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Eur J Clin Pharmacol (2004) 60: 29–35DOI 10.1007/s00228-003-0719-7 P H A R M A C O E P I D E M I O L O G Y A N D P R E S C R I P T I O N Len Bowers Æ Patrick Callaghan Æ Nicola ClarkCatharine Evers Comparisons of psychotropic drug prescribing patternsin acute psychiatric wards across Europe Received: 23 July 2003 / Accepted: 28 November 2003 / Published online: 28 January 2004Ó Springer-Verlag 2004 Abstract Objective: To compare prescribed daily doses these drugs have been challenged consistently [2, 3, 4].
(PDDs) of psychotropic drugs in several European Snowdon found that half the antidepressants prescribed to elderly patients were tricyclics likely to exacerbate Method: A one-day census of psychotropic drug pre- cognitive deficits and delirium. Keks and Burrows [5] scriptions to 613 patients in 39 acute psychiatric wards found that only 11% of patients were prescribed so-called new-generation anti-psychotics such as ola- Results: Patients in Spain were on most drugs; patients nzapine, which they considered more effective than in Germany were on the fewest. Chlorpromazine typical anti-psychotics and less likely to cause extrapy- equivalents in Denmark, England, Germany and Spain were at high levels as were diazepam equivalents in Data from studies of prescribing practices within Belgium, Finland, The Netherlands and Norway. Newer different European countries showed variation in pre- anti-psychotics were used in the majority of centres, scribing patterns of psychotropic drugs with a particular although older anti-psychotics were used commonly tendency among psychiatrists to prescribe doses in excess of those recommended by recognised authorities [3].
Conclusion: The high doses of psychotropic drugs pa- There is also concern among the psychiatric community tients receive in some centres may be having little addi- of the increasing number of deaths attributed to medi- tional therapeutic effect and could increase their risk of cation type and doses and unease that some patients are side effects. The use of older anti-psychotics in some on drug doses that are above the recommended doses [6].
centres may be causing side effects that could be reduced However, there is little evidence from studies of pre- scribing practices among different European countriesshowing the PDDs of patients on acute psychiatric wards.
Keywords Drug Æ Treatment Æ Psychiatric Psychotropic drugs may be used to contain disrup- tive, aggressive and disturbed behaviour in psychiatricinpatients. Their mode of action in this case seems likelyto be a combination of the sedative effects of these drugs and their anti-psychotic action. A recent systematicreview by the Royal College of Psychiatrists in the UK Psychotropic drugs play a central role in the treatment [7] concluded that the use of psychoactive drugs was an of most mental and behavioural disorders that require efficacious and safe method of treating patients with admission to hospital [1]. However, the appropriateness acute and disruptive symptoms, whilst pointing out that of drugs used and the prescribed daily doses (PDD) of psychiatric symptomatology was not the only cause ofviolent behaviour by patients, and that other methods ofcontrol may also be effective.
L. Bowers (&) Æ P. Callaghan Æ N. Clark Æ C. Evers Research into drug prescribing patterns in Europe Department of Mental Health and Learning Disability, was pioneered by the work of Engels and Siderius at the City University London, Philpot Street, London, E1 2EA, UK European Regional Office of the World Health Organi- sation (WHO) in 1967 [8]. Engel and Siderius found wide Tel.: +44-20-70405824Fax: +44-20-70405811 variation in drugs used across six European countries.
The WHO Collaborating Centre for Drug Statistics Methodology was established in 1982 to improve, among St. Bartholomew School of Nursing and Midwifery,City University, Philpot Street, London, E1 2EA, UK other things, drug prescribing patterns across Europe.
There has been little comparative work of psychotropic Table 1 Demographic characteristics of sample drug prescribing patterns across Europe.
The impetus for this study arose from discussion in the European Violence in Psychiatry Research Group (EViPRG), suggesting that aggressive behaviour by patients in some centres was a lesser problem because of high prescribing rates of psychotropic medication.
