On November 15, Mad in America published a report on the marketing of two new drugs for tardive dyskinesia (TD), Ingrezza and Austedo, which cost up to $7000 per month and are being touted as “breakthrough medications.” The report provided an in-depth look at the financial influences present in their development and marketing, and told of how these expensive new medications are really “me-too” compounds, with little benefit over an existing generic used to treat TD symptoms.
Given that TD is a disorder caused by antipsychotics, there is an obvious outrageous element to this story: the pharmaceutical industry is now profiting by developing drugs to treat the harm caused by its own products.
There is another aspect to this story, one that can be dug out from the scientific literature, that needs to be known. TD is regularly presented as a disorder of involuntary movements, and thus a dysfunction of the basal ganglia. But this common conception of TD obscures a more devastating truth: TD should be understood as drug-induced brain damage that leads to a global decline in brain function. The motor dysfunction is often accompanied by an increase in psychotic symptoms, a decline in cognitive function, and an increased risk of early death.
Moreover, while the new drugs may reduce the visible manifestations of TD—the tics, spasms, and other motor abnormalities—they do nothing to repair the brain damage caused by antipsychotics. Indeed, an examination of the “mechanism of action” of the TD drugs reveals that they can be expected to worsen brain function over time. These drugs impair the normal functioning of multiple neuronal pathways in the brain.
This is the latest chapter in a long-running story of medical harm on a grand scale, to which psychiatry—and our society—has mostly turned a blind eye for decades. History is repeating itself, and to a tragic end.
The First Wave of TD
When chlorpromazine was introduced in the 1950s, clinicians noted that it regularly caused Parkinsonian symptoms—tremors, muscle rigidity, slower movements, and so forth. Researchers soon came to understand that chlorpromazine and other new “neuroleptics” worked by blocking dopamine receptors in the brain, thereby thwarting the neuronal activity in the basal ganglia that controls motor movements.
The Parkinsonian symptoms were understood to be an acute effect of the drugs. The first case reports of what came to be known as tardive dyskinesia were published a few years later, and they told of a more lasting dysfunction in motor movement. In 1959, French psychiatrists described the symptoms:
“The tongue [is] is permanently projected forward and backward following a rapid rhythm; at times the projection is to the side, sometimes to the right, sometimes to the left . . . the lips participate in this dyskinesia in the form of stereotyped suction motions, pursing, rolling and incessant champing in synergy with rhythmic contractions of the jaw.”
This strange movement disorder appeared to be related to the Parkinsonian symptoms that appeared with the initiation of antipsychotic treatment, and yet opposite in kind. The Parkinsonian symptoms arose from a deficit in neuronal activity. The bizarre orofacial movements that characterized tardive dyskinesia appeared to be related to a hyperactivity of these same dopaminergic pathways.
Over the next decade, case reports fleshed out the scope of this dysfunction. People suffered from jerky, spasmodic motions of all types. Arms, ankles, fingers, toes, torso, neck and larynx could all be affected. Those suffering from TD could have difficulty walking, sitting or standing. At times, their speech became incomprehensible, and they had so much trouble swallowing that eating became problematic.
In 1973, National Institute of Mental Health physician George Crane wrote that TD, in its severe forms, resembled “in every respect known neurological diseases, such as Huntington’s disease, dystonia musculorum deformans, and post encephalitic brain damage.”
This was also not a rare side effect. At least nine studies in the 1960s told of how TD afflicted more than 10% of all schizophrenia patients, with one report stating that the percentage might rise to 40% of all patients who were on the drugs for longer periods of time.
A Direct Effect of the Drugs
Although the etiology of TD is still not fully understood, it is thought to be due, at least in large part, to a “dopamine supersensitivity” induced by antipsychotics. This hypothesis was first put forward in the late 1970s and early 1980s.
