psychotropic drug use in older people with mental illness with particular reference to...

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY

Int J Geriatr Psychiatry 2005; 20: 842–847.

Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/gps.1365

Psychotropic drug use in older people with mental illness withparticular reference to antipsychotics: a systematic studyof tolerability and use in different diagnostic groups

Stephen Curran1,2*, Debbie Turner2, Shabir Musa2 and John Wattis1,2

1Ageing and Mental Health Research Unit, School of Human and Health Sciences, University of Huddersfield, Huddersfield,UK2South West Yorkshire Mental Health NHS Trust, Wakefield, UK

SUMMARY

Objective The objective of the study was to provide observational clinical data on psychotropic drugs used in older peoplewith mental illness.Methods This was an observational, single-centre, one-week prevalence study of psychiatric symptoms, disorders andpsychotropic drug use in older with mental illness cared for by the South West people Yorkshire Mental Health NHS Trust(Wakefield Locality), UK. The clinical assessment included completion of the Psychosis Evaluation Tool for Common useby Caregivers.Results A total of 593/660 older patients with mental illness (mean� SD age, 76� 8.1 years were assessed. 44.5% haddementia (excluding vascular dementia) and 33.7% had a mood disorder. Of the total, 20.4% did not receive CNS activemedication. Of those receiving CNS active medication approximately half (51.3%) took antipsychotics and 46.2% antide-pressants. Of 304 patients taking antipsychotics, 87% took only one medication. However, patients with schizophrenia andrelated disorders were significantly more likely to be prescribed two or more antipsychotics (p< 0.001). Risperidone was themost frequently prescribed antipsychotic (n¼ 136, 44.7%). Risperidone doses were significantly lower for patients withdementia and mood disorders than with schizophrenia (p< 0.002). Side-effects from antipsychotics were significantlygreater in patients with schizophrenia, suggesting a dose-related effect. Risperidone appeared to be well tolerated in allpatients with no evidence of cerebrovascular side-effects in patients taking it.Conclusions Psychotropic drugs were commonly used by older people in contact with mental health services. The dosesof antipsychotics used in dementia and affective disorders were significantly lower than in schizophrenia. Risperidone wasthe most commonly used drug in all diagnostic groups including dementia. Despite a relatively large numbers of patientsreceiving risperidone in this naturalistic study, no serious side-effects were reported or identified. In this paper we focus ourfindings on antipsychotics in the light of recent advice from the Committee on Safety of Medicines (UK). Copyright # 2005John Wiley & Sons, Ltd.

key words— psychotropics; antipsychotics; older people; mental illness; BPSD; risperidone; CSM

INTRODUCTION

The use of atypical antipsychotics has been well stu-died in younger adults with psychotic symptoms,

although there is less information regarding their usein older adults. In the UK, no atypical antipsychoticdrug is licensed for the treatment of older patientswith behavioural and psychological symptoms ofdementia (British Medical Association, 2004). How-ever, in clinical practice until recently, atypical anti-psychotics were increasingly being used for thispurpose and clinical trials have been conducted in thisindication (Lee et al., 2004). Indeed, a review ofexpert opinion recommended atypical antipsychotics,

Received 23 November 2004Copyright # 2005 John Wiley & Sons, Ltd. Accepted 5 April 2005

*Correspondence to: S. Curran, Ageing and Mental HealthResearch Unit, HW3-02 Harold Wilson Building, School of Humanand Health Sciences, University of Huddersfield, HD1 3DH, UK.Tel: 01484 472443. Fax: 01484 473 760.E-mail: [email protected]

Contract/grant sponsor: Janssen-Cilag (UK).

particularly risperidone 0.5–2.0 mg/day, as first-linetreatment of older adults with agitated dementia withdelusions (Alexopoulos et al., 2004).

