The Drugs That Changed Our Minds

by Lauren Slater

  Rhône-Poulenc sent 200 grams of ‘the pure substance’ and SK&F set out to do its own testing. The atmosphere in the United States was very different from the atmosphere in Europe, vis-à-vis the treatment of mental patients. The French had always prized somatic treatments, whereas, in 1952, the United States was in the grip of psychoanalysis. Many psychiatric illnesses, even some of the most severe, were seen as stemming from repressed sexual desires or repressed rages turning and twisting the mind. SK&F knew this and thus decided to mine this new compound for its anti-emetic properties, having more solid clinical data supporting chlorpromazine’s anti-emetic function and believing, probably correctly, that it would be far easier anyway to get a drug that controlled nausea and vomiting approved than it would be to get an antipsychotic approved, especially as none had ever existed before. They retained every intention, however, of pushing chlorpromazine’s off-label uses in as many markets as possible, psychiatry prime among them. Their advertisements for chlorpromazine, as Thorazine, show that the company was soon hawking the ‘anti-emetic’ for every kind of ill imaginable, claiming it as a veritable panacea capable of treating everything from alcoholism to the pain associated with severe burns to the distortions and deliriums of dementia.

  Although officials at SK&F worked hard to get their product into the hands of North American psychiatrists, the introduction of the drug was tainted almost from the start by resistance and controversy, ‘especially from people who had emotional commitments to the psychological type treatments’, said Henry Brill, who ran Pilgrim State Hospital in New York, then the world’s largest mental hospital, home to almost fourteen thousand residents at its peak, in 1954. ‘These were the practitioners who defended psychoanalysis and psychotherapies and psychodynamic procedures of one type or another – the talking type of treatment. They were very unhappy and weren’t able to believe what was taking place.’

  The resistance to this new therapy reveals the degree to which psychoanalysis had developed cult-like qualities, sealing itself off from outside interventions and insisting on a kind of religious adherence by both practitioners and patients. Psychoanalysis and its psychodynamic offshoots in fact were a kind of religion, in that they operated on faith and an articulated system of beliefs. To try anything different or new was tantamount to sin. The resistance to the new drug also betrays the degree to which even supposedly ‘enlightened’ people can have a built-in knee-jerk conservatism when it comes to the novel, although, to be fair, in this case the novel threatened the entire underpinnings of psychoanalytic practice. If a drug could cure schizophrenia, then entrenched theories about bad mothering and repressed sexual conflicts as the seed of the illness would have to be shed.

  Even those North American doctors who were using biological rather than psychoanalytical treatments were not using drugs. Heinz Lehmann, the same Montreal psychiatrist who had once gone so far as to inject turpentine into a patient’s abdominal wall to bring on a fever, became one of the first to try the new drug on that side of the sea. ‘No one in his right mind was working with drugs,’ he admitted. ‘You used shock or various psychotherapies.’ Lehmann tried chlorpromazine on his patients not because Smith, Kline & French pushed him towards trial but because he had read the European reports one Sunday afternoon while taking a bath. He practised at the Verdun Protestant Hospital, living with his family on the grounds of the asylum, having emigrated from Germany in 1937, a Jew who would almost certainly have been exterminated by the Nazis were it not for a letter from a family friend inviting him to Quebec for a skiing holiday. He left Germany with his skis and enough luggage to last him for two weeks, intending never to return. Once in Canada, he was granted refugee status and a temporary medical licence.

  Lehmann was an enormously dedicated clinician, dealing with a personal load of more than six hundred patients, trying anything and everything to jolt his charges back into reality, but with little success. After reading the reports coming out of France, he obtained samples of chlorpromazine from SK&F and tried the drug on a group of seventy patients, many of whom began to respond. ‘Nowadays, of course, this would take years but in those days it didn’t take very long,’ Lehmann said. ‘We just chose seventy and we did them all, practically simultaneously, within one or two months. Also I didn’t have to ask permission from the Director of the Hospital. I didn’t have to get permission from the FDA [the US Food and Drug Administration] or the government. There were no ethical committees at the time, no guidelines, laws or regimentations . . . I don’t remember – this was in 1953 – whether I even asked the patients.’

