Brains are complicated. One of the ways in which they're complicated is the systematic way in which they work to maintain balance.
I’m going to use this concept to explain:
Tardive Dyskinesia
Tardive dyskinesia (TD) is a neurological disorder characterized by involuntary, repetitive, and uncontrollable movements of the face, limbs, and trunk.
In medicine, we call the balance that biological systems work towards homeostasis. So they are trying to get back to the middle. Whatever that middle is.
If you put too much water in, you'll pee out more water. If you put so much salt in, your pee will have more salt. So if you're out of breath, you will, to compensate, breathe more.
Biology is trying to keep things in balance.
One of the consequences of this? That Tardive Dyskinesia side effect I mentioned up top.
Dopamine-blocking medications, like antipsychotics1 and antiemetics2, lead to cellular attempts to "rebalance." This "pushback" from inside our cells can lead to side effects like Tardive Dyskinesia.
What is Tardive Dyskinesia?
That is a built-in confusing word, and it means late developing (“Tardive,” the same root as the word “tardy”) or movement disorder (“Dys”> disorder, “kinesia”> movement). Here is a video of a movement disorders neurologist who will attempt to explain it.
This ancient video from the 70s, which was made to train people like me (physicians) to identify this condition for research using the AIMS scale, is here:
Those movements? The movements of her face and tongue? Those aren’t voluntary. They happen if you want to do them OR NOT. So it’s a movement disorder.
That movement disorder is a side effect of dopamine-blocking medicine. The side effect does not show up immediately. It takes years, in some cases, to present itself. And when it does, you might be stuck with it. Scientology, a religion for the purposes of legal filings with the IRS, has a whole room in its antipsychiatry museum—"Psychiatry: An Industry of Death” dedicated to the topic of Tardive Dyskinesia.
That Time I Agreed with Scientology
Unfortunately— for this particular column only—they decided to lean in on their anti-ECT and anti-drugging campaign, led by the front organization, the "Citizen's Commission on Human Rights”…and not spend more time on complex adverse events that really happen. As an aside:
Scientology? The one time I want to agree with a thing you said, and you decide to rug me and not even have it on your fake website?
Ok, I will get over it. I promise it would have been overwrought.
Tardive dyskinesia is a late-developing movement disorder. It is a side effect of many medications and can happen many years after the fact.
The Numbers on TD
First-generation antipsychotics had higher rates of tardive dyskinesia, on the order of 6.5% risk per year. Still, it's cumulative, so in long-term use, about 20% of people will develop the side effect.
More modern antipsychotic agents have less risk of TD. Notably, clozapine has almost none. Many of the drugs we used to see advertised as an augmentation strategy for depression: Abilify, Rexulti?
These also have a nontrivial risk of permanent movement disorder. Nobody needs a permanent movement disorder. It can start many years after you start the drug. Some people have illnesses that make that risk worthwhile, but in depression, as a first-line augmentation strategy is hard to justify it:
The annualized TD incidence across FGA arms was 6.5% (95% CI: 5.3-7.8%) vs. 2.6% (95% CI: 2.0-3.1%) across SGA arms. TD risk and annualized rates were lower with SGAs vs. FGAs (RR=0.47, 95% CI: 0.39-0.57, p<0.0001, k=28; RaR=0.35, 95% CI: 0.28-0.45, p<0.0001, number-needed-to-treat, NNT=20).
The only gripe I have with the above science rating is the fact that the number calculated is a number needed to treat, and it really should be a number needed to “harm less.”
The prevalence in the United States of antipsychotic treatment is about 1.4% of the population.
Thus, in the US, 4.62 million people get antipsychotics annually.
That is 120,000+ people every year getting a potentially permanent movement disorder, TD.
If you multiply that by the number of years somebody is on drugs, about 20% of people with long-term exposure to these drugs will develop TD.
We have other options for depression. But, of note, antipsychotic drugs also cause massive weight gain and additional adverse severe effects:
Does it make sense to continue prescribing augmentation medication with severe adverse effects that, practically speaking, don't work that well! For example, the effect size for antipsychotic augmentation in treatment-resistant depression is roughly 0.2. For comparison, if Abilify were added to your height, it would be the equivalent of a magical elixir for people who are too short, making you 0.6 inches taller.
If anybody would accept a permanent movement disorder, as shown in the video above, to be just a little bit less depressed, that's a choice people are free to make. But if they don't know that's their choice, it's different.
I recently won a grant from the National Institute of Mental Health along with colleagues at a company called iRxReminder, at which I work. I'm proud to say the work was selected to be part of the APA Innovation Zone pitch contest at the annual meeting later this month (May 22!)
I am less proud to say I'm part of a profession that got called out by Scientology. And we didn’t take it seriously. We keep cranking out new “augmentation strategies” with this potentially horrible adverse effect. We ignore other potentially horrible adverse effects like metabolic syndrome. This is the “news” we see
It is time we stop trading our patients’ health—so casually—for the grim satisfaction of knowing we did just a little something.
It's time we focus on identifying tardive dyskinesia. It's time we reduced prescribing of augmentation agents for people who don't absolutely need to be on them. It is time we focus on wildly effective and vastly safer interventions.
It is time to get honest with ourselves. Is the informed consent process we provide as meaningful as it should be?
May 1-7 is tardive dyskinesia awareness week.
I am regularly an advocate of treatments that work. I am a cheerleader for the effective. But I'm a realist, and I don't want patients harmed.
If you're a physician, familiarize yourself with TD. Screen your patients. If you're a patient, familiarize yourself with the risks and benefits, and discuss it with your physician.
And everybody should learn other options are available.
Transcranial magnetic stimulation, ketamine, Esketamine, psychotherapy, and see a whole generation of psychedelic medications, electroconvulsive therapy, vagal nerve stimulation, deep brain stimulation, the gamma core device, the ketogenic diet, and the list goes on.
Hope is out there. Let’s not ignore the risks on the way.
—Owen Scott Muir, M.D.
The risk in 1st generation medicines, from chlorpromazine onward, was higher for TD and other movement system adverse effects. These include:
Chlorpromazine (Thorazine)
Haloperidol (Haldol)
Fluphenazine (Prolixin)
Thioridazine (Mellaril)
Trifluoperazine (Stelazine)
Perphenazine (Trilafon)
Thiothixene (Navane)
Loxapine (Loxitane)
Molindone (Moban)
Pimozide (Orap)
Clozapine, the first “Second Generation” or “Atypical” Antipsychotic medication, had no meaningful risk of TD, but all of the subsequent drugs do, including:
Aripiprazole (Abilify)
Asenapine (Saphris)
Brexpiprazole (Rexulti)
Cariprazine (Vraylar)
Iloperidone (Fanapt)
Lurasidone (Latuda)
Olanzapine (Zyprexa)
Paliperidone (Invega)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Ziprasidone (Geodon)
Mostly I'm talking about raglan here, a.k.a. Metoclopramide.
Nicely done.