Aus

tral

asia

n Ps

ychi

atry

• V

ol 8

, No

1•

Mar

ch 2

000

38

Abnormal movements in firstepisode psychosis

Alan D. Jager

Abnormal movements have long been described in psychiatricpatients. The eloquent descriptions by clinicians in the pre-neuroleptic era provide evidence of abnormal movements in

psychotic patients who had never been exposed to neurolepticmedication.

Kraepelin1 made the following observations of patients with “stereo-typy”: “twitching movements in different groups of muscles … ‘contor-tionist movements’, waving with the hands … smacking of their lips …the outspread fingers often show fine tremor … sprawling, irregular,choreiform, outspreading movements, which I think I can best charac-terize by the expression ‘athetoid ataxia’.” He suggested a cerebellarcause.

This spontaneous dyskinesia (SD), i.e. dyskinesia occurring in theabsence of a history of exposure to neuroleptics, can be compared withcontemporary definitions of tardive dyskinesia (TD) as in DSM-IV:“Involuntary choreiform, athetoid or rhythmic movements … of thetongue, jaw, or extremities…” The similarities between tardive dyskine-sia and these earlier clinical descriptions are compelling.

An examination of the aetiological basis of spontaneous dyskinesiacommenced with epidemiological studies. Brandon et al.2 concluded,from a study of 910 psychiatric inpatients, that “in rare individual casesdyskinesia appears to be caused by phenothiazines exposure, but in gen-eral the association between the two is of theoretical rather than clin-ical significance”. Baldessarini3 reviewed 18 studies of neuroleptic-naivepatients which found the mean rate of SD to be 5.8%. A recent study4

examined 79 patients and found 7.6% to have SD, but some of thesepatients had been exposed to antipsychotics. 10.2% of their 49 un-medicated patients were found to have SD.

The finding of abnormal movements in psychotic patients in the pre-neuroleptic era casts doubt on the concept of TD. The contribution ofthe neuroleptic drugs has subsequently been assumed to be paramount,despite a paucity of evidence supporting causation.5 The finding of SDin populations of patients with first episode psychosis casts considerabledoubt on the prevailing practice of attributing all abnormal movementsto the effects of long term neuroleptic exposure. Rogers6 suggested thatneuroleptic medication might be acting by modifying the expression ofdisease-based motor disorder.

The American Psychiatric Association Task Force Report on Tardive Dysk-inesia7 noted that the results of dosage-reduction studies were dis-appointing in their relative impact on the incidence of TD. Also, in mostcases, TD is not progressive and, even with continued neurolepticadministration, there can be improvement over time. It concluded that“It is also clear that some individuals with schizophrenia and otherpsychotic disorders may have or develop abnormal involuntary move-ments unassociated with long-term treatment with antipsychotic drugs.”

Alan D. JagerSenior Lecturer in Forensic Psychiatry, University of TasmaniaClinical Director, Forensic Mental Health Services, Tasmania

Correspondence: 2 Terry Street, Glenorchy, Tasmania 7010.Tel: 03 6233 8683, fax: 03 6233 8797.Email: Alan.Jager@utas.edu.au

Neuroleptics are only one possible risk factor for thedevelopment of abnormal movements; other possi-bilities include gender, advancing age, diagnosis,negative symptoms, mental retardation, duration ofillness and concomitant medication. Of neuroleptic-related factors, total exposure to neuroleptics, lengthof drug exposure and drug type have all been con-sidered possible risk factors.

Fenton et al.8 concluded that, “the prevalence ofdyskinesia among neuroleptic-naive schizophrenicpatients may increase with age and duration ofillness.”

Ideally, a study aiming to clarify the question of thepathogenesis of abnormal movements in patientswith psychosis would be a controlled prospectivestudy of patients with schizophrenia and wouldinvolve a neuroleptic-treated group and a drug-freegroup. It would be unethical to withhold knowneffective agents (neuroleptics) from patients suffer-ing such a potentially devastating illness as schizo-phrenia. Patients would have to be randomlyassigned to drug or no drug treatment in large num-bers for long periods of time to assess the role ofneuroleptic treatment in the development of TD. Areview of the literature did not reveal such a study.

The methodology of the current study allows for a“natural” control group of non-compliant patientsto be followed and examined.

METHOD

Eighteen patients were recruited from the catchmentarea of the Southern Healthcare Network in thesouthern suburbs of Melbourne, Australia over a oneyear period, in 1994.

Eligible patients were in the acute phase of psy-chosis, about to be prescribed antipsychotic medica-tion for the first time. Patients were considered to beneuroleptic-naive if they and their family or carergave such a history and case records revealed no his-tory of neuroleptic use.

Patients were excluded if they gave a history of pre-vious antipsychotic drug treatment (i.e. they werenot neuroleptic-naive), had a history of severe orpersistent substance abuse or had a separate neuro-logical illness. After complete description of thestudy to the subjects, written informed consent wasobtained.