  Like the psychiatrists in Lyon and Paris, Lehmann was astonished by what happened. Within just four or five weeks, many of his schizophrenic patients were symptom-free. ‘I thought it was a fluke – something that would never happen again,’ he said. ‘In 1953 there just wasn’t anything that ever produced something like this.’ Indeed the patients’ turnarounds were so dramatic and positive that Lehmann later called it ‘unthinkable – hallucinations and delusions eliminated by a pill! I suppose if people had been told, “Well, they’ll die two years later,” they’d still have said it’s worth it. It was so unthinkable and so new and so wonderful . . . Chronic schizophrenics who had been divorced because they had been psychotic for ten years, now all of a sudden they were symptom-free and their husbands or their wives were married again. It was a very strange time.’

  By publishing his results, Lehmann, along with American psychiatrists who also tried chlorpromazine on their patients with successful results, was instrumental in getting the medical establishment in North America to accept that chlorpromazine was not simply another sedative that briefly covered up the real symptoms of schizophrenia. These doctors believed, in large part on the basis of the conditioned avoidance tests done with rats by Courvoisier and Charpentier, that chlorpromazine had specific antipsychotic properties and that it was acting in some distinct and unique fashion to rebalance a brain that had lost its bearings.

  Entering Asylums

  Despite its initial marketing as an anti-emetic in North America, chlorpromazine quickly made inroads into psychiatry, in part because of the published studies coming out of France and then the United States. With the initial resistance to the drug from psychotherapists and doctors in private practice, in many ways it was the state asylum systems, particularly large institutions like Pilgrim State, that brought chlorpromazine as an antipsychotic into circulation in this country, by proving that it had a profoundly positive effect on the schizophrenic mind. Before the introduction of chlorpromazine at Pilgrim, Henry Brill, the hospital’s clinical director, described the wards as dark and desperate places where each psychiatrist had 165 patients under his or her care, making it virtually impossible to practise any form of psychodynamic therapy. Mary Holt, a doctor there, wrote that a few years prior to the arrival of chlorpromazine, the women in the two buildings she was in charge of were so ‘wild’ that she ‘just couldn’t keep them decent. They’d soil themselves, tear their clothes, smash the windows and gouge the plaster out of the walls. One of them would even rip radiators right off the wall.’ What Brill and his colleagues wanted was a quick, clean somatic approach, something sweeping and easy to administer on a large scale that would not necessarily cure their charges but that would allow them some specks of humanity and decency.

  Working in the basest conditions, with the sickest subjects, and with the impossible mandate of practising depth psychology or psychoanalysis on thousands of raving mental patients incapable of stringing a simple sentence together, psychiatrists at asylums like Pilgrim had little to lose and much to gain by trying chlorpromazine. And so, by the mid-1950s, that’s exactly what they did. Brill, encouraged by the early literature he had read about the new compound, was tentative but hopeful. ‘Once I had seen a small handful of cases that confirmed what had been said, I had no more real doubts,’ he wrote. ‘The most memorable experience I remember was walking into the dayroom and seeing this small group of patients dressed,
quiet, cooperative and in surprisingly good contact – with their psychiatric symptoms wiped away. That was perhaps the most spectacular demonstration anyone can ask for.’

  Pilgrim transformed. The park-like grounds became places for play and conversation among patients now able to socialise. Brill conceived of a medicine cabinet that would be hung above patients’ beds and in which they could keep the private possessions that had previously been stripped from them upon entering the ward. Glasses, penknives, money – all this and more would be returned to the patients, who could now be trusted to tend to themselves. One psychologist described visiting Pilgrim in the late 1950s and witnessing a group of patients parading up and down the walkways, making music with tambourines and trombones, others laughing and clapping as the procession made its way down the lane. In short, the entire tenor of the hospital was profoundly altered, and previously useless activities, like occupational therapy, now provided patients with the chance to try tools that would have been much too dangerous for them prior to the drug. Patients worked with saws and drills, gaining skills and feeling for the first time in who knows how many years the particularly human pleasure of making things.

