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PAPERS:
Hiroto Ito, Asuka Koyama, and Teruhiko Higuchi
Polypharmacy and excessive dosing: psychiatrists’ perceptions of antipsychotic drug prescription
The British Journal of Psychiatry 2005; 187: 243-247 [Abstract] [Full text] [PDF]
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Electronic letters published:

[Read eLetter] Polypharmacy, excessive dosing and psychiatrists
Muzaffar Husain   (29 September 2005)
[Read eLetter] Poly pharmacy in 2 long stay psychiatric wards
Reza Kiani, Mohammed Abbas, SHO in Psychiatry, Lincolnshire Partnership NHS Trust   (29 September 2005)
[Read eLetter] Clarification needed for 'As Required' medication
Yasir Abbasi, Nottinghamshire Healthcare NHS Trust   (29 September 2005)
[Read eLetter] Polypharmacy and Excessive Dosing
hannele variend   (18 November 2005)
[Read eLetter] Polypharmacy and excessive dosing: Authors' reply
Hiroto Ito, Asuka Koyama and Teruhiko Higuchi   (21 December 2005)

Polypharmacy, excessive dosing and psychiatrists 29 September 2005
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Muzaffar Husain,
SHO in General Adult Psychiatry
Eilleen Skellern 3, Maudsley Hospital, London, UK

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Re: Polypharmacy, excessive dosing and psychiatrists

Muzaffar.Husain{at}iop.kcl.ac.uk Muzaffar Husain

Ito et al’s paper(1) on polypharmacy and excessive antipsychotic dosing amongst psychiatrists (and their reasons) made thought provoking reading. It allowed one to reflect on one’s own experience of the matter.

I have two questions for the research group.

The paper states that 78 psychiatrists were asked about the 139 patients they were treating. In view of the differences between the standard dosage and non-standard dosage patient groups, how were the non- standard group patients distributed amongst the 78 psychiatrists? It would be interesting if these patients (who according to table 2 had been ill for longer and in a more severe manner) happened to cluster under the care of those psychiatrists who did not have much faith in treatment algorithms and evidence base. Not all patients fit in to algorithms, just as not all patients fit into diagnostic categories. Furthermore, perhaps patients mould clinical practice, just as much as (one hopes) clinical practice helps them.

A second query regards the role of pharmacists in the Japanese mental health services. Most psychiatric wards in the UK have a pharmacist attached to them, who oversees and advises on most psychopharmacological issues. This also aides decisions regarding the physical side effects and risks of most neurotropic medication. Were there any pharmacists attached to the 19 acute wards surveyed in this study?

In this age of aggressive pharmaceutical marketing, one does come across very sceptical old fashioned psychiatrists, who like to do things the ‘old way’. However, polypharmacy and excessive dosing reflects confusion rather than any clearly defined clinical strategy.

1. Ito, H, Koyama, A and Higuchi, T (2005) Polypharmacy and excessive dosing: psychiatrists’ perceptions of antipsychotic drug prescription. British Journal of Psychiatry, 187, 243-247

Poly pharmacy in 2 long stay psychiatric wards 29 September 2005
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Reza Kiani,
SHO in Psychiatry ,
Mohammed Abbas, SHO in Psychiatry, Lincolnshire Partnership NHS Trust

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Re: Poly pharmacy in 2 long stay psychiatric wards

reza.kiani{at}lpt.nhs.uk Reza Kiani, et al.

Ito et al (2005) reported a high prevalence rate of poly pharmacy (69%) in acute treatment of inpatients with Schizophrenia in Japan. Similar practices have been reported by other researchers in USA, Canada and East Asia (Ito et al, 05).

We examined the case notes and medicine cards of 23 patients with a diagnosis of schizophrenia to establish the extent of the problem in two long stay psychiatric wards in Lincolnshire (Male/Female: 17/6, Mean age: 43, SD: 10).

Our study revealed a high prevalence of poly pharmacy (39%). Only in one case, combination included Clozapine along with another antipsychotic (Amisulpride). This is an acknowledged exception to the NICE guideline and supported by current evidence (Shiloh et al, 1997).

