Department of Clinical Research, Crichton Royal Hospital, Dumfries, UK
Correspondence: Dr Jennifer Halliday, Department of Clinical Research, Crichton Royal Hospital, Dumfries DG1 4TG, UK. Tel: 01387 244000; fax: 01387 257735; e-mail: mikejenq{at}tinyworld.co.uk
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Aims To examine the current prevalence of movement disorders among all people with schizophrenia in a discrete geographical area, to compare the prevalence in patients receiving and not receiving atypical antipsychotic drugs; and to compare current prevalence with prevalence over the past 20 years.
Method In Nithsdale, south-west Scotland, in 1999/2000, we replicated previous studies by using the Abnormal Involuntary Movements Scale, SimpsonAngus scale and Barnes Akathisia Rating Scale to measure tardive dyskinesia, parkinsonism and akathisia, respectively. Mental state was assessed by the Positive and Negative Syndrome Scale.
Results In 136 patients the prevalence of probable tardive dyskinesia was 43%, of parkinsonism 35% and of akathisia 15%. Parkinsonism was present as often in those receiving atypicals as in those receiving standard oral antipsychotics. The prevalence of tardive dyskinesia has doubled over 20 years.
Conclusions Movement disorders remain significant problems for patients despite the introduction of atypical antipsychotic drugs.
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
METHOD |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Patient identification
The identification of patients by the key informant method
has been described previously (McCreadie,
1982; Kelly et al,
1998). There are regular censuses of people with schizophrenia in
Nithsdale; patients in the present study were identified in April 1999 and
examined over the following 12 months. The census includes all in-patients,
day patients and out-patients on the census date with an address in Nithsdale
and an ICD10 (World Health
Organization, 1992) clinical diagnosis of schizophrenia. In
addition, general practitioners are asked to update the list, as are social
workers, community psychiatric nurses and voluntary agencies. Diagnoses using
the Operational Checklist for Psychiatric Disorders (OPCRIT;
McGuffin et al, 1991)
with a computer-generated ICD10 diagnosis were generated by J.H.
Assessment
Socio-demographic data were obtained from both case records and interviews.
We recorded age, gender, duration of illness (as estimated from the time of
the first psychotic episode) and medication both at the time of interview and
over the preceding year. Dyskinesia was assessed by four psychiatrists (J.H.,
S.M., T.M., R.M.) using the Abnormal Involuntary Movements Scale (AIMS;
US Department of Health, Education and
Welfare, 1976). Dyskinesia was defined as probably present
(Schooler & Kane, 1982) if
movements were mild in at least two of seven body areas or
moderate in at least one. Parkinsonism was assessed using the
SimpsonAngus Rating Scale (Simpson
& Angus, 1970) and was said to be present if the score was
more than 0.3.
Akathisia was measured using the Barnes Akathisia Rating Scale (BARS) and was said to be present if the score was 2 (mild) or more on the global scale (Barnes, 1989).
Mental state was assessed by the same psychiatrists using the Positive and Negative Syndrome Scale (PANSS) for schizophrenia (Kay et al, 1987); this gives a total score and also scores on positive, negative and general psychopathology sub-scales.
Patients completed a questionnaire about their smoking habits, as in a health and lifestyle survey of the general population in south-west Scotland (Waldron et al, 1995).
Training and practice sessions in the assessment of mental state and movement disorders took place before the study began under the supervision of R.M.
Statistical analysis
Differences in proportions were measured using the chi-squared test, with
Yate's correction for 2 x 2 tables. Normally distributed data were
presented with means and standard deviations, and t-tests were used
to measure significance: tests were two-tailed. As there were many
comparisons, only differences significant at least at the 1% level are
reported. In order to account for the possible correlations between variables,
logistic regression was used to identify variables independently associated
with tardive dyskinesia. All statistical analyses were performed using Arcus
Quickstat Biochemical (Biomedical version 1.2; Longman Software, 1999).
Dumfries and Galloway Local Research Ethics Committee approved the study.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
Factors associated with extrapyramidal disorders
In males there were no significant differences between those with and
without tardive dyskinesia in age, mental state and smoking status. Male
patients with tardive dyskinesia had a significantly longer duration of
illness (Table 2). No other
significant differences in males were found.
|
In females, patients with tardive dyskinesia had significantly higher negative symptom, general psychopathology and total scores on the PANSS (Table 2).
