Tardive Dyskinesia and other drug-induced movement disorders among handicapped children and youth

Applied Research in Mental Retardation, Vol. 1, pp. 55-69, 1 9 8 0 Printed in the USA. All rights reserved.

0270-3092/80/010055-15502.00/0 Copyright © 1980 Pergamon Press Ltd.

Tardive Dyskinesia and Other Drug-Induced Movement Disorders Among Handicapped Children and Youth C. T. Gualtieri, M. D. and Barbara Hawk, M.S. The University of North Carolina

Neuroleptic drugs are used in substantial numbers o f mentally retarded children and youth. Many children are treated f o r very long periods o f time, often with the sole purpose o f suppressing undesirable behavior. Neuroleptic drugs can exert untoward effects upon many biological systems, and movement disorders or dyskinesias are among the most important consequences o f neuroleptic use. The literature concerned with tardive dyskinesias, the most serious o f these movement disorders, is examined. A brief discussion o f neuroleptic-induced movement disorders, as well as o f withdrawal emergent symptoms and acute extrapyramidal effects, is presented. Studying abnormal drug-induced movements in a population already prone to abnormal movements (e.g., stereotypies) even without drugs is extremely difficult but vital to establishing proper guidelines f o r neuroleptic use.

A m o n g children and adolescents, neuroleptics ("antipsychotic" drugs or "major tranquilizers") are used in a variety of clinical circumstances: severe anxiety disorders, hyperkinesis, behavior disorders, "borderline" states, and the various psychoses of childhood. Neuroleptics are used among mentally retarded people for many of the same conditions, although much of the time they are applied simply to suppress undesirable behaviors (Sprague & Baxley, 1978). In most clinical situations among children, neuroleptics are broght to bear more for their sedative action than for their relatively specific antipsychotic effects. Thus, chlorpromazine and thioridazine, the This work was supported in part by USPH Grant No. HD 10570to Dr. Gualtieri from the National Institute of Child Health and Human Development, Grant NO. 77-20 to Dr. Gualtieri from the North Carolina Alcohol Research Authority, and Grant No. MH-33127 to Dr. Gualtieri from the National Institute of Mental Health. Reprints may be obtained from C. Thomas Gualtieri, M.D., Department of Child Psychiatry, North Carolina Memorial Hospital, Chapel Hill, NC 27514. 55

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two most highly sedating neuroleptics, are also the two most commonly used neuroleptics among institutionalized mentally retarded persons (Lipman, 1970). We have no idea how frequently neuroleptic drugs are used among children and adolescents, although Lipman's study (1970) of mentally retarded persons suggests that the total number of neuroleptic-treated patients in this category, at least, may exceed 100,000. Lipman also found that over 50% of the mentally retarded patients who were treated with neuroleptics had been treated for more than two years. Thus, although we have no precise figures, antipsychotic drugs are used in substantial numbers of children, and a large number of young people treated with neuroleptics are treated for very long periods of time. Although the clinical indications for neuroleptic drug prescription among young people are often questionable, the clinical consequences of neuroleptic treatment are sometimes quite serious. Neuroleptic drugs are biologically very active, and can exert untoward effects upon a number of systems. Movement disorders, or dyskinesias, are among the most important consequences of neuroleptic use, and the most serious of these is a disorder called tardive dyskinesia. There is a vast literature concerned with the problem of tardive dyskinesia in adult psychiatric patients, but little is known about the condition, its frequency and severity among children, young adults, or mentally retarded people. Tardive dyskinesia is a complex syndrome of hyperkinetic involuntary movements characterized by a variable mixture of orofacial dyskinesias (e.g., tongue movements, grimacing, involuntary spasms of extraocular muscles, torticollis), chorea (e.g., flailing arms, etc.), athetosis (involuntary movements characterized by slow, worm-like movements of limbs and digits related to extrapyramidal damage), dystonia (fixed postures or contortions), and tics (Baldassarini & Tansey, 1978). The evidence for association between late onset dyskinesias and neuroleptic drug treatment is mainly epidemiologic, but it is convincing. The term tardive dyskinesia may actually embrace a number of different disorders. In its "classic" form, as first described by Uhrbrand and Faurbye in 1960, it comprises movements of the tongue, lips and jaw (BLM, or buccolingualmasticatory movements); the disorder has been described most commonly in older, chronically hospitalized schizophrenic patients, who had been treated with high doses of neuroleptics for long periods of time. "Classic" forms of tardive dyskinesia usually emerge only upon neuroleptic withdrawal, or after dose reduction - an "escape" phenomenon. Chronic blockage of dopaminergic neurons in the basal ganglia by neuroleptic drugs supposedly induces a "supersensitivity" state, in which the neuron becomes more sensitive to dopamine after the drug is reduced or withdrawn, than it was prior to drug treatment. This dopamine-supersensitivity state causes the

