When Sir William Osler made his valedictory address to the University of Pennsylvania in 1889, he chose the subject "Aequanimitas." He said, "In the physician or surgeon no quality takes rank with imperturbability." Then he defined the word: "Imperturbability means coolness and presence of mind under all circumstances, calmness amid storm, clearness of judgment in moments of grave peril, immobility, impassiveness, or to use an old and expressive word, phlegm." He was doubtful that it could be acquired except by inheritance and he thought that some of his students, "owing to congenital defects," might never be able to acquire it. He counseled, nevertheless, that education with practice and experience might help to attain Imperturbability in fair measure. The doctor, Osler felt, should develop an "inscrutable face by education of his nerve centers.

The mental equivalent to imperturbability, which Osler called "a bodily endowment," is a calm equanimity. He considered that one of the first essentials in securing a good equanimity is "not to expect too : much of the people amongst whom you dwell." Osler recognized that prosperity is an aid to equanimity and enables us to hear with composure the misfortunes of our neighbors.

One wonders what Sir William Osler might have said had he had available in 1889 such aids to imperturbability and equanimity as have come with the new tranquilizing drugs. This is in the nature of a medical revolution. Ten years hence statistics of institutions for the mentally disturbed and for the alcoholic may indicate the results of an administration of these and other new remedies that are bound to come. Already the great progress that has been made is an indication of the future.

At a recent meeting of the Society of Biologic Psychiatry, the president, Dr. Harold E. Himwich, said, "A few short years ago it would have been impossible to read a paper on the new tranquilizing drugs but now we know that Chlorpromazine and Reserpine are valuable in the treatment of disturbed psychotic patients." Since that paper was read, other drugs have been added to the list, notably Frenquel, Miltown, and Equanil. These are the drugs that affect the brain. Both Reserpine and Chlorpromazine depress the hypothalamic mechanisms, particularly that part concerned with the patterns for emergency, for fight, and flight. Chlorpromazine Depresses not only these mechanisms but also the sympathetic and parasympathetic nervous systems. Other research has indicated that chlorpromazine prevents the awakening, alerting, or arousal reaction producing what is in effect a pharmacologic lobotomy. Frenquel, according to Dr. Himwich, depresses neither the hypothalamusn or the activating system and is still a potent tranquilizing drug.

The mechanism by which these drugs have their effect is not clearly established. However, some evidence indicates that a neurohormone called Serotonin is involved. When it is insufficient in amount to produce its normal effects, abnormal behavior may be observed. In concluding his address Dr. Himwich wrote, "These new drugs are not a flash in the pan but their therapeutic values have been widely corroborated. However, they are not a complete answer to our therapeutic problem because no one drug is able to ameliorate the condition of all of the patients and none of them is as efficacious for melancholia as is electric shock."

The discovery of new drugs of this type invariably sets off a chain reaction in which old drugs are tested for specific effects Already there are combinations of Reserpine with various sedative drugs of the barbiturate series and with other active ingredients. In one study Reserpine and Chlorpromazine were given in combination and the combination was said to have certain advantages over therapy with Reserpine alone. Indeed the authors say that Chlorpromazine seemed to potentiate the clinical effects of Reserpine. "The course of combined therapy," say Drs. J. A. Barsa and N. S. Kline, "was less stormy and less distressing to the patient because of the milder and shorter turbulent period." Already these drugs are said to have worked miracles in state institutions for the mentally disturbed, permitting great numbers of patients to be discharged to their homes beyond what might have been possible in previous years. Dr. A. E. Bennett says that "both drugs have facilitated psychotherapy through physiologic relief of anxiety, tension, insomnia or somatic symptoms in some cases."

In addition to the drugs already mentioned consideration must be given to the pharmacological properties of Miltown, which is a meprobamate, a drug that is related to mephenesin and that was found in a study of such preparations to be the most potent anticonvulsant in the series and also possessing a muscle-relaxant action of considerable intensity and long duration. Dr. J. C. Borrus found that it was most effective in anxiety and tension states through a lessening of tension, reduced irritability and restlessness more restful sleep, and generalized muscle relaxation. Chiefly in its favor is an absence of toxicity both subjectively and objectively as compared with other drugs and "there were no withdrawal phenomena noted on cessation of therapy." Dr. Lowell S. Selling confirmed its non-habit-forming character and found it of most value in the so-called anxiety-neurosis syndrome especially when the primary symptom was tension. His studies and other studies made since his first publication indicated a special value to Miltown in accomplishing withdrawal from alcohol with a minimum of discomfort. Among the special qualities listed for this drug, based on clinical studies, are: as an agent in anxiety and tension states and muscle relaxant, particularly in fibrositic rheumatic disorders and in such conditions as torticollis and also back pain, for control of spasticity in such conditions as cerebral palsy, and as a somnifacient of a different order than the hypnotics or sedatives. Few allergic reactions have been reported, all of which responded to therapy with antihistamines. In a new series of studies by Dr. F. Lemere this drug proved effective in 70 per cent in a group of 250 non-hospitalized patients and he considers it "the drug of choice for the relief of tension, anxiety, and insomnia."

Another discovery has reported this drug selectively effective in a high percentage of cases of petit mal and several reports by general practitioners have indicated its desirability in what are commonly called tension states but which might include psychoses, psychoneuroses and personality disorders as well as a wide variety of conditions classified en masse as psychosomatic, including headaches, dysmenorrhea, hypertension, motion sickness, peptic ulcers, and a variety of dermatological disorders.

Meratran And Depression

People who are depressed have in the past been treated frequently with benzedrine, or amphetamine, which stimulates but which has the undesirable effect of raising the blood pressure. A drug called Meratran has little effect on the breathing, the pulse rate, or the blood pressure but does act directly on the brain to overcome depression. If the central nervous system is underactive, this drug seems to restore it to a more normal level of activity. Obviously drugs of this type are not given to people who are overexcited. The drug has been useful in the condition called narcolepsy, in which there is a sudden irresistible desire to sleep. This condition has also been treated with amphetamine. The new drug is used in cases of fatigue, drowsiness, or what is called a low-down feeling. Another use has been in disorders of the liver, in infections, deficient action of the thyroid gland, depression that comes during the menopause, and alcoholic hangovers. The drug does not affect the appetite, so that it is given be fore or after meals.