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The cardiovascular health of young people with severe mental illness: addressing an epidemic within an epidemic

  • Sue Bailey (a1) (a2), Clare Gerada (a3), Helen Lester (a4) and David Shiers (a5)

Summary

For young people with emerging psychosis, early weight gain and its potential cardiac and metabolic consequences amplify worrying UK public health trends for young people in general. This paper will argue that if clinicians dismiss these changes as of secondary concern in psychiatric treatment for their young patients, they may be inadvertently condoning a first critical step on a path towards physical health inequalities. Greater recognition is needed for this patient population in their 20s and 30s, at ages not normally considered for active primary or secondary cardiovascular prevention, who are at high risk of dying prematurely. The early phase of psychosis presents an important treatment window for protecting cardiometabolic health.

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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Footnotes

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Declaration of interest

D.S. received a fee for keynote presentation on early intervention in psychosis with a particular focus on the physical health issues at a Janssen-Cilag educational meeting in 2010. He provides paid consultancy to the National Audit of Schizophrenia by the Royal College of Psychiatrists' Centre for Quality Improvement.

Footnotes

References

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21 Vancampfort, D, Probst, M, Sweers, K, Maurissen, K, Knapen, J, De Hert, M. Relationships between obesity, functional exercise capacity, physical activity participation and physical self-perception in people with schizophrenia. Acta Psychiatr Scand 2011; 123: 423–30.
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29 NHS Employers, British Medical Association. Quality and Outcomes Framework Guidance for GMS Contract 2011/12: Delivering Investment in General Practice. NHS Employers, 2011 (http://www.nhsemployers.org/SiteCollectionDocuments/QOFguidanceGMScontract_2011_12_FL%2013042011.pdf).
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31 Álvarez-Jiménez, M, Hetrick, SE, González-Blanch, C, Gleeson, JF, McGorry, PD. Non-pharmacological management of antipsychotic-induced weight gain: systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry 2008; 193: 101–7.
32 El-Mallakh, P. Doing my best: poverty and self-care among individuals with schizophrenia and diabetes mellitus. Arch Psychiatr Nurs 2007; 21: 4960.
33 Cimo, A, Stergiopoulos, E, Cheng, C, Bonato, S, Dewa, C. Effective lifestyle interventions to improve type II diabetes self-management for those with schizophrenia or schizoaffective disorder: a systematic review. BMC Psychiatry 2012; 12: 24.
34 Holt, RI, Abdelrahman, T, Hirsch, M, Dhesi, Z, George, T, Blincoe, T, et al. The prevalence of undiagnosed metabolic abnormalities in people with serious mental illness. J Psychopharmacol 2010; 24: 867–73.
35 Weiden, PJ. Switching antipsychotic medications: not enough, too often, or just right? Am J Psychiatry 2011; 168: 9.
36 Morrison, AP, Hutton, P, Shiers, D, Turkington, D. Antipsychotics: is it time to introduce patient choice? Br J Psychiatry 2012; 201: 83–4.
37 Morrison, AP, Hutton, P, Wardle, M, Spencer, H, Barratt, S, Brabban, A, et al. Cognitive therapy for people with a schizophrenia spectrum diagnosis not taking antipsychotic medication: an exploratory trial. Psychol Med 2012; 42: 1049–56.
38 Fulford, KW. Bringing together values-based and evidence-based medicine: UK Department of Health initiatives in the 'personalization' of care. J Eval Clin Pract 2011; 17: 341–3.
39 Newall, H, Myles, N, Ward, P, Samaras, K, Shiers, D, Curtis, J. Efficacy of metformin for prevention of weight gain in psychiatric populations: a review. Int Clin Psychopharmacol 2012; 27: 6975.
40 National Institute for Health and Clinical Excellence. Preventing Type 2 Diabetes – Risk Identification and Interventions for Individuals at High Risk. NICE, 2012.
41 Lester, H, Shiers, DE, Rafi, I, Cooper, SJ, Holt, RIG. Positive Cardiometabolic Health Resource: An Intervention Framework for Patients with Psychosis on Antipsychotic Medication. Royal College of Psychiatrists Centre for Quality Improvement, 2012, in press.

The cardiovascular health of young people with severe mental illness: addressing an epidemic within an epidemic

  • Sue Bailey (a1) (a2), Clare Gerada (a3), Helen Lester (a4) and David Shiers (a5)

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The cardiovascular health of young people with severe mental illness: addressing an epidemic within an epidemic

  • Sue Bailey (a1) (a2), Clare Gerada (a3), Helen Lester (a4) and David Shiers (a5)
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eLetters

Physical health epidemic in mental health

David Shiers, Retired GP and former joint lead on National Early Intervention in Psychosis programme of National Mental Health Development Unit.
17 January 2013

We welcome the letters to our article (1).