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abnormal movements, a clinical event that is not dissimilar to Huntington's chorea. Other forms of tardive dyskinesia might stem from an entirely different physiological background, and in some patients, movements may actually decrease after drug withdrawal (Casey & Denney, 1977). The dopaminesupersensitivity model, although it is probably appropriate only to "a subgroup of tardive dyskinesias, is supported by some interesting preclinical experiments (Creese, Burt & Snyder, 1977) and also some promising new therapeutic interventions (Carroll, Curtis & Kokmen, 1977; Growdon, Hirsch, Wurtman & Wiener, 1977). Certain "risk factors" have been linked to tardive dyskinesia, although many of the original ideas concerning clinical elements that might predispose a given patient to tardive dyskinesia have not been supported by further research (Baldassarini & Tansey, 1978). Chronic neuroleptic treatment is the sine qua non for the development of tardive dyskinesia. The disorder is probably more frequent in patients treated with high doses of antipsychotic drugs for long periods of time. However, cases have been reported among patients who have been treated with low doses of neuroleptic drugs for only a few months (Asnis, Leopold, Duvoisin & Schwartz, 1977). Tardive dyskinesia was once felt to be associated with advanced age, and was thought to be more common among female patients. Both of these connections are questionable (Baldassarini & Tansey, 1978). No particular diagnostic group of psychiatric patients seems to be more or less vulnerable to the disorder. Neither organic brain syndrome, psycho-surgery, nor electro-convulsive therapy (ECT) render the patient at greater risk. The development of acute extrapyramidal symptoms upon initiation of drug treatment does not identify a group of patients at greater risk. No particular neuroleptic is more or less likely to induce tardive dyskinesia. Some researchers believe that the chronic use of anticholinergic agents in association with neuroleptics may increase the chances that tardive dyskinesia will develop (Casey & Rabins, 1978). Periodic drug holidays are usually recommended as a preventive measure, but one cannot be sure that intermittent treatment with neuroleptic drugs is necessarily safer than continuous treatment. A recent study suggests that frequent "drug holidays" may, in fact, render the patient at greater risk to develop irreversible tardive dyskinesia (Jeste, Potkin, Sinha, Feder & Wyatt, 1979). If this proves to be true, then we are faced with a terrible dilemma. Trial withdrawals are the only way to determine if a patient really does need to be on a neuroleptic drug. But frequent drug holidays may predispose to irreversible dyskinesias. Tardive dyskinesia is an important clinical entity because it is preventable, and because it can be extremely debilitating. The severity of tardive

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dyskinesia can range from purely cosmetic or nuisance symptoms to severe, incapacitating, even life-threatening reactions (Growdon et al., 1977). Studies of reversibility of the syndrome are inconclusive. In some patients, tardive dyskinesia is reversible, while in others it is not (Baldessarini & Tansey, 1978). No particular treatment has been found to be of unequivocal benefit for the majority of patients with tardive dyskinesia, although some hopeful developments might arise out of current work with acetylcholine precursors (Growdon et al., 1977) and with dopamine receptor desensitization techniques (Carroll et al., 1977). Other Movement Disorders Induced by Drugs

