Introduction  1 2 3 7 8 This European study was conducted to investigate to what extent atypical antipsychotics, conventional antipsychotics and anticholinergics are being prescribed simultaneously in daily clinical practice. Method The study was carried out with the co-operation of members of the ‘European Pharmacists for Psychiatry and Neurology’ (EPPN), an organisation of hospital pharmacists working in psychiatry and neurology. All participating hospital pharmacists were working in psychiatric hospitals. Data were collected between November 1998 and October 1999. In that period the hospital pharmacists screened their hospital pharmacy database on one single day for patients who had been using an atypical antipsychotic for a minimum of 6 weeks. The 6-week period was chosen so that titration to the atypical antipsychotic should have been completed. No restrictions were imposed with regard to age and diagnosis. 9 Median doses of the antipsychotics are given, because of positively skewed distributions. The frequencies with which antipsychotic polypharmacy was practised and anticholinergics were prescribed are calculated for the total group of patients and per individual atypical antipsychotic. 10 11 Results n n n n 1 Table 1 Number of hospitals and patients included in the participating countries with the mean age of patients and the percentages of male patients Country Number of hospitals (%) Number of patients (%) Mean age (sd) % of males Belgium 19 (42.2%) 1115 (40.9%) 47.9 (15.6) 59% The Netherlands 5 (11.1%) 715 (26.2%)  46.1 (17.9) 54% France 10 (22.2%) 449 (16.5%) 42.3 (14.5) 61% Denmark 4 (8.9%) 217 (8.0%) 48.1 (16.4) 52% Scotland 6 (13.3%) 183 (6.7%) 45.8 (17.7) 51% Germany 1 (2.2%) 46 (1.7%) 38.5 (13.9) 60% Total 45 (100%) 2725 (100%) 46.2 (16.4) 57% 2 Table 2. n Atypical antipsychotic Number of patients (%) Median dose (mg)  Antipsychotic polypharmacy (%) (including low-potent antipsychotics) Antipsychotic polypharmacy (%) (excluding low-potent antipsychotics)* Anticholinergic prescription (%) No co-prescription of antipsychotics or anticholinergics (%) Risperidone 1095 (40.2%) 4.0 45.1 24.7 36.5 42.0 Clozapine 683 (25.1%) 400.0 31.2 18.9 24.5 57.7 Olanzapine 562 (20.6%) 15.0 37.0 22.1 20.3 56.2 Sulpiride 133 (4.9%) 300.0 49.2 25.8 31.1 41.7 Amisulpride 132 (4.8%) 600.0 54.1 23.3 45.9 28.6 Sertindole 37 (1.4%) 16.0 62.2 24.3 27.0 29.7 Quetiapine 16 (0.6%) 550.0 50.0 12.5 12.5 43.8 Zotepine 2 (0.1%) 225.0 0 0 0 100 Two atypicals 65 (2.4%) ** *** *** 40.0 **** Total 2725 (100%) – 42.1% 24.4% 30.1% 47.1% 3 ** Total median dose not calculated *** By definition 100% **** By definition 0% n n n 3 Table 3 The frequencies and median doses antipsychotics prescribed concurrently for patients using atypical antipsychotics Antipsychotic Antipsychotic prescribed concurrently (%)  Median dose (mg) Levomepromazine* 16.6% 50.0  Haloperidol 11.2% 10.0  Prothipendyl* 9.5% 80.0  Cyamemazine* 7.1% 100.0  Zuclopenthixol 7.6% 28.5  Pipamperon* 5.6% 80.0  Dehydrobenzperidol 4.7% 10.0  Thioridazine* 4.4% 100.0  Clotiapine 4.4% 40.0  Chlorpromazine* 3.1% 200.0  Flupenthixol 2.7% 5.9  Fluphenazine 2.4% 9.0  Bromperidol 2.4% 7.5  Chlorprothixeen* 1.8% 100.0  Perphenazine 1.5% 16.0  Pimozide 1.4% 4.0  Other conventional antipsychotics 9.2% – Second atypical 4.2% – Total 100.0% – * Considered as low-potent antipsychotic In total 30.1% of the patients were prescribed an anticholinergic drug. The anticholinergics prescribed most often were biperiden (28.3%), procyclidine (19.9%), trihexyphenidyl (16.7%) and tropatepine (13.4%). In total 47.1% of the patients are prescribed the atypical antipsychotic without any other antipsychotic or anticholinergic, 22.8% are prescribed an atypical plus one or more other antipsychotics, 10.8% are given an atypical plus an anticholinergic and 19.3% an atypical plus an anticholinergic and one or more other antipsychotics. Discussion This European study clearly shows that it is common clinical