Medicine: PILLS FOR THE MIND

New Era in Psychiatry

THE treatment of mental illness is in the throes of a revolution. For the first time in history, pills and injections (of two inexpensive drugs) are enabling psychiatrists to 1) nip in the bud some burgeoning outbreaks of emotional illness, 2) treat many current cases far more effectively, and 3) in some instances reverse long-standing disease so that patients can be freed from the hopeless back wards of mental hospitals where they have been “put away” for years.

When Cincinnati’s Dr. Douglas Goldman told fellow psychiatrists last May that “the revolution is at hand,” some doctors scoffed, and most were skeptical. But at two recent meetings in Manhattan and Galveston, psychiatrists packed the halls to hear dozens of papers reporting almost identical successes in scores of mental hospitals and also in consulting-room practice.

At the same time, even the most enthusiastic advocates of the drugs were at pains to emphasize that by themselves the pills and injections probably do not cure anything; in the main, they make other treatments more effective. They are not going to empty the state hospitals, and far from reducing the need for more intensive research into psychic disorders, they accentuate it and facilitate the work.

From the Snakeroot. The new drugs are as important, in their way, as the germ-killing sulfas discovered in the 1930s. Two drugs ushered in the new era: chlorpromazine* (TIME, June 14), a synthetic compound, and reserpine †(TIME, June 21), a pure alkaloid from the juices of the snakeroot (Rauwolfia serpentina), crude extracts of which had been used for centuries by medicine men in India. Both drugs became available in the U.S. in 1953. But most ivory-tower mental hospitals, attached to medical schools with good research facilities, passed up the chance to be first to try the drugs. Far more receptive were the heads of state hospital systems, in whose complexes of dingy, red brick buildings were thousands of long-term “regressed” or “deteriorated” patients.

First in North America to use chlorpromazine on mental patients was Berlin-born Dr. Heinz Edgar Lehmann, who has one foot in the ivory-tower camp, as assistant professor of psychiatry at McGill University, and one among the red bricks, as clinical director of Verdun Protestant Hospital on Montreal’s outskirts. With Dr. Gorman Hanrahan, he tried chlorpromazine first on victims of manic-depressive psychosis in the manic phase—the kind of patients who are admitted to the hospital “swinging from chandeliers that aren’t there,” who throw their shoes at attendants, keep other patients awake by shouting all night, often try to assault attendants and doctors.

Results with Chlorpromazine. Injections of chlorpromazine worked wonders. Men and women who had been continuously manic for a year or more quieted down, were soon content to lie down on their beds, and seemed to spend much of the time sleeping. But this was no drugged, disordered sleep such as follows heavy dosing with barbiturates, scopolamine or insulin. A gentle shake of the shoulder would bring the patient wide awake at once, able to give sense-making answers. After a few days the somnolence wore off, but the patients remained calm. They willingly took pills instead of requiring injections, fed themselves, ate heartily and slept well. Not all patients responded equally well. But among 77 manics, Dr. Lehmann saw no total failures; 27 were somewhat improved, nine improved enough to go home despite some lingering illness, and 37 went home “recovered.” In four cases, incipient attacks of mania were averted.

Early success with this type of case prompted the Montreal doctors to try chlorpromazine on schizophrenia victims. Some types of schizophrenia are marked by extreme excitement and by persecution delusions. It was in these types that Dr. Lehmann found chlorpromazine most effective; most patients calmed down dramatically, and many lost so much of their fear and anxiety that they could easily talk about their troubles. Again patients’ responses varied widely; the longer the illness had lasted, the less likely was it that the patient would recover enough to go home. In the U.S., 300,000 schizophrenics fill about half the mental hospital beds, and after a stay of two years or so, their chances of being discharged have been slim indeed. The new drugs have already begun to change this.

Results with Reserpine. One of the biggest mental institutions in the U.S. is Illinois’ Manteno State Hospital, 45 miles south of Chicago. Rated for 5,000 patients, it holds 8,200. Its physical plant, dating from the 1930s, is reasonably modern. In its overcrowded red brick buildings, Psychiatrist Dean C. Tasher had seen hundreds of patients drift downhill to the “very disturbed” wards where they persisted in lying naked on the floor in their own filth, and some eventually to the hydrotherapy ward, where they had to be kept in tubs or wet packs for most of the day.

When he got reserpine last summer, Dr. Tasher made his test as rigorous as possible. He chose patients in whom all the approved treatments—and others now discarded—had failed to bring lasting improvement. They had got as much psychotherapy as the short staff could provide—all to no avail.

