Severe cases of tardive dyskinesia can affect the arms, legs, ankles, hands, fingers, toes, feet, trunk, and voice box, with resulting impairment of speech, breathing, and posture. The larynx or voice box may spasmodically jump up and down giving the impression the person is attempting to swallow, though he actually isn't. Real attempts to swallow can become quite difficult, making eating a hard labored chore; loss of weight may result. Breathing can become irregular, with the person taking rapid, shallow breaths or deep, slow ones. His voice may become hoarse and he may only be able to speak with a spasmodic exhaling of breath, and even then that which is articulated may be incomprehensible.

The fully developed syndrome of tardive dyskinesia, which would involve the oral region, trunk and limbs, need not be present for the person to be severely disabled: * In patients in whom tongue movements were gross they greatly interfered with eating and drinking . . . speech was usually hoarse, came in expiratory bursts and was accompanied by marked contortions of the face; in the 3 worst cases it was unintelligible. Attacks of respiratory distress occurred in mid-inspiration, when they clenched their mouth, grimaced and appeared to make a respiratory effort against a closed glottis." At such times their eyes bulged, they became cyanosed and grabbed at any object within reach to aid their attempts to overcome the obstruction [of breathing], while their tongue and jaw kept working-a most pitiful and distressing sight.37

36

Though tardive dyskinesia does not bear the close resemblance to idiopathic disease that the other drug-induced conditions can, it does at times, particularly in more severe cases, have some of the characteristics of a neurological disorder known as Huntington's Chorea. This condition is characterized by the occurrence of various patterns of movement that are quick, jerky, and often violent. They seem to be voluntarily performed but, in fact, are not. The movements themselves can be rather strange:

*** There may be saluting gestures, shrugging of the shoulder girdle, twisting of the body, and flail-like movements of the limbs. The facial expression becomes contorted and is associated with clucks, grunts and grinding of the jaws.38

The term "choreiform' means resembling or having the appearance of chorea. Choreiform movements of the limbs and trunk in tardive dyskinesia are often seen in conjunction with another abnormal neurological manifestation, athetosis. Athetotic movements chiefly consist of involuntary sinuous twisting motions of the hands and feet. The term "choreoathetosis" means having the characteristics of both chorea and athetosis.

Choreoathetotic movements associated with tardive dyskinesia include jerky flexing and extending motions of the fingers, toes, and ankles. As the fingers open and close the arms may be unnaturally extended out from the sides of the body, with the shoulders rocking, the feet far apart, and the neck and spine overextended. Twisting motions of the hands, "piano playing fingers," and flinging movements of the arms are other abnormal conditions of the upper extremities seen in tardive dyskinesia.

Involuntary movements of the toes and feet or continuous overextension of the big toes can actually cause the top of the person's shoes to wear away and allow the big toe on each foot to peek through the top of the shoe. The wearing away of shoes in this manner of course has an injurious effect upon the feet.

When tardive dyskinesia is so severe as to involve the trunk it can be particularly crippling. In such cases the person's body moves side to side or rocks back and forth. There may also be rhythmical movements of the head. The trunk can be affected too by a "body twisting." In this reaction the upper part of the body and the shoulders involuntarily twist. Still another feature of tardive dyskinesia, albeit rare, involves a back and forth movement of the spine in which the back bows and the chest thrusts in.39 "Pelvic thrusting movements" have also been observed to occur.40

35 Glottis-That opening at the upper end of the windpipe which when closed restricts the air allowed to enter into the lungs.

36 Cyanosed-Cyanos is a blueness of the skin caused by oxygen starvation.

37 Richard Hunter et al, "An Apparently Irreversible Syndrome of Abnormal Movements Following Phenothiazine Medication," Proceedings of the Royal Society of Medicine, v. 57, p. 758-62, 1964

38 Ayd, "Persistent Dyskinesia: A Neurologic Complication of Major Tranquilizers," Medical Science, v. 18, p. 35, June, 1967.

39 ACNP-FDA Task Force, "Neurological Syndromes Associated with Antipsychotic Drug Use," Archives of General Psychiatry, v. 28, p. 463-67, 1973.

40 Jonathan O. Cole, "Pharmacotherapy of Psychosis," in Psychopharmacology in the Practice of Medicine, ed. Jarvik, Murray, P. 213, 1977.

As if the many aspects of tardive dyskinesia were not damning enough, it may be further complicated by the simultaneous occurrence of Parkinsonism of akathisia (inability to remain seated or still.)