Atypical antipsychotics have been favoured overtypical antipsychotics as they are thought less likelyto cause extrapyramidal side-effects (Jeste et al.,1999; Wirshing, 2001). However, some randomisedcontrolled trials have suggested that atypical antipsy-chotics may be associated with an increased risk ofcerebrovascular events in older people with dementia(Wooltorton, 2002, 2004). However, the risk of strokemay not be significantly higher with atypical thantypical antipsychotics (Herrmann et al., 2004; Gillet al., 2005). In March 2004 the Committee on Safetyof Medicines (CSM) in the UK advised avoidingolanzapine and risperidone for the treatment of beha-vioural symptoms in patients with dementia, reflect-ing concern over the excess risk of stroke (Duff,2004). They advised that all patients with dementiacurrently receiving these medications should havetheir treatment reviewed and that many can be mana-ged without medication. As a result, there is concernthat antipsychotic treatment will be unnecessarilywithheld and that clinicians will adopt greater useof typical antipsychotics (Mowat et al., 2004).

The aim of the present study was to provide a betterunderstanding of psychotropic drug use and particu-larly antipsychotic use in older people with mental ill-ness as well as exploring tolerability and prescribingissues in different diagnostic groups.

METHODS

Study design

This was an observational, single-centre, one weekprevalence study of psychiatric symptoms, disordersand psychotropic drug use carried out in the WakefieldLocality, South West Yorkshire Mental Health NHSTrust, UK over 12 months in 2002/2003. The serviceconsisted of two acute wards, one day-hospital, outpa-tient clinics for three consultant teams, three Commu-nity Units for the Elderly, and two CommunityMental Health Teams. The study was approved bythe Wakefield Research Ethics Committee.

Patient selection

All consenting patients under the care of psychiatricservices for older people in the Wakefield Locality(total population over 65 years approximately55,000) were included in the study. Patients identifiedfrom Trust records were contacted by a Research

Nurse to ask if they would like to take part in thestudy. All patients and caregivers received an infor-mation sheet before taking part in the study and gavewritten consent.

Assessments

The Research Nurse undertook a detailed clinicalassessment, which included demographic details,clinical information, diagnosis and treatmentresponse (classified as first episode, stable-dissatis-fied, stable-satisfied, treatment resistant, and uncon-trolled), medication, symptoms and side-effects.These were part of a computer-based package, thePsychosis Evaluation Tool for Common use byCaregivers (PECC), developed from the work ofLindstrom et al. (1997). The PECC was specificallydesigned to be used by a wide variety of health careworkers including nurses. The reliability and validityhas been described in both younger and older people(de Hert et al., 1999). Prior to undertaking the studythe Research Nurse attended a three-day trainingcourse organised by the PECC development team inBelgium.

The assessment also included an interview with thecaregiver, discussions with medical and nursing staffand a review of medical notes including GP records.This specifically included a review of patients’ cur-rent physical health and laboratory and other investi-gations. Patients were assessed in a variety of settingsincluding the two acute wards, OP clinics, the threeCommunity Units for the Elderly and in their ownhomes. The assessment took approximately one hourto complete and after the assessment a copy was madeavailable to the appropriate clinical team. Diagnosiswas based on DSM-IVR criteria (APA, 1987). Somepatients attended several parts of the service, e.g. dayhospital and OP clinic but were only included once.

Symptoms and side-effects were based on the pre-vious seven days and a standardised protocol wasused for defining and scoring individual symptomsand side-effects. Symptoms were recorded on aseven-point scale (1¼ absent, 7¼ extreme burden,all areas of functioning are disturbed, supervisionnecessary) and included positive (e.g. delusions andhallucinations) and negative symptoms (e.g. motorretardation, blunted affect, poor rapport and passivesocial withdrawal) as well as depressive, cognitiveand excitatory symptoms. Side-effects were measuredon a four-point scale (1¼ absent; 4¼ severe, obviousinfluence on functioning, intervention necessary) andincluded extrapyramidal side-effects (EPS), anticholi-nergic, hormonal, dizziness, daytime somnolence,

psychotropic drug use in older people with mental illness 843

Copyright # 2005 John Wiley & Sons, Ltd. Int J Geriatr Psychiatry 2005; 20: 842–847.

drowsiness, sexual dysfunction, insomnia, weightgain and orthostatic hypotension.