A second class of movement disorders associated with neuroleptic agents are the acute dysklnesias: pseudoparkinsonism (characterized by akinesia, or a slowing of volitional movements, a mask-like facies, and rigidity and tremors at rest, usually of the upper extremities), acute dystonia (fixed postures or contortions), and akathisia (an extrapyramidal side effect in which the patient feels restless and compelled to change positions frequently). Although the clinical manifestations of these disorders sometimes resemble those of patients with unusual varieties of tardive dyskinesia, the association of acute extrapyramidal effects with the initiation of neuroleptic therapy and of tardive dyskinesia with long-term maintenance or neuroleptic withdrawal speaks to a major difference in the pathophysiology, and perhaps also in the neurochemistry of the different disorders (Clow, Jenner, Theodorou & Marsden, 1979). The main focus of this review will be upon tardive dyskinesia in children, adolescents and young adults, although some mention will be made of acute extrapyramidal symptoms in this population. If tardive dyskinesia is an important clinical issue in the treatment of adult patients, some of whom have been treated with neuroleptic agents for 25 years, it is a crucial issue for children, some of whom seem to be looking forward to a lifetime of neuroleptics.

REVIEW OF T H E L I T E R A T U R E

Tardive Dyskinesia A m ong Children and Young Adults

The literature of tardive dyskinesia among young schizophrenic, autistic and mentally retarded people is comprised entirely of case reports and clinical surveys. No clear conclusions from the work can be drawn beyond noting that tardive dyskinesia does occur among children and adolescents, that the condition embraces a wide range of clinical manifestations, that it is

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not always reversible and that it may be associated with low doses of neuroleptics over a short period of time.

Psychiatric Population In 1972, Treffert reported a retrospective study of 125 children (age 4 to 16 years) in a state psychiatric hospital who were treated long-term with phenothiazines. Eighty-six of the 125 were treated with only one drug; 39 received more than one phenothiazine. Ten children had symptoms of tardive dyskinesia. Seven were schizophrenic children, two were hyperkinetic and one was unsocialized/aggressive. The dyskinesias described were facial tics, "rhythmical and myoclonic-like" movements of the upper extremities, and akathisia. In all of the cases, symptoms arose between three and ten days after the neuroleptic was discontinued and then subsided completely in all of the children within twelve months. The children who developed tardive dyskinesia were compared to 64 children on chronic neuroleptic therapy who had no dyskinesia upon withdrawal from neuroleptics. The children with tardive dyskinesia tended to have been treated with higher doses of phenothiazines for longer periods of time. The syndrome was present in 10 of 16 children whose total phenothiazine intake over a period of 15 months or longer totalled 130 grams (chlorpromazine equivalents) and in 6 of 10 whose daily doses just prior to withdrawal were higher than 200 mg. Other authors have described tardive dyskinesia in young patients that was considerably incapacitating. In 1977, Tarsey, Grenacher and Bralower reported on two of "several young individuals with extensive and disabling tardive dyskinesia." One was a 23-year-old man with "acute undifferentiated schizophrenia" who had been treated with trifluoperazine and then with thioridazine for two years. He developed a severely incapacitating dyskinesia, characterized by generalized motor restlessness, continuous grimacing, spasmodic contractions of his tongue, jaw and facial muscles, torticollis and retrocollis (retraction or extension in torticollis), athetoid movements of his hands, and abnormal posturing of the arms. The movements were brought under control with haloperidol, but the patient developed pseudoparkinsonism, and subsequently committed suicide. The second case, a 19-year-old man with severe obsessive/compulsive disorder, developed a similar dyskinesia after eight years of treatment with high doses of trifluorperazine. The symptoms abated, but did not remit completely, on 60 mg of haloperidol per day. McLean and Casey (1978) reported the case of a 15-year-old schizophrenic male who had been treated with low doses of haloperidol and then with low doses of thioridazine for three years. After the patient developed mild jerking movements of the trunk and limbs, the thioridazine was increased.