To compare the dosage of psychotropic drugs pre- scribed to patients in selected acute psychiatric wards indifferent European centres.
The design was a 1-day census of drug prescribing on acute psychiatric wards in Europe. A comparative group design was employed in which prescribing patterns of psychotropic medica- tions in acute psychiatric wards between ten different European centres were compared. In most centres, this data came from a single hospital site, but in Spain, Italy and The Netherlands, datawere collected from two or more hospitals. As the study was un- funded, the size of the sample in each centre was dependent on the access and goodwill of the EViPRG member collecting the data.
Collaborators were asked to collect details on the maximumnumber of patients whose current records were available to them collection instrument, instructions on its completion and a return envelope. Group members then contacted local clinicians for per-mission to collect data on their wards. In some cases (e.g. Italy), theclinicians collected the data themselves. Each Centre collected dataon the total daily dosage in milligrams of each psychotropic drug taken by each patient in a 24-h period on the same day. Theresearchers did not record data on drugs prescribed, but refused by Data were collected on all patients in the selected wards in each the patient. The completed data was sent to the main centre (Lon- country and Table 1 shows these patients’ characteristics. Wards don) for analysis. During data entry, each drug was identified, either were selected on the basis of their close contact with members of from standard pharmaceutical handbooks (British National For- the EViPRG, using a common definition agreed in advance, mulary) or, where this was not possible, via inquiry with the par- namely: first line 24-h psychiatric facilities providing care to adult ticipating centre submitting the data. Information on drugs being patients on a time-limited, acute basis. In the study, 613 patients given for the treatment of non-psychiatric conditions was discarded.
participated: the majority were males, middle aged with a diagnosisof schizophrenia.
Most of the patients in the sample were middle-aged Data were collected using a specially designed form in foursections. In section 1, demographic data about the country, region, males with a diagnosis of schizophrenia. Other than hospital, unit and patients’ sex and year of birth were elicited.
schizophrenia, some patients had a diagnosed mood Section 2 recorded the patients’ primary diagnosis (from case disorder, and a small percentage had personality and notes) using the 10th edition of ICD-10 [9]. In section 3, the generic behavioural disorders. This is fairly typical of the range name, trade name and daily dosage in milligrams of each drugprescribed was recorded. Finally, in section 4, the compound name, of diagnoses one might expect to find in acute psychi- trade name, dosage and frequency and dosage of each depot drug was recorded. A separate form was used for each patient. Each Of the 613 patients who were included in the drug country except Norway—who used a Norwegian version—used the census, 476 (78%) were on anti-psychotic drugs. The English language version of the form.
diagnostic patterns are shown in Table 2, and the drugprescribing patterns in each participating centre are Wide variations are displayed between centres on the A draft of the data collection instrument was sent to members of the proportion of patients on anti-psychotic drugs, and EViPRG in each participating country for comment. Following this these patterns may be somewhat related to variations in consultation exercise, section 4 was appended to the data collectioninstrument and, in June 1999, each EViPRG member in the par- diagnosis. For example, the top four centres in terms of ticipating country was sent a census pack, consisting of the data numbers of patients prescribed anti-psychotic drugs Organic Substance Neurotic Behavioural Personality Learning Table 3 Drug prescribing patterns across centres *Ireland recorded only neuroleptic drug prescriptions (England, Spain, Denmark and Germany) overlapped Britain (RPSGB) [10]. For example, 50 mg clozapine is with the top four centres for numbers of patients with a the equivalent of 100 mg chlorpromazine. Where the diagnosis of schizophrenia (Ireland, Denmark, England chlorpromazine equivalent was not listed, it was calcu- lated by computing how much above the recommended Despite this variation, schizophrenia was the most daily dose was the prescription and this was converted to common diagnosis in all centres (39.7–77%), followed a chlorpromazine equivalent. For example, 20 mg by mood disorders, although the proportions of the olanzapine is double the average daily recommended latter diagnosis were more variable, ranging from 10.8% dose of 10 mg, and this would be equal to 1.3 g chlor- to 34.9% of census patients. The centres showed wider promazine—twice the recommended daily dose of variation in patient numbers being treated for substance 650 mg. Depot medications have different bioavailabil- use (0–35.3%) and personality disorder (0–16.3%).
