Tardive Dyskinesia

   A dyskinesia is an involuntary movement; tardive means that its onset is delayed. Tardive dyskinesia (TD) refers to an iatrogenic "extrapyramidal" disorder caused by the long-term administration of antipsychotic drugs. (See Extrapyramidal Side Effects [EPS].)

   The mechanism of TD is still obscure, but it may be related to hypersensitivity of the "postsynaptic" (downstream) D2 dopamine receptors in the basal ganglia (as opposed to neuroleptic-induced Parkinson’s disease, which is caused by a shortage of dopamine).

   Extrapyramidal side effects of various kinds may be induced by antipsychotics. Some of the side effects include symptoms of Parkinson’s disease, such as akinesia (inability to move) and tremor. But the extrapyramidal symptoms of TD, involving hypermotility of the muscles as in a chorea, are almost the opposite of those of neuroleptic-induced Parkinsonism. TD causes involuntary movements of the tongue and jaw in particular, especially lip-smacking and tongue-protrusion, and sometimes dyskinesias of the trunk and extremities as well. More than half of the cases remit after medication is discontinued, but some do not, and TD is among the more visible side effects of some of the classic antipsychotics such as haloperidol (trade name Haldol; developed by the Janssen company, introduced in Europe in 1959 and in the American market by McNeil Laboratories in 1967), or Smith Kline & French’s trifluoperazine, marketed as Stelazine in 1958. (Newer "atypical" antipsychotics such as Sandoz’s clozapine [Clozaril, introduced in the American market in 1990] and Lilly’s olanzapine [Zyprexa, marketed 1996] have less Parkinsonism, and clozapine may be used to suppress TD; that is why they are called atypical.)

   TD was first described in 1957 by Matthias Schönecker, on staff at a hospital in Essen-Brobeck, in The Psychiatrist (Der Nervenarzt) under the title "A Strange Kind of Oral Syndrome in Chlorpromazine Therapy" ("Ein eigentümliches Syndrom im oralen Bereich bei Megaphenapplikation"). The symptoms of lip-smacking struck him because they continued well after stopping the treatment. Jean Sigwald (1903–) and co-authors at the Brousse Psychiatric Hospital in Paris then characterized TD more fully in 1959 in the Revue neurologique, calling it "dyskinetic-hypertonic syndrome," especially "facial-buccal-lingual-pharyngeal dyskinesia" (p. 557). The term "TD" itself was coined in 1964 in the Acta Psychiatrica Scandinavica by Arild Faurbye (1907–1983), a psychiatrist at St. Hans Psychiatric Hospital in Roskilde, Denmark, and co-workers: "Tardive dyskinesia is first and foremost characterized by the occurrence of dyskinetic movements, besides that tremor and autonomic symptoms may occur, and the syndrome is often combined with [a] syndrome of rigidity" (p. 12). TD did not, however, loom prominently in the eyes of clinicians until the report of a joint task force in 1973 of the Food and Drug Administration and the American College of Neuropsychopharmacology, led by neurologist Daniel Tarsy of the Boston University medical school, and published in the American Journal of Psychiatry. Simultaneously, George E. Crane (1912–) had been warning about TD since 1968 when he was at the National Institute of Mental Health. As he wrote in a supplement of the American Journal of Psychiatry, "The frequency of this syndrome in samples of chronic patients appears to be considerable" (p. 41). In a 1973 article in Science on "late, unanticipated effects of neuroleptics," Crane said, "Many physicians are still unaware of this problem or seem to be completely unconcerned about it, although tardive dyskinesia has become a common sight in all wards of hospitals where drugs are administered routinely for long periods of time" (p. 127). By this time, Crane was research director of the Spring Grove State Hospital in Baltimore.

   The diagnosis TD entered the DSM system only in the fourth edition of the Manual in 1994 alongside the other "medication-induced movement disorders." They were put in the category of disorders "provided for further study."