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At this point, the patient developed such severe choreoathetosis and dystonia that he required hospitalization. The movements persisted for several months after the drugs were withdrawn. The patient could not walk because of the dyskinesia. The movements abated after a course of treatment with deanol. Caine, Margolin, Brown and Ebert (1978) described an extremely interesting case, a 15-year-old male who had an unusual combination of problems all of which could be attributed to excessive central dopamine function. He had been hyperkinetic since he was 5 years old. He developed facial tics at age 7, and Tourette's syndrome was diagnosed at age 11. The patient was treated with haloperidol, in high doses, for more than three years. When haloperidol was discontinued, he developed severe dyskinetic movements, his tics reoccurred, and he became psychotic. Fortunately, all of his symptoms resolved after the haloperidol was reinstated. Clearly, not all cases of tardive dyskinesia described among young patients are associated with high doses of long-term neuroleptic treatment. Asnis et al. (1977) reported a survey of 69 psychiatric outpatient adults treated with low doses of neuroleptic drugs for a relatively short period of time (47 °7o for less than two years). Thirty of the 69 patients had tardive dyskinesia. Four cases of tardive dyskinesia occurred in patients who were in their twenties. In a study of dyskinetic phenomena in 42 psychotic children treated with neuroleptic drugs, Polizos and Engelhardt (1978) described tardive dyskinesia in only two children. One was a 9-year-old girl who had been treated with trifluoperazine for 17 months. After 12 months of treatment, increasing the dose to 36 mg per day was correlated with abnormal tongue movements. After the dose was decreased to 10 mg per day, the movements disappeared. A 9-year-old boy was treated with thioridazine for 5 months. After 8 weeks of treatment, the dose was raised to 800 mg per day. Three weeks after the dose was increased, the boy developed tongue movements, choreoathetoid movements, and myoclonic jerks. These movements disappeared after the dose was lowered to 300 mg per day. However, these two cases were probably improperly labelled tardive dyskinesia. They both appear to represent acute dyskinesias associated with increase in the dose of neuroleptics, more similar to the acute dyskinesias that occur when neuroleptics are begun, than to tardive dyskinesia. Tardive Dyskinesia A m o n g Mentally Retarded People

In 1975, Paulson, Rizvi and Crane reported a study of 103 residents of a state mental retardation facility, age 11 to 16 years, who had received chronic neuroleptic drug treatment. Twenty-one children had "mild to

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moderate" symptoms of tardive dyskinesia while on neuroleptic drugs, After withdrawal, the dyskinesias grew worse in 7 children, and subsequently improved when drug treatment was reinstated. Two children, however, improved after the drugs were withdrawn. Four years later, the authors examined the same patients. There was no change in the dyskinesias among 6 patients, 4 had grown worse, and 5 were improved. Five children were logt to follow-up and one child could not be properly evaluated. None of the children was "incapacitated" because of tardive dyskinesia. Browning and Ferry (1976) described a 10-year-old boy who was severly mentally retarded and had autistic traits. He developed severe dyskinesia after three years of treatment with procholorperazine, 20 mg per day. The dyskinesia continued for several months after the drug was withdrawn, but the patient was lost to follow-up. Kumar (1976) described a severely mentally retarded 17-year-old girl who was treated for two years with high doses of thioridazine. She developed a dyskinesia which abated several months after drugs were withdrawn.

Withdrawal Emergent Symptoms In 1973, Polizos, Engelhardt, Hoffman and Waizer described a clinical situation they referred to as "withdrawal emergent symptoms." The syndrome is characterized by nausea and vomiting, loss of appetite, agitation, hyperkinesis, and a variety of peculiar movements. In a study of 34 psychotic children between the ages of 6 and 12 who were treated with a variety of neuroleptics for about one year, withdrawal symptoms upon acute discontinuance of medication occurred in 41%. In a subsequent report of 141 cases of acute neuroleptic withdrawal in schizophrenic and autistic children between the ages of 5 and 14 (Engelhardt, Polizos & Waizer, 1975), 48 % were found to have experienced withdrawal symptoms. Abnormal involuntary movements were found in 93% of the children. These were most frequently choreoathetoid movements of the trunk and extremities, myoclonic ballistic, and athetoid movements, posturing, dysmetria (inability to control accurately the range of movement in muscular acts, especially hand movements), tremor (involuntary, purposeless, rhythmic movements), and ataxia (incoordination of voluntary muscular action, especially muscle groups used in activities such as walking or reaching for objects). Oral dyskinesias, i.e., abnormal buccal, lingual movements, were found in only 16% of the children. Seventy per cent of the withdrawal symptoms arose within 14 days of drug discontinuance, and 93 % arose within 21 days. Spontaneous remission occurred within 85 days in 38 % of the cases. Anticholinergic drugs did not improve these symptoms, whereas reinstitution of neuroleptic treatment invariably led to remission.

