Why We Have Millions of Movement Disorders Caused By Our Medicines

The role of antipsychotic medicines in tardive dyskinesia

Welcome to the 886th installment of The Frontier Psychatrists. It is a daily-enough health-themed newsletter written by Owen Scott Muir, M.D., DFAACAP. That last string of letters is because I’m a “distinguished fellow” in child psychiatry. This means I have spent years talking to parents about their fear of medicines. However, those parent’s fears were understandable—what is this drug going to do over the long term to my child? As a parent, the worrying makes sense to me. There is, of course, a balance because, usually, people don’t see a sub-specialist doctor if “nothing is wrong.” I had the privilege of being one such sub-specialist. When I cautioned against medicines, in my lengthy appointments—some, in training, lasting three or more hours over several sessions—families would usually listen. I could offer “talk therapy as a first-line treatment,” for example. The evidence is great! Not every kid has parents who worry about them. Some are in foster care and have no family of their own. Many of the most vulnerable children have horrific trauma and receive care that is trying, desperately, to manage their “maladaptive behaviors” that, in the context of the kid’s life, seem pretty understandable.

Hanging out with great shrinks and innovators, like Raghu Appasani, Carlene MacMillan, and Larissa May ...

Often, doctors reach for medicines to treat the problems they are faced with. This approach is just as true for the doctors of adults who are suffering. Since most patients who are sick, particularly those with psychiatric illnesses, are impaired in terms of their day-to-day functioning, their ability to compare shops for which doctors is limited. Most people see the doctor they know, usually a primary care doctor. Those doctors and NPs prescribe the vast majority of psychiatric medicines.

Even as far back as 1998, 10s of millions of primary care visits resulted in psychiatric medicine prescribing:

The number of visits during which a psychotropic medication was prescribed increased from 32.73 million to 45.64 million; the proportion of such visits, as a proportion of all visits, increased from 5.1% to 6.5% (P≤.01).¹

Lest we think this is just a phenomenon in the US, it’s not. The UK saw tremendous rates of increase in the relatively conservative NHS as well, as this sample from the late 90s and early 2000s (when these “atypical antipsychotics” hit the scene in the UK highlights:

The total volume of prescribing of atypical antipsychotic drugs in primary care increased nearly six-fold from 1996/97 to 2000/01 in the West Midlands region. Olanzapine was the most commonly prescribed drug during 1999/2000, accounting for 45% of defined daily doses, while risperidone accounted for 38% of the total. In 1996/97.

Why am I highlighting data from the 1990s and 2000s? Because I’m gearing up to talk about late-developing movement disorders. Clever, I know. These numbers have only increased, and (at least in the UK) the prescribing of antipsychotic medicines is driven by poor social circumstances:

The strongest positive relation to increased prescribing of antipsychotics came from higher social disadvantage, higher population density (urban), and comorbidities e.g. chronic obstructive pulmonary disease (COPD).²

If you are poor or sick, you are more likely to be prescribed an antipsychotic medicine. We have seen similar data, with fatal outcomes, in youth on Medicaid in the US, who, when prescribed these antipsychotic medicines for non-psychotic disorders, such as depression augmentation, die at rates that exceed fentanyl overdose:

For [higher dose medicine exposed individuals], young adults aged 18 to 24 years had significantly increased risk of death, with 127.5 additional deaths per 100,000 person-years.³

Those same primary care doctors get better at managing depression when they see more of it:

Among 369 primary care physicians, greater volume of depression encounters per year… was associated with greater rates of achieving stability….AOR, 2.15 [95 % CI, 1.61 – 2.89];⁴

This is good news, but the tools they have to manage the overwhelming burden of psychiatric illnesses they are seeing matter, too. The fact of the matter is there are vastly more primary care doctors than there will ever be psychiatrists. This is even more true for children. Those primary care doctors are going to see patients suffering, and they're gonna try to help. They will try to help with tools at their disposal, which are overwhelmingly not psychotherapy. Psychotherapy is relatively hard to access and takes a lot of work. Not everyone who's a therapist is good at their job. And not even those great at their job aren't necessarily great for the patient who ends up in their office. Psychotherapy is an important, even crucial tool, but it's just not the easiest tool to reach for if your primary care doctor.

Primary care doctors are likely to reach for biological interventions. Historically, those biological interventions have been medicines. Those medicines have usually been pills. Those pills have risks. The problem with humans and risk? We are good at understanding risks that are immediate—

Patient: “Doc, I had this awful side effect!”

Doctor: “Great, thanks for telling me; we will immediately stop it!”

