A patient with chronic pain was treated for about 5 years with fluphenazine 4 mg daily for anxiety.

Fråga: A patient with chronic pain was treated for about 5 years with fluphenazine 4 mg daily for anxiety. She has developed irreversible tardive dyskinesia. How well documented is tardive dyskinesia in relation to low dose treatment of nonpsychotic conditions.

Sammanfattning: There are single case reports in the literature concerning treatment with low doses of neuroleptics and occurence of TD. The reports include non-psychotic patients. This stresses the need to weigh the benefit of treatment against the risks of side effects particularly when side-effects may be irreversible.

Svar: One of the neurological side-effects of neuroleptic therapy in both psychotics and non-psychotics is tardive dyskinesia (1,2,3). It is called "tardive" because unlike the other extrapyramidal side-effects (dystonia, akathesia, akinesia and Parkinsonism), it usually occurs later in the course of treatment. The syndrome is usually referred to, descriptively, as bucco-linquo-masticatory syndrome (BLM syndrome) or oral dyskinesia. Hyperkinesia, which is the main feature may affect other parts of the body. It may be irreversible after withdrawal of therapy. It should be noted that tardive dyskinesia can occur spontaneously in patient not on neuroleptic therapy (2).

Tardive dyskinesia is associated with virtually all neuroleptics in current use and none holds a preferential position. The American Psychiatric Association Task force (1) concluded that neither prolonged exposure nor exposure to large total amounts of drugs was the determining factor in TD development, despite the clear association between neuroleptics and TD (1). Increasing age has been consistently shown to be a risk factor. TD occurs in children as well and may follow the adult pattern (4,5,6). However it can also be seen with low dose short term treatment. Other suspected risk factors include alcohol related disorders and concurrent administration of anticholinergics (3,7). The role of dosage is uncertain. The total cummulative dosage may relate to the severity of TD. In a cross-cultural comparative study referred to in (8) if low and high dose neuroleptic therapy, no statistically significant difference in the prevalence of TD was noted. The role of pharmacogenetic factors can not be excluded in this study. There are conflicting reports about the influence of plasma levels of neuroleptics in the development of TD (9,10).

There are case reports in the literature concerning TD associated with low-dose neuroleptic therapy (5,7,11). In some of these the patients were non-psychotics and very small doses of neuroleptics (so-called "neurosis doses") were used. 10 such case are discussed in a review (11) and 5 of these patients had irreversible TD. In one report irreversible TD developed in a 58 year old non-psychotic moderate to heavy drinker after stoppping treatment with Stelabid (a preparation containing an anticholinergic isopropamide 5 mg and 2 mg of trifluoperazine). 1 Tardive dyskinesia. Br Med J 1981; 282: 1257-1258 2 Gerlach J: Tardive dyskinesia. Dan Med Bull 1979; 26: 209-245 3 Tardive dyskinesia. Lancet 1979; II: 447-448 4 Browning DH, Ferry PC: Tardive dyskinesia in a ten-year-old boy. An undesirable sequel of phenothiazine medication. Clin Pediatrics 1976; 15: 955-957 5 Meyler/Herxheimer, Side effects of drugs, 1981; Annual 6: 46-59 6 Petty LK, Spar CJ: Haloperidol-induced tardive dyskinesia in a 10-year-old girl. Am J Psychiatry 1980; 137: 745-746 7 Chounard G, Boisvert D, Bradwejn J: Tardive dyskinesia in a nonpsychiatric patient due to short-term use of a neuroleptic/anticholinergic combination drug. Can med Assoc J 1982; 126: 821-822, 827 8 Kane JM, Smith JM: Tardive dyskinesia. Prevalence and risk factors, 1959 to 1979. Arch Gen Psychiatry 1982; 39: 473-481 9 Fairbairn AF, Rowell FJ, Hui SM, Hassanyeh F, Robinson AJ, Eccleston D: Serum concentration of depot neuroleptics in tardive dyskinesia. Br J Psychiat 1983; 142: 579-583 10 Bolvig Hansen L, Larsen NE, Vestegard P: Plasma levels of perphenazine (Trilafon) related to development of extrapyramidal side effects. Psychopharmacol 1981; 74: 306-309 11 Meyler/Herxheimer, Side effects of drugs. 1983; Annual 7: 56-73