We, like Ito et al, found a tendency towards the prescription of typical Anti psychotic in our samples. Despite the availability of atypical Anti psychotics which could be used as PRN or Depot, Haloperidol was the most popular PRN medication and Zuclopenthixol decanoate the most commonly prescribed depot.

Furthermore, we were unable to trace any records of the following test results in the case note of patients with poly pharmacy; FBC (20%), U&E (26%), LFT (33%), TFT (40%), Blood sugar (53%), lipids (86%), ECG (53%). This was concerning as poly pharmacy has been associated with higher risk of side effects and sudden death (Ray et al, 2001).

Use of more than one Antipsychotic might be justified in small number of patients with complex course of illness (Taylor et al, 2002), but educational interventions targeting the psychiatrists and nursing staff, as rightly pointed out by Ito et al, are necessary to minimize the morbidities and mortalities associated with their use.

References

1. Ito H et al (2005) ‘’Poly pharmacy and excessive dosing: psychiatrists’ perceptions of anti psychotic drug prescription’’ British Journal of Psychiatry, 187, 243-248.

2. Ray W et al (2001) Antipsychotics and the risk of sudden cardiac death. Archives of General Psychiatry, 58, 1161 -1167.

3. Shiloh R et al (1997) ‘’Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo- controlled study’’ British Journal of Psychiatry, 171, 569 -573.

4. Taylor D et al (2002) ‘’Co-prescribing of atypical and typical antipsychotics – prescribing sequence and documented outcome’’ Psychiatric Bulletin, 26, 170 -172.

Clarification needed for 'As Required' medication 29 September 2005
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Yasir Abbasi,
SHO in Psychiatry
Audit completed under supervision of Dr Alan Lee,
Nottinghamshire Healthcare NHS Trust

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Re: Clarification needed for 'As Required' medication

dryiabbasi{at}yahoo.com Yasir Abbasi, et al.

I conducted a similar kind of audit in my ward monitoring the co-prescription of typical and atypical antipsychotics and thus tried to understand the rationale behind polypharmacy. The NICE guidance on the use of newer (atypical) antipsychotic drugs for the treatment of schizophrenia states that atypical and typical antipsychotic drugs should not be prescribed concurrently except for short periods to cover changeover of medication. The co-prescription of typical antipsychotics with atypical drugs has been shown to increase the frequency of acute extra pyramidal side-effects to levels expected when typicals are used alone (Taylor et al, 2002). Presumably the risks of tardive dyskinesia and hyperprolactinaemia are similarly increased. The most serious adverse event that has been suggested regarding polypharmacy is that it is associated in some way with early death (Waddington et al, 1998), but this is very rarely seen. It is presumed that polypharmacy and high dose antipsychotics prolong the cardiac QT interval (in a dose-dependent fashion) and may cause torsade de pointes and sudden death (Glassman & Bigger, 2001) The audit was a retrospective analysis of the drug cards of all patients admitted in my ward at the Hospital. Data was collected initially in February 2005 and then again in July 2005 thus completing the audit loop. At the beginning of the audit in February 2005 it showed that the co-prescription of typicals and atypicals as ‘regular’ medication was about 16% (i.e. 4/25), while in the in the category of ‘as-required’ (PRN) medication the figures were astonishing. Out of a total of 25 inpatients 16 (64%) were co-prescribed with atypical antipsychotics as regular and typicals being PRN, 5 (20%) of patients were not on any co-prescription at all. Out of these 16 patients 8 (50%) had never used their PRN medication while the remaining 8 (50%) patients had been regularly requesting to have their ‘as-required’ medication. Awareness regarding co-prescription of antipsychotics was increased on the ward by discussing the details of the NICE guidelines with the nursing staff and having regular debate about it with my medical colleagues on the ward. The results of the audit were shown to them and it was evidenced that co-prescription should ideally not exist. The same ward was re-audited in July 2005 to complete the audit loop. The increased awareness seemed to have had an effect and there were no patients on ‘regular’ co- prescription, but there were still about 9/20 patients (45%) on ‘as-required’ (PRN) prescription of an antipsychotic even when they were receiving regular antipsychotics. Out of these 9 patients 6 (66.67%) were using there PRN medication quite regularly, while the remaining 3 patients had never used it. After the audit was completed it was observed that an improvement in prescribing practice was achieved as a result of increased awareness while doing the audit, so that the co-prescription of regular antipsychotic was decreased from 16 % to 0%. The NICE guidelines are not clear regarding the use of PRN medication and therefore no obvious instruction could be given out regarding its use. The questions to ask here are 1) why are we still using typical antipsychotics as PRN on such a regular basis? 2) As a number of patients had never used their PRN medication, thus is it the ‘habit’ of mental health professionals to write down typical antipsychotics as PRN? 3) Would the above mentioned side-effects and un-wanted effects occur with PRN use as well? References: NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE (2002) Guidance on the Use of Newer (Atypical) Antipsychotic Drugs for the Treatment of Schizophrenia. Technology Appraisal Guidance No. 43. London: NICE WADDINGTON, J. L., YOUSSEF, H. A. & KINSELLA, A. (1998) Mortality in schizophrenia. Antipsychotic polypharmacy and absence of adjunctive anticholinergics over the course of a 10-year prospective study. British Journal of Psychiatry, 173, 325-329. TAYLOR, D., MIR, S., MACE, S., et al (2002a) Co-prescribing of atypical and typical antipsychotics — prescribing sequence and documented outcome. Psychiatric Bulletin, 26, 170-172 REBECCA HORNE (Aug 2002) Co-prescribing of atypical and typical antipsychotics: true rate much higher; Psychiatric Bulletin., 26: 316. DAVID TAYLOR, (2002) Antipsychotic prescribing — time to review practice; BJP 26: 401-402
Polypharmacy and Excessive Dosing 18 November 2005
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hannele variend,
SHO psychiatry
Sheffield Care Trust

