Tardive dyskinesia: A two-year follow-up study

Tardive dyskinesia: A two-year follow-up study

RAMZY YASSA, M.D. VASAVAN NAIR, M.D. GEORGE SCHWARTZ, M.Sc. Tardive dyskinesia: A two-year follow-up study ABSTRACT: Eighty patients whose tardive dy...

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RAMZY YASSA, M.D. VASAVAN NAIR, M.D. GEORGE SCHWARTZ, M.Sc.

Tardive dyskinesia: A two-year follow-up study ABSTRACT: Eighty patients whose tardive dyskinesia (TO) had

been assessed two years previously were reevaluated. The majority (66%) showed no change in their TO. An almost equal number improved (18%) and worsened (16%). Patients whose TO improved were younger (P<.05). Those with mild TO were more frequently among the improved as compared with patients with moderate TO.

Tardive dyskinesia (TD) usually occurs relatively late in the course of neuroleptic treatment, although it may appear after as little as three to six months of treatment. I The onset generally is insidious, while the patient is still receiving medication. 2 At times it may occur after withdrawal or lowering of the neuroleptic dosage. 3 Although TD has been recognized since 1957,4little is known about its natural history. 5 Few attempts6 •9 have been made to study its course after the discontinuation of neuroleptics, an occurrence which has often led to relapse of the underlying disorder. 10

This study reports on the course of TD in a group of patients assessed in 1980 11 •12 and who were reevaluated in 1982. No special attempt was made to reduce dosages in these patients other than as required by the underlying psychopathology, as determined by the treating physician. Patients and assessments The population consisted of all those diagnosed in our inpatient and outpatient studies ll •12 as having TD in 1980. They were drawn from the inpatient chronic care wards and the outpatient population of

Drs. Yassa and Nair are associate professors in the department ofpsychiatry at McGill University, Montreal, and Mr. Schwartz is a research associate at the Douglas Hospital Centre. Reprint requests to Dr. Yassa, Douglas Hospital Centre, 6875 Lasalle Boulevard, Verdun, Quebec H4H 1R3, Canada. 852

Douglas Hospital. The total TD population consisted of 93 patients (46 inpatients, 47 outpatients), comprising 38 men and 55 women from 27 to 83 years old (mean 58.5 years). Sixty-five patients (70%) were diagnosed as having schizophrenia, 19 (20%) as having an organic mental disorder, and nine (10%) as having an affective disorder. The authors used the criteria suggested by DSM-m. 13 In the category of organic mental disorder, 14 patients were diagnosed as mentally retarded with psychosis and five as alcoholic with psychosis. First assessment (1980). Each patient was evaluated at least three times during 1980. Outpatients were assessed during their regular visits and inpatients every four months. Scoring was done using the Abnormal Involuntary Movement Scale,'4 and the criteria for the diagnosis of TD followed those suggested by the APA Task Force on TO. 15 A minimum score of 2 (mild) in any bodily area was considered as TD. All assessments were done by two independent evaluators. Second assessment (1982). PSYCHOSOMATICS

Eighty (49 women, 31 men) of the original 93 TO patients were reassessed approximately two years later. All assessments were done by one evaluator (RY), who was the main investigator in the previous studies. Six patients had died, including one suicide, and seven were lost to follow-up. Scoring. In comparing the scores in both assessments, any increase in total score, no matter how slight, was termed worse. This included either an increase in the preexisting severity of TO in particular bodily areas or the appearance of it in an area unaffected in 1980. For patients to be rated as better, the score for severity of TO had to decline, such as from 3 (moderate) to 2 (mild). The improved category included those patients who showed no TO (0) in 1982. The final scores were taken as the mean of all the assessments.