Dr Chaparala asks if we would have been better mentioning how duration of 'untreated' psychosis impacts on long term outcomes. Is not a20-year mortality gap for men, and 15 years for women a significant long term outcome and an impact of 'untreated' cardio-metabolic risk deserving of some earlier intervention?

Notwithstanding incontrovertible evidence that antipsychotics cause problematic weight gain (2, 3), we do not suggest antipsychotics are the sole explanation of increased cardiovascular disease but do highlight how antecedent risks can become established in the critical early treatment phase. This is further supported by two recent systematic reviews observing cardio-metabolic changes only after antipsychotic initiation (4,5). The subsequent trajectory of weight gain, increasing metabolic disturbance and sustained heavy smoking provides a compelling link betweenschizophrenia and cardiovascular disease (6), the single most important cause of premature death in this population.

Furthermore NICE are clear in their recommendations that these adverse cardiovascular risks should be identified at the earliest opportunity and managed using the appropriate NICE guidance for preventionof these conditions (7a). And yet when the recent National Audit of Schizophrenia (NAS) examined the implementation of NICE recommendations incommunity settings, it found that only 28% of people with schizophrenia across England and Wales had received an adequate assessment of cardio- metabolic risk within the previous 12 months; 43% had not even been weighed (8a).

Does this apparent lack of concern about adverse cardio-metabolic consequences revealed by the NAS matter? After all Dr Reed is reassured about antipsychotic safety by the FIN-11 study of Tilhonen et al. Howeverauthorities, De Hert, Correll & Cohen have challenged this study's conclusions, listing methodological weaknesses which include:

'incomplete reporting of data, questionable selection of drug groups and comparisons, important unmeasured risk factors, inadequate control forpotentially confounding variables, exclusion of deaths occurring during hospitalization leading to exclusion of 64% of deaths on current antipsychotics from the analysis, and survivorship bias due to strong and systematic differences in illness duration across the treatment groups.' (9)

Dr Reed raises the issue of switching antipsychotics and how this maydestabilise control of psychosis but may have missed the point of Weiden'seditorial that he refers to. Whilst indeed not advocating switching antipsychotics in someone established on treatment Weiden highlights how two randomised studies demonstrated the positive value of switching antipsychotics to counteract rapid weight gain and metabolic change (10, 11) concluding:

'Practice guidelines and public policy should recommend that clinicians consider the value of switching antipsychotics in patients withelevated metabolic risk.' (12)

Dr Chaparala suggests we are abandoning antipsychotics. No, but we are in good company in questioning the dominance of psychopharmacology (13). Moreover excessive reliance on antipsychotic treatment is suggestedby the NAS finding of wide variation in the availability of psychological treatments across England and Wales; even in those patients whose responseto antipsychotics had been unsatisfactory 34% were not offered any form ofpsychological treatment (8b) despite NICE recommendations that these should be considered (7b).

What we urge is responsible prescribing particularly in the critical early phase of illness and a sensitivity by us as doctors to how these young people may feel about the effects of our treatments. Perhaps the final word should go to the closing comment of Dr Tagore's letter:

'We must never be economical with the truth about the drugs we are all too happy to dish out.'

Authors:

David Shiers*, Susan Bailey , Clare Gerada, Helen Lester.

*David Shiers' Declaration of interests applies to this letter and tothe original article (1): Current member of two Guideline Development Groups (GDG) for NICE: a) NICE guidance for children and young people affected by psychosis and schizophrenia; and b) NICE guidance for adults with psychosis and schizophrenia; the views expressed are not those of either GDG, NCCMH or NICE.

References

(1) Bailey S, Gerada C, Lester H, Shiers D. The cardiovascular healthof young people with severe mental illness: addressing an epidemic within an epidemic. Psychiatrist 2012; 36: 375-378.

(2) Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y, Keet IP, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2007; 371: 1085-1097.

(3) Tarricone I, Ferrari Gozzi B, Serretti A, Grieco D, Berardi D. Weight gain in antipsychotic-naive patients: a review and meta-analysis. Psychological Medicine 2010; 40:187-200.

(4) Foley D, Morley KI. Systematic Review of Early Cardiometabolic Outcomes of the First Treated Episode of Psychosis. Arch Gen Psychiatry 2011; 68: 609-616.