Of the 221 patients first chosen, 82 were women who responded temporarily to electric shock. They had to have it once or twice a week to remain in partial contact with reality; otherwise they were certain to relapse into a far more serious state, and none could go home for more than a weekend. They had been at Manteno from one to six years. Dr. Tasher cut out the electric-shock treatments and let reserpine take over.

The effects at first were not marked: it works more slowly than chlorpromazine. But the effect is cumulative. Within a day or two, the women were calmer and quieter. Soon they began to eat better, and gained up to ten pounds in two weeks. Many who had been hostile to the attendants, or had mutely avoided them, sought them out and wanted to talk. They reported vivid but not unpleasant dreams.

At the end of ten weeks, the first patient was ready for discharge. A petite blonde, 36, wife of a journeyman carpenter, she had been in and out of state hospitals throughout the Midwest for ten years. In her hallucinations she heard voices: her dead mother calling “Come to me,” her own daughter calling “Mummy,” and finally a man telling her that her husband was unfaithful and she should leave him. She had left him many times, only to wind up in hospitals, where electric shock made her outwardly calmer but with no normal ebb and flow of emotional responses. After reserpine, and with no more help from the psychiatrists than she had always had, the woman went home on a maintenance dose of one reserpine pill a day. Her husband had only one complaint: she had become so demanding in her new-found love for him he wondered whether the doctors could make her pills a bit smaller.

Of the 82 patients in this group, 59 have been discharged or will be as soon as a home can be found for them; twelve have shown varying degrees of improvement, and only eleven are unchanged. In a more severe test on 104 women and 35 men who had had electric shock without benefit, Dr. Tasher has reported on only two months of treatment. But already 19 are home or ready to go (one man had been at Manteno for 13 years); 52 others have improved.

Otter Uses. By no means all the thousands of patients at a hospital like Manteno are fit to live in the wards. At any one time, hundreds are hospitalized with every disease in the book. Their plight had long been a nightmare to Dr. William J. Gallagher. Chlorpromazine to him has seemed like the answer to a prayer. Agitated patients who previously could not be kept quiet without undesirably heavy doses of barbiturates now rest comfortably. And, more important, they stop resisting the medical or surgical treatment that they need. After operations, they allow surgical wounds to heal.

Both chlorpromazine and reserpine have a wide variety of other uses. They quell much of the agitation and bickering of senile patients. General paresis (the result of long-standing syphilitic infection) has yielded spectacularly to treatment with reserpine. One patient at the District of Columbia’s mammoth St. Elizabeths Hospital has provided a wry quantitative measure of the drug’s effect. He had suffered for years from the hallucination that each night 1,000 women visited his room. After the calming effect of reserpine he is still hallucinated—but 99.9% improved: now he has visions of only one woman each night.

Equally striking is the effect of chlorpromazine on delirium tremens. Patients do not develop the usual panic, nausea and chills; tremor subsides so quickly that they can be discharged after half the usual time, or less.

At Brooklyn’s Maimonides Hospital, Drs. Charles E. Friedgood and Charles B. Ripstein have found chlorpromazine similarly effective in banishing the agonizing symptoms of withdrawal from narcotics (morphine and Demerol) and barbiturates. In Chicago, Police Surgeon Eugene F. Carey gives reserpine to narcotics addicts who are forced to “kick the habit,” i.e., give up narcotics abruptly, during detention before they are sent on to court and hospitals. It saves them, he reports, from the usual weeping, nausea, retching, chills and shakes.

The psychoneuroses are generally considered milder mental illnesses than the psychoses, but some of them can be as stubbornly difficult to treat. The results from chlorpromazine and reserpine in these cases have been spotty. Among the brilliant successes is one reported from Ohio’s Longview State Hospital by Dr. Goldman, concerning a young woman who was a mysophobe, i.e., a compulsive hand-washer. For years she had washed her hands 30 to 40 times a day, would not touch a doorknob with her bare hands. After four months on chlorpromazine she told the psychiatrist that her ideas about dirt had been foolish, and she had got over them.

In a similar class are many cases of chronic hiccuping. The drugs have arrested some of these. They are also exremely effective against nausea and vomting during pregnancy, or resulting from some forms of cancer, or from radiation and chemical treatments given to check cancer. The drugs seem to have no direct effect on the pain of cancer, but they make patients easier by removing their anxiety about the pain.

