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Polypharmacy and high-dose antipsychotic regimes in the community

  • Tongeji E. Tungaraza (a1), Seema Gupta (a2), Jane Jones (a2), Rob Poole (a3) and Gary Slegg (a4)...
Aims and method

To determine the pattern of psychotropic prescribing in a group of people with psychosis who were living in the community under community mental health team (CMHT) care. Case-note entries over the previous 12 months were examined.


Only a third of individuals were on one psychotropic medication. Atypical antipsychotics were prescribed to 80.6%. Polypharmacy was common. A third of people were taking three or more psychotropic drugs and 13.7% were on high-dose regimes, mostly involving two atypical antipsychotics.

Clinical implications

The use of atypicals has not eliminated polypharmacy or high-dose antipsychotic regimes. Clinicians need to be aware of this long-standing problem.

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Corresponding author
Tongeji E. Tungaraza (
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See editorial, pp. 41–43, and review article, pp. 58–62, this issue.

Declaration of interest

T.E.T. accepted sponsorship to attend conferences from Janssen-Cilag, Eli Lilly, Bristol-Myers Squibb and Otsuka Pharmaceuticals. R.P. has accepted speakers' fees from Lundbeck, Eli Lilly and Pfizer, and accepted sponsorship to attend conferences from Wyeth, AstraZeneca and Eli Lilly.

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1 Stahl, SM. Antipsychotic polypharmacy. Part 1: Therapeutic option or dirty little secret? J Clin Psychiatry 1999; 60: 425–6.
2 Canales, PL, Olsen, J, Miller, AL, Crismon, ML. The role of antipsychotic polypharmacotherapy in the treatment of schizophrenia. CNS Drugs 1999; 12: 179–88.
3 Lelliott, P, Paton, C, Harrington, M, Konsolaki, M, Sensky, T, Okocha, C. The influence of patient variables on polypharmacy and combined high dose of antipsychotic drugs prescribed for in-patients. Psychiatr Bull 2002; 26: 411–4.
4 Ito, H, Koyama, A, Higuchi, T. Polypharmacy and excessive dosing: psychiatrists' perceptions of antipsychotic drug prescription. Br J Psychiatry 2005; 187: 243–7.
5 National Institute for Health and Clinical Excellence. Schizophrenia: Core Interventions in the Treatment and Management of Schizophrenia in Primary and Secondary Care. NICE, 2002.
6 Royal College of Psychiatrists. Consensus Statement on High Dose Antipsychotic Medication (Council Report CR138). Royal College of Psychiatrists, 2006.
7 Barbui, C, Nosè, M, Mazzi, MA, Thornicroft, G, Schene, A, Becker, T, et al. Persistence with polypharmacy and excessive dosing in patients with schizophrenia treated in four European countries. Int Clin Pharmacol 2006; 21: 355–62.
8 Jensen, B. Antipsychotic comparison chart. RxFiles, 2003 (∼clpsych/orientation/Antipschotics%20Comparison%20Chart.pdf).
9 Taylor, D, Paton, C, Kerwin, R. The Maudsley Prescribing Guidelines (8th edn). Taylor & Francis, 2006.
10 Lieberman, JA, Stroup, TS, McEvoy, JP, Swartz, MS, Rosenheck, RA, Perkins, DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353: 1209–23.
11 Jones, PB, Barnes, TRE, Davies, L, Dunn, G, Lloyd, H, Hayhurst, KP, et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: cost utility of the latest antipsychotic drugs in schizophrenia study (CUtLASS 1). Arch Gen Psychiatry 2006; 63: 1079–87.
12 Centorrino, F, Eakin, M, Bahk, W, Kelleher, JP, Goren, J, Salvatore, P, et al. Inpatient antipsychotic drug use in 1998, 1993, and 1989. Am J Psychiatry 2002; 159: 1932–5.
13 Freudenreich, O, Goff, DC. Antipsychotic combination therapy in schizophrenia. A review of efficacy and risks of current combinations. Acta Psychiatr Scand 2002; 106: 323–30.
14 Tapp, A, Wood, AE, Secrest, L, Erdmann, J, Cubberley, L, Kilzieh, N. Combination antipsychotic therapy in clinical practice. Psychiatr Serv 2003; 54: 55–9.
15 Sernyak, MJ, Rosenheck, R. Clinicians' reasons for antipsychotic coprescribing. J Clin Psychiatry 2004; 65: 15971600.
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Polypharmacy and high-dose antipsychotic regimes in the community

