and norepinephrine (SNRI).

I have no training in medicine or neuroscience. But it seems logical to infer from the above that the long-term use or abuse of any drug which influences the neurotransmitter and/or receptor balance of the brain—cocaine, alcohol, antidepressants or other psychiatric medications—will influence brain function in the way described above. If studies show that “long-term drug use impairs brain functioning,” which the NIDA article claimed, this is equally true for recreational or psychiatric drugs. The question is, to what extent does the use of psychiatric medications like antidepressants effect the development of the adolescent brain?

A study by Lugo-Candelas et al. published in JAMA Pediatrics looked at the association between fetal brain development and prenatal exposure to SSRIs. Their findings suggested there was an association between prenatal SSRI exposure and fetal brain development, “particularly in brain regions critical to emotional processing.” The researchers said there was a need for “further research on the potential long-term behavioral and psychological outcomes of these neurodevelopmental changes.” In her review of the Lugo-Candelas et al. study for Mad in America, Bernalyn Ruiz said: “Overall, this study presents evidence that prenatal exposure to SSRI’s can affect infant neurodevelopment and may be associated with increased susceptibility to anxiety disorders, hyperactivity and maladaptive processing.”

A 2016 study by Cipriani et al. published in The Lancet concluded that the risk-benefit profile of antidepressant use in the acute treatment of major depression with children and adolescents did not seem to offer a clear advantage. The researchers said that fluoxetine (Prozac) was probably the best pharmacological treatment option. The study did not look at long-term antidepressant use as there has not been enough previous research to analyze, according to Cipriani. A STAT News review of the Cipriani et al. study quoted child psychiatrist Jon Jureidini as saying the study’s evidence for Prozac’s effectiveness was weak. He said the vast majority of children do not need to be medicated for depression.

What we’re up against is the marketing enterprise of the pharmaceutical industry combined with wishful thinking on the part of doctors and parents that there might be a good, simple solution for adolescent distress. . . . It’s something we need to take very seriously, but we don’t need to make it into a medical condition when it most times isn’t.

David Healy, Joanna Le Noury and Jon Jureidini wrote about their review of the benefits and risks of the use of antidepressants in children and adolescents for the International Journal of Risk & Safety in Medicine. They examined a total of 20 pediatric antidepressant studies conducted since 1990 and classified them as positive or negative according to the studies’ primary outcomes. In a review of the Healy, Le Noury and Jureidini study for Mad in America, Rebecca Troeger noted the authors found that all 20 trials performed between 1990 and 2005 were negative on primary outcome measures. That included the two fluoxetine (Prozac) trials “that provided the foundation for the drug’s regulatory approval” for use with children and adolescents. There was also evidence of an “excess of suicidality on active treatment” with these trials. “Of the 15 studies conducted since 2006 reviewed by the authors, nearly all were negative on primary outcome measures.”

At a global health conference in Aberdeen Scotland, Dr. Healy said every one of these trials produced more harms than benefits. Children became suicidal who would not have been suicidal if they had been kept off of antidepressants. He said if you follow the evidence, no one should be using these drugs. “At the same time, in teenagers, these drugs have become the most commonly used drugs.” The available evidence seems to question the wisdom and effectiveness of antidepressant use with children and adolescents.

03/9/18

Psychiatry Needs a Revolution

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Peter Gøtzsche wrote a January 2018 editorial in the British Medical Journal, where he elaborated on why he thinks, “Psychiatry is a disaster area in healthcare that we need to focus on.” In his editorial, Gøtzsche said the prevailing paradigm in psychiatry was to say psychiatric drugs have specific effects against specific disorders; and that their actions do more good than harm. However, he asserted that as a consequence of its liberal use of psychiatric drugs, psychiatry actually does more harm than good. Gøtzsche and other so-called “antipsychiatry,” critics are often dismissed by psychiatry. But there was a study that surveyed the attitudes of medical teaching faculty towards psychiatry and psychiatrists; and the results had more in common with the antipsychiatrists than you might think.

Stuart, Sartorius and Linamaa published “Images of Psychiatry and Psychiatrists” in the open access journal, Acta Psychiatra Scandinavica. They surveyed 1,057 teaching medical faculty members from 15 academic teaching centers in the United Kingdom, Europe and Asia. The overwhelming majority of respondents held negative views towards psychiatry as a discipline, psychiatrists and psychiatric patients. Some of their findings were startling: 90% thought psychiatrists were not good role models for medical students; 84% thought psychiatric patients should be treated only within specialized facilities.

When the survey asked about the perception of psychiatry as a profession, 8.9% thought psychiatry was unscientific; 7.7% thought it was not evidenced-based; and 8.0% thought psychiatry was not a genuine, valid branch of medicine. Perceptions of psychiatric treatment thought psychiatrists had too much power over their patients (25.0%); treatments were not as effective as in other branches of medicine (22.6%); and most who receive treatments do not find them helpful (20.4%). Then 28.6% said they would not encourage a bright student to enter psychiatry; and 75.4% said many students at their medical school were not interested in pursuing psychiatry as a career.