Neurons in the brain communicate in this manner: A “presynaptic” neuron releases a neurotransmitter (or chemical messenger) into the tiny gap between neurons, which is known as the synaptic cleft. The neurotransmitter then binds with receptors on the “postsynaptic” neuron. Dopamine is a neurotransmitter that excites the postsynaptic neuron and causes it to fire.
Antipsychotics “work” by blocking dopamine receptors in the brain, and in particular, a subtype known as a D2 receptor. At a therapeutic dose, antipsychotics block 70% to 90% of D2 receptors in the brain, thereby thwarting the activity of dopaminergic systems that are critical to the normal functioning of three regions of the brain: the basal ganglia, the limbic system, and the frontal lobes.
In response to this blockade, the brain tries to maintain the functioning of these pathways by increasing its own dopaminergic activity. Presynaptic neurons release more dopamine than normal; postsynaptic neurons increase the density of their receptors for this molecule. While the first compensatory mechanism—extra release of dopamine—seems to burn out after a period of time, the increase in dopamine receptors remains. The brain is now said to be in a “dopamine supersensitivity” state, with 30% to 100% more D2 receptors than normal.
In this new state, the dopaminergic pathways may become hyperactive. The dysregulation of the dopaminergic system in the basal ganglia can lead to the constant firing of neurons that control motor movement, and hence produce the rhythmic and bizarre movements that characterize tardive dyskinesia.
This understanding was first pieced together by two Canadian researchers, Guy Chouinard and Barry Jones, who published multiple papers on the topic in the late 1970s and early 1980s. Subsequent research, most notably by Philip Seeman and colleagues, fleshed out this picture. They determined that not only did antipsychotics stir an increase in D2 receptors, it pushed them into a high-affinity state (D2High) that increased their firing activity, and thus exacerbated this dopamine supersensitivity.
While dopamine supersensitivity is still seen as a primary cause of TD, researchers have hypothesized that antipsychotics may also damage the basal ganglia in direct ways. In rats, antipsychotics have been shown to cause a loss of cells in this brain region. Autopsy and magnetic resonance imaging studies have found lesions in the basal ganglia of some TD patients, leading researchers to compare TD to the degenerative process characteristic of Parkinson’s and Huntington’s disease. Still others have argued that antipsychotics damage neurons because they “elevate levels of oxidative stress.”
While the etiology may remain uncertain, it is evident that antipsychotics are causing neuronal damage that dysregulates their normal functioning. Moreover, TD was found to be “irreversible” in most patients, remaining after the offending antipsychotic was withdrawn, evidence that the brain damage was permanent.
Tardive Dyskinesia, Tardive Psychosis and Global Decline
Tardive dyskinesia has regularly been presented, both within the psychiatric profession and to the public, as a motor movement disorder. However, dopaminergic pathways are also essential to the normal functioning of the limbic system and the frontal lobes. The dysregulation of dopamine pathways could be expected to impair the functioning in these areas of the brain too, and, if so, cause a more global decline.
The limbic system is thought to be a mediator of psychotic symptoms, which led Chouinard and Jones to theorize that dopamine supersensitivity could lead to chronic psychotic symptoms. In a study of 216 schizophrenia patients, they put their theory to the test and determined that 30% were suffering from tardive psychosis. In more severe cases, Chouinard wrote in 1991, the “illness appears worse” than ever before. “New schizophrenic or original symptoms of greater severity will appear.”
Seeman, in his studies of drug-induced dopamine supersensitivity, concluded in 2007 that this was why antipsychotics fail over time. The drugs, which initially thwart dopaminergic activity, promote a dysregulated, hyperactive firing of neurons over the long term, with this pathology resulting, in particular, from the switch of D2 receptors into a high-affinity state.
This research reveals that antipsychotics may worsen the very symptoms they are supposed to ameliorate over the long term. Numerous other studies have found that TD is associated with a global decline in brain function. Many patients with TD show accelerated impairment in learning, memory, and a variety of other intellectual tasks. “The relationship appears to be linear,” reported Medical College of Virginia psychiatrist James Wade in 1987. “Individuals with severe forms of the disorder are most impaired cognitively.”
