The influence of patient variables on polypharmacy and combined high dose of antipsychotic drugs prescribed for in-patients

AIMS AND METHOD

A 1-day census, involving 3576 psychiatric in-patients prescribed anti-psychotic medication, was conducted as a prelude to a multi-centreaudit. The aim was to explore the extent to which a numberof patient variables explain antipsychotic polypharmacy andthe use of high doses of these drugs.

RESULTS

Prescriptions of more than one type of antipsychotic drug weremade for 50.5% of patients. Patient factors that influencedthe probability of polypharmacy were: younger age, being male,detained under the Mental Health Act and on a rehabilitationor forensic ward, and a diagnosis of schizophrenia. The effectof ethnicity was not significant. Polypharmacy was the mostpowerful factor influencing the probability of being prescribeda high dose. Identified patient variables accounted for only18% of the variance in dose prescribed.

CLINICAL IMPLICATIONS

The patient and clinician factors that account for the unexplainedvariance need to be identified.

Introduction

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Introduction

A large multi-centre audit (Harrington et al, 2002a, this issue)found that psychiatric in-patients in the UK are often prescribedmore than one antipsychotic drug concurrently (polypharmacy).Furthermore, the effect of polypharmacy is that patients areoften also prescribed a high dose of antipsychotic medication.A 1-day census of prescribing, conducted as a prelude to themulti-centre audit, was large enough to examine the extentto which these prescribing practices can be explained by anumber of patient variables.

Method

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Method

The sample and data collection
Forty-nine mental health services volunteered to participatein the initial census. All the psychiatric wards concernedspecialised in the care of people aged 18-65. However, patientsoutside of this age range were included if they occupied abed in one of these wards on the census day.

All patients prescribed an antipsychotic drug between midnight20 July and midnight 21 July 1998 were included. Data werecollected from prescription charts about the type, dose androute of administration of all antipsychotic drugs administeredand/or prescribed during the census period. In addition, theage, gender, ethnicity, diagnosis (according to ICD-10; World Health Organization, 1992)and Mental Health Act (MHA) statusof all 3576 patients were recorded together with the type ofpsychiatric bed that they occupied (acute, rehabilitation orforensic).

Data management
Data were returned to the Royal College of Psychiatrists' ResearchUnit and analysed using SPSS for Windows, version 8.

Missing data
Age was not recorded for 55 subjects (1.5%), gender for 20 (0.6%), ethnicity for 372 (10.4%), MHA status for 22 (0.6%) and diagnosisfor 111 (3.1%). All valid cases were included in each analysis.

Data analysis
Thirty-one different antipsychotic drugs were prescribed forthe patient sample (22 oral preparations, 4 drugs in aqueoussolution to be given parenterally and 5 in longer-acting preparationsto be given intramuscularly).

Furthermore, many patients were prescribed more than one antipsychoticdrug concurrently (see Results). For the regression analysis,the doses of these antipsychotic drugs had to be standardisedand summed. The method used is described in an accompanyingpaper (Harrington et al, 2002a, this issue).

The probability of a subject being prescribed polypharmacy wasmodelled using logistic regression. The dependent variablewas whether more than one antipsychotic drug was prescribedto be given during the 24-hour census period (yes/no). Theindependent variables (age, gender, ethnicity, MHA status, diagnosis and ward type) were entered individually and thenin combination.

A second set of logistic regressions was performed with thedose of antipsychotic prescribed as the dependent variable(high dose/standard dose) and polypharmacy (yes/no) as a furtherindependent variable. Linear regression was also carried outwith the dose prescribed expressed as a continuous variable(percentage of British National Formulary (BNF; British MedicalAssociation & Royal Pharmaceutical Society of Great Britain,1999) maximum) and using the same explanatory variables.

Finally, the regression analyses were repeated using dose ofantipsychotic medication actually administered as the dependentvariable. That is, medication that was prescribed but not givenduring the census period was excluded from the analysis.

Results

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Results

Description of the sample
A total of 3576 patients were prescribed at least one antipsychoticdrug during the census period. Sixty-one per cent (n=2169)were men; their mean age was 40 years (range 15-96; median38). Eighty-four per cent were White (n=2691), 10% Black (n=310),4% Asian (n=142) and 2% from another ethnic minority group(n=61). Nearly a half (49%; n=1757) were detained under theMHA. Sixty-two per cent (n=2202) were on an acute ward, 27%(n=969) on a rehabilitation ward and 11% (n=405) on a forensicward. The majority of patients (62%, n=2158) had a primaryICD-10 diagnosis of schizophrenic or delusional disorder (F2);22% (n=758) of mood disorder (F3); 5% (n=188) of personalitydisorder (F6); 4% (n=134) of organic mental disorder (F1);and 3% (n=113) of neurotic, stress-related or somatoform disorder(F4). The remainder (n=113) had a variety of other diagnoses.

There were differences between groups within the sample. Themean age of women was significantly higher than that of men(42.9 v. 39.0 years, 95%; CI of the difference=3.1-4.8; t-test,t=8.7, P<0.001). Men were more likely to be formally detainedthan women (54% v. 43%; ${chi}$ ²=37, P<0.001). Black and Asianpeople and those from other ethnic minorities were younger thanthe White people (36.1, 36.0 and 33.5 v. 41.0; Kruskal-Wallis, ${chi}$ ²=71, P<0.001). A higher proportion of those from the threeethnic minority groups were detained under the MHA than thosewho were White (78%, 61% and 66% v. 47%; ${chi}$ ²=120, P<0.001).