Results highlight the extent to which non-psychiatrist medical faculty hold negative opinions of psychiatry as a discipline, psychiatric treatments, psychiatrists as role models for medical students, psychiatry as a career choice, psychiatric patients, and psychiatric training. The most outstanding findings were that psychiatrists were not considered to be good role models for medical students, and psychiatric patients were considered to be emotionally draining and unsuitable to be treated outside of specialized facilities or in general hospitals.

“In Search of an Evidence-Based Role for Psychiatry,” by Read, Runciman and Dillon noted this was not the only study indicating negative views of psychiatry by other medical professionals. They cited a study by Curtis-Barton and Eagles that found medical students were discouraged from choosing psychiatry as a career either a lot or a little because of a perceived lack of evidence base (51%); and the scientific basis of psychiatry (53%). Only 4-7% of UK medical students saw it as a ‘probable/definite’ career because of its poor evidence base. Commenting further on “Images of Psychiatry and Psychiatrists,” Read, Runciman and Dillon said:

Even more revealing than the survey findings was psychiatry’s response to it. The researchers themselves, including a former President of the World Psychiatric Association, wondered whether their colleagues’ opinions are ‘well founded in facts’ or ‘may reflect stigmatizing views toward psychiatry and psychiatrists’. Their own answer to that question becomes abundantly clear when, instead of proposing efforts to address the problems identified by the medical community, such as having little scientific basis, they recommend only ‘enhancing the perception of psychiatrists’ so as to ‘improve the perception of psychiatry as a career.’

The responses to the survey, all written by psychiatrists, dismissed each concern “and blamed everyone but their own profession, including their supposedly ignorant, prejudiced medical colleagues and the biased media.” Read, Runciman and Dillon then described problems with how mental health issues are conceptualized, what causes them and how to treat them. “Despite all this, biological psychiatry is trying to expand the reach of what others consider to be an unscientific, reductionistic, simplistic and pessimistic ‘medical model’.” A truly evidence-based psychiatry would recommend psychiatric medications at a last resort (and for a short time period). The adverse effects of medications should be fully disclosed and “no medical treatment should be forced on anyone against their will.”

Read, Runciman and Dillon said there were three core research areas that psychiatry should be demonstrating progress in, if it is a legitimate scientific, medical discipline. They are: conceptualization, causation and treatment of the disorders.

With regard to the conceptualization of psychiatric disorders, “psychiatry’s primary contribution is an ever expanding list of labels.” Many do not reach even minimal scientific reliability levels and calling them ‘diagnoses’ is often a misnomer. Significantly, the NIMH announced when the DSM-5 was about to be published that it was abandoning the DSM diagnostic approach to classifying mental health problems for its research to develop scientifically robust ‘research domains.’ See “Patients Deserve Better Than the DSM” for more information on this.

“In terms of causation, psychiatry has focused predominantly on chemical imbalances, brain abnormalities and genetics.” But has repeatedly failed findings of any substance in support of that premise. Genetics has an important role, if the research is done on constructs that actually exist. There is also “the role of epigenetic processes whereby genes are activated and deactivated by the environment.”

Research suggests that the safety and efficacy of psychiatric drugs has been grossly exaggerated. Documentation in support of this claim is overwhelming. See the websites for Mad in America, Peter Breggin, and David Healy and RxISK for starters. You can also search this website or start with: “In the Dark About Antidepressants,” “Blind Spots With Antipsychotics.”

Peter Gøtzsche similarly noted concerns with the “liberal use of psychiatric drugs.” He identified four concerns with the prevailing paradigm in psychiatry and gave supporting evidence for each.

  • First, the effects of the drugs are not specific. “They impair higher brain functions and cause similar effects in patients, healthy people and animals.” For instance, not only does serotonin (SSRI antidepressants influence serotonin levels) seem to have a role in maintaining mood balance, it can effect social behavior, appetite and digestion, sleep memory and sexual desire and function.
  • Second, research in support of the paradigm that psychiatric drug have specific effects against specific disorder is flawed.
  • Third, the widespread use of psychiatric drugs has been harmful for patients. In every country where the relationship has been examined, an increased use of psychiatric medications has accompanied an increase in the number of chronically ill people and the number of people on disability pensions.
  • Fourthly, all attempts to use brain scans to show that psychiatric disorders cause brain damage have failed. “This research area is intensely flawed and very often, the researchers have not even considered the possibility that any brain changes they observe could have been caused by the psychiatric drugs their patients have taken for years” Yet this has been shown repeatedly in many reliable studies, especially for neuroleptic drugs.

Peter Gøtzsche said the prevailing paradigm in psychiatry, that its drugs have specific effects against specific disorders, is unsustainable when the research in support of it is critically appraised. He said psychiatry needed a revolution; reforms were not enough. “We need to focus on psychotherapy and to hardly use any psychiatric drugs at all.” Dr. Gøtzsche is a medical researcher and the Director of the Nordic Cochrane Center. Along with 80 others, he helped start the Cochrane Collaboration in 1993, which is “a global independent network of researchers, professionals, patients, carers, and people interested in health.” The work of the Cochrane Collaboration is recognized as an international gold standard for high quality, trusted information.

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.