The list of impairments associated with TD goes on and on. In one study, 44% of TD patients weren’t even aware of their motor dysfunction, evidence that they had lost the capacity of mind to monitor their own physical well-being. As one researcher concluded, the weird tongue movements may warn of a “larval dementia.” People with TD may lose their “road map to consciousness.”
This was the understanding of TD that emerged during the era of “first-generation” antipsychotics (FGAs). It told of drugs that caused disabling brain damage, and did so with great regularity. Studies concluded that 5% of patients developed TD within one year of exposure to the drug, with an additional 5% developing it with each additional year of use. TD, researchers determined, was also associated with increased mortality.
Yet, in spite of these findings, psychiatry mostly turned a blind eye to TD, or discounted the severity of this disorder, for more than 20 years.
Turning a Blind Eye to TD
Although the first case reports of TD appeared in the late 1950s, and studies in the 1960s found that it afflicted more than 10% of all schizophrenia patients, the FDA did not step in and require the pharmaceutical companies that sold antipsychotics to warn of this risk. The American Psychiatric Association also ignored this risk during this time, with psychiatrists regularly prescribing chlorpromazine, haloperidol, and other antipsychotics in high doses.
It was this inaction that led George Crane to publish repeated reviews of the scientific literature related to TD. In his articles, the first of which was published in 1968, Crane did not argue for the withdrawal of antipsychotics from the marketplace. Instead, he wanted this risk to be known and acknowledged so that psychiatrists could learn how to mitigate this risk. Prescribing antipsychotics at lower doses and taking patients off these drugs when TD symptoms first appeared could help minimize the harm done. Crane urged the APA to mount a public education campaign, writing that “mailing informative material to all physicians is essential.”
Crane’s colleagues did not respond kindly to his efforts. He was, they suggested, making a mountain out of a molehill. Tardive dyskinesia, wrote Nathan Kline in 1968, was a “rare side effect” that is “not of great clinical significance.” Jonathan Cole, who previously had directed NIMH’s Psychopharmacology Service Center, described Crane as “a Cassandra within psychiatry” who was needlessly “foreseeing doom in many aspects of our current scientific and clinical operations.”
Yet another physician, John Curran, chastised Crane’s alarms as “not only premature but misleading,” and reasoned that even if the drugs did cause brain damage, that wasn’t reason to stop using these drugs. “While it is true that any psychosis can remit spontaneously, I honestly do not see how one can withhold a treatment of proved efficacy for fear of inflicting or aggravating putative brain damage.” Others chalked up TD to brain damage from earlier therapies, particularly lobotomy and electroshock, or attributed it to the disease.
Meanwhile, Daniel Freedman, editor of the Archives of General Psychiatry, dismissed Crane’s call for a mailing to physicians. Psychiatrists already had at their disposal “considerable data and guidelines to help determine sound judgments,” he wrote.
All of this frustrated Crane to no end. “The majority of clinicians continue to ignore the existence of this complication,” he wrote in 1973. “The neglect of a serious health problem for so many years has deeper roots than mere ignorance of facts.”
That year, the FDA did begin requiring the pharmaceutical companies to warn about TD in their labels. But the APA continued to dawdle, and as Crane had written, there were “deeper roots” for its lack of action.
American psychiatry was in the process of turning away from talk therapy and embracing drugs as first-line therapies. The arrival of chlorpromazine, it was said, had made it possible to empty the asylums, and had kicked off a “psychopharmacological” revolution. The new drugs for schizophrenia, while initially called “neuroleptics,” were now understood to be “antipsychotics,” a name that told of how they were specific antidotes to psychosis. This was a narrative that enabled psychiatry to see itself in a new light, as physicians in white coats, and there was a financial incentive at work too: a psychiatrist could earn more by prescribing drugs than by talking to patients.
TD threatened all this. If the field came to understand that antipsychotics caused brain damage in a significant percentage of patients, that entire narrative would burst.