ity and could not be converted to chlorpromazine Up to eight psychoactive drugs were prescribed daily equivalents in this way. They were therefore excluded for each patient (median=2). The majority (n=188) of from the analysis. The mean and SD total chlorproma- patients were on one drug, 142 patients were on two zine equivalents for each centre are shown in Table 3.
drugs and 141 patients were on three drugs. Seven of the England had the highest mean total chlorpromazine patients were on a daily regime of seven drugs. Patients in Spain were on the highest number of drugs, patients Using the same PDD to make useful comparisons in Germany were on fewest drugs. There were differ- across centres, the researchers converted all benzodiaz- ences between males (mean=2.27±1.36) and females epine drugs prescribed into diazepam equivalents using (mean=2.63±1.40) in the number of psychoactive the guidelines and methods described above. The mean drugs prescribed. However, there was little difference in and SD total diazepam equivalents for each centre are doses of chlorpromazine or diazepam equivalents (see also shown in Table 3. Belgium had the highest mean total diazepam equivalents, England had the lowest.
Using PDDs to make useful comparisons across The researchers compared the most commonly centres, the researchers converted all anti-psychotic prescribed drug in each of four categories across the drugs prescribed into chlorpromazine equivalents using different centres and these results are shown in Table 4.
guidelines published by the British Medical Association Olanzapine was the most commonly prescribed (BMA) and The Royal Pharmaceutical Society of Great anti-psychotic drug; lithium was the mood stabiliser prescribed in all centres, venlafaxin was the anti-depressant prescribed in the majority of centres; diaze-pam was the most commonly prescribed anxiolytic and biperiden was the most commonly prescribed anti-Par-kinson’s drug.
This small scale pilot study aimed to gather some data inan area where there is currently little or no information.
The study was not funded and sampling of hospitals andwards was on the basis of proximity and access to EViPRG members. The centres participating in thisexploratory study may not have been representative of the countries in which they were located, and it seemslikely that there may be considerable within countryvariation in prescribing patterns, as well as the between country variation described. The lack of a statisticalrandom sampling methodology meant that statisticaltests could not be applied to our data. In addition, depotmedications were not included in this one-day census,partly because of the complexity they would add to thealready contentious issue of comparing prescribing lev- els using chlorpromazine equivalents as describedabove.
Patients were, on average prescribed two drugs, females were prescribed slightly more drugs than males,but there was little difference in the dosages of chlor- promazine and diazepam equivalents prescribed amongmales and females. There was wide variation betweenand within participating in chlorpromazine and diaze- pam equivalents and number of psychoactive drugs prescribed. Four centres—Denmark, England, Ger- many and Spain—were prescribing chlorpromazine equivalents higher than the recommended daily dose.
Three centres—Belgium, Finland and the Nether- lands—were prescribing diazepam equivalents at very A consensus statement issued by the Royal College of Psychiatrists [6] states that doses above the recom- mended daily dose are considered ‘high doses’. The high levels of chlorpromazine equivalent doses in some centres concurs with data reported by previous research.
