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2000 Martin Dunitz Ltd
International Journal of Psychiatry in Clinical Practice 2000 Volume 4 Pages 319 ± 325
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Relationship of akathisia to aggressive and selfinjurious behaviour: A prevalence study in a UK tertiary referral centre
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JEAN H STUBBS1 , DAVID A HUTCHINS2 AND CHRISTOPHER Q MOUNTJOY1 1 2
St Andrew’s Hospital, Northampton and De Montfort University, Leicester, UK
Correspondence Address Jean H Stubbs MSc MRPharmS, Pharmacy Department, St Andrew’s Hospital, Billing Road, Northampton NN1 5DG Tel: +44 (0) 1604 616217 Fax: +44 (0) 1604 232325
Akathisia is a common and distressing side-effect associated with antipsychoti c drug administration . The relationship between akathisia and five forms of expressed aggression is investigated. INTRODUCTION:
Sixty-four mentally disordered patients were assessed for the point prevalence of akathisia, using Barnes’ rating scale for drug-induced akathisia. 1 The five types of aggression studied were: verbal abuse/ aggression, threatening behaviour /violence, physical aggression, destruction of property and deliberate self-harm, all of which are routinely recorded for patients. METHOD:
Fourteen subjects (21.9%) experienced akathisia, which was approximat ely four times more likely to occur in women than in men: four (6.3%) had pseudoakat hisia. Akathisia was statistically significantly associated with threatening behaviour (P < 0.05) and physical aggression (P < 0.05). RESULTS:
The data provide evidence for a relationship between the experience of akathisia and the expression of two forms of aberrant behaviour. (Int J Psych Clin Pract 2000; 4: 319 ± 325) CONCLUSION:
Received 21 October 1998, revised 21 August 2000, accepted 1 September 2000
Keywords akathisia Barnes akathisia scale
INTRODUCTION
A
ntipsychotic drugs remain an essential element of the acute and chronic treatment of a range of psychotic disorders, particularly schizophrenia. They are also administered as an acute treatment to calm disturbed patients, both in emergencie s and during acute treatment before the onset of antipsychotic action. Paradoxically , treatment with neuroleptic drugs, rather than producing a state of tranquillity and calmness, is sometimes responsibl e for generating the restlessness known as akathisia (Greek, `not to sit’).2 Akathisia is characterize d by a distressing sense of inner restlessnes s and unease, usually accompanied by a desire or compulsio n to move (subjective features). In addition, patients exhibit typical patterns of restless movement, such as shufflin g or tramping their feet when sitting, and rocking from foot to foot or pacing when standing (objective features).3 ,4 The overwhelmin g and intense nature of the subjective experience of akathisia in severe cases has been reported as
neuroleptics aggressiv e behaviour
contributing to suicide attempts and violence.5 ± 9 It is particularl y important that akathisia should be recognized, and not misdiagnose d as agitation or psychotic excitement, which can lead to increasin g the dosage of antipsychotic medication.
METHOD The prevalence of neuroleptic- induced akathisia was investigated by a survey of all patients on five wards at St. Andrew’s Hospital, Northampton. The research proposal for the study was approved by the St. Andrew’s Research and Ethics Committee.
SELECTION OF PATIENTS Patients were eligible for the study if they were inpatients on any of the five wards of the Adult Behavioural Treatment Unit at St Andrew’s Hospital, and were willing
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to participate. These patients had been regarded as `difficul t to place’ due to their challengin g behaviour. The most common problems they presented were self-injury , property damage, physical aggressio n and threatening behaviour. Many patients exhibited a combination of these problems, and had a range of diagnoses including personalit y disorder, schizophreni a, affective psychosis , organic psychosis and learning disability. Sixty-four patients consented to take part in the study, eight patients declined, and 15 were not included due to non-availabi lity (n=2) or other practical reasons (n=13). Patients were excluded if they were too disturbed, for whatever reason, to engage in the interview (n=4). Details of the psychiatric diagnosis and the drug treatment of individual s were not known to the investigators at the selection stage.
ASSESSMENT PROCEDURE Akathisia was assessed using Barnes’ rating scale for druginduced akathisia (BARS).1 This rating scale is routinely used by the first author (J.H.S.) in St Andrew’s Hospital movement disorder clinic. Initial training was provided by Dr Halstead, a clinician experienced in assessing movement disorders. 1 0 ,1 1 The scale includes items for rating the objective features of motor restlessness , the subjective complaints of restlessnes s and the associated distress. There is also a global severity rating on a six-point scale (0 ± 5), with operational definitions for each scale point. The scale provides a recommended examination procedure and incorporates diagnostic criteria for mild, moderate, marked and severe akathisia as well as pseudoakathis ia (pseudoakathisia is a condition in which the characteristi c restless movements are present but there is no report of the typical sense of restlessness ). High inter-rater reliabilit y has been reported for the Barnes Akathisia Rating Scale,1 ,1 2 ,13 and its validity is based on signs and symptoms found to be characteristi c of the condition of akathisia in studies of both acute psychiatric admissions receiving antipsychotic medication3 and outpatients suffering from schizophren ia and on maintenanc e medication.1 4 Most of the patients were interviewe d in the morning, in a side room of their own ward, and were usually assessed on their own by one of the authors (J.H.S.). A nurse was in attendance if staff felt it advisable on the grounds of safety, or when it was thought that patients would be unduly agitated if they were not in the presence of someone they knew. Patients were assesse d on at least one occasion.
BEHAVIOUR RECORDINGS Observations of five types of aggressiv e behaviour are routinely gathered by nursing staff on the Unit; training and regular team discussio n ensure that this is done consistently. The five types are:
· · · · ·
verbal abuse/aggression , when directed at another person; e.g. swearing, shouting, screaming, provoking fellow patients; threatening behaviour/violence ± verbal, gesture or using objects to threaten; physical aggressio n ± physical contact with another person with the intent to cause harm; destruction of property ± intentional destruction of furniture, property belonging to self or others; deliberate self-harm ± self-lacerat ions, swallowin g substances or items, the use of ligatures, insertion of objects into the anatomy, head-bangin g and other such behaviour in which aggressio n is directed towards the self.
During the study, the investigators remained blind to the outcome from the routine recordings of behaviour made before the assessmen t of akathisia.