Statistical analysis

Statistical analyses were carried out using SAS/STATsoftware (version 8.12). Comparisons of continuousvariable used ANOVA, and pair-wise comparisons(Chi squared test—�2, Cochran-Mantel-Haenzel test)for categorical variables were performed with adjust-ment for multiple comparisons employing the Tukey-Kramer’s method.

RESULTS

Patient characteristics

Of a total of 660 older patients, 593 patients took partin the study. Two hundred and ninety-three patients(approximately 50%) had a diagnosis of dementiawith 4.9% of the total population having vasculardementia (VaD). Of the remaining patients 200(33.7%) had an affective disorder and 65 (11%) schi-zophrenia or a related disorder. In addition, the major-ity of patients had their mental illness for a relativelyshort period (Table 1).

Age of the patients ranged from 44 to 97 years, themean age� SD was 76� 8.1years, and 44% were aged71 to 80 years. There was a statistical difference in theage of the patients between the diagnostic groups(F¼ 8.37, p< 0.001). More specifically, patients withVaD and other types of dementia were older thanpatients with affective disorders (p¼ 0.035,p< 0.001, respectively) and were older than those withschizophrenia and related disorders (p< 0.0005).

Sixty-nine percent (n¼ 409) of patients werefemale and there were more females (� 67%) ineach diagnostic category (�2, p¼ 0.001), with the

exception of VaD dementia (males n¼ 19, 65.5%;females n¼ 10, 34.5%). There were no differencesin the level of education, occupational status or mar-ital status between the diagnostic groups. Treatmentresponse was rated as ‘stable-satisfied’ for the major-ity of patients (n¼ 537, 90.6%) with seven patients(1.2%) rated as ‘stable-dissatisfied’. Only two patients(0.3%) were rated at ‘treatment resistant’. The time inyears since patients were first diagnosed with theirmain mental disorder ranged from 0 to 28 years. Thiswas numerically greater for patients with schizophre-nia and related disorders but there were no statisti-cally significant differences between the diagnosticgroups (p¼ 0.97; Table 1).

Psychoactive drugs

Of the 593 patients, 121 (20.4%) did not receive apsychoactive drug. A total of 348 antipsychotics weretaken by 304 (51.3%) of patients, 280 antidepressantsby 274 (46.2%) patients, 130 hypnotics and sedativesby 130 (21.9%) patients, 45 anxiolytics by 42 (7.1%)patients, 29 antiepileptics by 28 (4.7%) patients and29 anticholinergics by 29 (4.9%) patients.

Intake of antipsychotics

An antipsychotic was more likely to be prescribed topatients with schizophrenia and related disorders(92.3%) than to patients with VaD (48.3%), dementia(40.5%) and affective disorders (55%) (�2¼ 61.2,p< 0.001). Overall, approximately half of all patients(51%) were prescribed an antipsychotic but 13% wereprescribed two or more antipsychotics. The number ofantipsychotics prescribed for each patient was alsosignificantly different between the diagnostic groups.Patients with schizophrenia and related disorderswere significantly more likely to be prescribed twoor more antipsychotics (Cochran-Mantel-Haenszeltest, p< 0.0001).