The last thing doctors want to do is harm their patients. We are worse at mitigating risks that happened decades later, and in the case of both metabolic syndrome and tardive dyskinesia, those risks take a long time to come. Incidence is measured in “disease per year:”

The incidence of neuroleptic-induced TD is lower among younger individuals (3–5% per year) and higher in middle-aged and elderly patients, particularly women, reaching incidence rates as high as 30% after 1 year of cumulative exposure to neuroleptics….with the total annual incidence rate ranging from 0.8% in patients younger than 50 years to 5.3% in those older than 50 years.⁵

Patients come to a doctor suffering today and want something to ease their suffering promptly. They don't want to fret about what may happen 20 years from now.

I remember very clearly seeing my doctor when I first started taking antipsychotic medications. You could've told me they were going to kill me in one year, and I would've still said yes. Having severe depression means you want the pain to be over, and you're willing to take a lot of risks to make that happen. People who are suicidal are taking the risk that they might kill themselves every day that passes without getting well. They're desperate. Thus, they're likely to say yes, regardless of the risk, a significant portion of the time. People say yes to surgery all the time when they have serious problems. It's not because surgery is perfectly safe; it's because surgery is better than not having surgery when you're suffering.

We have a situation where the vast majority of medications for psychiatric distress are being prescribed by doctors who are not trained in that sub-specialty. These days, many of the people prescribing those medicines are not physicians, they're often nurse practitioners, or physicians assistants. There are just not enough physicians to go around. By definition, general doctors are not specialists, and my sub-specialty training as a psychiatrist took four years. Then, it's another two years for child psychiatry after that. That's six years of training, and my colleagues doing the vast majority of psychiatric care have had none of that training. Scientists in industry created antidepressants, and then more antidepressants, and then drugs to augment those antidepressants when they didn't work well enough—which was often.

Thus, to do the long-term population rates of movement disorders, a solid, I'm gonna do some education, for everybody, right here, and right now, about the long-term risk risks of movement disorders that can arise from the prescribing of antipsychotic medications.

What is an Antipsychotic Medication?

I'm going to start with just the names because that's going to make your life easier. I'm leaving a link to my articles on some of them, but it's worth briefly mentioning that I have a whole book on these medicines called Inessential Pharmacology, which is on Kindle. Right now, it's zero dollars if you have Kindle Unlimited.

First-Generation (Typical) Antipsychotics

• Chlorpromazine – Thorazine

• Haloperidol – Haldol

• Fluphenazine – Prolixin, Modecate (Depot)

• Perphenazine – Trilafon

• Thioridazine – Mellaril

• Trifluoperazine – Stelazine

• Loxapine – Loxitane

• Pimozide – Orap

• Thiothixene – Navane

• Molindone – Moban

Second-Generation (Atypical) Antipsychotics

• Clozapine – Clozaril, Fazaclo, Versacloz

• Risperidone – Risperdal

• Olanzapine – Zyprexa

• Quetiapine – Seroquel

• Ziprasidone – Geodon

• Aripiprazole – Abilify

• Paliperidone – Invega

• Asenapine – Saphris, Secuado (patch)

• Lurasidone – Latuda

• Iloperidone – Fanapt

• Brexpiprazole – Rexulti

• Cariprazine – Vraylar

• Lumateperone – Caplyta

What Are These Medicines Prescribed For?

These medicines are generally prescribed for schizophrenia and bipolar disorder and, commonly, for augmentation of insufficient relief from an oral antidepressant. Sometimes, in kids, off-label, they are prescribed for behavior disorders. Some of these medicines have an FDA label for agitation in autism. They're often prescribed in the elderly, even though that's overwhelming when a bad idea, for agitation associated with dementia.

What is Tardive Dyskinesia (TD)?

I have already written a couple of articles about this, which I'm going to link here for your convenience.

The Forgotten Horrors of Tardive Dyskinesia

That Time I Did Not Disagree with Scientology: Tardive Dyskinesia Sucks

This Physician Realizes He Might Have The Movement Disorder He's Been Researching.

We will start with a video demonstrating what the movements look like in “classic” tardive dyskinesia:

The movements are involuntary, stereotypic, usually around the mouth, and they involve processing of the lips, chewing motions, grimacing, moving your tire around inside your mouth, and the like.

These movements can appear elsewhere in the body: in the fingers, trunk, toes, almost anywhere.