  • Tongeji E. Tungaraza (a1), Seema Gupta (a2), Jane Jones (a2), Rob Poole (a3) and Gary Slegg (a4)...
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Polypharmacy- How bad are we really? The jury is still out !

Chandan Sehgal, Staff Grade Psychiatrist
17 May 2010

Lepping and Harborne (1) highlight the unfortunate conflation of “psychotropic polypharmacy” and “antipsychotic polypharmacy” which is seenin the study by Tungaraza et al (2) and which may confuse the reader. Their response falls foul of this issue when they refer to the statement that “only a third of patients were on one psychotropic medication”, and draw an implication of a shortfall in compliance with the NICE schizophrenia guideline(3). The NICE guideline advocates sequential use of antipsychotic monotherapy, but does not discuss polypharmacy involving other psychotropic medication. The authors rightly point out that both Taylor (4) and Tungaraza have madeassessments about the temporal change of incidence of antipsychotic polypharmacy without references, but later they mention studies of Clozapine-Amisulpride and Clozapine-Quetiapine combinations which are unreferenced. An internal inpatient survey of antipsychotic polypharmacy in our own trust demonstrated an incidence broadly similar to that found in the literature at the time, but that antipsychotic polypharmacy regimes were not centred around attempts to optimise clozapine treatment. Rather a variety of regimes involving diverse antipsychotics was seen. It is perhaps speculative to presume that in the Wrexham cohort most people on two or more antipsychotics were taking Clozapine.In the forensic setting, complexity and diagnostic plurality is the norm, so antipsychotic polypharmacy is perhaps unavoidable at times. It is the concern of the authors that procedural aspects, such as pre-conditions forassured concordance prior to transfer to step-down services, may sometimescolour the prescribing decisions and drive the co-administration of depot antipsychotics with oral atypicals.We could not find reference to non-medical prescribers in Taylor’s article, indeed we feel that Tungaraza et al suggest that the emergence ofnew groups of prescribers points out the urgency of resolving issues around antipsychotic polypharmacy, broadly anticipating the concerns of Lepping and Harborne.Finally, one of the authors respectfully suggests that the word polypharmacy be reconsidered, since pharmacy is seldom the originator of the plan!-References-

1/Polypharmacy: How bad are we really? Peter Lepping, et al. The Psychiatrist Online, 20 Feb 2010

2/Tongeji E. Tungaraza, Seema Gupta, Jane Jones, Rob Poole, and Gary Slegg Polypharmacy and high-dose antipsychotic regimes in the communityThe Psychiatrist 2010; 34: 44-46

3/CG82 Schizophrenia (update): quick reference guide 25 March 2009

4/Antipsychotic polypharmacy - confusion reigns David TaylorThe Psychiatrist 2010 34: 41-43.
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Conflict of interest: None Declared

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Polypharmacy: How bad are we really?

Peter Lepping, Consultant Psychiatrist/Honorary Senior Lecturer/Associate Medical Director
20 February 2010

Authors:Peter Lepping (Consultant Psychiatrist/Honorary Senior Lecturer/Associate Medical Director) and Giles C Harborne (Consultant Psychiatrist/Chief of Staff Mental Health), both Betsi Cadwaladr University Health Board, Wrexham, North Wales.

Title:Polypharmacy: How bad are we really?