Similar significant differences in PANSS scores were found between females with and without parkinsonism (negative subscale: mean 20 (s.d.=8.8) v. 12.2 (s.d.=5.9); t=4.10, d.f.=61, P=0.0001; general psychopathology subscale: mean 30.5 (s.d.=9.1) v. 25.7 (s.d.=6.4); t=2.37, d.f.=61, P=0.02; total score: mean 66.2 (s.d.=18.7) v. 50.6 (s.d.=14.8); t=3.54, d.f.=61, P=0.0008). Female patients with akathisia had higher positive symptom scores (mean 18.5 (s.d.=6.5) v. 12.6 (s.d.=5.9); t=2.8, d.f.=61, P=0.006).
More female patients with tardive dyskinesia had parkinsonism (54%
v. 15%, 2=8.8, P=0.003) and more had
akathisia (33% v. 5%,
2=6.8, P=0.009).
The variables that were significantly different in female patients with and without tardive dyskinesia on univariate analysis were re-examined using logistic regression. Negative symptoms and akathisia remained independently significantly associated with those females who had tardive dyskinesia (P=0.01, P=0.007, respectively).
Medication
Patients receiving antipsychotic medication were grouped into three
categories: those receiving long-acting intramuscular anti-psychotic drugs
with or without other anti-psychotics; those receiving standard oral
antipsychotic drugs, including sulpiride and thioridazine, with or without
oral atypicals; and those receiving atypical oral antipsychotic drugs alone
(Table 3). In males and females
separately, and in the total group, there were no significant differences
between any of the medication categories in the number of patients with and
without tardive dyskinesia, either over the past year or at the time of
interview (Table 3). At the
time of interview, 52% of patients receiving only atypicals had tardive
dyskinesia.
|
The drugs and their doses are recorded in
Table 4. Numbers of patients
receiving individual antipsychotic drugs were small and there were no
statistically significant differences in the doses of the various drugs in
those who did and did not have tardive dyskinesia. Within the group receiving
intramuscular antipsychotics, no patient taking zuclopenthixol decanoate had
tardive dyskinesia (Fisher's exact test 2=6.50; d.f.=1,
P=0.005).
|
We examined more closely the patients who were receiving atypicals alone (n=48). The mean length of time for which the 25 who had tardive dyskinesia had been receiving their current drug was 31 months (s.d.=26). The reasons for that drug being started were: fresh episode or worsening of psychotic symptoms (n=16, 64%); unacceptable extrapyramidal side-effects (n=3, 12%); other side-effects (n=4, 16%); not known (n=2, 8%). Of the 23 without tardive dyskinesia, the mean length of time on the current drug was not significantly different (mean 23 months, s.d.=19). The reasons for starting were: fresh episode or worsening of psychotic symptoms (n=13, 57%); unacceptable extrapyramidal side-effects (n=1, 4%); other side-effects (n=5, 22%); not known (n=4, 17%).
Medication status was also examined in patients with parkinsonism and akathisia over the past year and at the time of interview. When males and females were considered separately, no significant differences between the groups were found. However, in the total group parkinsonism was significantly more common in patients receiving long-acting intramuscular antipsychotic medication (Table 5). Of those receiving atypicals alone, 29% had parkinsonism and 18% had akathisia.
|
With regard to parkinsonism, we examined more closely those patients receiving only standard oral antipsychotic medication (n=34). Of the 25 patients who were receiving sulpiride or thioridazine, 6 (24%) had parkinsonism. Of the 9 on the other standard antipsychotic medication (e.g. trifluoperazine) 6 (67%) had parkinsonism.
In a further comparison of patients with and without movement disorders, there were no significant differences in the numbers of patients receiving either antidepressant or antiparkinsonian medication at the time of interview or over the previous year.