DATA COLLECTION Patients’ records were examined to identify and record age, sex, ethnic origin, psychiatric diagnosis, intelligenc e and details of current medication. The study was undertaken early in 1996, before the widespread use of atypical antipsychotic s. The antipsychotic drug dose was converted to chlorpromazi ne equivalent s as mg/day, through published tables.1 5
STATISTICAL ANALYSIS Data were analysed using the Statistical Package for the Social Sciences (SPSS).1 6 The subjects with and without akathisia were compared by using a Student’s t-test for the mean age and Fisher’s exact probabilit y test for categorical variables. The pseudoakathi sia group was excluded from the analysis because there were only four patients with this condition. Analysis of variance (ANOVA) was employed to test the null hypothesis: ``There is no relationship between akathisia and aberrant behaviours.’’ Difference s in the total numbers of five recorded aberrant behaviour types were compared for those patients with akathisia and those without akathisia. The associatio n between the global clinical assessmen t of akathisia on the Barnes Akathisia Rating Scale and the incidence of recorded aberrant behaviour types was assessed by Spearman’s correlation coefficient . All hypotheses were two-tailed tested, with values of P < 0.05 considered significant .
RESULTS Sixty-four patients consented to take part in the study and their characteristic s are shown in Table 1. Their demographic, clinical and treatment characteristic s did not differ from those of the patients who declined to take part in the study.
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Table 1 Demographic data, diagnosis and intelligence of patients with akathisia, pseudoakathisia and no akathisia
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No akathisia
No. of subjects Age, mean (sd) Sex (M:F) Ethnic group Caucasian African Afro-Caribbean Asian
a
Akathisia
Pseudoakathisia
Total n
%
46 31.3 (8.2) 36:10
14 32.5 (8.6) 5:9
4 31.2 (3.7) 4:0
64 31.5 (8.0) 45:19
35 1 7 3
13 0 1 0
4 0 0 0
52 1 8 3
81.3 1.6 12.5 4.7
Primary diagnosis Personality disorder Schizophrenia Affective psychosis Organic psychosis Other psychosis Fragile X Autism
12 25 3 1 3 0 1
7 4 2 1 0 0 0
0 1 0 1 1 1 0
19 30 5 3 4 1 1
29.7 46.9 7.8 4.7 6.3 1.6 1.6
Intelligence Normal IQa Low average IQ Borderline LDb Mild LD Moderate LD
24 5 10 6 1
4 3 3 4 0
0 2 1 0 1
28 10 14 10 2
43.8 15.6 21.9 15.6 3.1
IQ=Intelligence Quotient
b
LD=Learning disability
Based on the global clinical assessmen t scale of the BARS (score of 2, mild, or higher), 14 subjects (21.9%) were rated as having akathisia; four patients had pseudoakathisia; most patients (71.9%) had no akathisia. There were 45 male (70.3%) and 19 female (29.7%) patients, whose ages ranged from 20 to 60 years (mean 31.5 years, sd 8.0 years). There was no statistically significan t differenc e in age between the sexes (males, mean age 31.6, sd 8.4 years; females, mean age 31.3, sd 7.3 years) (unpaire d ttest, t=0.13, df=62, P=0.899).
CHARACTERISTICS OF THE PATIENTS The pseudoakathi sia patients were excluded from the statistical analysis of patient characteristic s, leaving two groups ± those with akathisia (n=14), and those without akathisia (n=46). There was no significant difference in the mean age of patients with akathisia and those without akathisia (unpaire d t-test, t=0.47, df=58, P=0.637). A compariso n of the two groups of patients was undertaken for the categorical variables of ethnic origin, primary diagnosis and intelligence . No statistical significance was found for the relationship s between akathisia and ethnic origin, psychiatric diagnosis or learning disability.
Fisher’s exact probabilit y test was used to examine the relationshi p between gender and akathisia. The proportion of women with akathisia was significantl y higher than the proportion of men (P < 0.05).
RELATION BETWEEN AKATHISIA AND CURRENT ANTIPSYCHOTIC MEDICATION (TABLE 2) The study was conducted blind to the patients’ medication. A retrospective review of the clinical notes showed that nine patients had not been prescribed such drugs within at least the previous 2 months: none of these patients had akathisia, but one had pseudoakathi sia. At the time of assessmen t another four patients were not receiving antipsychotic medication, although, as required, antipsychotics had been administered in the 3-week period leading up to that assessment : none of these patients had akathisia or pseudoakathi sia. Of the 51 patients receiving antipsychotics, 27.5% were experiencin g akathisia and 5.9% experienced pseudoakathis ia. Thus for those patients on antipsychotic s, approximately 1 in 3 suffere d from a variant of akathisia, whereas none of those who were not treated with such drugs developed akathisia. Nine patients were on clozapine: only one experienced akathisia. This patient also received two typical antipsychotic s.
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The mean total daily dose of antipsychotic drugs, at the time of assessment of akathisia in mg/day of chlorpromazi ne equivalents , was less for the patients experiencin g akathisia (mean 848 mg; sd 666) than for those without akathisia (mean 929 mg; sd 1162), but the association between akathisia/no akathisia and antipsychotic dosage failed to reach statistical significance (unpaired t-test, t=0.25, df=58, P=0.806). In addition, there was no statistically significan t correlation between the severity of akathisia and antipsychotic dosage.
RELATION BETWEEN AKATHISIA AND NON-ANTIPSYCHOTIC MEDICATION (TABLE 2) In addition to antipsychotic medication, 33 patients received antiparkinso nian medication, 10 received antidepressants, two propranolo l and six benzodiazepin es, at the time of assessment of akathisia. Prescribin g of benzodiazepi nes was significant ly higher in the akathisia group (Fisher’s exact probability test, P=0.002). There was no statistically significan t relation between akathisia and the use of antiparkinson ian medication or antidepressa nts. The two patients receiving propranolol were from the akathisia group.
RELATION BETWEEN AKATHISIA AND ABERRANT BEHAVIOUR One-way analysis of variance (ANOVA) showed that the patients experiencin g akathisia (ranging in severity from mild to marked) were significant ly more likely to exhibit threatening behaviour and physical aggressio n than were the patients with no akathisia. No significan t difference s were found for the other behaviour types (Table 3). The correlation between the severity of akathisia and the incidence of each of the five recorded behaviour types is shown in Table 4. There was a significant negative association between the severity of akathisia and the incidence of threatening behaviour/violence and physical aggression , with the incidence of these behaviour types being greatest for those patients with mild akathisia, and diminishin g with increasing severity of akathisia.