The three most commonly prescribed antipsycho-tics were risperidone (n¼ 135), thioridazine (n¼ 38)and trifluoperazine (n¼ 27). The mean� SD dose ofrisperidone was 1.6� 1.3 mg/day (range 0.25–7 mg),of thioridazine 40.3� 47.5 mg/day (range 7.5–200 mg) and of trifluoperazine 4.6� 6.2 mg/day(range 2–30 mg). Daily doses of risperidone signifi-cantly differed between the diagnostic groups(F¼ 4.41, p¼ 0.002). Patients with schizophreniaand related disorders had significantly higher dosesthan patients with affective disorders and dementia.Daily doses of thioridazine were also significantlygreater in patients with schizophrenia compared with

Table 1. Frequency distribution of main diagnoses and time inyears since the main diagnosis was made

Diagnosis Main diagnosis Time in years sincen (%) main diagnosis

patients Mean�SDyears (range)

Vascular dementia 29 (4.9) 0.4� 0.8 (0–4.0)Other dementia 264 (44.5) 0.5� 1.2 (0–8.9)Affective disorders 200 (33.7) 0.4� 0.9 (0–7.3)Schizophrenia, schizotypal 65 (11.0) 1.7� 5.0 (0–28.0)& delusional disordersOther diagnosis 33 (5.6) 0.3� 0.3 (0–0.9)Unknown 2 (0.3) 1.2� 1.3 (0.3–2.1)No additional diagnosis — —Total 593 (100) 0.6� 2.0 (0–28)

844 s. curran ET AL.


patients with affective disorders and dementia(F¼ 3.18, p¼ 0.03). However, no significant dif-ferences were found in daily doses of trifluoperazinein the different diagnostic groups. Other antipsycho-tics used included amisulpride (n¼ 14, 156.1�188.8 mg/day, range 25–700 mg), chlorpromazine(n¼ 1, 75 mg/day), droperidol (n¼ 1, 1.5 mg/day),flupenthixol (n¼ 5, 1.1� 0.6 mg/day, range 0.5–2.0 mg), haloperidol (n¼ 12, 3.5� 4.5 mg/day, range0.5–15 mg), olanzapine (n¼ 17, 7.9� 5.3 mg/day,range 2.5–20 mg), quetiapine (n¼ 2, 162.5�53.0 mg/day, range 125–200 mg) and zuclopenthixol(n¼ 1, 20 mg/day).

Risperidone, the most commonly prescribed anti-psychotic, was taken by 31.% (n¼ 9) patients withVaD, 26.5% (n¼ 70) patients with other types ofdementia, 17.0% (n¼ 34) patients with affective dis-orders, 30.8% (n¼ 20) patients with schizophreniaand 9.1% (n¼ 3) patients with another diagnosis. Ris-peridone was more commonly used in patients withdementia or schizophrenia and related disorders com-pared with patients with mood and other disorders(�2¼ 13.4, p¼ 0.02).

Evaluation of symptoms

There were significant differences between the diff-erent diagnosis groups for the mean scores ofcognitive (F¼ 56.7, p< 0.001), depressive (F¼44.4, p< 0.001), negative (F¼ 8.5, p< 0.001), andpositive (F¼ 27.9, p< 0.001) symptoms (Table 2).Not unexpectedly, patients with dementia had moreproblems with cognitive function, those with affectivedisorders had greater depressive symptoms, and nega-tive and positive symptoms were greatest in patientswith schizophrenia and related disorders. Excitatorysymptoms (e.g. hyperactivity, agitation, poor impulsecontrol and hostility) were not significantly differentbetween the diagnostic groups (F¼ 2.1, p¼ 0.08).

Evaluation of side-effects

There was a statistically significant difference betweenthe different diagnostic groups for the mean scores ofanticholinergic side-effects (F¼ 2.9, p¼ 0.02) andEPS (F¼ 15.6, p< 0.001). Patients with schizophreniaand related disorders had significantly higher levels ofanticholinergic and EPS side-effects. Hormonal side-effects were not significantly different between thediagnostic groups (F¼ 0.3, p¼ 0.87) but drowsinesswas significantly higher in patients with affective disor-ders (F¼ 7.8, p< 0.001). These are summarised inTable 2. T

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DISCUSSION

The principal objective of this study was to obtain abetter understanding of the use and tolerability of psy-chotropic drugs and particularly antipsychotic drugsin older people with mental illness.