In fact, the various movements of the mouth, tongue, lips and jaw, and the twisting and jerky movements of the limbs, and a compulsion to change body position all comprise that set of symptoms quite commonly found in advanced cases of the disorder. In the worst cases there is hardly any part of the body which remains unaffected:

* *

"*** In October 1959, his hands were called "useless" because of their incessant motion. He was unable to shave or stand still, and he paced the floor continually. He developed lip smacking and mouthing movements, shifted his weight from foot to foot, and was unable to keep his arms still, continually clasping, unclasping, and wringing his hands. He talked through clenched teeth ** by December 1962 the mouth and facial movements had become so severe as to interfere with eating. He had lost nearly a hundred pounds over the preceding several months. All phenothiazines 42 Dec. 15, 1962, without benefit. Involuntary shuffling of the feet, inability to stand still, aimless movements of the arms, hands, and legs, lip smacking, lip licking, and chewing movements were still present when he was last seen (October 1965), despite the withdrawal of phenothiazines since December 1962." 43

66# * *

Even death may result indirectly from tardive dyskinesia and the other disorders of movement involved with it:

66*

* *

**Her clinical appearance was truly remarkable. She walked with a suffling gait, marche a petits pas" and loss of associated movements. There was a pillrolling tremor, 45 and cogwheel rigidity 46 was present in all extremities, particularly in the arms * Rather than the expected masked facies,47 she exhibited continuous mouthing, chewing movements, lip smacking, and lip licking. Her tongue was continually engaged in winding, serpentine motions, alternately protruding, retracting, or pushing out against her lips and cheeks. Although the movement were protracted, the tongue did not become locked in any position for long, and neither the face nor the neck was involved in dystonic 48 posturing. The most bothersome feature to her was the akathisia 49 to which she referred as "nervousness," pleading for something "to make me better." During every waking moment her face, arms, legs, and torso were engaged in perpetual purposeless motion with aimless fidgeting of the hands and arms, shuffling of the feet, and crossing and uncrossing of the legs. She was utterly unable to sit still, rocking back and forth in her chair, and after a few seconds jumping up and pacing about. When she walked, the Parkinsonian features predominated, but there were periods during which the akathisia and dystonia of the tongue would emerge. In addition, all areas of her skin exposed to light had taken on increased pigmentation of a grayish cast.

* * *

**She died suddenly in April 1964 following a severe head injury sustained in a fall her neurological difficulties probably contributed directly to her death." 50 The movements of tardive dyskinesia are incessant; the only time they really abate is during sleep and those patients with severe cases in which respiration is affected may not be afforded respite at even this time. Tardive dyskinesia is a peculiar disorder. As long as an antipsychotic drug is administered the dyskinesia may remain masked, but when the dosage is significantly reduced or stopped alto

41 Parkinsonism-Parkinsonism is a drug-induced neurological disorder that can in every way mimic naturally occurring Parkinson's disease. Parkinsonism is characterized by trembling the limbs, muscular rigidity, weakness, drooling, a blank or expressionless face, and simian or ape-like posture.

42 Phenothiazine-Phenothiazines are a class of drugs that includes Thorazine, Stellazine, Mellaril, Prolixin, Compazine, and many others.

43 William R. Schmidt et al, "Persistent Dyskinesias Following Phenothiazine Therapy,” Archives of Neurology, v. 14, p. 369-77, April, 1966.

44 Marche a petits pas-A tendency to take short accelerating steps, sometimes with falls resulting.

45

Pill-rolling tremor-A type of tremor seen in Parkinsonism in which the person repetitively rubs his thumb against his first two fingers.

46 Cogwheel rigidity-Cogwheel rigidity is a phenomenon associated with parkinsonism in which a limb (arm) moves in a jerky, ratchet-like fashion.

47 Masked facies-A blank, expressionless look of the face.

48 Dystonic-Dystonia is a neuromuscular disorder characterized by abnormal muscular tension such as lockjaw or the head twisted to one side and frozen in that position.

49 Akathisia-A neurological disorder which varies in intensity from an inner feeling of uneasiness or disquiet to an inability to sit or lie in one position. It is in slang parlance called the "jitters," the person feels compelled to constantly move.