Letter to the Editor

Dr Professor Casey

The February edition of The Psychiatrist features a number of articles about psychotropic polypharmacy. Taylor concludes that “rates ofpolypharmacy seem not to have changed” (1) whilst Langan and Shajahan conclude that “polypharmacy is increasing” (2) without providing any evidence for this. Both authors assert that polypharmacy is by and large very undesirable with little evidence backing its use, with the exception possible of using aripiprazole as co-therapy with clozapine in order to reduce patients’ weight (3). The two authors of this letter work in the Trust (now Health Board), in which Tungaraza et al did their research intopolypharmacy and concluded that “only a third of individuals were on one psychotropic medication” (4). This implies a poor compliance with NICE Guidelines on Schizophrenia which suggest that polypharmacy is best avoided unless there are exceptional circumstances and clozapine has been offered. We would like to explore the results of this study as well as its underlying presumptions.

1.“Is it the patients?”: It is surprising that this is the first community study looking at polypharmacy and we obviously applaud Tungarazaet al for having conducted it. We also agree with the general sentiment that polypharmacy is by and large undesirable. However, the patient groupthey investigated is on the whole quite an ill cohort. The Schizophrenia Services in the old North East Wales Trust where Tungaraza et al conductedthe study is moderately recovery focused. The standard of Primary Care ishigh and many people with good outcome and responsive schizophrenic illnesses are looked after in Primary Care, mostly on antipsychotic mono-therapy. The patients in Secondary Care often include people who used to live in hospital settings, have complex illnesses and problems, and are often treatment resistant. They would all fall into the remit of having asevere and enduring mental illness as prescribed by the National Service Framework for Wales. In other words these are patients with complex problems and significant co-morbidity. Achim et al put the combined co-morbidity of anxiety type disorders at a staggering 50.1% (5). Dernovsek and Sprah remind us that 40% of people with chronic psychotic disorders have clinical levels of depression and 60% have anxiety symptoms (6). In asample we examined ourselves the rate of active symptoms of an anxiety disorder was 10% (7). These patients need treatment for their depressive and anxiety disorders as well as for their schizophrenia, which almost always requires additional medication on top of the antipsychotic. In summary, the patients that are seen in community care today are a cohort of patients with complex and often treatment resistant problems and with high levels of co-morbidity.

2.“Is it the guidelines?”: Guidance is only guidance, so there is an expectation that exceptions may occur. The main problems with guidancehowever, is that it is only as good as the evidence that it is based on. Lack of evidence for efficacy is not the same as evidence for lack of efficacy. Only because something has a poor research base does not automatically make it unreasonable or ineffective. We agree that there have not been many large scale studies looking at polypharmacy but there have been some studies that suggest that polypharmacy might be useful in limited situations and circumstances. Mortimer reaffirms that “amisulpridehas the best evidence as an affective adjunct to clozapine treatment” (8).The other problem with evidence based research that primarily considers RCT’s is that it always looks at an average. This does not take into account the fact that whilst some patients will have a good effect from anintervention, others will have no effect from a particular intervention even if the overall effect size might be average. This means that to get an average effect size we need some people who had particularly good effects and others who had no effect. Whilst we admit that we often do not know who is going to respond particularly well it is clearly necessaryto find inventive solutions for people who will otherwise remain treatmentresistant. Additionally, the recent update of the NICE Guidelines for Schizophrenia take into account the increasing amount of evidence that suggests that second generation antipsychotics are not a homogenous group and some of them are clearly more effective than others (9). This evidenceis emerging and has been changing the way in which psychiatrists practice all around the world.

3.“Is it the Drugs?”: Karunakaran et al (10) have shown that clozapine/aripiprazole combinations can be a useful regime to allow peopleon clozapine to reduce their clozapine dose without a loss of efficacy. Similar studies have shown such effects for amisulpride and quetiapine. The service that Tungaraza et al researched in North Wales has a specialist Clozapine Clinic and a high number of patients on clozapine (143 in February 2010). Many of them are enabled to reduce their clozapine dose and thus their clozapine related side effects by introducing a second antipsychotic. We question whether this should be seen as good practice rather than be condemned as polypharmacy.