Abnormal movements were assessed by the applica-tion of each of three scales: the Abnormal Involun-tary Movements Scale (AIMS),9 the Simpson andAngus EPSE10 and the Barnes Akathisia Scale.11 Thediagnosis of TD was made if there were at least“moderate” abnormal movements in one or morebody areas or at least “mild” abnormal movementsin two or more body areas. The Simpson and Angus

EPSE scale is graded from 0–4 and the sum dividedby 10 to achieve a global score. A score of 0.3 orgreater is considered to be significant. The BarnesAkathisia Scale measures the objective and subjectiveelements of restlessness. Results span a range fromabsent, questionable, mild, moderate, marked, tosevere akathisia.

Patients were assessed at time zero, when they wereall neuroleptic-naive, at two weeks (or at time of dis-charge from hospital, if applicable, whichever wassooner), at three months, at 12 months and annuallyfor up to three years, ending in 1997.

Except for the first examination, patients were askedto provide a blood specimen at each assessment formeasurement of the presence of neuroleptics, unlessthey were receiving depot neuroleptic medication.Other data collected included, sex, age, duration ofillness, clinical diagnosis and result of computerizedtomography (CT) of the brain. Clinical and personalinformation was obtained from the subject, theircarers, where applicable, the treating staff and casefile.

All examinations were performed by the author andthis study constituted his Part II examination forFellowship of the Royal Australian and New ZealandCollege of Psychiatrists.

Results were examined by comparing means, using a2-tailed Student’s t-test and Levene’s Test for Equal-ity of Variances. The data were assessed for normal-ity using the Kolmogorov-Smirnov Test and found tobe normally distributed.

RESULTS

Eighteen patients (12 male and 6 female) wererecruited. The mean age was 27.9 years, althoughtwo patients were significantly older, being a 50-year-old man and 78-year-old woman, respectively.Setting those subjects aside, the mean age was 23.4years.

All 18 patients had an unequivocal clinical diagnosisof psychosis. When DSM-IV criteria were applied tothe clinical diagnoses, 12 (66.7%) had a diagnosis ofschizophrenia, two (11.1%) had schizophreniformdisorder (provisional), two (11.1%) had brief psy-chotic disorder (provisional), one (5.6%) had delu-sional disorder and one (5.6%) had bipolar I disorder.

At three months, dropout rates were, unfortunately,spectacular. Eight patients (44%) were not examined(one had moved overseas, two had moved residenceout of area, two had moved residence and were notcontactable and three refused). Of the 10 patientsseen at three months, 4 patients refused blood test-ing for presence of neuroleptic medication.

Mean duration of illness at time of entry to the studywas 19.1 months. All patients had either a normal

Australasian Psychiatry • Vol 8, N

o 1• M

arch 2000

39

brain CT scan (n=17) or normal neurologicalexamination (n=1).

At time zero, the global AIMS scores revealed that, ofthe 18 patients assessed, two (11.1%) had a score ofthree or more, fulfilling criteria for TD, had theybeen exposed to neuroleptic medication for the req-uisite three months. These two patients were a 15-year-old female and 20-year-old male and both hadschizophrenia. Neither of the two patients whoscored two (a 50-year-old male and 23-year-oldfemale) had abnormal movements in more than onebody area.

The mean duration of illness for patients with defi-nite dyskinesia was 30 months compared with 17.7months for those without definite dyskinesia but thedifference was not significant (p=0.243). Comparingpatients with a duration of illness less than 18months (n=8) with patients with a duration of illnessmore than 18 months (n=10), there was a significantdifference in the number of cases of dyskinesia (two)in the longer duration group compared with zero inthe shorter duration group (p=0.003).

Numbers at subsequent follow-up declined furtherand are therefore not presented in detail. No cases ofTD developed during the follow-up section of thestudy. Both cases of SD remitted only after com-mencement of antipsychotic medication, one onHaloperidol 5mg per day, the other on Trifluoper-azine 5-10mg per day. One continued in remission atlast follow-up, at two years, having tested negative,at that time, for presence of neuroleptic. At threeyears, the other was in remission while still onantipsychotic medication.

At time zero, one (5.6%) of the 18 patients recordeda Simpson & Angus score of 0.3 or greater, fulfillingthe definition of having EPSE.

At time zero, one (5.6%) patient recorded mildakathisia. Five out of 15 (33.3%) patients with nega-tive tests for neuroleptic scored a level of at leastmild akathisia compared with two out of nine(22.2%) patients with tests that were positive forneuroleptic. This was not significant.

Compliance with medication was poor. Of 24 testsfor neuroleptic medication in serum (23) or urine (1),only nine (37.5%) tested positive.

DISCUSSION

The findings presented in this study are tempered bythe small number of subjects and the high dropoutrate, making interpretation of the results difficult.

The results presented in this study parallel findingsin other studies of neuroleptic-naive patients withpsychoses. The prevalence of SD of 11.1% and abnor-mal movements, in total, of 22.2% is similar to find-

ings by Fenton et al.8 of 15% and 23% respectively.Baldessarini3 found a prevalence of SD of 5.8%.