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Re: Polypharmacy and Excessive Dosing

hannelevariend{at}hotmail.com hannele variend

In a recent audit of our local forensic service we also found that rates of polypharmacy prescribing and excessive dosing was prevalent. Prescribing of more than one antipsychotic was found in 8 / 60 patients and 2 / 60 were prescribed antipsychotics at excessive doses. In addition we discovered that prescribing of medications not licensed for that particular use was also relatively common these included anticholinergics for hypersalivation, and mood stabilisers in patients without a documented diagnosis of a mood disorder. In addition to excessive doses of antipsychotics we also found that 3/60 patients were prescribed benzodiazpines at excessive doses or for a greater length of time than recommended in the BNF (4 weeks).

We were unable to find any local or national guidelines on the use of prescribing more than one antipsychotic, excessive dosing, or use of medications not licensed for that particular use.

We recognise the importance of doctors advising the use of medicines outside the recommendations of the licence, or to override the warnings and precautions given in the licence (as laid down by the Medicines Act 1968). Patients who are prescribed medications which do not have a license for that particular use should be informed of this and this should be clearly documented in the patients notes (as recommended by the Royal College of Psychiatrists special interest group on psychopharmacology). This should also apply to patients prescribed doses in excess of BNF limits and informed consent should be gained when possible.

In Ito et als study the authors omitted some important factors from their investigation they did not take in to consideration the patients level of clinical or historical risk, whether a pharmacist was present on ward rounds, whether the patients suffered from any comorbidity or patients request for additional medication.

Ito et al conclude that ‘educational interventions are necessary for psychiatrist and nurses to follow evidence-based guidelines or algorithms’. However, the study did not examine the psychiatrists use of algorithms rather it looked at opinions /attitudes towards them. Psychiatrists were asked to rate how much they agreed with statements such as ‘I understand the contents of an algorithm’, ‘An algorithm disregards individual patient characteristics’, ‘I doubt the validity and evidence of an algorithm’ and ‘I think that an algorithm is necessary for clinical practice’. These questions do not necessarily represent a valid picture of psychiatrist’s perceptions since the statements are difficult to generalise. For example, the statement ‘I think that an algorithm is necessary for clinical practice’, would have been better phrased ‘I think that an algorithms are important for clinical practice’.