DISCUSSION DEMOGRAPHIC ISSUES In the present study the prevalence of akathisia was 21.9% overall and 27.5% for those patients treated with
Table 2 Current antipsychotic and nonantipsychotic medication associated with akathisiaa Drug
Number (%) of patients in each group prescribed each drugb No akathisia Akathisia Fisher’s (n=46) (n=14) exact test n % n % P-value
Antipsychotic Anticholinergic Antidepressant Propranolol Benzodiazepine
34 25 7 0 1
71 54 15 0 2
14 7 4 2 5
29 50 29 14 36
0.052 1.000 0.264 0.051 0.002
a
Pseudoakathisia patients were excluded All of the patients in Table 2 were prescribed antipsychotic medication in addition to their nonneuroleptics, except one of the patients in the no-akathisia category who was on anticholinergics, and another who was on antidepressants in the absence of current antipsychotics b
Table 3 Relation of akathisia to the incidence of aberrant behaviour typesa
a
Recorded behaviour type
Mean (sd) incidence of aberrant behaviours No akathisia Akathisia (n=46) (n=14)
Verbal abuse/aggression Threatening behaviour Physical aggression Property destruction Deliberate self-harm
11.5 1.3 2.0 1.2 2.3
Pseudoakathisia patients were excluded
(41.0) (1.9) (4.6) (3.4) (7.5)
16.8 7.8 13.2 2.3 2.9
(32.2) (20.2) (30.1) (4.8) (3.9)
F(1,58)
P-value
0.20 4.88 6.15 0.96 0.08
0.658 0.031 0.016 0.331 0.782
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Table 4 Relation between the severity of akathisia and aberrant behaviour in 60 patients a
Recorded behaviour
Mean (sd) number of recorded incidents of aberrant behaviour for each category of akathisiab No akathisia Mild akathisia Moderate akathisia Marked akathisia Spearman’s rs (n=46) (n=8) (n=5) (n=1) value
Verbal abuse/aggression Threatening behaviour Physical aggression Property destruction Deliberate self-harm
11.5 1.3 2.0 1.2 2.4
a
(41.0) (1.9) (4.6) (3.4) (7.5)
16.1 10.3 17.9 2.4 1.9
(38.8) (27.0) (40.1) (6.3) (2.9)
20.6 4.8 7.8 2.0 5.2
(25.8) (4.2) (5.5) (2.1) (5.0)
3.0 3.0 3.0 3.0 0.0
0.21 0.29 0.43 0.18 0.23
P-value 0.112 0.025 0.001 0.171 0.082
Pseudoakathisia patients were excluded There were no patients with severe akathisia
b
antipsychotic medication. This is consistent with the prevalence figures reported in the literature. A figure of around 20% has been commonly accepted.1 The proportion of patients with pseudoakathi sia (6.3% overall and 5.9% for those treated with antipsychotic s) was similar to that found by McCreadie and colleague s (5%):1 2 it was relatively low, however, compared to the figures of 12 ± 21% reported elsewhere. 1 ,14 In the present study, there was no evidence that age was related to the presence of akathisia. In the study by Halstead and colleagues , patients with akathisia were significantl y younger than those without akathisia.1 0 Ganesh and colleague s found a similar correlation between age and akathisia.1 7 However, in both those studies there was a trend for the dosage of antipsychoti c medication to fall markedly with age, suggesting that the onset of akathisia is related more to the dose of drug than to the age of the patient. A link between high doses of antipsychotic medication and akathisia has been reported.3 The authors are unaware of any publishe d work suggesting that any particular racial group is more vulnerable to the development of drug-induce d akathisia, nor was such a relationship found in this study. Most studies have failed to reveal any gender difference s in the vulnerabilit y to develop akathisia.3 ,1 2 , 17 Our finding that women had a significantl y greater vulnerabili ty to the development of akathisia is therefore of particular interest and warrants further investigation . Braude and colleagues included patients with affective disorder and personalit y disorder as well as schizophren ic sufferers. 3 There was no suggestion that any diagnostic group was particularly more likely to develop akathisia, which is in agreement with the findings of the present study. The prevalence of akathisia did not differ significantl y between the patients with normal intelligenc e and those with learning disabilities . Ganesh et al describe d the difficult y in making a definitive diagnosi s in individual s with learning disabilities who may be unwilling or unable to provide a subjective account.1 7 In their study of akathisia
in such patients treated with neuroleptics , they cited a prevalence of 7%, which is considerabl y lower than the usual reported prevalence of approximately 20%. However, in the present study, which included 26 patients (40.6%) with learning disabilities , no communication problem was encountered in eliciting the subjective features of akathisia. Only two of the patients in the study had more than a mild level of learning disability.
RELATION BETWEEN AKATHISIA AND CURRENT ANTIPSYCHOTIC MEDICATION This study has not found a significan t associatio n between akathisia and the dosage of current antipsychotic medication. Akathisia can be a dose-related condition of acute onset. The findings of two studies of acute neurolepticinduced akathisia in consecutive psychiatric admissions3 ,1 8 suggested that the likelihood of developing akathisia is markedly increased with the administratio n of rapidly increasing doses of antipsychotic s. Surveys of long-stay patients with schizophreni a on maintenance medication, such as those included in the present study, have presented conflicting results.1 2 ,19 Our data do not suggest a causeand-effect relation between dosage of antipsychotic medication and the incidence and severity of akathisia. Patients on higher doses of medication had a lower probability of developing akathisia. This suggests a possible `window effect’ in the relation between antipsychotic dose and akathisia. Alternatively , the expression of akathisia may be masked at higher doses by the emergence of other neurologica l reactions such as rigidity and hypokinesia . The doses of antipsychotic s used are relatively high (mean of 848 and 928 mg/day), which is a reflection of the tertiary and comorbid nature of the patient group.
RELATION BETWEEN AKATHISIA AND NON-NEUROLEPTIC MEDICATION A significantl y greater proportion of the patients with akathisia than of those without akathisia were prescribed
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benzodiazepi nes. The results raise some interesting possibilities. First, benzodiazepi nes may be given to alleviate the neurologica l reaction: treatment strategies for drug-induce d akathisia have included the use of benzodiazepi nes, although they may provide only limited benefit.2 Second, the patients with akathisia may appear more anxious: when reporting subjective experiences , patients describe vague feelings of inner tension, emotional unease or anxiety.2 Third benzodiazepi nes may be employed in the management of aggressiv e behaviour: as previousl y described, akathisia is reported to have contributed to violence. It may well be that one or more of these factors influence d the decisions to prescribe benzodiazepi nes. There was no statistically significan t association between akathisia and the use of antiparkinson ian medication or antidepressan ts. This is consistent with other published reports. 1 0,1 2 Two patients in the study were prescribed propranolo l for the control of aggressiv e behaviour, in addition to their antipsychotic medication. Both patients had akathisia.