I

Results The eighty (80) 1982 patients were subdivided into four groups in relation to their neuroleptic intake. • Group 1 was made up of 55 patients (36 women, 19 men) with no change in their medication during the two-year period, as determined by chart review. The mean age (± SEM) was 59.3 years (± 1.1) with a range of 38 to 83. Thirty-five patients (64%) were diagnosed as having schizophrenia, 13 (23%) an organic mental disorder, and seven (13%) an affective disorder. The majority of these patients (41 or 75%) had no change in their TO. Five (9%) became worse, two (3%) improved, and in seven (13%) the TO disappeared. • Group 2 comprised three women and four men with dosage reductions in most cases. The mean age was 58 years (± 5.0) with a range of 32 to 70 years. Four pa-

tients received a 50% reduction in their medication six months before the first assessment in 1982. Two patients received a 30% reduction. The remaining patient was receiving no medication at the time of the first assessment in 1982. These changes were maintained during all of 1982. Four patients were diagnosed as having schizophrenia and the other three as having an organic mental disorder. Three patients had no change in their TO and three others became worse. In one patient the TO disappeared. • Group 3 included five men and five women with dosage increases. The mean age was 51.2 years (±4.2) with a range of 29 to 72 years. In four patients, the medication was doubled six to eight months before the first 1982 assessment. One patient had received no medication in 1980 and chlorpromazine 150 mg/d in 1982. Medication

Table-Patient Characteristics In the Three Outcome Groups for liIrellve DyskInesia (TO) I

Characteristics

TO unchanged

TO Improved or dlaappeared

TOwol'1l8

Total

Number of patients

53 (66%)

14(18%)

13 (16%)

80 (100%)

Mean age (yr) ± SEM

58.6 ± 2.3

52.6 ± 3.3"

61.4 ± 2.1"

57.5 ± 2.2

21 32

4 10

20.9 ± 1.5

19.5 ± 1.6

Schizophrenia

35

11

7

53

Organic mental disorder

11

3

5

19

7

0

1

8

Sex:

,

Male Female Mean duration of neuroleptic treatment (yr) ± SEM

6 7

21.9 ± 1.4

31 49

20.8 ± 1.5

Diagnosis:

Affective disorder 'StalisllcaUy significant difference (P<.05)

NOVEMBER 1984" VOL. 25 • NO 11

853

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was increased tenfold in two patients. By 1982 three patients were receiving another neuroleptic in addition to the previous ones. Six patients had a diagnosis of schizophrenia, three of organic mental disorder, and one of affective disorder. Five patients had no change in their TO, two became worse, and two improved. One had no TO when reexamined. • Group 4 consisted of five women and three men in whom the 1980 neuroleptic had been replaced by a different one by 1982. The mean age was 57 years (± 2.7) with a range of 41 to 68 years. All eight were diagnosed as having schizophrenia. Of this group, four remained the same and three became worse, while in one person the TO disappeared. As the Table shows, two thirds (53) of the eighty (80) 1982 TO patients showed no change in the severity of TO. Among the 13 patients who became worse, eight belonged to groups 1 and 2 with the same or decreased dosage. In the remaining 14 patients the TO either improved or disappeared. The patients whose TO worsened were noticeably older than those whose TO improved (P<.05). There was no statistically significant difference in the mean duration of neuroleptic treatment in the three groups nor in the diagnoses of the patients who improved or became worse. There was an equal number (seven) of inpatients and outpatients whose TO improved or disappeared. In eight inpatients and five outpatients the TO worsened. Changes in relation to initial TO severity Thirty-three (60%) of the 55 patients with mild TO showed no 854

change in the severity of their TO, as compared with 20 (80%) of 25 patients with moderate TO. This disorder disappeared in nine patients with mild TO and in one with moderate TO. Of the bodily areas affected, it was the tongue that most often showed improvement (13 cases). The jaws and lips improved in four cases and the arms in two other. Twelve patients with mild TO and one with moderate TO became worse. In all these patients, mouth movements worsened. Four patients had, in addition, an extension of TO into other areas: the hands in two cases, the legs in one, and the shoulders in the fourth. The actual dosages of neuroleptics were converted to chlorpromazine (CPZ) equivalent. 16 The mean CPZ equivalent for patients who improved was 653 mg/d (± 190) with a range of 0 to 2,000 mg/d, while for patients who worsened it was 352 mg/d ( ± 72) with a range of 75 to 1,000 mg/d. This difference was not statistically significant. Of the total group, four women and one man were not receiving medication in 1980 and were still receiving none in 1982. Their ages ranged from 60 to 72 years with a mean of 66.4 years. Four of these patients showed no change in their TO (three mild and one moderate), while one patient with moderate TO in 1980 had no abnormal movements when reevaluated two years later. Discussion In our study the number of patients in whom TO worsened was almost the same as the number in whom it improved or disappeared. Age was an important factor: TO patients who improved were younger (P<.05) than those who worsened. PSYCHOSOMATICS