When you start digging into tardive dyskinesia as a phenomenon, you find out it's a lot more than that. It's not just these involuntary movements; a whole syndrome of movement disorders develops later. The uncomfortable sensation of an inability to sit still or remain motionless is called akathisia, and this is the side effect of antipsychotic medications (like Abilify, discussed here) when patients start taking them. It can also have onset later, as one of the tardive syndrome phenomena:

Involuntary movement and restlessness are uncomfortable. For those who have restless leg syndrome, which is a movement disorder in the evening that “just happens”—it's not necessarily the result of drug exposure—you might have a good sense of how uncomfortable this can be. There can be some uncomfortable sensory experiences as part of this phenomenon, where you feel like you have to move and move, which sucks:

The patients often have repetitive and stereotypical movements (rocking in a chair, crossing/uncrossing of legs when sitting, pacing on a spot, shifting weight from one foot to another when standing, face or scalp touching or scratching) in an attempt to relieve feelings of restlessness. The movements sometimes resemble limb and trunk stereotypies of TD without akathisia, but tardive stereotypy lacks the sensory component of akathisia.⁶

As if all of that wasn't awkward enough, for the person experiencing it, vocalizations that are also involuntary can be part of this phenomenon:

Repetitive vocalizations such as moaning and grunting are also common features of akathisia⁷

Not all try to syndromes are about too much motion, some are about the inability to move appropriately, such as tardive dystonia. This video is a little hard to watch, but it's a good demonstration of what can happen and how quickly. The person in this video is 42 years old, and he developed the symptoms over two weeks of ziprasidone 60 mg:

There are more manifestations as well, but suffice to say, movement disorders you can get from a drug or a real thing. There have been rare reports of movement disorders related to SSRI and SSRI medications as well, for reasons unclear. In many cases, the brain circuits that control feelings and the brain circuits that control movements are the same—or closely related—circuits.

It's important that we understand that this risk exists, and so I'm sharing these videos with gratitude to the patients who agreed to allow them to be filmed in the first place so that both doctors and patients can have a better sense of what could happen. Only with this knowledge can we understand what we see in our office and maybe across our kitchen tables.

How Can We Screen for TD?

I want to add hope! I've been working for several years, as I wrote yesterday, on an AI algorithm that will help screen for these movement disorders with vastly greater simplicity. It's a screening tool that exists now. If you're a health professional, you can download it, and use it with your patients. It was made along with the teams at iRxReminder and Videra Health. These are your tax dollars that are hard at work. NIH funding helped support this research. It’s available here:

TDscreen.ai

This tool, which will be published in the scientific literature soon, is probably my most important contribution to science yet. I'm deeply grateful to both my colleagues who helped make it possible and the patients who consented to the clinical trials that allowed for the development of this rapid, 90-second screening tool for TD.

There is more good news, which is that some individuals get relief after stopping the drug, even if they don't do anything:

In one study, 33% of the patients experienced remission of their TD 2 years after discontinuation of the offending drug⁸

And now we have not one but two medicines that can help treat TD (as well as being useful for the movement disorder component of Huntington's Chorea, which is an eventually fatal genetic condition, but at least now has some treatments to relieve the suffering in the process). They are called tetrabenazine and valbenazine, and I'm happy that they exist for the greater than 2 million people who could benefit from them. Unfortunately, less than 50,000 are prescribed treatment for TD at present.

In Summary

Movement disorders, collectively called tardive syndromes, can be caused by long-term exposure to dopamine-blocking medications. This includes medications. They are primarily antipsychotics— but even anti-emetics, like Reglan, which block dopamine, can cause it.

Doctors, particularly primary care doctors, should think carefully about prescribing antipsychotics when people don't have a psychotic illness. We should all consider medicines without these often irreversible long-term risks and spend adequate time in the consent process to help people understand that bad things could happen later. I'm personally a strong advocate for safer and more effective non-medication treatment for depression. This includes a vastly broader use of transcranial magnetic stimulation and other neuromodulatory approaches, of which more are coming to market soon.

Right now, before insurance companies pay for TMS, doctors are forced to prescribe oral medications that are likely to not be helpful in treatment-resistant depression. This includes antipsychotic medication augmentation. I don't believe we should be forced to keep doing that. I think it's contrary to good clinical judgment.

Brain simulation approaches, like TMS, are not risk-free. The risks are limited compared to oral antipsychotics, and perhaps those risks should be more carefully considered in insurance prior authorization algorithms.

Nobody who doesn't need an antipsychotic medication should take one if there is a better and safer option that can be used first.

To be clear, this includes psychotherapy. For a long time, this was a first-line treatment because it works. It's not gonna work for everybody, but before we pull a drug out of our pocket, even as a primary care doctor, we can meet with our patients a little bit more regularly, we can offer them support, and we can see if they get better, especially in a first episode of depression, without having to resort to medications that are likely going to be hard to discontinue later.

Thanks for reading. Please consider sharing this with the world—that's how we spread the word.

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