RELATION BETWEEN AKATHISIA AND ABERRANT BEHAVIOUR The patients experiencin g akathisia showed an increase in all of the recorded types of behaviour, albeit at a nonsignifican t level for some. Patients with akathisia demonstrated significant ly more incidents of threatening behaviour and physical aggressio n than the patients without akathisia. No statistical significanc e was found for the relationship between akathisia and the other recorded types of aberrant behaviour. This suggests that the akathisia may be contributing selectivel y to some of the patients’ aberrant behaviour. It is of interest that deliberate self-harm, verbal aggressio n and property damage showed no significan t association with akathisia (see methodologica l issues, below). Thus a selective increase in threatening and aggressiv e behaviour may prove to be an index of the onset of akathisia, as a medication problem for patients cared for in a similar treatment environment . The observed inverse relation between the severity of akathisia and the incidence of threatening behaviour and physical aggression is difficult to reconcile with case reports which have suggested that it is the overwhelmin g and intense nature of the subjective experience in severe akathisia which is thought to have contributed to violence. If the incidence of threatening behaviour and physical aggressio n are greatest in mild akathisia, this is important, because it is the milder forms of the condition which are particularly prone to be overlooked or misinterpreted .2 0 This clearly requires further study with a larger cohort of patients.
METHODOLOGICAL ISSUES There are a number of issues to consider when interpreting the results of this study.
First, the small number of patients with pseudoakathis ia preclude separate analysi s of this condition. A more extensive study in a larger group of these subjects is needed. Second, the behavioura l response of some of the patients who developed akathisia may have been modified by a successfu l behavioura l treatment programme and the relative lack of opportunity for deliberate self-harm within a secure ward environment . This may account for the difference between our findings and those which have shown a positive association between akathisia and suicidal behaviour. 6 ,9 ,21 Finally, the nature of the study group and the setting may limit the generalizatio n of the results to subjects recruited from other treatment systems. Specifically , the patients included are all tertiary referrals, whose existing behavioura l problems have failed to respond to treatment before their admission to St Andrew’s Hospital. Nonetheless, the value of the present study is that it does identify an associatio n between akathisia and two types of problem behaviour that are of common concern in the management of patients, whatever the care environment . It also suggests that the relation between antipsychotic dosage and the development of akathisia is complex and there may be a `window effect’ in the development of this reaction.
CONCLUDING COMMENTS The results of this study suggest an association between the presence of akathisia and the incidence of threatening behaviour and physical aggression , but not the incidence of deliberate self-harm. In a clinical setting in which one of the ways of monitoring progress or relapse is based on the recording of aberrant behaviour , it is clearly important that akathisia should be recognized as a possible source of problematic behaviour. Routine assessmen t of akathisia and increase d awareness of this adverse drug side-effec t would enable attention to be focused on treatment strategies designed to prevent or alleviate the condition. Future studies should assess the consequence s of such an approach.
KEY POINTS
· · · · ·
This survey uses the Barnes rating scale Data was analysed using the statistical package for the social sciences (SPSS) There was no cause and effect relationshi p between dosage of antipsychotic and incidence and severity of akathisia The incidence of aggressiv e and threatening behaviour were greater in mild akathisia Routine assessment s would encourage better treatment strategies for prevention and alleviation of akathisia
Ak athisia and expressed aggression
ACKNOWLEDGEMENTS We gratefully acknowledge the assistance of Dr S Halstead and other members of the St Andrew’s Hospital Research
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Committee. Thanks are also due to colleagues at St Andrew’s Hospital and the patients who participated in the study.
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REFERENCES 1. Barnes TRE (1989) A rating scale for drug-induced akathisia. Br J Psychiatry 154: 672 ± 6. 2. Anon (1986) Akathisia and antipsychotic drugs (Editorial). Lancet ii: 1131 ± 2. 3. Braude WM, Barnes TRE, Gore SM (1983) Clinical characteristics of akathisia. A systematic investigation of acute psychiatric inpatient admissions. Br J Psychiatry 143: 139 ± 50. 4. Barnes TRE (1990) Movement disorder associated with antipsychotic drugs: the tardive syndromes. Int Rev Psychiatry 2: 355 ± 66. 5. Keckich WA (1978) Violence as a manifestation of akathisia. JAMA 240: 2185. 6. Drake RE, Ehrlich J (1985) Suicide attempts associated with akathisia. Am J Psychiatry 142: 499 ± 501. 7. Schulte JL (1985) Homicide and suicide associated with akathisia and haloperidol. Am J Forensic Psychiatry 6: 3 ± 7. 8. Shaw ED, Mann JJ, Weiden PJ et al (1986) A case of suicidal and homicidal ideation and akathisia in a double-blind neuroleptic crossover study (Letter). J Clin Psychopharmacol 6: 196 ± 7. 9. Azhar MZ, Varma SL (1992) Akathisia-induced suicidal behaviour. Eur Psychiatry 7: 239 ± 41. 10. Halstead SM, Barnes TRE, Speller JC (1994) Akathisia: prevalence and associated dysphoria in an in-patient population with chronic schizophrenia. Br J Psychiatry 164: 177 ± 83. 11. Stubbs JH, Halstead SM (2000) Pseudoakathisia: A review and two case reports. Compr Psychiatry 41: 70 ± 2.
12. McCreadie RG, Robertson LJ, Wiles DH (1992) The Nithsdale schizophrenia surveys. IX: Akathisia, parkinsonism, tardive dyskinesia and plasma neuroleptic levels. Br J Psychiatry 161: 793 ± 9. 13. Chengappa KNR, Shelton MD, Baker RW et al (1994) The prevalence of akathisia in patients receiving stable doses of clozapine. J Clin Psychiatry 55: 142 ± 5. 14. Barnes TRE, Braude WM (1985) Akathisia variants and tardive dyskinesia. Arch Gen Psychiatry 42: 874 ± 8. 15. Bazire S (1995) Psychotrophic Drug Directory. Mark Allen Publishing Ltd, Wilts. 16. SPSS Version 7 for Windows (1996) SPSS Inc. Chicago. 17. Ganesh S, Rao JM, Cowie VA (1989) Akathisia in neuroleptic medicated mentally handicapped subjects. J Ment Defic Res 33: 323 ± 9. 18. Sachdev P, Kruk J (1994) Clinical characteristics and predisposing factors in acute drug-induced akathisia. Arch Gen Psychiatry 51: 963 ± 74. 19. Kahn EM, Munetz MR, Davies MA, Schulz SC (1992) Akathisia: clinical phenomenology and relationship to tardive dyskinesia. Compr Psychiatry 33: 233 ± 6. 20. Weiden PJ, Mann JJ, Hass G et al (1987) Clinical nonrecognition of neuroleptic-induced movement disorders: a cautionary tale. Am J Psychiatry 144: 1148 ± 53. 21. Healy D (2000) Emergence of antidepressant induced suicidality. Primary Care Psychiatry 6: 23 ± 28.
