The birth of modern psychiatry has probably been memorialized more than a few times. Among the events that qualify is the first use of an antipsychotic drug on a psychiatric patient. I’d love to say it ushered in a golden age of psychiatry and psychotropic drugs, but no two descriptions of the patient and the course of therapy are alike, so for all I know it ushered in a unicorn doing the soft-shoe and whistling dixie through its twisted horn. Like the disparate stories in Akira Kurosawa’s Rashomon, the Chlorpromazine stories all have the same dramatic crux. In Rashomon, a man dies and everyone lies. In the Chlorpromazine story, a man recovers from severe mental illness and everyone makes up details of the story that suit their purpose, or lies, as it’s called in common parlance.
A Scottish gentleman informs us (excerpt above, top left) in his Guide to Extra-pyramidal Side-effects of Antipsychotic Drugs that the drug worked very well for a young man in a manic phase of bipolar disorder, but his doctors only grudgingly praised the drug. They’d changed the history of medicine, but apparently didn’t realize it. They made it clear that they did not regard Chlorpromazine as a new therapy for mania. The doctors come off as a little dim, unless the trial didn’t go as smoothly as the bow-tie-sporter alleged.
How about this?
The French doctors portrayed by the Scotsman as humble grumblers were in stony-faced damage-control mode for the duration of Dr. Ban’s version (above, bottom left). They dealt with perivenous infiltration, in which the drug ends up inside the patient but outside the vein, and venous irritation, which sounds trivial but can be serious. For some reason, perhaps the adverse events, the “severely agitated psychotic (manic)” patient was taken off Chlorpromazine and put on barbies and 240 volts of house current more than once during a three-week ordeal. It’s hard to credit Chlorpromazine with miraculous powers when it left the patient in such bad shape that Sodium Pentothal thiopental and electroconvulsive therapy were needed to keep him from climbing the walls. Dr. Ban didn’t guess at the doctors’ states of mind when they realized the patient had not only survived but also appeared to have recovered. They were probably fighting over the leftover pentothal.
In an esteemed American physician’s version (above, top right), the French doctors were ecstatic about the total eradication of symptoms in a violent “psychotic” and the “psychotic” person’s return to full functioning, which was accomplished by one new drug in just 21 days. They were flabbergasted. Part of the American’s physician’s twisted telling of the birth of the neuroleptic is reproduced above. Here’s the full-length disco version:
Working in a French military hospital in Tunisia—not exactly the epicenter of the medical world—Laborit experimented with a group of compounds called antihistamines. Today these drugs are commonly used to treat allergies and cold symptoms, but at the time scientists had just learned that antihistamines affect the autonomic system. Laborit noticed that when he gave a strong dose of one particular antihistamine, known as chlorpromazine, to his patients before surgery, their attitudes changed markedly: They became indifferent toward their imminent operation, an apathy that continued after the surgery was completed. Laborit wrote about this discovery, “I asked an army psychiatrist to watch me operate on some of my tense, anxious Mediterranean-type patients. Afterwards, he agreed with me that the patients were remarkably calm and relaxed.”
Impressed by the notable psychological effects of the drug, Laborit wondered if chlorpromazine might be used to manage psychiatric disturbances. In 1951, to test his idea, Laborit administered a dose of chlorpromazine intravenously to a healthy volunteer at a French mental hospital. The subject was a psychiatrist who agreed to serve as a human guinea pig in order to provide feedback about the drug’s mental effects. At first the psychiatrist reported “no effects worthy of mention, save a certain sensation of indifference.” But then, as he got up to go to the toilet, he fainted—the result of a drop in blood pressure, a side effect. After that, the director of the hospital’s psychiatric service banned further experimentation with chlorpromazine.
Undeterred [as if patient safety had ever deterred a true neuroscientist!], Laborit attempted to persuade a group of psychiatrists at another hospital to test the drug on their psychotic patients. They were not particularly enthusiastic about his proposal, since the prevailing belief was that the disruptive symptoms of schizophrenia could only be reduced by strong sedatives, and chlorpromazine was not a sedative. But Laborit persevered and finally convinced a skeptical psychiatrist to try his drug on a schizophrenic patient. [Please note that all other reports describe the patient as manic, not schizophrenic.]
On January 19, 1952, chlorpromazine was administered to Jacques L., a highly agitated twenty-four-year-old psychotic prone to violence. Following the drug’s intravenous administration, Jacques rapidly settled down and became calm. After three steady weeks on chlorpromazine, Jacques carried out all his normal activities. [This omits mention of the two other drugs and electro-convulsive (“shock”) treatments described by Dr. Ban and others.] He even played an entire game of bridge. He responded so well, in fact, that his flabbergasted physicians discharged him from the hospital. It was nothing short of miraculous: A drug had seemingly wiped away the psychotic symptoms of an unmanageable patient and enabled him to leave the hospital and return to the community. [“Seemingly” is appropriate. In reality, that isn’t what happened. Even if it had, there was no control group and neither patient nor researcher was blinded as to treatment. A demonstration of this kind isn’t evidence of anything.]