Comparison with previous reviews
The prevalence of tardive dyskinesia has been assessed in Nithsdale using
the AIMS scale on seven occasions, including 1999/2000, since 1981
(Table 6). For each assessment,
all known patients with schizophrenia are identified. Each cohort contains
patients from the previous cohort, still alive and living in Nithsdale, and
also new patients who have developed the illness for the first time or who
have moved to the area; some from the previous cohort will have moved away or
died. Thus, the mean age of the patients over the years remains very similar
(Table 6). The prevalence of
tardive dyskinesia has more than doubled over 20 years (2 for
linear trend=16.89, P < 0.0001). The prevalence of parkinsonism
and akathisia, assessed less often, has remained broadly the same
(Table 6).
|
Current medication in 1981 and 1999/2000 was examined. Only four drugs
prescribed in 1981 were prescribed to five or more patients in 1999/2000,
namely: thioridazine (22 patients in 1981 and 22 in 1991/2000); chlorpromazine
(15 and 6 patients, respectively); flupentixol decanoate (29 and 9 patients,
respectively); and fluphenazine decanoate (27 and 5 patients, respectively).
For the patients receiving thioridazine, the mean dose was significantly lower
in 1999/2000 (97 mg (s.d.=48) v. 184 (94); t=3.88, d.f.=42,
P=0.0004). There were no differences in the mean doses of the other
drugs. There was no statistically significant difference in the numbers of
patients in 1981 and 1999/2000 receiving more than one antipsychotic (21% and
16%, respectively). More patients in 1981 were receiving no antipsychotic
medication (23/117 v. 10/131; 2=6.74, d.f.=1,
P=0.009).
In the 1981 cohort, 34 patients comprising 19 males and 16 females, mean age 40 years (s.d.=10), mean duration of illness 14 years (s.d.=9), were still alive and living in Nithsdale in 1999/2000, and were re-examined. Of the 34, 23 had been rated on 7 occasions, 9 on 6 occasions, 1 on 5 occasions and 1 on 4 occasions. Seven patients (21%) had never shown tardive dyskinesia compared with 27 (79%) who had tardive dyskinesia on at least one occasion. Of those who had tardive dyskinesia on at least one occasion, 7 (26%) developed the persistent condition (positive rating on the last three assessments); the remaining 20 (74%) had no clear pattern. No patient had persistent tardive dyskinesia (positive on three consecutive occasions) which remitted.
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Tardive dyskinesia
We found the prevalence of probable tardive dyskinesia to be 43%. This is
in keeping with a review (Casey,
1995) that reported mild forms of the condition in approximately
20% of patients, rising to 50% in high-risk groups such as the elderly.
Several risk factors for tardive dyskinesia have been identified, such as
advanced age and duration of illness
(McCreadie, 1982;
Kane et al, 1992).
Conflicting results have been found with gender
(Yassa & Jeste, 1992) and
smoking (Kelly & McCreadie,
1999). The only risk factor in our study significantly associated
with tardive dyskinesia was longer duration of illness in male patients. The
association of tardive dyskinesia with negative symptoms has been reported
elsewhere (Liddle et al,
1993). In our study, female patients with tardive dyskinesia were
likely to have more negative symptoms and general psychopathology. The finding
with regard to negative symptoms remained independently significant on
logistic regression. In females, parkinsonism and akathisia were associated
with tardive dyskinesia, but following logistic regression only akathisia
remained independently significantly associated. We can only speculate why
akathisia is associated with tardive dyskinesia in females but not in males.
The influence of oestrogen on movement disorders is complex. It has been
suggested that females experience a higher frequency of akathisia, possibly
because of the additive effects of oestrogen and antipsychotics on dopamine
blockade. Also, oestrogen decline in postmenopausal women may precipitate
tardive dyskinesia by relieving dopamine blockade, as may withdrawal of
antipsychotic medication (Leung &
Chue, 2000). So, the presence of oestrogen in the young and lack
of it in the old may be responsible for the association of akathisia with
tardive dyskinesia in women.
Parkinsonism and akathisia
Drug-induced parkinsonism occurs especially during the initial period of
antipsychotic medication exposure (Casey,
1995). Prevalence rates of 20%
(Modestin et al,
2000) and 36% (van Harten
et al, 1996) have been reported. This range is in keeping
with our study, where the prevalence was 35%.
The prevalence of akathisia, one of the most intolerable extrapyramidal side-effects which often leads to non-compliance, has been reported as 11% (Modestin et al, 2000), much the same as our finding of 15%.