2000 Martin Dunitz Ltd
International Journal of Psychiatry in Clinical Practice 2000 Volume 4 Pages 319 ± 325
319
Relationship of akathisia to aggressive and selfinjurious behaviour: A prevalence study in a UK tertiary referral centre
Int J Psych Clin Pract Downloaded from informahealthcare.com by The University of Manchester on 10/30/14 For personal use only.
JEAN H STUBBS1 , DAVID A HUTCHINS2 AND CHRISTOPHER Q MOUNTJOY1 1 2
St Andrew’s Hospital, Northampton and De Montfort University, Leicester, UK
Correspondence Address Jean H Stubbs MSc MRPharmS, Pharmacy Department, St Andrew’s Hospital, Billing Road, Northampton NN1 5DG Tel: +44 (0) 1604 616217 Fax: +44 (0) 1604 232325
Akathisia is a common and distressing side-effect associated with antipsychoti c drug administration . The relationship between akathisia and five forms of expressed aggression is investigated. INTRODUCTION:
Sixty-four mentally disordered patients were assessed for the point prevalence of akathisia, using Barnes’ rating scale for drug-induced akathisia. 1 The five types of aggression studied were: verbal abuse/ aggression, threatening behaviour /violence, physical aggression, destruction of property and deliberate self-harm, all of which are routinely recorded for patients. METHOD:
Fourteen subjects (21.9%) experienced akathisia, which was approximat ely four times more likely to occur in women than in men: four (6.3%) had pseudoakat hisia. Akathisia was statistically significantly associated with threatening behaviour (P < 0.05) and physical aggression (P < 0.05). RESULTS:
The data provide evidence for a relationship between the experience of akathisia and the expression of two forms of aberrant behaviour. (Int J Psych Clin Pract 2000; 4: 319 ± 325) CONCLUSION:
Received 21 October 1998, revised 21 August 2000, accepted 1 September 2000
Keywords akathisia Barnes akathisia scale
INTRODUCTION
A
ntipsychotic drugs remain an essential element of the acute and chronic treatment of a range of psychotic disorders, particularly schizophrenia. They are also administered as an acute treatment to calm disturbed patients, both in emergencie s and during acute treatment before the onset of antipsychotic action. Paradoxically , treatment with neuroleptic drugs, rather than producing a state of tranquillity and calmness, is sometimes responsibl e for generating the restlessness known as akathisia (Greek, `not to sit’).2 Akathisia is characterize d by a distressing sense of inner restlessnes s and unease, usually accompanied by a desire or compulsio n to move (subjective features). In addition, patients exhibit typical patterns of restless movement, such as shufflin g or tramping their feet when sitting, and rocking from foot to foot or pacing when standing (objective features).3 ,4 The overwhelmin g and intense nature of the subjective experience of akathisia in severe cases has been reported as
neuroleptics aggressiv e behaviour
contributing to suicide attempts and violence.5 ± 9 It is particularl y important that akathisia should be recognized, and not misdiagnose d as agitation or psychotic excitement, which can lead to increasin g the dosage of antipsychotic medication.
METHOD The prevalence of neuroleptic- induced akathisia was investigated by a survey of all patients on five wards at St. Andrew’s Hospital, Northampton. The research proposal for the study was approved by the St. Andrew’s Research and Ethics Committee.
SELECTION OF PATIENTS Patients were eligible for the study if they were inpatients on any of the five wards of the Adult Behavioural Treatment Unit at St Andrew’s Hospital, and were willing
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to participate. These patients had been regarded as `difficul t to place’ due to their challengin g behaviour. The most common problems they presented were self-injury , property damage, physical aggressio n and threatening behaviour. Many patients exhibited a combination of these problems, and had a range of diagnoses including personalit y disorder, schizophreni a, affective psychosis , organic psychosis and learning disability. Sixty-four patients consented to take part in the study, eight patients declined, and 15 were not included due to non-availabi lity (n=2) or other practical reasons (n=13). Patients were excluded if they were too disturbed, for whatever reason, to engage in the interview (n=4). Details of the psychiatric diagnosis and the drug treatment of individual s were not known to the investigators at the selection stage.
ASSESSMENT PROCEDURE Akathisia was assessed using Barnes’ rating scale for druginduced akathisia (BARS).1 This rating scale is routinely used by the first author (J.H.S.) in St Andrew’s Hospital movement disorder clinic. Initial training was provided by Dr Halstead, a clinician experienced in assessing movement disorders. 1 0 ,1 1 The scale includes items for rating the objective features of motor restlessness , the subjective complaints of restlessnes s and the associated distress. There is also a global severity rating on a six-point scale (0 ± 5), with operational definitions for each scale point. The scale provides a recommended examination procedure and incorporates diagnostic criteria for mild, moderate, marked and severe akathisia as well as pseudoakathis ia (pseudoakathisia is a condition in which the characteristi c restless movements are present but there is no report of the typical sense of restlessness ). High inter-rater reliabilit y has been reported for the Barnes Akathisia Rating Scale,1 ,1 2 ,13 and its validity is based on signs and symptoms found to be characteristi c of the condition of akathisia in studies of both acute psychiatric admissions receiving antipsychotic medication3 and outpatients suffering from schizophren ia and on maintenanc e medication.1 4 Most of the patients were interviewe d in the morning, in a side room of their own ward, and were usually assessed on their own by one of the authors (J.H.S.). A nurse was in attendance if staff felt it advisable on the grounds of safety, or when it was thought that patients would be unduly agitated if they were not in the presence of someone they knew. Patients were assesse d on at least one occasion.