  Martin Fleischman, an asylum psychiatrist in California, also saw his hospital transformed by chlorpromazine: ‘Patients became quieter, wards became quieter and psychiatric aides became quieter. Lest everything be evaluated in terms of decibels, let it also be recalled that delusions and hallucinations decreased, and the understandability and predictability of patients increased. In short, patients became people and even more important, they became identified as people by the people who took care of them.’

  Given these remarkable results, why, one wonders, in a country that has always prided itself on its biomedical breakthroughs, on its technological finesse and prowess, were so many psychiatrists in private practice set against this new drug? Why did it take so much time for these private practitioners to accept that there might be a chemical cure for their sickest patients? ‘In those days, the idea of treating psychosis was considered ridiculous, because psychosis by definition was an incurable disease,’ said Belgian scientist Paul Janssen. ‘The idea that it could be cured with a pill was ridiculed as simply too childish an idea.’

  Another possibility: in the United States, psychiatry in general and psychoanalysis in particular had a large number of Jewish practitioners, many of them émigrés from Nazi Germany, who had escaped concentration camps and come across the sea seeking asylum. These Jewish practitioners had seen firsthand the Nazi obsession with biomedical technology, the terrible experiments performed upon mental patients and Jews, all in the name of progress. It could be that for them, any type of chemical treatment smacked of Germany circa 1935–1945, while a talking treatment ensured a gentleness and humanity these Jewish psychiatrists sought above all for their patients. Whatever the reason, chlorpromazine was at first roundly rejected by those tightly tied to Freudian notions, and it made its way into psychiatric circles largely through the very back door, the underground door, if you will, which is to say the locked doors of the toughest mental institutions set high on hills and isolated from the public, places of such deep desolation that the doctors, even if sceptical, were willing to try new treatments that came their way.

  As news of psychiatric success stories spread, however, it was no longer merely asylums but hospitals all across the United States that were asking Smith, Kline & French for samples of chlorpromazine and using the drug on vast swathes of patients who came to clarity under its influence. Wards were revolutionised. Patients walked and talked appropriately. Reports of atmospheres in asylums being completely altered came in from Alabama, Maryland, California, Arkansas, Arizona and Colorado, to name just a few states. In 1955, the year after chlorpromazine was approved by the FDA, SK&F took in $75 million. (At least one psychopharmacologist was so impressed with the profits and the power of the drug that he double-mortgaged his house to buy shares in the company.) As evidence of the drug’s rapid adoption and broad application, within a year of its being marketed, 4 million prescriptions for chlorpromazine had been written. Within a decade, the drug had been taken worldwide by 50 million people, and SK&F’s profits doubled three times in the fifteen years after the drug was introduced.

  It is safe to say that every state asylum was profoundly changed by chlorpromazine. The use of other types of somatic therapies waned. Straitjackets gathered dust in locked cupboards. Quiet rooms were transformed into dayrooms where patients could mingle and mix. Psychosurgeries – previously used on thousands and thousands of patients, leaving a considerable portion of them with a blunting of personality, or a literal loss of voice – finally began to decrease, and this was another of chlorpromazine’s great victories.

  Then the inevitable happened. No longer wracked with symptoms, and in many instances clearly coherent and capable, patients became ready for ever-increasing amounts of independence. At Traverse City State Hospital in Michigan, for example, in 1955 far fewer patients needed to be spoon-fed – a drop from twenty-seven to two. The number of patients now fit to eat in the dining hall went up by 150 per cent, while soilers decreased markedly as well, down from twenty-five to five. All of this in a single hospital, although asylums across the country were reporting similar statistics. Eventually, patients became ready to be released back into the community, to be treated by psychiatrists in their own hometowns or at community mental health centres that sprang up everywhere to meet the needs of those flowing out of the huge and soon-to-be obsolete asylums. Within twenty years, the population of mental hospitals fell to less than a quarter of what it had been before chlorpromazine came on the scene.