And so the APA dawdled. In the early 1980s, more than 20 states—responding to the APA’s lack of action—passed laws requiring physicians to tell their patients about this risk. Yet, even this legal mandate failed to have any marked effect on prescribing practices. A national survey found that disclosure rates about the risk of TD were lowest in states where it was mandatory.
Indeed, America’s psychiatrists were busily ramping up this risk with their prescribing habits. From 1973 to 1985, the average daily doses of prescriptions of antipsychotics doubled, with psychiatrists prescribing the drugs at dosages that were four times higher than those prescribed by non-psychiatrists.
In 1984, Thomas Gualtieri, a physician at the University of North Carolina, summed up this dismal record: “A review of the history of TD demonstrates nothing as clearly as this fact: since 1957, published guidelines, scientific articles, presentations at professional meetings and draconian admonitions in the Physicians Desk Reference seem to have had little, if any, effect on actual physician behavior with respect to neuroleptic drugs.”
Finally, in 1985, after several highly publicized lawsuits found psychiatrists negligent for failing to warn patients of this risk, the APA sent out a letter to its members. Financial concerns were noted in the missive. “We are further concerned about the apparent increase in litigation over tardive dyskinesia,” the APA wrote.
The history told here—of a profession that turned a blind eye to TD for decades—is well known, even within the field. In a 2006 editorial on TD published in the American Journal of Psychiatry, John Kane revisited it one more time:
“The history of tardive dyskinesia holds many instructive lessons regarding long-term adverse drug effects. First described in the late 1950s shortly after the introduction of antipsychotics, it took many years before its prevalence, incidence, and long-term course were well investigated. At first there was resistance and skepticism from many quarters as to the risk of this condition and its apparent association with long-term exposure to antipsychotic medication . . . Some might argue that it was until the threat of litigation became more and more a reality that clinical practice included adequate consideration of and monitoring for tardive dyskinesia.”
TD in the Atypicals Era
After the APA sent out its warning letter in 1985, the field’s recommended “best practices” did change. Antipsychotics should be prescribed at the lowest possible dose, physicians were told, and with certain groups of psychotic patients, such as those who had suffered a brief psychotic episode, they should try to limit their long-term use.
The risk of TD was finally being acknowledged. This was a serious, irreversible disorder and prescribers needed to keep it in mind when treating psychotic patients. And the risks of these drugs were such that they shouldn’t be used “off-label” for less severe conditions.
But then risperidone and olanzapine were brought to market in the mid-1990s, and a new story emerged. The field now had safer drugs that didn’t carry this same risk.
When risperidone was approved for sale, Janssen told of how its new drug didn’t appear to cause Parkinsonian symptoms. The risk was said to be the same as “placebo.” And if this was so, it seemed likely that that the longer-term risk of TD might dissipate too. Soon published reports from one-year extension trials, funded by Janssen, told of how the one-year year incidence of TD with this new drug was 0.3% or even less.
Eli Lilly told much the same story about Zyprexa (olanzapine). The risk of Parkinsonian symptoms with this new drug was much less than with the FGAs. The company also reported that in an extension trial in schizophrenia patients, the one-year incidence of newly emergent TD was 0.52%, compared to 7.45% in the haloperidol patients. “Our results indicated a significantly lower risk of tardive dyskinesia with olanzapine than with haloperidol.”
This became the common wisdom, and subsequent reviews of the industry-funded extension trials further cemented this understanding. A 2005 review of seven one-year trials of risperidone reported there were only two cases of TD among 1,156 patients treated with the drug (0.2%). The incidence rate was 0.4% for those treated for longer than one year. The same review reported that while the data from three extension trials of olanzapine weren’t quite as good, the incidence of TD (2.6%) was still markedly lower than in those treated with haloperidol (8%).
Yet another review reported that the annual incidence of TD in children treated with second-generation antipsychotics (SGAs) was 0%.