50 William R. Schmidt et al, "Persistent Dyskinesias Following Phenothiazine Therapy," Archives of Neurology, v. 14, p. 370, April, 1966.

gether the syndrome may appear for the first time within a few days. This masking effect prohibits an entirely accurate report of the incidence of tardive dyskinesia. Almost any report necessarily provides an undercount of actual prevalence. In spite of this there are percentages cited in the medical literature giving approximate incidence. Some publications conservatively claim that in a group of psychiatric patients of various ages the rate of dyskinesia is 3 percent to 6 percent and that among elderly psychiatric patients the rate is 20 percent." It is, however, not at all difficult to find sources in the literature which provide figures far in excess of these. A book published in 1977, Psychopharmacology by Bruce Woodley and Donald Naftulin, states that tardive dyskinesia may occur with an overall frequency as high as 15-20 percent and higher yet among the elderly.52 Dr. Jonathan O. Cole of Boston State Hospital states that in his facility an incidence of 25-50 percent may be found, depending upon what standards are employed to evaluate the presence of abnormal movements.53

Always among the elderly the degree of prevalence is greatest: of those aged individuals (older than 60) who have been given antipsychotic drugs for three years or more, better than half may be afflicted with tardive dyskinesia.54 Other sources place the percentage even higher, up to 60 percent of those in psychiatric-geriatric wards.55

Whatever statistics one elects to place his faith in, this fact sharply intrudes: among elderly persons administered antipsychotic drugs the incidence of tardive dyskinesia is extraordinarily high. And among all persons, including the elderly, who are administered antipsychotic drugs on a continuous basis the situation is only getting worse:

**The percentage of chronic patients with tardive dyskinesia is considerable, and the number is steadily increasing. This is sufficient proof that current practices of prescribing drugs for patients of all categories are medically unsound. One does not know how many persons are severely disabled, or how many die as the result of excessive exposure to drugs. I have seen a considerable number of patients who, by all standards, are permanently disabled or severely disfigured. 56

Tardive dyskinesia is by no means a disease exclusively of the aged. It may affect young and middle-aged adults and even children. In children choreiform 57 movements of the extremities predominate while abnormal movements of the mouth and face are fairly uncommon.58

In those instances where tardive dyskinesia disappears altogether it is almost always among those who are middle-aged or younger. A complete remission of the disorder among such individuals can occur and may take as little time as a week, though a period of months (18-36) is more likely.59 Unfortunately, the elderly constitute that age group most vulnerable to tardive dyskinesia and the group in which an abatement of symptoms is least likely. Among the aged, tardive dyskinesia is irreversible in almost all cases; mere improvement of the condition, with all antipsychotic medication withdrawn, can take years.

60

Just what the relationship is between the dose of a particular antipsychotic drug and the length of time it is administered and the subsequent occurrence of tardive dyskinesia is not something that has ever been precisely determined. While it is generally acknowledged that a larger dosage size and an extended period of treatment predispose the individual more to tardive dyskinesia, this yardstick does not allow any real predictability of when the disorder will occur. Frequently, a person with tardive dyskinesia has consumed some 1,000,000 mg. of chlorpromazine or an equivalent amount of some other drug.61 Consumption of this sort, however, is unnecessary for the development of TD. In the elderly it may develop with the

51 ACNP-FDA Task Force, "Neurological Syndromes Associated with Antipsychotic Drug Use," Archives of General Psychiatry, v. 28, p. 464, 1973.

52 Bruce Woodley and Donald Naftulin, Psychopharmacology, p. 16, 1977.

53 Cole, "Pharmacotherapy of Psychosis," p. 214.

54 George E. Crane, "Clinical Psychopharmacology in Its 20th Year," Science, v. 181,

1973.

55 W.E. Fann and G.L. Maddox, Drug Issues in Geropsychiatry, p. 26, 1973.

56

p. 124-28,

George E. Crane, "Tardive Dyskinesia: A Review," in Neuropharmacology by Boissier, Hippius, and Pichot, p. 353, 1974.

57 Choreiform-Choreiform means resembling or having the appearance of chorea. Chorea is a neurological disorder characterized by a series of involuntary movements which are quick, jerky and complex.

58 ACNP-FDA Task Force, "Neurological Syndromes Associated with Antipsychotic Drug Use," Archives of General Psychiatry, v. 28, p. 464.