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High potency neuroleptics were more likely to induce withdrawal symptoms. However, the incidence of withdrawal symptoms did not correlate with the occurrence of acute extrapyramidal symptoms during the initiation of treatment. Jacobson, Baldessarini and Manschreck (1974) described similar withdrawal dyskinesias in three young psychotic adults, ages 18, 19, and 24. Winsberg, Hurwic, Sverd and Kutch (1978) studied 11 children who had been treated with chronic neuroleptic drugs. Five had withdrawal symptoms but 6 did not. Using a Probenecid loading technique (Probenecid blocks passage of acid neurotransmitter metabolites from the cerebrospinal fluid, leading to an accumulation of same and thus to easier measurement), the authors could not find any differences in cerebrospinal fluid, homovanillic acid, or 5-hydroxyindoleacetic acid between the subjects who had withdrawal emergent symptoms and the subjects who did not. It is not clear whether withdrawal dyskinesias are clinical entities entirely distinct from tardive dyskinesia, or simply a variant of the same problem, limited to a shorter time frame. A clear separation cannot be made purely on the basis of the nature or the severity of the movements. Usually, withdrawal dyskinesias resolve spontaneously within a few weeks of discontinuing treatment, and are often accompanied by other symptoms of withdrawal, such as nausea and vomiting (Engelhardt et al., 1975; Polizos et al., 1973). The onset of abnormal movements with neuroleptic withdrawal may be accompanied by behavioral deterioration, hyperactivity or even psychosis (Chouinard & Jones, 1980; Polizos et al., 1973). These behavior changes are frequently interpreted by clinicians to mean that the patient "really needs" the drug, and the trial withdrawal is abruptly terminated. However, behavioral deterioration may in some cases be a manifestation of a withdrawal syndrome, or of a different kind of dopamine-supersensitivity states. A withdrawal period of 12 weeks may be necesary to establish that the behavioral changes are not simply an artifact of drug withdrawal (Polizos et al., 1973). A cute E x t r a p y r a m i d a l E f f e c t s

Since our primary focus is on the problem of tardive dyskinesia, we cannot offer an exhaustive review of the literature concerning acute dyskinesias among children treated with neuroleptic drugs. Suffice it to say that the full gamut of extrapyramidal symptoms described in adults, including pseudoparkinsonism, acute dystonia, akathesia, drug-induced catatonia, and oculogyria, have all been described among children treated with neuroleptics (Campbell, Fish, Shapiro & Floyd, 1971; Dietze, 1963; Fish,