(5) Mitchell AJ, Vancamfort D, De Herdt A, Yu W, De Hert M. Is the Prevalence of Metabolic Syndrome and Metabolic Abnormalities Increased in Early Schizophrenia? A Comparative Meta-Analysis of First Episode, Untreated and Treated Patients Schizophrenia Bulletin; Advance Access published August 27, 2012 doi:10.1093/schbul/sbs082

(6) Newcomer, J & Hennekens, J,H. (2007) Severe Mental Illness and Risk of Cardiovascular Disease JAMA, 298, 1794-6.

(7) National Institute of Health and Clinical Excellence (2009) Schizophrenia: Core Interventions in the Treatment and Management of Schizophrenia in Primary and Secondary Care. Clinical Guideline 82. London: NICE. a) pp370-371 Recommendation 10.4.1.3 b) pp368-369

(8) Royal College of Psychiatrists (2012). Report of the National Audit of Schizophrenia (NAS) 2012 London:Healthcare Quality Improvement Partnership. a) p88-91. b) p84-86.

(9) De Hert M, Correll CU, Cohen D. Do antipsychotic medications reduce or increase mortality in schizophrenia? A critical appraisal of theFIN-11 study. Schizophrenia Research 2010; 117: 68-74.

(10) Stroup TS, McEvoy JP, Ring KD, Hamer RH, LaVange LM, et al. Schizophrenia Trials Network: A randomized trial examining the effectiveness of switching from olanzapine, quetiapine, or risperidone to aripiprazole to reduce metabolic risk: Comparison of Antipsychotics for Metabolic Problems (CAMP). Am J Psychiatry 2011; 168:947-956

(11). Newcomer JW, Campos JA, Marcus RN, Breder C, Berman RM, et al. A multicenter, randomized, double-blind study of the effects of aripiprazole in overweight subjects with schizophrenia or schizoaffective disorder switched from olanzapine. J Clin Psychiatry 2008; 69:1046-1056

(12) Weiden PJ. Switching Antipsychotic Medications: Not Enough, Too Often, or Just Right? Editorial Am J Psychiatry 2011; 168: 9.

(13) Tyrer P. From the editor's desk: the end of the psychopharmacological revolution. Brit J Psychiatry 2012: 201: 168.

Conflict of Interest: *David Shiers Declaration of interests applies to this letter and to the original article.

(1): Current member of two Guideline Development Groups (GDG) for NICE: a) NICE guidance for children and young people affected by psychosisand schizophrenia; and b) NICE guidance for adults with psychosis and schizophrenia; the views expressed are not those of either GDG, NCCMH or NICE.

Conflict of Interest:*David Shiers' Declaration of interests applies to this letter and to the original article (1): Current member of two Guideline Development Groups (GDG) for NICE: a) NICE guidance for children and young people affected by psychosis and schizophrenia; and b) NICE guidance for adults with psychosis and schizophrenia; the views expressed are not those of either GDG, NCCMH or NICE.
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Conflict of interest: None Declared

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Physical health epidemic in mental health

Hemagireswari Chaparala , GP Trainee
02 November 2012

We would very much welcome the focus on physical health from secondary mental health, as advocated by Bailey et al (1). However, we would like to raise the following points.The Quality Outcomes Framework (2) now includes HbA1c levels recorded in the past 15 months to identify diabetes for patients aged 40 years and over with schizophrenia, bipolar affective disorder and other psychoses (MH20). The World Health Organization has included HbA1c in its diagnosticcriteria for diabetes and this is also being backed up by the National Institute for Health and Clinical Excellence (3). We think that it is important to have HbA1c levels recorded, especially in patients on antipsychotics.

The incidence of metabolic syndrome in psychiatric patients has been covered recently in this journal (4), but Bailey et al could have highlighted the need for baseline physical health monitoring before commencing on antipsychotics. Moreover, there is a known higher incidence of diabetes in patients with psychosis. Therefore, psychiatrists play a major role in reminding other clinicians and reiterating in their communication to GPs the importance of following parameters such as weight, blood pressure and glucose levels in the early weeks, so the primary care team are aware and the patients are appropriately followed upand supported.