The issue of antipsychotic drug use in patients withdementia has become topical in the UK with the pub-lication of new prescribing advice by the Committeeon Safety of Medicines in early 2004 concerning theuse of risperidone and olanzapine in patients withdementia. This advice has not been generally wellreceived by UK old age psychiatrists. Both thesedrugs have a good evidence base compared with otherantipsychotics in patients with dementia and none ofthe currently available drugs used for the managementof behavioural and psychological symptoms indementia (BPSD) are licenced in the UK (Lee et al.,2004). The older antipsychotics have significant side-effect profiles and other atypicals have been recom-mended but little is known about their efficacy andsafety in this patient group. The management and par-ticularly the pharmacological management of BPSDneeds to be more vigorously debated.

This study was undertaken before the CSM adviceon antipsychotic drug use in patients with dementiawas issued. Within the Wakefield Locality of the SouthWest Yorkshire Mental Health NHS Trust (UK), half ofall older patients have dementia and over one-thirdhave mood (affective) disorders as a main diagnosis.Nevertheless, one-fifth of all older patients in the Trustwere not taking any psychotropic medication.

It is interesting that there were no differences in thelevel of education, occupational status or marital sta-tus between the diagnostic groups. The time in yearssince patients were first diagnosed with their mainmental disorder was relatively short and ranged from0 to 28 years. It is likely that since most patientsdeveloped their illness later in life this did not havea significant impact on their education and lifechoices such as occupation and marriage.

In addition over 90% of patients reported feeling‘satisfied’ with their treatment. Seven percentreported feeling ‘dissatisfied’ and 2% were classifiedas treatment resistant. The definition of treatmentresistance was not clearly defined in this study andno patients with dementia were categorised as treat-ment resistant. Overall this is probably an underesti-mate of the true prevalence of treatment resistance.However, the main focus of this study was drug useand tolerability rather than efficacy.

Findings from this study support the view that anti-psychotics are frequently used in older people with

mental illness for a variety of psychiatric disorders.Only 1% of the population had a main diagnosis ofschizophrenia, schizotypal or delusional disorders,and 80% of antipsychotics used were for indicationsother than these. A wide range of typical and atypicalantipsychotics were prescribed and, although a smallproportion of patients were taking more than one anti-psychotic, monotherapy was the usual practice. Themost commonly prescribed antipsychotic was risper-idone, which was prescribed at lower doses in olderpatients with dementia than in those with schizophre-nia. Side-effects from all antipsychotic medications,such as anticholinergic effects and EPS, were signifi-cantly greater in patients with schizophrenia suggest-ing a dose related effect. For all patients anddiagnoses, risperidone was well tolerated and no ser-ious side-effects were recorded, including cardiovas-cular events. However, this was not a prospectivestudy and side-effects were only reported for the pre-vious seven days making it less likely that serious rareside-effects would be identified.

Clinicians need clear advice on the use of antipsy-chotics in older people and particularly in patientswith dementia. This advice should be based on goodquality efficacy, tolerability and safety data from ran-domised-controlled studies. In individual patients arange of factors need to be considered when prescrib-ing including the balance of risks and benefits of themedication and the wishes of patients and carers. Inour view this balance has not been achieved by therecent CSM guidance leaving clinicians unclear aboutthe use of antipsychotics in older people with mentalillness and particularly those with dementia.

KEY POINTS

* Psychotropic drugs and antipsychotics in parti-cular are commonly prescribed to older peoplewith mental illness.

* Atypical antipsychotics were significantly morelikely to be prescribed compared with olderantipsychotics and the majority of patients wereprescribed only one drug.

* Psychotropic drugs were well tolerated in olderpeople with mental illness and over 90% ofpatients were satisfied with their treatment.

* Advice on the use of antipsychotics in olderpeople needs to be clearer and should take intoaccount the risks and benefits of treatment aswell as patient and carer views.

846 s. curran ET AL.


ACKNOWLEDGEMENTS

This was an Investigator Initiated Project funded byan unconditional educational grant from Janssen-Cilag (UK).

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