BEHAVIOUR RECORDINGS Observations of five types of aggressiv e behaviour are routinely gathered by nursing staff on the Unit; training and regular team discussio n ensure that this is done consistently. The five types are:
· · · · ·
verbal abuse/aggression , when directed at another person; e.g. swearing, shouting, screaming, provoking fellow patients; threatening behaviour/violence ± verbal, gesture or using objects to threaten; physical aggressio n ± physical contact with another person with the intent to cause harm; destruction of property ± intentional destruction of furniture, property belonging to self or others; deliberate self-harm ± self-lacerat ions, swallowin g substances or items, the use of ligatures, insertion of objects into the anatomy, head-bangin g and other such behaviour in which aggressio n is directed towards the self.
During the study, the investigators remained blind to the outcome from the routine recordings of behaviour made before the assessmen t of akathisia.
DATA COLLECTION Patients’ records were examined to identify and record age, sex, ethnic origin, psychiatric diagnosis, intelligenc e and details of current medication. The study was undertaken early in 1996, before the widespread use of atypical antipsychotic s. The antipsychotic drug dose was converted to chlorpromazi ne equivalent s as mg/day, through published tables.1 5
STATISTICAL ANALYSIS Data were analysed using the Statistical Package for the Social Sciences (SPSS).1 6 The subjects with and without akathisia were compared by using a Student’s t-test for the mean age and Fisher’s exact probabilit y test for categorical variables. The pseudoakathi sia group was excluded from the analysis because there were only four patients with this condition. Analysis of variance (ANOVA) was employed to test the null hypothesis: ``There is no relationship between akathisia and aberrant behaviours.’’ Difference s in the total numbers of five recorded aberrant behaviour types were compared for those patients with akathisia and those without akathisia. The associatio n between the global clinical assessmen t of akathisia on the Barnes Akathisia Rating Scale and the incidence of recorded aberrant behaviour types was assessed by Spearman’s correlation coefficient . All hypotheses were two-tailed tested, with values of P < 0.05 considered significant .
RESULTS Sixty-four patients consented to take part in the study and their characteristic s are shown in Table 1. Their demographic, clinical and treatment characteristic s did not differ from those of the patients who declined to take part in the study.
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Table 1 Demographic data, diagnosis and intelligence of patients with akathisia, pseudoakathisia and no akathisia
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No akathisia
No. of subjects Age, mean (sd) Sex (M:F) Ethnic group Caucasian African Afro-Caribbean Asian
a
Akathisia
Pseudoakathisia
Total n
%
46 31.3 (8.2) 36:10
14 32.5 (8.6) 5:9
4 31.2 (3.7) 4:0
64 31.5 (8.0) 45:19
35 1 7 3
13 0 1 0
4 0 0 0
52 1 8 3
81.3 1.6 12.5 4.7
Primary diagnosis Personality disorder Schizophrenia Affective psychosis Organic psychosis Other psychosis Fragile X Autism
12 25 3 1 3 0 1
7 4 2 1 0 0 0
0 1 0 1 1 1 0
19 30 5 3 4 1 1
29.7 46.9 7.8 4.7 6.3 1.6 1.6
Intelligence Normal IQa Low average IQ Borderline LDb Mild LD Moderate LD
24 5 10 6 1
4 3 3 4 0
0 2 1 0 1
28 10 14 10 2
43.8 15.6 21.9 15.6 3.1
IQ=Intelligence Quotient
b
LD=Learning disability
Based on the global clinical assessmen t scale of the BARS (score of 2, mild, or higher), 14 subjects (21.9%) were rated as having akathisia; four patients had pseudoakathisia; most patients (71.9%) had no akathisia. There were 45 male (70.3%) and 19 female (29.7%) patients, whose ages ranged from 20 to 60 years (mean 31.5 years, sd 8.0 years). There was no statistically significan t differenc e in age between the sexes (males, mean age 31.6, sd 8.4 years; females, mean age 31.3, sd 7.3 years) (unpaire d ttest, t=0.13, df=62, P=0.899).
CHARACTERISTICS OF THE PATIENTS The pseudoakathi sia patients were excluded from the statistical analysis of patient characteristic s, leaving two groups ± those with akathisia (n=14), and those without akathisia (n=46). There was no significant difference in the mean age of patients with akathisia and those without akathisia (unpaire d t-test, t=0.47, df=58, P=0.637). A compariso n of the two groups of patients was undertaken for the categorical variables of ethnic origin, primary diagnosis and intelligence . No statistical significance was found for the relationship s between akathisia and ethnic origin, psychiatric diagnosis or learning disability.
Fisher’s exact probabilit y test was used to examine the relationshi p between gender and akathisia. The proportion of women with akathisia was significantl y higher than the proportion of men (P < 0.05).
RELATION BETWEEN AKATHISIA AND CURRENT ANTIPSYCHOTIC MEDICATION (TABLE 2) The study was conducted blind to the patients’ medication. A retrospective review of the clinical notes showed that nine patients had not been prescribed such drugs within at least the previous 2 months: none of these patients had akathisia, but one had pseudoakathi sia. At the time of assessmen t another four patients were not receiving antipsychotic medication, although, as required, antipsychotics had been administered in the 3-week period leading up to that assessment : none of these patients had akathisia or pseudoakathi sia. Of the 51 patients receiving antipsychotics, 27.5% were experiencin g akathisia and 5.9% experienced pseudoakathis ia. Thus for those patients on antipsychotic s, approximately 1 in 3 suffere d from a variant of akathisia, whereas none of those who were not treated with such drugs developed akathisia. Nine patients were on clozapine: only one experienced akathisia. This patient also received two typical antipsychotic s.
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The mean total daily dose of antipsychotic drugs, at the time of assessment of akathisia in mg/day of chlorpromazi ne equivalents , was less for the patients experiencin g akathisia (mean 848 mg; sd 666) than for those without akathisia (mean 929 mg; sd 1162), but the association between akathisia/no akathisia and antipsychotic dosage failed to reach statistical significance (unpaired t-test, t=0.25, df=58, P=0.806). In addition, there was no statistically significan t correlation between the severity of akathisia and antipsychotic dosage.
RELATION BETWEEN AKATHISIA AND NON-ANTIPSYCHOTIC MEDICATION (TABLE 2) In addition to antipsychotic medication, 33 patients received antiparkinso nian medication, 10 received antidepressants, two propranolo l and six benzodiazepin es, at the time of assessment of akathisia. Prescribin g of benzodiazepi nes was significant ly higher in the akathisia group (Fisher’s exact probability test, P=0.002). There was no statistically significan t relation between akathisia and the use of antiparkinson ian medication or antidepressa nts. The two patients receiving propranolol were from the akathisia group.