Bailey et al seem to be suggesting that antipsychotics have no role in the management of psychosis and the disorder can be treated with a multiprofessional approach. It might have been better to mention the impact of duration of untreated psychosis on the long-term patient-relatedoutcomes (5), and so I would have thought that antipsychotics would be theessential part of a biopsychosocial approach rather than a treatment of last resort.Finally, I am glad to hear about the Royal College of General Practitioners' involvement with the Royal College of Psychiatrists in coming up with a collaborative framework. I welcome the Bailey et al article and the joint collaboration and would hope more joint work is carried out in the future between primary and secondary care teams.

References

1.Bailey S, Gerada C, Lester H, Shiers D. The cardiovascular health of young people with severe mental illness: addressing an epidemic within an epidemic. Psychiatrist 2012; 36: 375-8.

2.British Medical Association, NHS Employers. Quality and Outcomes Framework for 2012/13: Guidance for PCOs and Practices. NHS Employers, 2012.

3.Diabetes UK. New diagnostic criteria for diabetes (Jan 2011). Diabetes UK (http://www.diabetes.org.uk/About_us/Our_Views/Care_recommendations/New_diagnostic_criteria_for_diabetes_/).

4.Gubbins A, Lally J, McDonald C. Metabolic syndrome in patients attending psychiatric day centres: prevalence and associations. Psychiatrist 2012; 36: 326-31.

5.de Haan L, Hinszen HD, Lenior ME, de Win ED, Gorsira R. Duration ofuntreated psychosis and outcome of schizophrenia: delay in intensive psychosocial treatment versus delay in treatment with antipsychotic medication. Schizophr Bull 2003; 29: 341-8.

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Conflict of interest: None declared

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Cardiovascular disease and schizophrenia. Do we know enough?

Richard E Hodgson, Consultant Psychiatrist
15 October 2012

We read the paper by Bailey et al(1) with interest and find the aims laudable. However, we would like to add a note of caution. Our main concern is that many of the recommendations are not evidence based. They assume that people with schizophrenia are the same as the general population, the so called 'ecological fallacy'. In their article the authors describe potential differences such as the increased risk of metabolic abnormalities including diabetes which predate the prescription of antipsychotics. Therefore, it cannot be assumed that what is effective in the general population will be equally so in the schizophrenia population. For example, controversy surrounds the diabetogenic effect of statins in the general population and Nielsen (2) demonstrated that lipid lowering medication was a greater risk factor for the development of diabetes in a cohort of people with schizophrenia than 'high risk' antipsychotic medication. Furthermore, a Finnish (3) cohort study replicated the finding ofpoor outcomes for cardiovascular disorders in schizophrenia patients and that the excess morbidity could not be explained by prescription rates of lipid lowering drugs.

The paper presents a comprehensive overview of cardiovascular (CVD) risk management and, whilst we may be guilty of the same assumption described above, we would like to emphasise the importance of cardiorespiratory fitness as a modifiable risk factor. The importance of this risk factor is often neglected or understated with guidelines emphasising medical managements. However, Kilbourne (4) reported that physical inactivity HR= 1.66 CI (1.59-1.74) was a greater risk factorthan smoking HR= 1.32 CI(1.26-1.39) for cardiovascular mortality in acohort of people with schizophrenia.The complexity of mortality risk factors in early schizophrenia is furtherillustrated when one examines the relationship between body mass index (BMI) and suicide in the general population. Suicide and not cardiovascular disease is the major mortality risk in younger people with schizophrenia. An emerging paradox is linking an inverse association between BMI and suicide risk in the general population Hence a lower BMI may reduce CVD risk but increase suicide risk5. Whilst there is emerging evidence that patients with schizophrenia are receiving medical treatment for CVD risk factors3 there is little evidence, so far, that this has reduced mortality1. If the people with schizophrenia are seen as a high CVD risk population with attendant early and aggressive medical intervention then the impact on core symptom outcomes needs to be studied as some of the antipsychoticswith the greatest liability for metabolic side effects are also be the more effective. Clearly, more research is required to understand the relative importance of mortality risk factors in schizophrenia and their management (5).