The rate of SD in this young group was comparableto that found in older groups. This was not a findingthat was predictable from most previous research butis consistent with a study that found a rate of SD of4.9% in a cohort of young people with schizo-phrenia.12

This study identified a trend, only, towards increas-ing duration of illness being associated with ab-normal movements. Both of the cases with SD hadbeen unwell, and untreated, for a long period (24and 36 months respectively). Both had schizophre-nia, both were young (15 and 20 respectively) andthe SD remitted in both. This trend is consistentwith the finding that outcome may be affected byduration of illness13 and suggests a role for illness-related features, in the development of abnormalmovements. Furthermore, it suggests that a toxicprocess is occurring which may be ameliorated bythe use of antipsychotic medication.

The presence of a history of neuroleptic exposure inpatients with abnormal movements provides insuffi-cient evidence of causation. The fact that manypatients develop TD on treatment is not convincingevidence of a causal role for medication, when it isconsidered that patients are often non-compliantwith medication and that “drug holidays” are associ-ated with a higher prevalence of TD. It is plausiblethat early treatment with antipsychotic medicationmay offer some protection to patients with schizo-phrenia from developing dyskinesia, but, at the sametime, provide an increased risk of other abnormalmovements such as EPSE and akathisia.

Despite the methodological shortcomings, someaspects of the study may provide an ethical protocolfor following a neuroleptic-free cohort in the post-neuroleptic era, in that there is a high non-compliance rate in schizophrenia. Larger, longerstudies using this model, particularly in a countrywith a closed, universal public health system may beable to determine what proportion of risk is attribut-able to illness and what is attributable to antipsy-chotic medication.

In the meantime, TD remains an area of medicolegalconcern. Doctors would be wise to treat all patientswithin the framework of informed consent, whichincludes a discussion of diagnosis, prognosis and therisks and benefits of treatment. Patients shouldexpect to be warned of the possibility of developingspontaneous abnormal movements and also shouldbe told that there is a possibility of medication con-tributing to their development. The presence of TDshould cause the clinician to consider medication orpoor compliance as possible contributing factors.Given the evidence currently available, psychiatristsA

ustr

alas

ian

Psyc

hiat

ry •

Vol

8, N

o 1

• M

arch

200

0

40

Australasian Psychiatry • Vol 8, N

o 1• M

arch 2000

41

would be wise to keep an open mind. It is possiblethat early treatment of schizophrenia, especiallywith low-dose atypical antipsychotics, may providean opportunity to prevent the development of thecomponent of abnormal movements attributable tothe disease process itself.

REFERENCES

1. Kraepelin EL. Dementia Praecox. Edinburgh: Churchill Livingstone, 1919.

2. Brandon S, McClelland HA, Protheroe C. A study of facial dyskinesia in a mentalhospital population. British Journal of Psychiatry 1971; 118: 171–184.

3. Baldessarini RJ. Clinical and epidemiologic aspects of tardive dyskinesia. Journalof Clinical Psychiatry 1985; 46: 8–13.

4. Gervin M, Browne S, Lane A, et al. Spontaneous abnormal involuntary movementsin first-episode schizophrenia and schizophreniform disorder: Baseline rate in agroup of patients from an Irish catchment area. American Journal of Psychiatry1998; 155: 1202–1206.

5. Jeste DV, Potkin SG, Sinha S, Feder S, Wyatt RJ. Tardive dyskinesia: Reversibleand persistent. Archives of General Psychiatry 1979; 36: 585–590.

6. Rogers D. The motor disorders of severe psychiatric illness: A conflict of para-digms. British Journal of Psychiatry 1985; 147: 221–232.

7. Tardive Dyskinesia Task Force. Tardive Dyskinesia: A Task Force Report of theAmerican Psychiatric Association. Washington, DC: American Psychiatric Associa-tion, 1992.

8. Fenton WS, Blyler CR, Wyatt RJ, McGlashan TH. Prevalence of spontaneous dysk-inesia in schizophrenic and non-schizophrenic psychiatric patients. British Journalof Psychiatry 1997; 171: 265–268.

9. National Institute of Mental Health. Abnormal Involuntary Movements Scale.Bethesda, Maryland: Public Health Service, 1974.

10. Simpson GM, Angus JWS. A rating scale for extrapyramidal side effects. ActaPsychiatrica Scandinavica 1970; 212(Suppl.): 11–19.

11. Barnes TRE. A rating scale for drug-induced akathisia. British Journal of Psychiatry1989; 154: 672–676.

12. Gervin M, Browne S, Lane A, et al. Spontaneous dyskinesia in first episode schiz-ophrenia/schizophreniform psychosis. Schizophrenia Research Special Issue.Abstracts of the VIth International Congress on Schizophrenia Research, ColoradoUSA 1997; 24: 270.

13. Loebel AD, Lieberman JA, Alvir JMJ, Mayerhoff DI, Geisler SH, Szymanski SR.Duration of psychosis and outcome in first-episode schizophrenia. American Jour-nal of Psychiatry 1992; 149: 1183–1188.