Worries about TD faded away. Newly trained psychiatrists, fresh out of medical school, could have concluded that this was a harmful side effect from the distant past. “It is not surprising that tardive dyskinesia has been somewhat less of a focus among clinicians and investigators,” Kane wrote in his 2006 editorial. “The current preponderance of prescriptions of second-generation antipsychotics means that a new generation of clinicians has been trained without the extensive exposure to TD that older clinicians and patients experienced.”
A 2007 review in Current Drug Therapy summed up the good news. The annual incidence of TD with the first-generation antipsychotics had been 5%; it was 0.5 to 1% with the second-generation antipsychotics. TD with the new drugs developed “five to ten times less often” than before, the authors wrote.
Upon Further Review
Those were the published results that enabled the manufacturers of the “atypicals” to promote their use for off-label purposes: as adjuncts to antidepressants and bipolar medications, for anxiety and sleeping disorders, and for pediatric uses. Although these drugs were known to cause adverse metabolic effects, the specter of tardive dyskinesia had more or less disappeared.
However, that benign picture of the second-generation antipsychotics (SGAs) had emerged from short-term RCTs and open-label extension trials that had been funded by the makers of these drugs. The authors of those reports regularly had financial ties to the pharmaceutical companies; the 2005 review was authored primarily by members of the speakers bureaus for Janssen and Eli Lilly.
A different result emerged from studies of the new drugs that were publicly funded, or when researchers looked more critically at the industry-funded research, identifying the ways those trials had been designed to make the new drugs look better than the old.
In 2003, Stefan Leucht and colleagues reported that there was no significant difference in TD when the second-generation drugs were compared to low-potency drugs from the first generation at similar dosages. Next, in 2005, results from the NIMH-funded CATIE study were published. This study compared four SGAs to a first-generation drug, perphenazine, and researchers found there was no significant difference in their effectiveness or tolerability.
Moreover, the NIMH reported, “movement side effects (rigidity, stiff movements, tremor, and muscle restlessness) primarily associated with the older medications were not seen more frequently with perphenazine than with the newer drugs.” There also was no difference in the emergence of TD in those treated with the older drug.
A government-funded RCT in the UK, known as the CUtLASS study, produced similar results. There was no difference in outcomes for those treated with FGAs compared to those treated with SGAs (if anything, quality of life was better for the FGA group). The incidence of newly emergent TD was the same in both groups as well.
Next, in 2010, Scott Woods from Yale Medical School reported on the emergence of TD in 352 patients treated at a conventional health center from 2000 to 2003. At baseline, this group of patients did not show signs of TD, and then, during the study, the disorder developed in 6.6% of patients each year (the incidence rate.) Researchers had studied a similar group of patients at the same community center in the 1980s, and the yearly incidence of TD in that study was 5.3%, or slightly less than in this new “atypicals” era. The severity of the newly emergent cases in the two eras was the same too.
Moreover, the prevalence of TD in all patients treated at the community center during the 1980s and during the 2000s was the same: 33%. TD was very much the same problem it had been before the arrival of the SGAs.
“Despite the feeling among some clinicians that TD is much less of a problem now in the atypical era, such a conclusion may unfortunately be premature,” Woods and his collaborators wrote. “In the 1960s and 1970s, there was some well-intentioned resistance and skepticism about conventional antipsychotics being associated with risk of TD, and now, during the atypical era, we are perhaps not immune to some of the same forces. Until we are certain that we have developed antipsychotics that carry minimal risk, we should continue to inform patients prescribed antipsychotics about TD and continue monitoring for it.”
Meanwhile, researchers were also now looking at TD in children and adolescents, and the results were chilling. Investigators at the University of Maryland reported that 10% of 116 pediatric patients they studied developed TD after they had been on SGAs for one to two years. Spanish investigators found that 38% of children and adolescents on antipsychotics for longer than one year showed signs of mild TD.