Conclusions: Rather than lamenting that only a third of patients researched in North East Wales were on mono-therapy I think it would be more appropriate to applaud the fact that no patient was on more than two antipsychotics. Most of the patients on two antipsychotics would have been on clozapine and either aripiprazole or amisulpride, which is used inorder to reduce side effects caused by clozapine. Additional psychotropicmedication would primarily include antidepressants used to treat depression and anxiety disorders in our patients with schizophrenia or mood stabilisers in bipolar affective disorder, both following current NICE Guidelines. This means that we have followed NICE Guidelines even if it means using polypharmacy. We therefore feel that in many of the cases that sound like undesirable polypharmacy there may actually be very good reasons in accordance with guidance why two or three psychotropic drugs are being used. This is in order to benefit patients whose side effect profile can be improved and their debilitating anxiety or depressive disorders are treated on top of the treatment for their schizophrenic illness. We would therefore like to see a more balanced view with regard to polypharmacy in a patient group that is often not responding to medication and usually has complex co-morbidities. Furthermore, we would dispute the notion that Taylor (1) suggested which is that non-medical prescribers may improve the situation. We have concerns which are rather in contrast to this. Non-medical prescribers are more likely to follow guidance but if guidance changes or is flawed as we have seen with the NICE Guidelines for Schizophrenia non-medical prescribers are more likely to lack the flexibility to respond adequately to these challenges and may therefore contribute to sub-optimal treatment rather than improve it. Lastly, we wholeheartedly embrace the recommendations that Langen and Shajahan put forward (2), which ask for the regular review of all cases ofpolypharmacy including clear documentation as to why polypharmacy is continuously used.

Yours sincerely

P Lepping and GC Harborne


1.Taylor D. Antipsychotic polypharmacy - confusion reigns. The Psychiatrist 2010; 34: 41-432.Langan J, Shajahan P. Antipsychotic polypharmacy: review of mechanisms,mortality and management. The Psychiatrist 2010; 34: 58-623.Fleischhacker WW, Heikkinen T, Olie JP, Landsberg W, Dewaele P, McQuadeRD, et al. Weight change on aripiprazole-clozapine combination in schizophrenic patients with weight gain and suboptimal response on clozapine: 16 week double-blind study. Eur Psychiatry 2008; 2 (23): s114-5.4.Tungaraza TE, Gupta S, Jones J, Poole R, Slegg G. Polypharmacy and high-dose antipsychotic regimes in the community. The Psychiatrist 2010; 34: 44-465.Achim AM, Maziade M, Raymond E, Olivier D, Mérette C, Roy MA. How Prevalent Are Anxiety Disorders in Schizophrenia? A Meta-Analysis and Critical Review on a Significant Association. Schizophr Bull 2009 Dec 3. [Epub ahead of print]6.Dernovsek MZ, Sprah L.Comorbid anxiety in patients with psychosis. Psychiatr Danub. 2009 Sep;21: Suppl 1:43-507.Sharma VK, Lepping P, Cummins AG, Copeland JR, Parhee R, Mottram P.The Global Mental Health Assessment Tool--Primary Care Version (GMHAT/PC). Development, reliability and validity. World Psychiatry. 2004 Jun;3(2):115-98.Mortimer AM.Update on the management of symptoms in schizophrenia: focus on amisulpride. Neuropsychiatr Dis Treat. 2009;5:267-779.Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM.Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009 Jan 3;373(9657):31-4110.Karunakaran K, Tungaraza TE, Harborne GC.Is clozapine-aripiprazole combination a useful regime in the management of treatment-resistant schizophrenia? J Psychopharmacol. 2007 Jun;21(4):453-6.
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