Chlorpromazine’s use as an antipsychotic – the first antipsychotic – swept through the mental hospitals of Europe with the force of a tidal wave. In the psychoanalysis-obsessed United States, in contrast, reaction to the miracle med was muted. The Smith, Kline and French pharmaceutical company (a forerunner to GlaxoSmithKline) licensed chlorpromazine for distribution in the U.S., where it was endowed with the American trade name Thorazine (in Europe it was called Largactil), and launched a major marketing campaign to convince medical schools and psychiatry departments to test it on their patients. But American shrinks derided Laborit’s drug as “psychiatric aspirin,” waving it off as just another sedative, like chloral or the barbiturates —a distracting siren […]
Dr. Lieberman ascribed untarnished success to the drug as a solo agent, but more detailed reporting reveals that to be false. Dr. Ban’s version hinted at what it really took to get the patient back in street clothes and pointed at the exit. It doesn’t sound like a course of treatment that would flabbergast, unless the doctors were especially prone to flabbergasty, or especially relieved that the patient didn’t stroke out, seize up, or stop breathing on them.
Wait a minute. THIS.
On January 19, 1952, [Chlorpromazine] was administered for the first time, as an adjunct to an opiate (petidine [demerol]), a barbiturate (pentotal) and electroconvulsive therapy, to Jacques Lh., an extremely agitated manic patient aged 24, who rapidly began to calm down, maintaining a state of calm for several hours. By February 7, Jacques had calmed down sufﬁciently to be able to play bridge and carry out normal activities, though he maintained certain hypomanic attitudes. Finally, after a 3-week treatment, with a total quantity of 855 mg of [Chlorpromazine] administered, the patient was discharged from hospital. Colonel Jean Paraire presented these data on February 25, at a meeting of the Société Médico-Psychologique in Paris, and they were published in March of that same year of 1952 . In prophetic tone, he said “We have quite probably introduced a series of products that will enrich psychiatric therapy.”
And that is what Francisco López-Muñoz and his co-authors had to say about it in the Annals of Clinical Psychiatry, the official Journal of the American Academy of Clinical Psychiatrists, in 2005 (also above, bottom right).
The differences among the four versions aren’t just differences of interpretation. They differ on matters fact. At least one is a flat-out fabrication. Of the four accounts, three wouldn’t have reached a wide readership, but one is for sale on Amazon.com in hardcover, paperback, audiobook, and Kindle®. It’s the flat-out fabricated one. I can’t find the 1952 original study, so I am going to go out on a limb and say the fourth story, that of Dr. López-Muñoz et al., which appeared in a peer-reviewed journal, is the closest to a description of what happened, and that the mishaps in Dr. Ban’s article, also peer-reviewed, probably happened. The key is in the details. The full story is very likely be a merger of the two, with drug details coming from Dr. López-Muñoz, et al., and adverse events supplied by Dr. Ban.
Why would an august physician omit troubling information in his story of first use of a certain class of drug on a human patient, and embellish what was left? Well, the august physician is a fan of antipsychotic drugs and a vocal opponent of those who oppose their wide use. It’s not that he thinks they’re such excellent drugs. He knows that “antipsychotics” don’t cure anything and do have life-wrecking effects that are not necessarily dose- or duration-dependent, but he believes it’s in the best interests of the non-medical public to believe in the drugs. He just thinks it’s terrible when people disobey their doctors. There is so much evidence in favor of non-drug treatments for people who experience disturbing hallucinations and are deemed “out of touch with reality” that you really have to wonder why Jeffrey Lieberman is still flogging the old neurotoxic chemicals.
It’s an abuse of power. Yes, power. Being to go-to guy for mainstream media’s facile coverage of psychiatric drugs is a power. It’s possible that he continues to advocate for the drugs because to stop now and admit their harms would open him to criticism and worse, for all the years he pushed them on the public. Keeping the true story of antipsychotic drugs’ rocky introduction out of his popular press book, which was marketed as a brave exploration of psychiatry’s grim history is not just an omission, it’s deception. In truth, psychiatry was more grim and misguided than he lets on, and it’s still grim and misguided in the present. In fact, Chlorpromazine (Thorazine, as it was branded in the U.S.) did not live up to any hype supplied by drug companies and enthusiastic psychiatrists. “The hope that was placed in chlorpromazine’s ability to treat schizophrenia was dimmed by evidence of serious side effects.” All the so-called antipsychotic drugs that followed plague patients with undesired effects.