There is still an ongoing debate regarding the comparative risk of TD with the FGAs and the SGAs. Various authors have concluded that the one-year incidence rate with the SGAs is 3% or a little lower, or about two-thirds the incidence rate with the FGAs. However, the FGAs are still being prescribed to a small percentage of patients diagnosed with schizophrenia, which could lead to a higher overall prevalence rate. Polypharmacy, which is a common practice, increases the risk of TD as well. As a result, the prevalence of TD among long-term users of antipsychotics today may be only slightly diminished from earlier decades.
There is one other factor at work now with TD: the expanded prescribing of antipsychotics exposes a much larger number of people to this risk.
“Given the increased use of SGAs in today’s clinical practice, including frequent off-label use for non-psychotic conditions (major depressive disorder, personality disorder, autism spectrum disorder, sleep disorder, etc.) the occurrence of TD and its burden may continue to rise,” the authors of a 2014 report concluded.
The “New” TD Drugs
At the start of the atypicals era (1997), .8% of the U.S. population was prescribed an antipsychotic in an outpatient setting. A decade later, this percentage had risen to 1.3%. Today, according to a survey of outpatient antipsychotic usage from 2013 to 2018, 1.6% of all adults are using the drugs. That’s 3.8 million adults.
This number doesn’t include usage of antipsychotics in institutional settings (psychiatric hospitals, nursing homes, and so forth). It also doesn’t include the prescribing of antipsychotics on an outpatient basis to children and adolescents. Such prescribing virtually never happened prior to the arrival of risperidone on the market, but has become almost commonplace since then, with prescriptions for an antipsychotic written at one in every 62 outpatient visits by children and adolescents, ages 4 to 18, in 2010.
This would put the total number of people exposed to antipsychotics each year to well north of four million, and even if the yearly incidence of TD is 3% (compared to higher findings of 5% in some studies), this would lead to more than 100,000 new cases of TD each year.
For its part, Neurocrine Biosciences, the maker of the TD drug Ingrezza, estimates that there are 500,000 people in the United States with TD, and that only 20% of this population has been so diagnosed. With Neurocrine and Teva Pharmaceuticals selling their drugs for TD at a yearly cost of $80,000 per patient, this would, in theory, create a $40 billion annual market for these medications.
The new drugs—valbenazine (Ingrezza) and deutetrabenazine (Austedo)—are both VMAT-2 inhibitors, as is a generic that has been on the market since 2008, tetrabenazine. These drugs inhibit the release of monoamines—doapamine, norephinephrine, serotonin, and histamine—from presynaptic neurons, and thus diminish neuronal activity along those neurotransmitter pathways.
Their inhibition of dopamine release means that VMAT-2 inhibitors have an effect similar to antipsychotics on motor movement. VMAT-2 inhibitors reduce dopamine levels in the synaptic cleft; antipsychotics block D2 receptors on the postsynaptic neurons. They are different mechanisms but with a common end: they both put a brake on dopaminergic activity in the brain and thus still motor movements.
A 2018 paper in CNS Spectrums summarized their effects in this way:
As can be seen in this description, valbenazine and deutetrabenazine do not provide any remedy for the pathology—antipsychotic-induced dopamine supersensitivity—thought to be a primary cause of TD. Rather, these drugs interrupt neuronal activity essential to normal brain function, the release of dopamine and other common neurotransmitters into the synaptic cleft.
The makers of these new TD medications urge patients to continue taking their antipsychotic medication. This mix of antipsychotics and VMAT-2 inhibitor leads to a double dose of agents blocking normal dopamine activity in the brain, which act in opposition to dopaminergic neurons that are primed to fire in a dysregulated, hyperactive manner. It’s a bewildering mix of stop and go signals.
This isn’t the end of the disruption in brain function that occurs on this antipsychotic-VMAT drug mix. VMAT-2 inhibitors also diminish the release of serotonin, norephinephrine, and histamine. SGAs also block serotonergic, histaminergic, muscarinic, and adrenergic receptors. Multiple neurotransmitter pathways are now being perturbed in ways that impair their normal functioning.