Galletly and Tsourtis [11] reported daily average chlor- promazine equivalent doses of 635 mg in patients who were on a single drug, but average doses of 1157 mg in The use of higher than therapeutic dosages suggests that medication may be being used, in part, as a sedative to calm disturbed and disruptive patients. The violentincident rates in the three Danish wards in a 30-month period between June 1997 and December 1999 totalled 92, or 1 per month per ward. These rates are lower than acute psychiatric wards in The Netherlands where violent incidents were occurring almost daily [12]. The chlorpromazine equivalents prescribed in the Nether-lands in our study were below the recommended daily dose, suggesting a link between low-level prescribing and disruptive behaviour. However, data from four medication error in patients and serious cardiovascular studies in Germany conducted between 1991 and 1999 and depressive side effects [22]. There is evidence, how- show on average two violent incidents per ward per ever, that combined drug regimes may improve clinical week [13, 14, 15, 16], notwithstanding the fact that this conditions, like refractory depression, that may be study has shown higher than recommended doses of chlorpromazine equivalents in Germany. Further re- The number of patients on anti-psychotic drugs search is required to disentangle the relationship be- ranged from 48% to 92% (median=77%). These figures are in excess of the percentage reported in a similar behaviour, as there are likely to be many additional international comparison of prescription patterns in 15 causes of variance between localities, for example different countries where 11.5% of patients were admission and patient management policies. The doses prescribed at least one psychotropic drug [1]. The of drugs may also be linked to staffing levels on acute differences in our results and those reported by Linden psychiatric wards. In Norway, for example, where the et al. [1] are very likely due to different levels of severity: chlorpromazine and diazepam equivalents are below this study is of acute in-patients, whereas Linden et al.
recommended levels, the staffing levels in psychiatric wards are high: a staff–patient ratio of 5:1 has been Other factors that may contribute to variation in reported [17]. A comprehensive survey of staffing levels prescribing are: cultural differences in physician pre- has recently been carried out by the EViPRG and is scribing patterns and patients’ responses to psychotropic drugs [24]; differences in the educational preparation of The average number of psychotropic drugs pre- prescribing professionals [25]. Variation in drug dosage scribed (median=2) is similar to the number of psy- patterns may also reflect the use of acute wards for chotropic drugs prescribed in previous comparative different functions. Lower drug doses may be due to research [1, 18]. Twenty-eight patients (4.6%) were on wards having a Psychiatric Intensive Care Unit (PICU) no drugs at all. However, in two cases, patients were or rehabilitation unit to refer the most difficult clients.
prescribed seven different types of drugs and, in one Some of the acute wards in the study may also have case, a patient was prescribed eight different drugs.
Linden et al. [1] reported that the number of drugs Many antipsychotics and antidepressants are sub- prescribed tends to increase with the severity of the strates for a hepatic enzyme CYP2D6, the activity of patient’s illness. The diagnosis of the patients on large which is largely genetically determined. Regarding numbers of drugs did not suggest that they were suf- ultrarapid metabolisers, there are differences across fering from multiple problems that may require such Europe; Mediterranean countries have the highest prescriptions. Of the two patients prescribed seven frequency, northern countries the lowest frequency. It is drugs, one was a 42-year-old female diagnosed with possible this (or other potential genetic differences) schizophrenia being treated in Spain. The other was a could explain some of the differences in prescribing 52-year-old male with schizophrenia in Italy. The patient on eight drugs was a 31-year-old male in Norway whose The variation in diazepam equivalents may reflect diagnosis was not recorded. The characteristics of the differences in societal reactions to the use of these drugs.
patients on between five and eight drugs shows that most For example, in England there has been public criticism were male with personality disorder in Denmark, or of the use of benzodiazepines [26]. Both England and Spain where they were mostly females with mood Germany have relatively low levels of diazepam equiv- disorders, or males with personality disorders. However, alents. Belgium and Finland have the highest levels of the researchers had no data on the severity of the diazepam equivalents, and this may reflect more toler- condition of patients on larger numbers of drugs.
ance towards the use of these drugs in these societies, or The large number of drugs prescribed to those with the tendency among psychiatrists to over-prescribe adult personality disorder may reflect uncertainty about benzodiazepines [3]. The Netherlands has a high level of the classification and treatment of such patients [19, 20].
diazepam equivalents, due partly to legal restrictions on The large number of drugs prescribed to patients with compulsory medication in that country, necessitating the mood disorders may be due to severity of the patients’ prescription of drugs that are acceptable to patients.
