Antipsychotic prescribing in light of the consensusstatement of the College

A retrospective survey was undertaken to evaluate the prescribing practices of medical staff in a District General Hospital in light of the Consensus Statement by the Royal College of Psychiatristson the use of high dose antipsychotics (1993). Two per cent of 247 patients were prescribed a higher than recommended dose of antipsychotic. None of these cases had been prescribed 'supra-BNF doses of antipsychotic on a regular basis, but with the addition of 'as required' (PRN) medication the recommended dose was exceeded. In only one patient was the high dosage administered. A further analysis of these patients is made. The relationship between dose and therapeutic

The relationship between dose and therapeutic efficacy of antipsychotics prescribed for patients suffering with schizophrenia remains unclear.It has been the rationale that very high doses may be required in a few patients to block dopamine receptors satisfactorily.Controlled studies com paring standard with high doses in 'treament resistant' patients have failed to show superior effectiveness of megadose regimes (Bjorndal et al. 1980;Kane, 1987).These findings are supported by positron emmission tomography studies which have shown that a level of dopamine D2 occupancy associated with antipsychotic efficacy (>65%) occurs at modest doses, e.g.chlorpromazine 300-400 mg (Farde et al, 1992).Patients who were resistant to normal doses of antipsychotics still had 80-85% of receptors occupied and were indistin guishable from those who responded to such drugs (Wolkin et al, 1989).
For nearly all antipsychotic drugs the BNF recommends a maximum dose, above which the risk of side-effects becomes unacceptable to the risk-benefit ratio.An agreed definition of high dose is "a total daily dose which exceeds the advisory upper limit for general use in the BNF product licence" (Royal College of Psychiatrists, 1993).There have been publications advising against the use of high dose of antipsychotics except as a last resort (Baldessarini et al, 1988;Drug and Therapeutics Bulletin, 1992).
A recent audit on the use of antipsychotic medication in a large psychiatric hospital found that nearly half of the patients on antipsychotics were prescribed doses in chlorpromazine equiva lents in excess of BNF guidelines (Warner et ai, 1995).However, this hospital included a regional unit for patients suffering with treatment-resis tant schizophrenia.The sample may therefore have included a higher than average proportion of patients prescribed high dosages of antipsy chotics.More recently Krasucki & McFarlane (1996) reported a rate of high-dose antipsychotic prescription of just 7.3% among a cross-section of all psychiatric in-patients, a rate equivalent to 14.1% of those patients prescribed antipsycho tics.This figure rose to 42.4%, however, when what might have been given within the confines of the prescription chart were considered (our calculations from Krasucki's data).
This study was designed to determine whether patients in a district general hospital are reg ularly prescribed antipsychotic medication in doses that exceed those recommended by the BNF.

The study
New Cross Hospital is a district general hospital serving a catchment population of 250000.A retrospective analysis was made of all schizo phrenic patients receiving in-patient care during 1993.The age, gender, clinical diagnosis, and details of all prescribed medication during the inpatient period were available for every patient from the case notes and prescription charts.Multiple admissions during this study period were considered together as a single 'in-patient' contact for each individual.The total dose for 408 Psychiatric Bulletin (1996). 21. 408-410 https://doi.org/10.1192/pb.21.7.408Published online by Cambridge University Press each antipsychotlc was converted into chlorpromazine equivalents using the BNF conversion table.Those patients prescribed antipsychotics in excess of the maximum BNF dosage recom mendations were identified and studied further.In these cases the following were noted: (1) patient ethnicity: (2) the seniority of the prescrib ing physician; (3) the rationale for the prescrip tion of high-dose antipsychotics (using the case notes) and, (4) whether the prescribed total daily dose was actually dispensed.

Findings
The case notes and medication charts of 247 patients were examined.We found that only five (2%) in-patients had been prescribed antipsy chotics in doses exceeding those recommended by the BNF.These five patients were male; four were Afro-Caribbean.In each of these five cases the prescription of regular medication was within dosage guidelines, but with the addition of 'as required' (PRN) drugs the total recommended dose of antipsychotics had been exceeded.In only one case, however, was the high dose actually administered.No documentation was made in any of the case notes to explain the potentially excessive combined dosage, and junior medical staff had made all but one of these prescriptions.

Comment
This study indicates that very few patients were prescribed 'supra-BNF' doses of antipsychotic.Our findings are contrary to those of Warner et al (1995) who demonstrated over-prescribing in nearly half of schizophrenic cases.However, their study was conducted among a sample including treatment-resistant schizophrenic patients which may account for the differences found.The rate of prescription of high dose antipsychotics in Krasucki's study was only 14.1%, but of more concern were the 42.4% of patients who potentially could receive high doses as a combination of regular plus as required (PRN)medication.
All our patients had been prescribed antipsy chotics within BNFguidelines for regular dosing, but any addition of PRN medication would have exceeded the recommended limit.Krasucki & McFarlane (1996) raised a valuable point that some patients are likely to have been written up for these potentially large antipsychotic doses inadvertently, as chlorpromazine dose equivalent totals take time to calculate and require conver sion data.The decision to administer these excessive quantities if and when needed was effectively passed to nursing staff.
Many of the PRNprescriptions were designated 'for oral or intramuscular use'.As the blood level of a drug administered by parenteral injection may reach up to five times the drug level achieved by oral administration, the combined total dose may have achieved significantly great er blood levels.
The Consensus Statement (Royal College of Psychiatrists, 1993) suggests that the decision to prescribe high-dose antipsychotic medication should be undertaken only by a senior psychia trist, and the reasons should be stated clearly in the case notes, a practice not adhered to in our sample.It is possible, however, that the pre scriptions made by junior staff were authorised by a senior psychiatrist quite legitimately, but documentation within the case notes was not made.
Four of the five patients prescribed high doses were Afro-Caribbean males.These patient num bers are of course very small, and we are unaware of any previous documention of poten tial differences in either prescribing practice, or drug response observed between patients of different ethnic origins.
In summary, the proportion of patients pre scribed high-dose antipsychotic medication was very small among a population of in-patients with schizophrenia.BNF recommended doses were not exceeded by regular prescription, but clinicians should be alert to the potential cumulative dose implications of concurrent 'as required' medication.
WOLKIN, A.. BAROUCHE.F.. WOLFE.A. P.. et al (1989) *K.L. Newton, SouÃ-h Kensington and Chelsea Edited by Dora Black, Martin Newman, Jean Harris Hendriks and Gillian Mezey This is the first UK textbook on psychological trauma and contains contributions by many of the country's leading authorities on responses to traumatic events.It is edited by four clinicians with extensive experience on this subject.The book discusses normal and abnormal responses to stress, disasters, war and civil conflict, and interpersonal violence, diagnosis, interventions and treatments, and legal aspects.There is reference throughout to the research findings, and discussion of future research needs.Each chapter contains a comprehensive bibliography for those who wish to read further.Published January 1997, price Â£30.00,424pp.ISBN 0 902241 98 2 Gaskell is the imprint of the Royal College of Psychiatrists.Gaskell books are available from good bookshops and from the Publications Department, Royal College of Psychiatrists, 17 Belgrave Square, London SW1X 8PG (Tel.+44(0)171 235 2351, extension 146).The latest information on College publications is available on the INTERNET at: http://www.demon.co.uk/rcpsych/