RELATION BETWEEN AKATHISIA AND ABERRANT BEHAVIOUR One-way analysis of variance (ANOVA) showed that the patients experiencin g akathisia (ranging in severity from mild to marked) were significant ly more likely to exhibit threatening behaviour and physical aggressio n than were the patients with no akathisia. No significan t difference s were found for the other behaviour types (Table 3). The correlation between the severity of akathisia and the incidence of each of the five recorded behaviour types is shown in Table 4. There was a significant negative association between the severity of akathisia and the incidence of threatening behaviour/violence and physical aggression , with the incidence of these behaviour types being greatest for those patients with mild akathisia, and diminishin g with increasing severity of akathisia.
DISCUSSION DEMOGRAPHIC ISSUES In the present study the prevalence of akathisia was 21.9% overall and 27.5% for those patients treated with
Table 2 Current antipsychotic and nonantipsychotic medication associated with akathisiaa Drug
Number (%) of patients in each group prescribed each drugb No akathisia Akathisia Fisher’s (n=46) (n=14) exact test n % n % P-value
Antipsychotic Anticholinergic Antidepressant Propranolol Benzodiazepine
34 25 7 0 1
71 54 15 0 2
14 7 4 2 5
29 50 29 14 36
0.052 1.000 0.264 0.051 0.002
a
Pseudoakathisia patients were excluded All of the patients in Table 2 were prescribed antipsychotic medication in addition to their nonneuroleptics, except one of the patients in the no-akathisia category who was on anticholinergics, and another who was on antidepressants in the absence of current antipsychotics b
Table 3 Relation of akathisia to the incidence of aberrant behaviour typesa
a
Recorded behaviour type
Mean (sd) incidence of aberrant behaviours No akathisia Akathisia (n=46) (n=14)
Verbal abuse/aggression Threatening behaviour Physical aggression Property destruction Deliberate self-harm
11.5 1.3 2.0 1.2 2.3
Pseudoakathisia patients were excluded
(41.0) (1.9) (4.6) (3.4) (7.5)
16.8 7.8 13.2 2.3 2.9
(32.2) (20.2) (30.1) (4.8) (3.9)
F(1,58)
P-value
0.20 4.88 6.15 0.96 0.08
0.658 0.031 0.016 0.331 0.782
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Table 4 Relation between the severity of akathisia and aberrant behaviour in 60 patients a
Recorded behaviour
Mean (sd) number of recorded incidents of aberrant behaviour for each category of akathisiab No akathisia Mild akathisia Moderate akathisia Marked akathisia Spearman’s rs (n=46) (n=8) (n=5) (n=1) value
Verbal abuse/aggression Threatening behaviour Physical aggression Property destruction Deliberate self-harm
11.5 1.3 2.0 1.2 2.4
a
(41.0) (1.9) (4.6) (3.4) (7.5)
16.1 10.3 17.9 2.4 1.9
(38.8) (27.0) (40.1) (6.3) (2.9)
20.6 4.8 7.8 2.0 5.2
(25.8) (4.2) (5.5) (2.1) (5.0)
3.0 3.0 3.0 3.0 0.0
0.21 0.29 0.43 0.18 0.23
P-value 0.112 0.025 0.001 0.171 0.082
Pseudoakathisia patients were excluded There were no patients with severe akathisia
b
antipsychotic medication. This is consistent with the prevalence figures reported in the literature. A figure of around 20% has been commonly accepted.1 The proportion of patients with pseudoakathi sia (6.3% overall and 5.9% for those treated with antipsychotic s) was similar to that found by McCreadie and colleague s (5%):1 2 it was relatively low, however, compared to the figures of 12 ± 21% reported elsewhere. 1 ,14 In the present study, there was no evidence that age was related to the presence of akathisia. In the study by Halstead and colleagues , patients with akathisia were significantl y younger than those without akathisia.1 0 Ganesh and colleague s found a similar correlation between age and akathisia.1 7 However, in both those studies there was a trend for the dosage of antipsychoti c medication to fall markedly with age, suggesting that the onset of akathisia is related more to the dose of drug than to the age of the patient. A link between high doses of antipsychotic medication and akathisia has been reported.3 The authors are unaware of any publishe d work suggesting that any particular racial group is more vulnerable to the development of drug-induce d akathisia, nor was such a relationship found in this study. Most studies have failed to reveal any gender difference s in the vulnerabilit y to develop akathisia.3 ,1 2 , 17 Our finding that women had a significantl y greater vulnerabili ty to the development of akathisia is therefore of particular interest and warrants further investigation . Braude and colleagues included patients with affective disorder and personalit y disorder as well as schizophren ic sufferers. 3 There was no suggestion that any diagnostic group was particularly more likely to develop akathisia, which is in agreement with the findings of the present study. The prevalence of akathisia did not differ significantl y between the patients with normal intelligenc e and those with learning disabilities . Ganesh et al describe d the difficult y in making a definitive diagnosi s in individual s with learning disabilities who may be unwilling or unable to provide a subjective account.1 7 In their study of akathisia
in such patients treated with neuroleptics , they cited a prevalence of 7%, which is considerabl y lower than the usual reported prevalence of approximately 20%. However, in the present study, which included 26 patients (40.6%) with learning disabilities , no communication problem was encountered in eliciting the subjective features of akathisia. Only two of the patients in the study had more than a mild level of learning disability.
RELATION BETWEEN AKATHISIA AND CURRENT ANTIPSYCHOTIC MEDICATION This study has not found a significan t associatio n between akathisia and the dosage of current antipsychotic medication. Akathisia can be a dose-related condition of acute onset. The findings of two studies of acute neurolepticinduced akathisia in consecutive psychiatric admissions3 ,1 8 suggested that the likelihood of developing akathisia is markedly increased with the administratio n of rapidly increasing doses of antipsychotic s. Surveys of long-stay patients with schizophreni a on maintenance medication, such as those included in the present study, have presented conflicting results.1 2 ,19 Our data do not suggest a causeand-effect relation between dosage of antipsychotic medication and the incidence and severity of akathisia. Patients on higher doses of medication had a lower probability of developing akathisia. This suggests a possible `window effect’ in the relation between antipsychotic dose and akathisia. Alternatively , the expression of akathisia may be masked at higher doses by the emergence of other neurologica l reactions such as rigidity and hypokinesia . The doses of antipsychotic s used are relatively high (mean of 848 and 928 mg/day), which is a reflection of the tertiary and comorbid nature of the patient group.