Medication
There was no difference in the prevalence of tardive dyskinesia in the
three medication categories; the condition was present in 52% of patients
currently receiving atypicals only. There are several possible reasons for the
findings in the present study. Tardive dyskinesia secondary to standard
antipsychotics may persist even when such drugs are discontinued; the patients
with tardive dyskinesia may have been preferentially switched to atypicals;
withdrawal dyskinesia may develop after discontinuation of standard
antipsychotics; and some patients have spontaneous rather than tardive
dyskinesia. With regard to the preferential switch to atypicals, tardive
dyskinesia was the reason for the change in only 8% of the 48 patients
receiving atypicals.
We must emphasise that our study is one of prevalence, not incidence. The only satisfactory way to assess the incidence of tardive dyskinesia produced by different drugs is to follow prospectively patients suffering their first episode of illness and treated with a single drug.
A recent review has shown that extrapyramidal symptoms, including parkinsonism, are less common with atypical antipsychotic medication than with standard antipsychotics (Geddes et al, 2000). In our study, parkinsonism was certainly less common than in those receiving long-acting intramuscular antipsychotics; yet the prevalence in those receiving atypicals was 29%. This is not because patients had recently been switched to atypicals and were still experiencing continuing side-effects produced by standard antipsychotics: the mean length of time patients had been receiving atypicals was 27 months. The prevalence of parkinsonism was similar in those receiving oral standards (27%) and atypicals (29%). However, 74% of patients on oral standards were receiving either thioridazine or sulpiride, two drugs which may be older atypicals; Baldessarini (1980) wrote more than 20 years ago that sulpiride and thioridazine are at least partial exceptions to the formerly almost inevitable association of neurotoxic with antipsychotic effects.
Movement disorders across 20 years
The prevalence of tardive dyskinesia has doubled over the past 20 years.
There are several possible reasons: more patients may be receiving medication;
doses may be higher; early intervention may mean patients are starting
medication at an earlier age and have been taking drugs longer; and, because
more patients are in the community, drug holidays are more likely
(van Harten et al,
1998). With regard to the first possibility, more patients indeed
were receiving medication in 1999/2000 than in 1981. This is probably the
result of more assertive community outreach. With regard to the second
possibility, only four drugs were prescribed to substantial numbers of
patients in both 1981 and 1999/2000; the mean dose of one of them,
thioridazine, was in fact lower in 1999/2000.
Of the 34 patients followed for 20 years, 79% had tardive dyskinesia on at least one occasion. This suggests that in almost all patients with chronic illness, dyskinesia is an inevitable occurrence. We can only speculate how much of this dyskinesia is drug-related and how much spontaneous. A recent review (Fenton, 2000) has suggested that 40% of those aged 60 years or over have spontaneous dyskinesia.
Although numbers are small, our results suggest there may be two types of dyskinesia: a milder form which fluctuates over time (the majority) and a more severe form which persists once it develops (the minority). It has long been known that milder forms of tardive dyskinesia may show temporal fluctuations (Bergen et al, 1989).
Although the number of assessments were fewer, our results suggest that the prevalences of parkinsonism and akathisia have changed little. If some of the reasoning as to why tardive dyskinesia is increasing is correct, then it might be expected that the prevalence of parkinsonism would also rise. However, the switch from long-acting intramuscular antipsychotics and old standards to atypicals may be having a protective effect.
We conclude that tardive dyskinesia and parkinsonism remain major problems despite the introduction of atypical antipsychotic medication 10 years ago. Further prospective studies are required to determine whether or not the use of atypicals will impact on the prevalences of these movement disorders.
![]() |
Clinical Implications and Limitations |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
LIMITATIONS
![]() |
ACKNOWLEDGMENTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Barnes, T. R. E. (1989) A rating scale for drug-induced akathisia. British Journal of Psychiatry, 154, 672-676.[Abstract]
Bergen, J. A., Eyland, E. A., Campbell, J. A., et al (1989) The course of tardive dyskinesia in patients on long term neuroleptics. British Journal of Psychiatry, 154, 523-528.[Abstract]
Casey, D. E. (1995) Neuroleptic-induced extrapyramidal syndromes and tardive dyskinesia. In Schizophrenia (eds S. R. Hirsch & D. R. Weinberger), pp. 546-565. Oxford: Blackwell.
Fenton, W. S. (2000) Prevalence of spontaneous dyskinesia in schizophrenia. Journal of Clinical Psychiatry, 61 (suppl. 4), 10-14.
Geddes, J., Freemantle, N., Harrison, P., et al
(2000) Atypical antipsychotics in the treatment of
schizophrenia: systematic overview and meta-regression analysis.