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Cambell, Shapiro & Floyd, 1969; Kozmin & Weiner, 1960; Lucas, 1967). Unfortunately, acute reactions to neuroleptic drugs among children and young adults have never been systematically studied, although it is thought that acute dystonias are more frequent among younger patients (American College, 1973; Swett, 1975). In one of the few surveys, Polizos and Engelhardt (1978) report that dystonias occurred in 25% of a sample of psychotic children treated with neuroleptic drugs. Pseudo-parkinsonism occurred in 23% of the children. Drowsiness was a problem for 19% of the children. Two children out of 42 developed akathisia. Gupta and Lovejoy (1967) described a 5-year survey of normal children admitted to the hospital for acute phenothiazine toxicity. Fourteen of these children had been treated with phenothiazines because of gastrointestinal problems, and 6 were victims of accidental ingestion. The children's ages ranged from 1 ½ years to 15. The commonest symptom was drowsiness, followed (in order) by muscular rigidity and cog-wheeling (rigidity or rhythmic contractions noted on passive stretching of muscles), ophisthotonos (condition in which the head and lower limbs are bent backward and the trunk is arched forward by a tetanic spasm of the muscles of the back), hyperreflexia (reflexes increased above normal), irritability, ataxia, dystonia, drooling, dysarthria (impairment of articulation), torticollis, tremors, lockjaw, oculogyria, and generalized convulsions. All of the symptoms cleared completely within 48 hours, and the authors noted the diphenhydramine was useful in treating the symptoms. Other authors agree that anti-cholinergic drugs are useful in the treatment of acute extrapyramidal symptoms among children (Engelhardt, Polizos, Waiver & Hoffman, 1973). Obviously, a literature that is based almost exclusively on anecdotal reports and uncontrolled studies is biased in the direction of the most severe cases. However, the severity of extrapyramidal symptoms in the occasional child on neuroleptic drugs is striking. Shields and Bray (1976) described a 5½-year-old girl who was treated with almost homeopathic doses of haloperidol for what appeared to be Sydenham's chorea. The child developed a severe dystonia, was unable to walk, and developed fixed extensor posturing, which could not be controlled with a variety of different medications. Over several months, most of the symptoms abated, but occasional dystonia persisted. In 1968, Angle, McIntire and Zellerman described a 10-year-old mentally retarded girl who ingested an unknown amount of trifluoperazine, chlorpromazine, phenobarbital, and phenytoin. She developed ceaseless incoordinated movements of the trunk, extremities and face, severe spasms of the right side of the neck and back, torticollis and scoliosis. There was only slight improvement with benzotropine and diphenhydramine, and the movements persisted for at least 7 months.

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Dabbous and Bergman (1966) describe a severe spastic quadriparesis which persisted for two years in a 5-year-old boy who was admitted to the hospital with initial symptoms of dyskinesia and behavior change. The child had large amounts of phenothiazines in his urine, and two different neuroleptic drugs were kept in his parents' medicine chest. The child also may have ingested unknown amounts of chlordiazepoxide and promethazine. Such catastrophic reactions to neuroleptic drugs are not unknown among adult patients (Paulson, 1975). However, in neither of the above mentioned cases can other factors be discounted: in the first case, a pre-existing (and undiagnosed) movement disorder, and in the second and third cases, a combination of medications. We do not know how common acute extrapyramidal symptoms are in the pediatric population. Chiles (1978) described acute extrapyramidal symptoms in 100% of a sample of psychotic adolescents (age 13 to 18) who were treated with rather high doses of haloperidol, thiothixene and fluphenazine. Other authors, however, using lower doses, describe much lower frequencies (Jacobs, 1966; Burk & Menolascino, 1968; Levann, Note 1).

Dyskinesias Associated with Other Medications

Acute dyskinetic movements have been described in children and young adults in association with methylphenidate (Denckla, Bemporad and MacKay, 1976), dextroamphetamine (McAndrew, 1974), phenytoin (Kokenge, Kutt & McDowell, 1965), antihistamines (Lavenstein & Cantor, 1976), chloraquin (Singhi, Singhi & Singh, 1977), vincristine (Carpentieri & Lockhart, 1978), ethosuximide (Ehyai, Kilroy & Fenichel, 1978), and carbamazepine (Crosley & Swender, 1979). Reports of acute dyskinesias in adults are associated with some of the above-mentioned drugs (Ashcroft, Eccleston & Waddell, 1965; Extein, 1978; Mattson & Calverly, 1968), as well as with anticholinergic medications (Fahn & David, 1972) and benzodiazepines (Kaplan & Murkofsky, 1978). Chronic dyskinesias resembling tardive dyskinesia have been described in adults on antihistamines (Sovner, 1977) and lithium (Beitman, 1978). The differential diagnosis of druginduced dyskinesias among children must necessarily take into consideration the impact of other concomitant medications. ANALYSIS OF RESEARCH ON TARDIVE DYSKINESIA Tardive Dyskinesia: R i s k Factors A m o n g Children

There is no way to predict which children are more likely to develop acute extrapyramidal symptoms, withdrawal emergent symptoms, or tardive

