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Thiopropazate Hydrochloride in Persistent Dyskinesia K 22 BRITISH MEDICAL JOURNAL 2 OCTOBER 1971 One patient developed severe haematemesis needing inpatient aware of the unreliability of subjective estimates of the difference therapy and had to be withdrawn from the trial. In retrospect in movement of the two sides of the face, but the statistically it was clear that he should not have been admitted to the trial significant differences reported here are considerable and it is Br Med J: first published as 10.1136/bmj.4.5778.22 on 2 October 1971. Downloaded from because he had a history of peptic ulceration. unlikely that observer error is responsible. The actual assess- ments of recovery in the severely denervated patients receiving corticotrophin mentioned above were 10%, 15%, 10%, 10%, Discussion 15%, and 15%, while all who took prednisolone were assessed at 50% recovery or above. Controlled trials of treatment in Bell's palsy are difficult to We had hoped to show that corticotrophin injections gave perform because of delay in starting therapy which is likely to better results than oral prednisolone if only because a previous prejudice the result. For this reason the patients were subdivided trial of cortisone for Bell's palsy gave a negative result (Tavemer, into early and late groups. Sixty-six started treatment on the 1954). In retrospect it is clear that the 1954 trial was intade- first or second day of paralysis and 120 on the third or fourth quately planned to produce a reliable result. The treatment was days. The results of earlier treatment were indeed better, started far too late to be effective, the dose of cortisone was too though both groups showed benefit. However, in very severe low, and the number of patients tested was too small. attacks the major damage may be done within the first few At present we believe that oral prednisolone is the treatment hours and treatment should be started at once. of choice in Bell's palsy and should be given in full doses from It has previously been shown that the outcome in untreated the day of onset. The small risk of serious side effects is accept- Bell's palsy becomes worse with increasing age (Langworth and able in view of the significant reduction in the incidence of Taverner, 1963) so the patients were further subdivided into severe denervation. young and older groups. There were 104 patients in the young group and 82 in the older group. The expected difference was observed, but in the whole series the mean age of the patients References who developed denervation was 44-6 years for the corticotrophin Jonsson, B., Reis, G. von, and Sahlgren, E. (1951). Acta Psychiatrica et group and 43 9 years for the prednisolone group. Neurologica, Suppl. No. 74, p. 60. Assessment of the result of treatment is a difficult problem Langworth, E. P., and Taverner, D. (1963). Brain, 86, 465. even if very elaborate methods are used. The presence or Miller, H., Newell, D. J., and Ridley, A. (1961). Lancet, 2, 1120. Peiris, 0. A., and Miles, D. W. (1965). British Medical_Journal, 2, 1162. absence of denervation can be determined by the appearance Ross, J., Colmant, H. J., and Bohm, P. (1958). Deutsche Zeitschrift fur of associated movements (Langworth and Taverner, 1963), Nervenheilkunde, 177, 475. Taverner,.D. (1954). Lancet, 2, 1052. and this is the strictest criterion available. The results now Taverner, D., Fearnley, M. E., Kemble, F., Miles, D. W., and Peiris, 0. A. reported are based almost entirely on this finding. We are well (1966). British Medical-Journal, 1, 391. Thiopropazate Hydrochloride in Persistent Dyskinesia http://www.bmj.com/ K. SINGER, M. N. CHENG British Medical Journal, 1971, 4, 22-25 other treatment. Further research is required to deter- mine the long-term effectiveness of the drug. Summary on 25 September 2021 by guest. Protected copyright. Thiopropazate (Dartalan) was found to be significantly more effective than a placebo in relieving dyskinesia in Introduction 23 patients with functional psychosis and persistent dyskinesia associated with prolonged phenothiazine The treatment ofpersistent dyskinesia associated with prolonged therapy. Each patient whose dyskinesia had persisted phenothiazine therapy has been unsatisfactory. Brandrup unchanged for at least one month after phenothiazine (1961) reported success with tetrabenazine in four patients withdrawal received thiopropazate by mouth for three (but we could find no further report on the value of this drug) weeks and the placebo for a similar period. Patients were and Roxburgh (1970) used thiopropazate successfully in two evaluated before the trial, at three weeks, and at six patients. weeks. Thiopropazate hydrochloride (Dartalan) is chemically The drug also improved psychotic behaviour. Possible described as 10-(3[4-(2-acetyoxyethyl)piperazin-1-yl]propyl)-2- side effects, which were generally mild, were noted in chlorophenothiazine dihydrochloride and is a phenothiazine eight patients, of whom six had Parkinsonism and four structurally closely related to chlorpromazine. It has been drowsiness. None had side effects while on the placebo. reported to be of value in