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Ludiomil maprotiline He]

Tablets: 25 mg, SO mg. 75 mg

This agrees with the work of Seeman,9who also found that it was the younger patients who improved. Severity of TO was another important factor in its improvement. By 1982 TO had disappeared in nine patients with the mild form, as compared with only one with the moderate form. Of the bodily areas affected, the movements of the tongue were the most conspicuously improved (13 of the 14 cases). On the other hand, this was also the area most affected in patients with worsened TO. The finding that one of the five drug-free patients for the two years improved seems to indicate that even though TO is irreversible in REFERENCES 1. Chouinard G, Jones BD: Early onset of tardive dyskinesia: A case report. Am J Psychiatry 136:1323-1324,1979. 2. Degkwitz R, Wenzel W: Persistent extrapyramidal side effects aher long-term application of neuroleptics, in Amsterdam BH (ed): Neuropsychopharmaco/ogy. International Congress Series No. 129, Amsterdam, Excerpta Medica, 1967. pp 608-615. 3. Hershon HI, Kennedy PF, McGuire RJ: Persistence of extrapyramidal disorders and psychiatric relapse aher withdrawal of longterm phenothiazine therapy. Br J Psychiatry 120:41-50,1972. 4. Schonecker M: Ein eigentumliches Syndrom im oralen Bereich bei Megaphen Applikation. Nervenarzt 28:35, 1957. 5. Casey DE, Toeniessen L: Tardive dyskinesia: What is the natural history? Int Drug Ther Newslelter 18: 13-16, 1983. 6. Wegner JT. Kane JM: Follow-up study on the reversibility of tardive dyskinesia. Am J Psychiatry 139:368-369. 1982. 7. Uhrbrand L, Faurbye A: Reversible and irreversible dyskinesia after treatment with perphenazine, chlorpromazine, reserpine, and electroconvulsive therapy. Psychopharmacologia 1:408-418, 1960. 8. Jus A, Jus K, Fontaine P: Long-term treat-

most established cases, occasional older patients (in our case a 69year-old woman) may benefit from discontinuation of neuroleptics. Other variables not found to contribute to improvement or worsening of TO were sex, diagnosis, current neuroleptic medication, and its duration. In conclusion, TO does not seem to worsen over time 1,5 in most cases. Some patients seem to improve spontaneously with or without drug discontinuation. This fact must be kept in mind when long-term studies are undertaken_ Age and severity of TO were the two criteria that positively related to improvement of TO in our patients. 0

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ment of tardive dyskinesia. J Clin Psychiatry 40: 72- 77. 1979. 9. Seeman MY: Tardive dyskinesia: Two-year recovery. Compr Psychiatry 22: 189-192, 1981. 10. Pyke J, Seeman MY: Neuroleptic-free intervals in the treatment of schizophrenia. Am J Psychiatry 138: 1620-1621, 1981. 11. Ananth J, Yassa R: Tardive dyskinesia and skin pigmentation. Br J Psychiatry 141: 194195,1982 12. Yassa R, Ananth J, Cordozo S, et al: Tardive dyskinesia in an outpatient population: Prevalence and predisposing factors. Can J Psychiatry 28:391-394,1983. 13. Diagnostic and Statistical Manual of Mental Disorders, ed 3. Washington DC. American Psychiatric Association, 1980. 14. Guy W: Assessment Manual for Psychopharmacology, publication (ADH) 76-338. US Dept of Health, Education, and Welfare, ECDEU, 1976, pp 534-537. 15. Tardive Dyskinesia: Task Force Report 18. Washington DC, American Psychiatric Association, 1980, pp 23-42. 16. Davis JM: Dose equivalence of the antipsychotic drugs, in Matthysse S, Kety SS (eds): Catecholamines and Their Enzymes in the Neuropathology of Schizophrenia. Elmsford, NY, Pergamon Press, 1974, pp 65-69.

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