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dyskinesia. Children treated with high potency neuroleptics (e.g., haloperidol or trifluoperazine) are probably more likely to develop extrapyramidal symptoms (Cambell et al., 1971; Chiles, 1978; Dietze, 1963; Engelhardt et al., 1973; Fish et al., 1969;Kozmin & Weiner, 1960; Lucas, 1967), although acute dyskinesias have also been reported with low potency neuroleptics (Polizos & Engelhardt, 1978). It appears that withdrawal emergent symptoms are more common in children who are abruptly withdrawn from high potency neuroleptics (Polizos et al., 1973; Engelhardt et al., 1975). It is likely that children treated for longer periods of time, on higher doses of medication, might be at greater risk for tardive dyskinesia (Treffert, 1972), but children treated on rather small doses, for short periods of time, may also suffer severe consequences. The presence of organic brain syndrome was originally felt to predispose the older patient to tardive dyskinesia, but subsequent studies have tended to discount this idea (Baldessarini & Tansey, 1978). In McAndrew's (1974) study, children with organic brain syndrome were not likelier to develop tardive dyskinesia. However, Angle, Mclntire and Zellerman (1968), in a survey of 1,033 normal children hospitalized for accidental poisoning, discovered an increased incidence of central nervous system (CNS) symptomatology among those children who had suffered antecedent CNS insuits, or who had had slow early development.

Difficulties in Studying Tardive Dyskinesia in Children We know that tardive dyskinesia should be a matter of concern for clinicians who treat children with neuroleptic medications, but we know very little beyond that. There are no systematic studies in the area. But systematic studies of dyskinesias in the pediatric population are by no means easy to do. One problem has to do with pre-existing movement disorders in children who are likely to be treated with neuroleptic drugs. Many mentally retarded and autistic children have stereotyped movements, and neuroleptic drugs can suppress stereotypies (Davis, Sprague & Werry, 1969). An abnormal movement that arises at the time of neuroleptic withdrawal may simply be a re-emergent stereotypy. Mentally retarded children with cerebral palsy may have choreoathetoid movements. Hyperkinetic children may also have choreiform movements. Many psychotic children exhibit posturing, grimacing, and other unusual mannerisms while institutionalized children frequently develop peculiar movements mimicking the mannerisms of other children on the ward. It is no simple matter to try to study abnormal drug-induced movements in a population that is all too prone to abnormal movements, e.g., stereotypies, even without neuroleptic drugs.

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The examination of the severely disturbed, uncooperative child is no easy business, either. Some children will not respond to the examiner's c o m m a n d to sit still, and the distress provoked by the examination can actually increase unusual movements. Many children who are treated with neuroleptic drugs are also treated with other medications, either concomitantly or serially. The commonest group of medications used in these children include stimulants, anticonvulsants and antihistamines, all of which are known to induce abnormal movements. Any study of tardive dyskinesia that tried to limit its scope to children who had no abnormal pre-existing movements, who could fully cooperate with examiners, and who never took other medications would likely have a very small number of subjects. Research in the problem of tardive dyskinesia in children will have to develop new strategies such as multicenter, collaborative research, to untangle a very knotty problem. SUMMARY

We are left with a confusing array of anecdotal reports and uncontrolled studies, a heterogeneous array of children with a variety of diagnoses and movements, and a wide range of intercurrent problems and medications. The scientific community is trying to study a syndrome in which the careful delineation of dyskinesia can be confused with a myriad of other peculiar movements. Even if there were no such symptoms as tardive dyskinesia, extrapyramidal symptoms, or withdrawal emergent symptoms, one would advise caution in the application of neuroleptic drugs a m o n g young people. Effects on the child's general demeanor, his/her level of alertness, and his/her personality, not to mention his/her learning patterns, would mitigate against the use of these agents except in carefully chosen circumstances. However, some children are prone to psychosis; some can be severely disorganized; and some do have behavior problems that do not respond to other therapies. Therefore, even in the best of worlds, neuroleptics are likely to be used a m o n g mentally retarded children and youth. In this light, the problem of tardive dyskinesia becomes very important. Proper guidelines for the application of neuroleptics a m o n g young people have not been set down. When they are, they must be guided by the fruits of systematic research efforts. R E F E R E N C E NOTE

1. Levann, L. J. Haloperidol in the treatment o f behavioral disorders in children and adolescents. Paper presented at the Canadian Psychiatric Association Meeting, Regina, Saskatchewan. June 1968.

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