BMJ, 321,
1371-1376.
Kane, J. M., Jeste, D. V., Barnes, T. R. E., et al (1992) Tardive Dyskinesia: A Task Force Report of the American Psychiatric Association. Washington, DC: American Psychiatric Association.
Kay, S., Fishbein, A. & Opler, L. (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin, 13, 261-275.[Medline]
Kelly, C., McCreadie, R. G., MacEwan, T., et al (1998) Nithsdale schizophrenia surveys, 17: Fifteen year review. British Journal of Psychiatry, 172, 513-517.[Abstract]
Kelly, C. & McCreadie, R. G. (1999) Smoking
habits, current symptoms, and premorbid characteristics of schizophrenic
patients in Nithsdale, Scotland. American Journal of
Psychiatry, 156,
1751-1757.
Leung, A. & Chue, P. (2000) Sex differences in schizophrenia, a review of the literature. Acta Psychiatrica Scandinavica, 101 (suppl. 401), 3-38.[CrossRef]
Liddle, P. F., Barnes, T. R. E., Speller, J., et al (1993) Negative symptoms as a risk factor for tardive dyskinesia in schizophrenia. British Journal of Psychiatry, 163, 776-780.[Abstract]
McCreadie, R. G. (1982) The Nithsdale schizophrenia survey. I: Psychiatric and social handicaps. British Journal of Psychiatry, 140, 582-586.[Abstract]
McCreadie, R. G., Barron, E. T. & Winslow, G. S. (1982) The Nithsdale schizophrenia survey. II. Abnormal movements. British Journal of Psychiatry, 140, 587-590.[Abstract]
McCreadie, R. G., Robertson, L. J. & Wiles, D. H. (1992) The Nithsdale schizophrenia surveys. IX: Akathisia, parkinsonism, tardive dyskinesia and plasma neuroleptic levels. British Journal of Psychiatry, 160, 793-799.[Abstract]
McGuffin, P., Farmer, A. E. & Harvey, I. (1991) A polydiagnostic application of operational criteria in studies of psychotic illness: development and reliability of the OPCRIT system. Archives of General Psychiatry, 48, 764-770.[CrossRef][Medline]
Modestin, J., Stephan, P. L., Erni, T., et al (2000) Prevalence of extrapyramidal syndromes in psychiatric inpatients and the relationship of clozapine treatment to tardive dyskinesia. Schizophrenia Research, 42, 223-230.[CrossRef][Medline]
Schooler, N. R. & Kane, J. M. (1982) Research diagnoses for tardive dyskinesia. Archives of General Psychiatry, 39, 486-487.
Simpson, G. M. & Angus, J. W. (1970) A rating scale for extrapyramidal side effects. Acta Psychiatrica Scandinavica Supplementum, 212, 11-19.[Medline]
US Department of Health, Education and Welfare (1976) Abnormal involuntary movement scale (AIMS). In ECDEU Assessment Manual (ed. W. Guy). Rockville, MD: US Department of Health, Education and Welfare.
van Harten, P. N., Matroos, G. E., Hoek, H. W., et al (1996) The prevalence of tardive dystonia, tardive dyskinesia, parkinsonism and akathisia. The Curacao Extrapyramidal Syndromes Study I. Schizophrenia Research, 19, 195-203.[CrossRef][Medline]
van Harten, P. N., Hoek, H. W., Matroos, G. E., et al
(1998) Intermittent neuroleptic treatment and risk for
tardive dyskinesia: Curacao Extrapyramidal Syndromes Study III.
American Journal of Psychiatry,
155,
565-567.
Waldron, G., Chalmers, J., Bone, A., et al (1995) Health and Lifestyle in Dumfries and Galloway in 1995. Dumfries: Dumfries and Galloway Health Board.
World Health Organization (1992) The ICD10 Classification of Mental and Behavioural Disorders. Geneva: WHO.
Yassa, R. & Jeste, D. V. (1992) Gender differences in tardive dyskinesia: a critical review of the literature. Schizophrenia Bulletin, 18, 701-715.[Medline]
Received for publication January 21, 2002. Revision received May 27, 2002. Accepted for publication June 26, 2002.
Related articles in BJP:
HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Psychiatric Bulletin | Advances in Psychiatric Treatment | All RCPsych Journals |