practice to prescribe an atypical antipsychotic and one or more other antipsychotics simultaneously. Low-potent antipsychotics may be added to an atypical antipsychotic mainly because of their sedative, anxiolytic and anticholinergic properties, rather than because of their antipsychotic properties. Even when the low-potent conventional antipsychotics are not included in the analysis, we found that antipsychotic polypharmacy was prescribed for almost a quarter of the patients. Additionally, we did not expect to find that almost a third of the patients were prescribed an anticholinergic in addition to the atypical drug. The results of this study imply that more than half (52.9%) of the patients are not being treated in the way according to the psychiatric handbooks and guidelines: The atypical is frequently combined with another antipsychotic and/or an anticholinergic. 2 12 14 3 7 1 Secondly, it is also possible that antipsychotic polypharmacy is continued although the patient shows no improvement because psychiatrists are hesitant to discontinue any medication in patients with persistent psychotic symptoms. Thirdly, it could be that in some patients the recommended doses of the atypical antipsychotics are too low to be effective and that adding a second antipsychotic is in fact a dose-increase strategy. In such cases, however, a higher dose of one particular atypical might be just as effective. 15 16 17 16 12 14 3 18 The frequencies of atypical polypharmacy in the separate countries range between 26.1% (Germany) and 49.1% (Belgium), without the low-potent antipsychotics it varies between 17.1% (Denmark) and 31.6% (Belgium). However, these numbers should be appraised cautiously because this study was not primary set up to detect differences between the various countries (some countries are under represented). Furthermore, the study does not allow to draw inferences about differences between the various atypicals in antipsychotic polypharmacy and anticholinergic use. These differences could easily be biased as a result of the different introduction data of the atypicals in the diverse countries. For example, at the moment of data-collection olanzapine and sertindole had been introduced very recently in most countries, quetiapine was available only in Scotland and zotepine was used only in a clinical trial. Nevertheless, the similarity between the frequencies with which antipsychotic polypharmacy is prescribed for the various atypicals (excluding quetiapine and zotepine, on account of their low frequencies) is remarkable: Excluding low-potent antipsychotics the frequencies range from 18.9% to 25.8%. The study however has its limitations. First of all, the population included is not a random sample from Western European countries that participated. Therefore, hypothetically it could be argued that the results were biased because only hospitals practising extremely high rates of antipsychotic polypharmacy were included. However, it is unlikely that only such hospitals were selected. 3 Thirdly, we did regard PRN-medication as “used” medication. This may have heightened our results somewhat but cannot explain the frequent prescription of antipsychotic polypharmacy. A major advantage of this study is the large number of patients included and the differentiation made between high- and low-potent antipsychotics. This makes extrapolation more feasible. Conclusion It is common practice to prescribe a combination of atypical and conventional antipsychotics. Furthermore, the use of atypical antipsychotics does rule out the use of anticholinergics. On the contrary, atypical antipsychotics are often prescribed in combination with anticholinergics. Apparently, monotherapy involving the atypicals is not considered to be an effective therapy for a substantial number of patients in clinical practice. Possible conflicts of interest P.N. van Harten gives lectures on symposia and congresses that are sponsored by pharmaceutical companies.