Tke Dangers. Both chlorpromazine and reserpine have marked and undesirable side effects which make them potentially dangerous in the haphazard use which some general practitioners and office psychiatrists are now making of them. Early in treatment, both cause a drop in blood pressure which may make the patient faint if he stands up suddenly. Some individuals have an allergic reaction to the drugs. About one in 20, especially on reserpine, may develop symptoms which look like Parkinson’s disease (tremor, stooped posture, masklike face, inability to raise the arms except in jerks). All these disagreeable symptoms usually disappear quickly after the drug is withdrawn, and in many cases the same patients can start taking it again soon, without recurrence of the trouble.

More serious side effects are a form of jaundice that appears in from 1% to 5% of patients on chlorpromazine, and agranulocytosis, in which certain white blood cells disappear and the throat and digestive tract become ulcerated. There have been four confirmed cases of agranulocytosis, with one death. But doctors feel that even this risk is justified, provided the patients are watched closely, because with modern antibiotics the disease can nearly always be cured.

Ivory v. Red Brick. The gulf between the ivory-tower and red-brick schools of psychiatry over the new drugs has significance far beyond the profession. On its resolution depends the full and effective use of important new psychiatric tools. Essentially the trouble goes back to the Freudian revolt against the 19th century’s physiological approach to mental illness. Freud admitted that the usefulness of his method was virtually limited to the neuroses and could not yet reach the psyhoses. Experience has shown that it takes countless hours of the most grueling work by a topnotch psychotherapist to bring a “deteriorated” schizophrenic back to something like normal. Even if all U.S. psychiatrists dropped everything else and no more new cases cropped up, most inmates would be dead before a doctor got around to them.

Some orthodox psychiatrists have performed thousands of lobotomies, in which a knife is slashed through the cortex, the most essentially human part of the brain. Some do not hesitate to give patients scores or even hundreds of electric or insulin-shock treatments, or to put them in an insulin coma. Alongside these procedures, the red-brick school points out, the use of chlorpromazine and reserpine is gentle. It can make the patient readily accessible if the overworked psychiatrist has a few minutes to practice psychotherapy on him. If psychotherapy can prove its worth even in psychoses, these drugs give it its chance.

The ivory-tower critics argue that the red-brick pragmatists are not getting to the patient’s “underlying psychopathology” and so there can be no cure. These doctors want to know whether he withdrew from the world because of unconscious conflict over incestuous urges or stealing from his brother’s piggy bank at the age of five. In the world of red bricks, this is like arguing about the number of angels on the point of a pin. Psychiatrists who have worked on the back wards readily admit that they can claim no technical cures—they will have to wait at least five years after a patient’s discharge for that. What they do claim is an impressive number of “social recoveries”: cases in which a patient for whom there had been little hope has been brought around to the point where he can go back to a normal life. They know that there will be many relapses, but they are confident that these also can be treated successfully.

Middle Ground of Hope. Eventually, says Montreal’s Dr. Lehmann, the physiological and analytic schools will have to meet on common ground in the middle. His quietly persuasive argument: the analysts talk of ego defenses being torn down in a psychosis, and when this happens the already anxious patient is overwhelmed. Psychotherapy tries to restore the ego, but this is extremely difficult because the anxiety, now almost a physical entity, has unleashed a flood of physiological processes.

What do drugs like chlorpromazine do? Nobody knows precisely, but they seem to act on a primitive part of the midbrain or on the nerve pathways connecting this to the cortex. At any rate, this primitive part of the brain seems to be a center for mobilizing anxiety, even though the anxiety is experienced only in the cortex. This explains both the anxiety-relieving effect of the lobotomy and the different type of reaction to chlorpromazine.

In many hospital systems, lobotomies are now being abandoned or used rarely. There are other changes. Use of electric shock is down, in some cases as much as 90%. Patients who formerly had to be restrained, either mechanically (with cuffs or camisoles) or chemically (with large doses of barbiturates), are now calm without being groggy. In many hospitals, attendance at church, at dances, requests for occupational therapy and work assignments have doubled. Whatever its long-range effects on mental illness, the pills-for-the-mind revolution has already brought a striking new atmosphere of hope into the dark reaches of the back wards.

* Marketed in the U.S. under the trade name Thorazine by Smith, Kline & French; in Canada as Largactil by Poulenc, Ltd.

† Biggest U.S. supplier, under the trade name Serpasil, is Ciba Pharma ceutical Products Inc.