schizophrenia (Hamilton et al., 1960). The findings indicate that thiopropazate is of value in Reports on its effectiveness in controlling choreiform movements persistent dyskinesia associated with prolonged pheno- have been confined to Huntingdon's chorea (Mathews, 1958; thiazine intake-a condition hitherto unresponsive to Bruyn, 1962; Lyon, 1962) apart from, so far as we can trace, one case each of non-hereditary chorea (Lyon, 1962), probable senile chorea with polycythaemia (Heathfield, 1968), and Sydenham's chorea activated by oral contraceptives (Lewis and University of Hong Kong, Hong Kong Harrison, 1969). Kabat and McLeod (1959) reported improve- K. SINGER, M.R.C.P.ED., D.P.M., Lecturer in Psychiatry and Specialist in Charge, Mental Health Service ment of involuntary movements in 24 cases of cerebellar ataxia and intention tremor. Castle Peak Hospital, Hong Kong Persistent dyskinesia affecting the face, mouth, tongue, M. N. CHENG, M.B., B.S., Medical Officer and jaw (oral dyskinesia) is well known as an insidious and late BRITISH MEDICAL JOURNAL 2 OCTOBER 1971 23 development of protracted phenothiazine intake. The syndrome was a functional psychosis; and (5) there was no organic has been reviewed by Crane (1968) and Kline (1968) and its disorder present known to cause involuntary movements, such relation to other phenothiazine-induced dysfunctions discussed as Huntington's chorea, senile and other choreas and athetoses, Br Med J: first published as 10.1136/bmj.4.5778.22 on 2 October 1971. Downloaded from by Faurbye (1970). Some of the patients also showed dyskinesia presenile and senile dementia, or a family history of involuntary affecting the neck, limbs, and trunk, manifesting usually as movements or dementia. While every effort was made to obtain a generalized restlessness or minor choreiform movements at the homogenous group, and particularly to exclude cases with an extremities (Faurbye et al., 1964; Hunter et al., 1964; Pryce organic "flavour," it was impracticable to exclude those who and Edwards, 1966). More violent generalized choreiform had had electric convulsion therapy (all patients) and leucotomy movements may also occur (Druckman et al., 1962; Roxburgh, (two patients). 1970; Singer and Wong, 1970). While there is general agreement that the above syndrome exists, there is divergence of opinion on its frequency, aetiology, and clinical characteristics. The relation between dyskinesia and phenothiazines has not been finally established but the DEFINITION OF DYSKINESIA evidence strongly suggests it exists. Apart from the known By dyskinesia was meant involuntary, stereotyped, and rhythmic effect of phenothiazines on the extrapyramidal system, the movements which included choreiform, choreo-athetotic, and dosage of phenothiazine seems to have a direct bearing on the athetotic movements, as follows. (1), Oral dyskinesia, in which development of dyskinesia (Pryce and Edwards, 1966). Kline one or more of the following regions were involved: tongue (1968) argued that most of the reported cases are accountable (as exemplified by forwards and backwards, side-to-side, for by concomitant or pre-existing organic lesions. Certainly torsion, and rotatory movements), lips (pursing, sucking, there are indications that organic and constitutional factors twisting, and opening and closing movements), face (grimacing and old age predispose to the development of the syndrome movements), jaw (chewing and munching movements), and (Brandon et al., 1971), but many cases show no evidence of throat (dysarthria and swallowing difficulties). (2) Bodily brain damage and have a history only of prolonged phenothiazine dyskinesia, in which one or more of the following regions were intake. In the present state of knowledge it seems that prolonged involved: neck (spasmodic, writhing, nodding, torticollic, or intake ofphenothiazine is one of a number ofpossible aetiological retrocollic movements), limbs (choreic, athetotic, and choreo- factors. athetotic movements), trunk (spasmodic, writhing, and rotatory We report here a clinical evaluation of thiopropazate hydro- movements and respiratory irregularities). chloride in the treatment of persistent dyskinesia associated Care was taken to exclude functional habit spasms and the with prolonged phenothiazine therapy. mannerisms of psychotics. One-sixth of the patients selected also had mild to moderate Parkinsonism (rigidity). Patients and Methods The trial was double-blind with a cross-over design. Each patient was allotted a serial number and randomly allocated to one of two groups (A and B) by an independent colleague ASSESSMENT whose only knowledge of the patients was a list of their names. Patients were evaluated the day before the trial and at three The code was given to the pharmacist with instructions to treat and six weeks. Complete psychiatric and physical examinations http://www.bmj.com/ the two groups according to the following schedule: were carried out on each occasion and reporting forms completed. Patients were also seen at weekly intervals at least First 3-week Period Second 3-week Period and separate entries were made in their case notes.
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