The study set out to examine psychiatrists perceptions of prescribing practice yet the methodology is not clearly described. The questions asked covered cost considerations, familiarity with research literature and importance of ‘experienced –based’ prescribing. More disappointing was the lack of results, the authors simply state that there was no significant difference in the perceptions of prescribing practice between the standard and non-standard dosing groups.

Polypharmacy and excessive dosing: Authors' reply 21 December 2005
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Hiroto Ito,
Researcher
National Institute of Mental Health,
Asuka Koyama and Teruhiko Higuchi

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Re: Polypharmacy and excessive dosing: Authors' reply

ItoHiroto{at}ncnp.go.jp Hiroto Ito, et al.

To Dr. Muzaffar Husain,

Husain's first question on analysis of 78 psychiatrists rather than 139 patients is a good point to focus on characteristics of psychiatrists. In our study, we analyzed the data based on patients including patient demographics and clinical characteristics. With his advice, we re-analyzed the data based on psychiatrists, but there were no significant relationships between the standard and non-standard groups.

With regard to the second question about the role of pharmacists in Japan, there were no pharmacists attached to the 19 acute wards in this study. Pharmacists are usually in charge of dispensing drugs physicians ordered and educating patients for better compliance. Their role is reviewed now but so far they advise psychiatrists of contraindications of the ordered drugs but rarely of polypharmacy and excessive dosing. Better communication with psychiatrists and pharmacists as well as nursing staff on polypharmacy and excessive dosing is needed.

To Dr. Reza Kiani and Dr. Yasir Abbasi,

We are glad that Kiani and Abbasi share our interest in polypharmacy and thank them to report on polypharmacy phenomenon in the psychiatric wards. It is interesting that polypharmacy persistently prevails in eas- requiredf (PRN) prescription or Depot of typical antipsychotics, which we could not examine due to our research protocol.

As Kiani and Abbasi pointed out, polypharmacy is associated with higher risk of sudden death (Ray et al, 2001). Since female inpatients showed longer QTc (Ito et al, 2004), gender differences may also influence on degree of the risks. The cause of polypharmacy is multi-faceted, its multiple impacts must therefore also be taken into consideration.

We agree with Abbasifs observation that an audit was effective to reduce co-prescription of typical and atypical antipsychotics. The audit is a good chance to review the guidelines and the prescribing patterns through discussion with nursing staff and other psychiatrists so that psychiatrists are more aware of their prescription. Abbasi also raised the question of PRN medication, and asked for clarification. Whicher et al. concluded in their systematic review that the current practice has no support from high quality evidence but rather clinical experience and habit. Randomised trials are necessary to develop guidelines.

1. Ray WA, et al (2001) Antipsychotics and the risk of sudden cardiac death. Archives of General Psychiatry, 58, 1161-1167.

2. Ito H et al (2004) Gender difference in QTc prolongation of people with mental disorders. Annals of General Hospital Psychiatry, 3, 3.

3. Whicher E, et al (2002) 'As required' medication regimens for seriously mentally ill people in hospital. The Cochrane Database of Systematic Reviews 2002, Issue 1. Art. No.: CD003441. DOI: 10.1002/14651858.CD003441.

To Dr. Hannele Variend,

Variend reported that polypharmacy prescribing and excessive dosing were prevalent also in the forensic service, and doctorfs advice is important regarding the use of medicines outside the recommendations of the license.

As Variend pointed out, there are several limitations in our research. Since our research was a multi-center study, detailed information (e.g., patient clinical or historical risk, role of pharmacist and patientfs request for additional medication) was limited. We need to include such information in the next study.

In addition, we asked psychiatrists about general opinions / attitudes toward algorithms and did not examine the actual psychiatristfs use of algorithms on each prescription. It is not the standardized questionnaire, and our next step is to develop the Attitudes toward Medication Algorithms Scale (AMAS). To our knowledge, however, there are no studies on relationships between prescription of antipsychotics and psychiatristsf perception of algorithms, therefore we believe it is still informative.

Our research may be the first step to analyze psychiatristsf decision-making process on prescribing antipsychotics. This kind of research contributes to better understanding of the phenomenon and give some clues for more effective interventions to improve polypharmacy and excessive dosing phenomenon.