  While these discharges represented clinical triumphs, they did not come without problems. As in France, patients who had been locked in inaccessible psychotic states for years found themselves in a completely changed world and in some cases on their own. Family members did not always welcome the newly released patients back into the fold. Job skills were rusty or nonexistent.

  Setbacks

  Perhaps it was equally inevitable, then, that the seemingly unstoppable good news about chlorpromazine was not entirely unalloyed. Baltimore psychiatrist Frank Ayd, who received the first official permit from the FDA to use chlorpromazine in the treatment of schizophrenia, discovered troublesome side effects. Within the first six weeks of using chlorpromazine, two of his patients got jaundice. The first had viral hepatitis, so Ayd could not be sure that the jaundice was from the chlorpromazine. The second, however, whom Ayd described as ‘chronically agitated’, though clearly jaundiced as a result of the chlorpromazine prescription, did not want to stop taking the drug. ‘I do feel better,’ she insisted, ‘even though I’m yellow.’ Ayd also reported that women on chlorpromazine began to lactate. He had the breast milk analysed, curious to see its components, and found that it was precisely the same as normal breast milk. Ayd was also one of the first to discover and report on the phenomenon of false pregnancy tests that occurred as a result of chlorpromazine use, evidence that the drug was interfering with normal hormonal processes in women in ways we don’t understand.

  But perhaps most troubling to Ayd was the discovery that, when given in hefty doses, the drug produced what is called a dystonic reaction, a rigidity in muscle movements and an awkwardness of gait, a shuffling sort of step – and sometimes still worse symptoms. In 1955 Ayd shot a film of a patient on a high dose of chlorpromazine who had become twisted up like a pretzel, his limbs entwined. Concerned, and perhaps confused, Ayd showed the film to pharmacologists at Smith, Kline & French, who in turn asked for input from neurologists, some of whom, still under the psychoanalytic sway in this country, dismissed the reaction as ‘hysterical’. In those days, even Parkinson’s disease, an affliction of dopamine deficiency which leads to loss of motor control and causes patients to spasm and stiffen, tended to be seen as a condition related to repressed anger immobilising the victim.

  But the dystonic reactions that Ayd had observed could not be ea
sily dismissed. As doctors experimented with doses, raising them in the hopes of making a good effect great, over time some patients displayed bizarre behaviours – tongue thrusting, lip smacking, restlessness, involuntary movement of their torso and limbs, a constellation of symptoms known as tardive dyskinesia. The condition could in some, but not all, cases be reversed with the administration of anticholinergic drugs, which are intended to counteract the release of the neurotransmitter acetylcholine at neuromuscular junctions and thereby prevent muscle contraction. Tardive dyskinesia eventually affects 32 per cent of patients taking neuroleptics after five years, 57 per cent after fifteen years and 68 per cent after twenty-five years. Given the severity of the side effects, one would think that the newfound enthusiasm for chlorpromazine might have been dampened, but it wasn’t. The profits of SK&F continued to rise while newly released patients slowly felt their way into lives so quiet and calm they must have seemed almost as strange as their now defunct hallucinations once had.

  Whence the Magic

  Whatever its pros and cons, the invention and dissemination of chlorpromazine is ultimately as significant for what it did not do as for what it did. Yes, the drug reversed states of psychosis so severe they had trapped patients for years. Yes, by doing so, the drug helped to birth the deinstitutionalisation movement and the corresponding rise of the community mental health centre. And in the United States the drug finally put a dent in the deeply held American affinity for psychoanalysis, as even the clinicians most dedicated to ‘the talking cure’ had to concede that this capsule could clear the mind more effectively and efficiently than could any leather sofa and conversation. But the drug did not, at least initially, spur anyone to ask how or why it was working. No one had the slightest idea. It was simply enough for everyone that it was working. Clearly the capsule suggested that mental illness, at least in some respects, was a brain-based phenomenon, but beyond that, few had a clue.