RELATION BETWEEN AKATHISIA AND NON-NEUROLEPTIC MEDICATION A significantl y greater proportion of the patients with akathisia than of those without akathisia were prescribed
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benzodiazepi nes. The results raise some interesting possibilities. First, benzodiazepi nes may be given to alleviate the neurologica l reaction: treatment strategies for drug-induce d akathisia have included the use of benzodiazepi nes, although they may provide only limited benefit.2 Second, the patients with akathisia may appear more anxious: when reporting subjective experiences , patients describe vague feelings of inner tension, emotional unease or anxiety.2 Third benzodiazepi nes may be employed in the management of aggressiv e behaviour: as previousl y described, akathisia is reported to have contributed to violence. It may well be that one or more of these factors influence d the decisions to prescribe benzodiazepi nes. There was no statistically significan t association between akathisia and the use of antiparkinson ian medication or antidepressan ts. This is consistent with other published reports. 1 0,1 2 Two patients in the study were prescribed propranolo l for the control of aggressiv e behaviour, in addition to their antipsychotic medication. Both patients had akathisia.
RELATION BETWEEN AKATHISIA AND ABERRANT BEHAVIOUR The patients experiencin g akathisia showed an increase in all of the recorded types of behaviour, albeit at a nonsignifican t level for some. Patients with akathisia demonstrated significant ly more incidents of threatening behaviour and physical aggressio n than the patients without akathisia. No statistical significanc e was found for the relationship between akathisia and the other recorded types of aberrant behaviour. This suggests that the akathisia may be contributing selectivel y to some of the patients’ aberrant behaviour. It is of interest that deliberate self-harm, verbal aggressio n and property damage showed no significan t association with akathisia (see methodologica l issues, below). Thus a selective increase in threatening and aggressiv e behaviour may prove to be an index of the onset of akathisia, as a medication problem for patients cared for in a similar treatment environment . The observed inverse relation between the severity of akathisia and the incidence of threatening behaviour and physical aggression is difficult to reconcile with case reports which have suggested that it is the overwhelmin g and intense nature of the subjective experience in severe akathisia which is thought to have contributed to violence. If the incidence of threatening behaviour and physical aggressio n are greatest in mild akathisia, this is important, because it is the milder forms of the condition which are particularly prone to be overlooked or misinterpreted .2 0 This clearly requires further study with a larger cohort of patients.
METHODOLOGICAL ISSUES There are a number of issues to consider when interpreting the results of this study.
First, the small number of patients with pseudoakathis ia preclude separate analysi s of this condition. A more extensive study in a larger group of these subjects is needed. Second, the behavioura l response of some of the patients who developed akathisia may have been modified by a successfu l behavioura l treatment programme and the relative lack of opportunity for deliberate self-harm within a secure ward environment . This may account for the difference between our findings and those which have shown a positive association between akathisia and suicidal behaviour. 6 ,9 ,21 Finally, the nature of the study group and the setting may limit the generalizatio n of the results to subjects recruited from other treatment systems. Specifically , the patients included are all tertiary referrals, whose existing behavioura l problems have failed to respond to treatment before their admission to St Andrew’s Hospital. Nonetheless, the value of the present study is that it does identify an associatio n between akathisia and two types of problem behaviour that are of common concern in the management of patients, whatever the care environment . It also suggests that the relation between antipsychotic dosage and the development of akathisia is complex and there may be a `window effect’ in the development of this reaction.
CONCLUDING COMMENTS The results of this study suggest an association between the presence of akathisia and the incidence of threatening behaviour and physical aggression , but not the incidence of deliberate self-harm. In a clinical setting in which one of the ways of monitoring progress or relapse is based on the recording of aberrant behaviour , it is clearly important that akathisia should be recognized as a possible source of problematic behaviour. Routine assessmen t of akathisia and increase d awareness of this adverse drug side-effec t would enable attention to be focused on treatment strategies designed to prevent or alleviate the condition. Future studies should assess the consequence s of such an approach.
KEY POINTS
· · · · ·
This survey uses the Barnes rating scale Data was analysed using the statistical package for the social sciences (SPSS) There was no cause and effect relationshi p between dosage of antipsychotic and incidence and severity of akathisia The incidence of aggressiv e and threatening behaviour were greater in mild akathisia Routine assessment s would encourage better treatment strategies for prevention and alleviation of akathisia
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ACKNOWLEDGEMENTS We gratefully acknowledge the assistance of Dr S Halstead and other members of the St Andrew’s Hospital Research
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Committee. Thanks are also due to colleagues at St Andrew’s Hospital and the patients who participated in the study.
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12. McCreadie RG, Robertson LJ, Wiles DH (1992) The Nithsdale schizophrenia surveys. IX: Akathisia, parkinsonism, tardive dyskinesia and plasma neuroleptic levels. Br J Psychiatry 161: 793 ± 9. 13. Chengappa KNR, Shelton MD, Baker RW et al (1994) The prevalence of akathisia in patients receiving stable doses of clozapine. J Clin Psychiatry 55: 142 ± 5. 14. Barnes TRE, Braude WM (1985) Akathisia variants and tardive dyskinesia. Arch Gen Psychiatry 42: 874 ± 8. 15. Bazire S (1995) Psychotrophic Drug Directory. Mark Allen Publishing Ltd, Wilts. 16. SPSS Version 7 for Windows (1996) SPSS Inc. Chicago. 17. Ganesh S, Rao JM, Cowie VA (1989) Akathisia in neuroleptic medicated mentally handicapped subjects. J Ment Defic Res 33: 323 ± 9. 18. Sachdev P, Kruk J (1994) Clinical characteristics and predisposing factors in acute drug-induced akathisia. Arch Gen Psychiatry 51: 963 ± 74. 19. Kahn EM, Munetz MR, Davies MA, Schulz SC (1992) Akathisia: clinical phenomenology and relationship to tardive dyskinesia. Compr Psychiatry 33: 233 ± 6. 20. Weiden PJ, Mann JJ, Hass G et al (1987) Clinical nonrecognition of neuroleptic-induced movement disorders: a cautionary tale. Am J Psychiatry 144: 1148 ± 53. 21. Healy D (2000) Emergence of antidepressant induced suicidality. Primary Care Psychiatry 6: 23 ± 28.