Olanzapine is the anti-psychotic drug of choice in the co-morbidity, other complicating factors or simply majority of centres, being more favoured in Scandinavia psychiatrists’ preferences. It may be that these large than elsewhere on the continent. This is not surprising doses are being used for sedative effect, although a and reflects the growing popularity in the use of atypical previous review of multiple drug use in the treatment of anti-psychotics world-wide [27] and possibly the average mood disorders suggested that this may have an effective age of the patients in our study. In an Australian study of adults in acute wards, Galletly [28] found that It has been argued that the high rate of drug com- olanzapine was the drug prescribed in the majority binations in some countries is unsatisfactory for severalreasons: little evidence that combinations of drugs are 1We are grateful to one of the reviewers of this manuscript for more effective than one-drug regimes, greater risk of alerting us to these points during the review process.
(61%) of cases. In an Australian study of older adults Work reported by Schmidt et al. [38] may be of use in this living in nursing homes, olanzapine was the least pre- respect. Responding to increases in prescribing practices scribed drug [4]. The older anti-psychotics such as hal- above recommended doses of psychoactive drugs in operidol are favoured in England, Italy and Spain.
Swedish nursing homes Schmidt et al. found that regular Famuyiwa [22] found that haloperidol was used com- multi-disciplinary team meetings to discuss prescribing monly in his study of psychotropic drug use in three patterns between doctors, nurses and pharmacists sig- hospitals in Nigeria. Tinsley et al. [29] found that halo- nificantly improved prescribing patterns by reducing the peridol was the drug most often prescribed to adults by number of prescriptions of various psychoactive drugs primary care physicians in the USA. Keks [30], however, that were higher than the recommended daily doses. The criticised the use of the older anti-psychotics as less emphasis of the intervention in this study was to improve effective and more likely than the newer anti-psychotics teamwork among the key professionals involved in the to cause extra-pyramidal symptoms. However, olanze- prescription and administration of drugs.
pine also has side effects, some potentially serious, as a The sample in the reported study may not be fully representative of acute psychiatric wards across Europe.
There is variation in the type of anti-depressant pre- However, our study is significant in that we compared scribed across the different centres. Venlafaxin was the prescribing patterns across ten different European preferred anti-depressant choice in the majority of cen- centres and it, therefore, provides data previously tres. Isacsson et al. [31] found that amitryptyline was the unavailable. Nevertheless, we did not compare the anti-depressant of choice of 228 physicians in Sweden.
duration of drug prescribing nor did we investigate Snowdon [4], however, reported that tricylclics increased the factors that influenced the prescribing patterns of the patients’ risks of cognitive deficits. Lithium is the pre- psychiatrists in our sample. These issues are ripe for ferred mood stabiliser in the majority of centres. This is surprising given the pattern of reduced use of lithium in The number of psychotropic drugs prescribed to many countries [32]; however, this may be due to the acute psychiatric in-patients across Europe conforms to higher level of acuity in this inpatient sample.
prescribing patterns from world-wide comparative Benzodiazepines were the most commonly prescribed studies. The high doses of psychotropic drugs patients anxiolytic drugs across all centres. Diazepam is the most receive in certain European centres may increase common and this finding concurs with previous studies patients’ risk of harmful and unpleasant side effects. The of prescribing patterns of anxiolytic drugs [4, 33, 34].
use of more typical anti-psychotics in some centres may Clonazepam, however, was the most prescribed anxio- be causing patients to experience side effects that may be lytic in the data reported by Galletly [34].
reduced by the use of newer, atypical anti-psychotics.
There is little variation in the patterns of anti-Par- kinson’s drugs used across centres. Finland has the Acknowledgements The authors thank the members of the EViPRG highest percentage of patients on anti-psychotic drugs in each country for co-ordinating the data collection and the cli-nicians in each country for recording the prescribed daily doses.
(Table 4) but no anti-Parkinson’s drugs were prescribedin this study. This may be due to the chlorpromazineequivalent doses in Finland being below the recom- mended daily dose, or because relatively more atypicaldrugs were used there.
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