These are excerpted from patient reviews of Haloperidol, an antipsychotic drug in the tradition established by Chlorpromazine. It’s commonly used in the U.S., a mainstay of the American emergency room, psychiatric “hospital,” Veterans Administration and nursing home.
A 31 year old nurse was given 30 milligrams, once, to help with nausea and vomiting:
I can’t begin to describe it. Tremendous restlessness and anxiety, paranoia, feelings of impending doom/death. I “knew” I was going to die. […] I didn’t sleep for 36 hrs and I lost a day. By that I mean one second it was Friday, and the next it was Sunday. Then my tongue swelled up, which was also terrifying. It started to become difficult to get air. I went to the ER and got a shot of Benadryl which was miraculous. The relief that came over me was amazing. Never before or since have I had such a paralyzing fear.
An 89 year old woman was given Haloperidol twice in one evening, to “calm her down” which meant keeping her from getting out of bed. She became unresponsive died three days later. You have to ask: was staying in bed medically necessary?
She [was in the hospital with] congestive heart failure and high blood pressure. [After being given haloperidol] [s]he was unresponsive, unable to eat, talk, sit up, swollen tongue. When we asked what they did to her, we were told something was given to her to calm her down. Mother passed away 3 days later. All she wanted to do was get out of bed.
The psychiatrist who gave her this never knew Mom […] We asked him what he gave her, said he would be right back, we never saw him again, never.
It was given to a physically disabled 25 year old man in an emergency room to “calm” him so he would accept an IV line.
My son is disabled and in a wheelchair. Last night over 24 hours ago he was given a Haldol/Ativan injection to “calm” him. They wanted to insert an IV and he was waving his arms around in fear. […] [He] has been experiencing horrible side effects – drooling, swelling of face and tongue, cannot eat drink or speak clearly. He is lethargic, cannot urinate, has uncontrolled body movements. Pulse is elevated. This is a nightmare.
In his mass market book, Dr. Lieberman applauds a new, thoughtful sort of neuroscientist/clinician who thoughtfully balances psychotherapy and psychotropic drugs, even as Lieberman exemplifies the opposite: a clinician who not-so-thoughtfully misreports the first, problematic Chlorpromazine trial as miraculous, rather than as the touch-and-go near-fiasco it was. Although the misreporting won’t distort the scientific record, it is not unimportant. In a popular-press paperback it reaches a large audience, some of whom might be prescribed a drug like Chlorpromazine some day. Most of them shouldn’t take it. If they do, they should be able to recognize the drug’s adverse effects for what they are, instead of believing they are getting worse despite “treatment.” Dr. Lieberman’s description of the first antipsychotic as a “miracle med” makes that hard to do.
Why would a professor with the guts to wear a Tartan bow-tie shy away from describing the difficulties of the first Chlorpromazine patient in his book on side effects of antipsychotics? Why would an esteemed physician/professor/self-proclaimed scientist miss the chance to educate the public about the complications that arose the first time an antipsychotic drug was used on patient? Why, for that matter, do Dr. Ban and Dr. López-Muñoz have different explanations for the adjunctive therapies that were a significant part the first Chlorpromazine trial? I guess they might all have been misinformed. Who knows? It might be misinformation all the way down.
In Rashomon, the truth finally came out. In medicine, the truth about Chlorpromazine has been out for a long time. It’s unfortunate that lies about it go uncriticized and unpunished.
The birth of chemical interventions for difficult behaviors was not an easy one, and the baby didn’t turn out exactly as its fathers hoped. It was the kind of baby that has to be decorated with a bow so people will know how to greet her.
“What a handsome child you have. What’s hi-, um, what do you call your baby?”
“Patsy,” mother says, smiling broadly with her gaze fixed on the stranger’s eyes. Big sister gives a yank on Patsy’s headband, hoping to bring a lavender rosette into view. Patsy roars, enraged because she doesn’t like her headband fussed with.
“Pat–Oh! Oh, yes, Patsy. Isn’t she pretty?”
and that Chlorpromazine? It’s a wonder drug. No, wait. It’s a miracle med.
I’d like to credit the New York-based student of psychology who posted two of the Chlorpromazine stories on his blog, and I will, soon. (I don’t remember his name.) His purpose in posting was different than mine, but he too noted the incompatible fact patterns in the versions he quoted, one of which was the excerpt from Dr. Lieberman’s Shrinks.
*Dr. Thomas Ban was born in 1930. In his early career, insulin shock was a common treatment for schizophrenia. He was a long-term member of the Collegium Internationale Neuro-Psychopharmacologicum (CINP), founded in 1957 to encourage and promote international scientific study, teaching and application of neuropsychopharmacology. As of this writing, he is 86 years old, retired, and living in Arizona.