Polypharmacy
Half of patients were prescribed more than one anti-psychoticdrug concurrently (50.5%; n=1807). The results of the logisticregression for polypharmacy can be summarised as follows:

the odds for a person to be prescribed more than one antipsychoticdrug decreased by about 12% for an age increase of 10 years;the great majority of this sample were aged 18-65
the oddsfor men were 1.4 times those for women
the odds for a persondetained under the MHA were 1.9 timesthose for a person withinformal MHA status
the odds for a person on a rehabilitationward or forensic wardwere 1.3 times those for a person onan acute ward
a person with schizophrenic or delusional disorderwas morelikely to be on polypharmacy than a person sufferingfrom anothertype of disorder
the effect of ethnicity wasnot significant.

Doses of antipsychotics
Although 23.3% (n=832) of patients were prescribed a high dose, this was actually administered to only 10.4% (n=371) duringthe 24-hour census period. The difference was almost entirelyaccounted for by ‘as required’ medication thatwas written on the prescription chart but not given duringthe census period.

Effects of variables on dose of antipsychotics
Fewer than 1% of patients (n=34) were prescribed a single antipsychoticdrug at a dose that exceeded BNF limits. For the remainder,high dose was owing to the effect of the concurrent prescriptionof more than one antipsychotic. Thus, only 2% of the 1769 subjectsprescribed a single antipsychotic drug were prescribed a highdose compared with 44% of the 1807 subjects who were prescribedmore than one antipsychotic drug. This difference was highlysignificant ( ${chi}$ ²=900, P<0.0001).

The effects identified by the regression involving high dosecan be summarised as follows:

polypharmacy is by far the most powerful factor influencingthe probability of a subject being prescribed a high dose.For a patient prescribed more than one antipsychotic drug,the odds of also being prescribed a high dose were 41 timesthose for a patient who was prescribed a single drug
for thispatient sample, the great majority of whom were aged18-65,the odds of a person being prescribed a high dose decreasedby 11.9% for every 10-year increase in age
the odds for aman were 1.7 times those for a woman
the odds for a persondetained under the MHA were 2.4 timesthose for an informalpatient
the odds for a person on a rehabilitation or forensicward wereabout 1.6 times those for a person on an acute ward
a person with a diagnosis of schizophrenic or delusional disorder(F2) was much more likely to be prescribed a high dose thana person with another diagnosis
the effect of ethnicity wasnot significant.

The effects of each explanatory variable changed little aftercontrolling for all the others, apart from age and gender,which became insignificant.

Using dose of antipsychotic actually administered as the dependentvariable in the regression gave very similar results to thatwhich used dose prescribed.

The linear regression, using prescribed dose expressed as apercentage of BNF maximum, yielded very similar results tothe logistic regression analysis. Age, gender, ethnicity, MHAstatus, diagnosis and ward type in combination explained only18% of the variance in high-dose prescribing. However, 40%of the variation was explained when polypharmacy entered the linear regression model along with these six other explanatoryvariables.

Differences between patients in different types of beds
Patterns of prescribing by bed type are given in Table 1. Comparedwith acute and rehabilitation wards, forensic wards had a higherproportion of patients receiving high-dose antipsychotic medication,who were on depot medications.

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Table 1. High-dose prescribing and polypharmacy by bed type

Discussion

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Discussion

The finding that most high-dose prescribing is strongly associatedwith polypharmacy replicates the conclusion of one small-scalesurvey in the UK (Chaplin & McGuigan, 1996) and a muchlarger one in Italy (Tibaldi et al, 1997). That high-dose prescribingis more common for younger people and for those with a diagnosisof schizophrenic or delusional disorder has also been reportedfor patients in Italy (Muscettola et al, 1991; Tibaldi etal, 1997) and in the US (Benson, 1983). A recent study inthe US has reported that African American patients with schizophreniaare more likely than White patients to be treated with higherdoses of antipsychotic medication (Walkup et al, 2000). Theabsence of any effect of ethnicity on either polypharmacy orhigh-dose prescribing in this UK sample is striking, giventhe concern commonly expressed that psychiatric services responddifferently to patients of different ethnic origin (Bhui, 1998).

Being detained under the MHA approximately doubled the oddsof being prescribed or receiving either more than one antipsychoticdrug or a high dose. It could be argued that patients admittedcompulsorily are more disturbed than those admitted informally.However, this argument is uncertain, given the current pressureon inpatient beds (Harrington et al, 2002b, this issue).

The results of this study highlight the need for further andmore detailed examination of the patient characteristics thatinfluence prescribing practice. Despite the significant contributionsfound for the explanatory variables measured in this study,together they explained less than a fifth of the variance inthe combined dose of antipsychotic medication. Other characteristicsof the patient that might account for some of this unexplained variance include: length of illness, history of relapse, levelof disturbance, resistance of symptoms to antipsychotic medicationand pharmacokinetic differences between individuals. Some ofthe variance might also be due to differences between clinicians(Wilkie et al, 2001) and/or the characteristics of the treatment setting. These factors are considered more fully elsewhere (Harrington et al, 2002b, this issue).

Acknowledgments

The census was conducted as part of the multi-centre audit ofthe prescribing of antipsychotic medication. Staff of the 49mental health services that participated collected the data.

References

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