In clinical trials, the safety and efficacy records of the two TD drugs were much the same. The list of common side effects for both drugs includes fatigue, sedation, somnolence, insomnia, depression, restlessness (akathisia), agitation, and nausea. Less common, yet potentially more serious risks with VMAT-2 inhibitors include severe depression, suicidality, symptomatic hypotension, prolongation of the QTc interval (a risk for cardiac arrest), and neuroleptic malignant syndrome.
The Abnormal Involuntary Movement Scale (AIMs) was used to assess efficacy in the trials. This is a 28-point scale based on physician ratings of the severity of abnormal movements (0 to 4 for seven items).
In a 12-week randomized trial of deutetrabenazine, symptoms in the medicated group dropped 3 points, versus 1.6 points for the placebo patients. While this 1.4-point difference was statistically significant, it didn’t translate into clinically noticeable differences as measured by the Clinical Global Impression of Change and Patient Global Impression of Change instruments.
In a six-week trial of valbenazine (KINECT-3), symptoms in the treated group dropped 2.9 points, while the placebo group worsened slightly.
The valbenazine patients were then entered into a 46-week extension study. Their symptoms improved slightly during the first 42 weeks, and then, once valbenazine was withdrawn, their symptoms quickly worsened. Their AIMS scores climbed back toward baseline figures, evidence that the treatment had not done anything to ameliorate the underlying TD pathology. The drugs—by reducing dopaminergic activity and thus quieting movement—had simply reduced the visible symptoms of the disorder.
The period of worsening following withdrawal of valbenazine, the researchers concluded, was evidence of “the need for continuation treatment.”
The Harm Rolls On
In their promotional materials, Neurocrine Biosciences and Teva Pharmaceuticals tell a story of medical progress. Antipsychotics are presented as essential medications that help people diagnosed with schizophrenia or some other serious disorder live normal lives, surrounded by family and flourishing in the workplace. TD is presented as an adverse side effect of antipsychotics and other psychotropic drugs that leads to tics, spasms, and other abnormal movements—there is no mention of other impairments. Thanks to the new TD drugs, there is now an effective remedy for the motor impairments, the ads featuring “patients” who smile brightly and move about their worlds with a physical ease.
The articles on TD published in medical journals, while sober and academic in tone, ultimately tell a similar story of medical progress and benefit from psychiatric drugs. There is little or no mention of antipsychotic-induced “brain damage.” Most of the articles focus on the abnormal motor movements as the primary impairment associated with TD; there is little mention of how TD is associated with a worsening of psychotic symptoms and global impairments. Their articles tell of how valbenazine and deutetrabenazine have been found to be “safe and effective.” Few readers of this literature would know that VMAT-2 drugs work by blocking the normal release of dopamine and other essential neurotransmitters into the synaptic cleft.
Together, the promotion of these drugs to the public and the articles in the medical journals protect current prescribing practices. The prescribing of antipsychotics for off-label purposes can continue. So too the prescribing of antipsychotics to children and adolescents. The risk of developing TD is described as low; most cases of TD with the SGAs are described as mild; there are now drugs that can quiet TD symptoms.
A recently published study tells of how the TD epidemic can be expected to roll on. The number of American youth treated with psychotropic polypharmacy nearly tripled from 1999 to 2015, with 293,492 put on such a regimen during the years 2011 to 2015. The percentage prescribed an antipsychotic as part of their drug cocktail rose from 38% to 75%. There were even a significant number of children 0 to 4 years old put on such cocktails.
Here are the type of questions that go unasked in the medical literature: How many of these children and adolescents will develop TD? How many will develop severe cases? How will their lives be impaired as a result?
Today, psychiatry looks back at its earlier response to TD as mistaken, as a past that should serve as a lesson for the future. But starting with the arrival of the SGAs, history began to repeat itself and the TD toll has rolled on and on.
MIA Reports are supported, in part, by a grant from the Open Society Foundations