59 George E. Crane, "Tardive Dyskinesia: A Review," p. 351.

60 Ibid., p. 350.

61 George W. Paulson, "Tardive Dyskinesia", Annual Review of Medicine, v. 26, p. 79, 1975.

administration of relatively small doses.2 The time of administration need not be protracted; a period of but several weeks is all that is required and the syndrome is present. It is absolutely impossible as long as antipsychotic drugs are given to eliminate the possibility that tardive dyskinesia may occur:

* Since we do not know whether any particular drug is more likely to induce tardive dyskinesia than any other and we do not know whether the total amount of medication given over time or the total amount given in any one day has any effect whatever on the likelihood that the patient would develop tardive dyskinesia, it is almost impossible to alter one's prescribing behavior to maximize the odds that the patient will never ever get tardive dyskinesia.64

In a field like psychiatry where almost nothing is factually known it is a quite common situation for the problem of mental irrationality to be handled with some offbeat solution and then that solution itself becomes a new problem. For example, an elderly person might suffer from some of the confusion and disorientation not infrequently seen among the aged. The solution is Thorazine. The drug is administered for a time and tardive dyskinesia develops. The solution (drug treatment) has now become the problem and it is most certainly of greater magnitude than any problem which existed before. Does psychiatry have any solution to this problem? Yes. But only their typical solutions.

It is worth taking a look now at how psychiatry views the disease it fostered. In November 1964 a piece appearing in the Canadian Medical Association Journal attempted to defuse any "unnecessary alarm" on tardive dyskinesia and exhorted that the disease must be accepted:

66* *

*There is no adequate substitute for phenothiazines in the treatment of schizophrenia, and this and other side effects must be accepted as an unfortunate but at present inevitable price for the benefits of this therapy."65

Some one and a half years later in April 1966, an article published in the Archives of Neurology sounded this note of caution and simultaneously spoke of the vilest of "medical" practices-namely, the deliberate induction of physical disease: ** If, as it seems persistent [tardive] dyskinesia is a possible hazard of phenothiazine therapy, then the appearance of abnormal movements should not be taken so lightly as in the past. The conscious attempt to produce severe extrapyramidal syndromes 66 in order to gain maximal therapeutic effect must be undertaken with this risk in mind, and the concept that organic disease must be produced in order to combat functional illness 67 needs careful re-examination.” [Emphasis added.] 68

By 1972 there was no longer urging to accept tardive dyskinesia as the "lesser of two evils" but frank admission that such had been done, and that the continued use of antipsychotic drugs was allegedly essential in spite of their deleterious effects: Because of the lack of adequate substitutes for the neuroleptic drugs in the treatment of psychosis, tardive dyskinesia has been accepted as an undesirable but occasionally unavoidable price to be paid for the benefits of prolonged neuroleptic therapy. However, those familiar with this syndrome realize that it may impose limitation on the patient's social adjustment even though there is a remission of psychotic symptomatology. Oral dyskinesia may be disturbing to the patients not only from a cosmetic viewpoint, but it can, albeit rarely, impair speech, feeding, and breathing. It may thus constitute a real handicap for patients whether they are inside or outside the hospital. Fortunately or unfortunately, the tardive dyskinesia patients at our hospital tend to be severely impaired by their psychosis and do not complain about their neurological disabilitty

** 69

It is rather amazing how the writers of this article can state in one breath that there are no "adequate substitutes for neuroleptic drugs in the treatment of psycho

62 S. Turunen et al., "The Bucco-Linguo-Masticatory Syndrome as a Side-effect of Neuroleptics Therapy," Psychiatric Quarterly, v. 41, p. 275, 1967.

63 Leo Hollister, "Antipsychotic Medications: Schizophrenia," in Psychopharmacology From Theory to Practice edited by J. Barchas, P. Berger, and G. Elliot, p. 145, 1977. ACNP-FDA Task Force, "Neurological Syndromes Associated with Antipsychotic Drug Use," Archives of General Psychiatry, v. 28, p. 464, 1973.

64 Jonathan O. Cole, "Tardive Dyskinesia-Legal and Therapeutic Aspects" in Neuropharmacology by Boissier, Hippius, and Pichot, p. 369, 1974.

65 Canadian Medical Association Journal, v. 91, p. 1081, November 14, 1964.

66

Extrapyramidal syndrome-The extrapyramidal nervous system is that part of the central nervous system which controls movement or motion. Thus, an extrapyramidal syndrome is a disorder of normal movement or motion such as parkinsonism or tardive dyskinesia.

67 Functional illness-Mental aberration of some sort for which there is no determinable organic cause such as a brain tumor or stroke.

68 William R. Schmidt, "Persistent Dyskinesias Following Phenothiazine Therapy," Archives of Neurology, v. 14, p. 375.

69 Kazamatsuri et al., "Therapeutic Approaches to Tardive Dyskinesia," Archives of General Psychiatry, v. 27, p. 492, 1972.