(1)Bailey S Gerada C Lester H Shiers D. The cardiovascular health of young people with severe mental illness: addressing an epidemic within andepidemic. Psychiatrist 2012; 36: 375-378. (2)Nielsen J, Skadhede S, Correll CU. Antipsychotics Associated with the Development of Type 2 Diabetes in Antipsychotic-Na?ve Schizophrenia Patients. Neuropsychopharm 2010; 35:1997-2004 (3)Lahti M, Tiihonen J, Wildgust H, Beary M, Hodgson R et al. Somatic Hospital Treatment, Lipid-Lowering and Antihypertensive Pharmacotherapy, and Cardiovascular Mortality in Patients with Schizophrenia Psychol Medicine 2012; 12 March Epub head of print (DOI: 10.1017/S0033291712000396) (4)Kilbourne AM, Morden NE, Austin K, Ilgen M, McCarthy JF, et al. Excess heart-disease-related mortality in a national study of patients with mental disorders: identifying modifiable risk factors. Gen Hosp Psych2009; 31: 555-563. (5)Beary M, Hodgson R, Wildgust HJ. A critical review of major mortality risk factors for all-cause mortality in first-episode schizophrenia: clinical and research implications. J Psychopharmacol. Suppl 2012; 26: S52-S61

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Conflict of interest: REH and MB have received research funding and hospitality from Pharma. HW is a retired pharma (Lilly) employee.

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First Do No Harm

Paul F Reed, Consultant Psychiatrist
15 October 2012

First Do No Harm

I read with interest and welcomed the Special Article by Bailey et al.(1) I share the concern of the authors over the "scandal of premature mortality" and note their recommendation to urgently review antipsychotic medication when certain adverse effects are experienced (rapid early weight gain or cardiometabolic blood disturbance). The authors do not implicate any particular antipsychotics, but guidelines suggest that Clozapine and Olanzapine are the most likely antipsychotics to be associated with these side effects.(2) Neither do the authors suggest what the outcome of such a review might be, although I deduce it is implicit inthe recommendation that reducing the dose or switching antipsychotic wouldbe likely possible outcomes.

I do however have one concern with this suggestion which relates to the risk-benefit balance of antipsychotics.

Tiihonen et al (2009)(3) present data from a large study in which examined the effects of antipsychotics on all cause mortality, suicide, and deaths from ischaemic heart disease. One strength of this study is theexamination of all cause mortality.

Tiihonen et al (2009)(3)also found that for people with schizophrenia antipsychotic use is associated with a reduced risk of death of about one third, when compared with no antipsychotic treatment (Hazard ratio 0.68 (CI 0.65-71))

They also concluded that clozapine was associated with a substantially lower risk of all cause mortality and also suicide. They found that no pronounced differences between antipsychotics (including Clozapine and Olanzapine) were noted for mortality from ischaemic heart disease.

Thus in the event that a patient is switched from clozapine to an alternative antipsychotic, their risk of death may in fact be increased rather than reduced. Further, switching antipsychotics (even Olanzapine) appears not be associated with a reduction in risk of all cause mortality or even death from ischaemic heart disease.

Given that switching antipsychotic medication is associated with harm, for example by increasing risk of relapse (Weiden 2011), this leads me to question the wisdom of the author's recommendation to urgently review the antipsychotic prescription in the circumstances they describe.

There may be other reasons for switching antipsychotics but Tiihonen et al's data suggest that reducing the "scandal of premature mortality" isnot one of them.This raises a dilemma for practicing clinicians as to how to proceed in these circumstances.

I would very much value the opinions of the authors about Tiihonen etal's (3)findings and the implications for antipsychotic prescribing.

References

(1) Bailey S, Gerada C, Lester H, Shiers D. The cardiovascular health of young people with severe mental illness: addressing an epidemic within an epidemic. Psychiatrist 2012; 36: 375-378.(2) Taylor D, Paton C, Maudsley Prescribing Guidelines in Psychiatry, Eleventh Edition Wiley-Blackwell, 2012.(3) Tiihonen J et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 2009; 374: 620-627.(4) Weiden P, Switching antipsychotic medications: not enough, too often, orjust right. Am J Psychiatry 2011; 168: 882-884

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Conflict of interest: None declared

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Iatrogenicity-are we largely to blame for this epidemic?

Aashish Tagore, Specialist Registrar in Adult Psychiatrist
15 October 2012

Notwithstanding the premorbid genetic and psychosocial predispositions Bailey et al refer to, the authors correctly highlight theincontrovertible evidence that the obesity and metabolic syndrome epidemicwe are facing is largely drug-induced, as highlighted by the EUFEST study1. Given this fact, we must accept that we are essentially complicit in greatly increasing our own patients' morbidity and mortality, and that this "epidemic within an epidemic" is an iatrogenic one. I can't help but wonder whether we, as clinicians, tend to ignore a side-effect which we consider to be "benign," in relation to the perceived lack of an immediateneed to address it urgently, as opposed to, for example, an acute EPSE or massively raised prolactin or marked ECG changes. Additionally, I wonder whether our complacency in addressing this adverse effect profile may be borne out of a sense of our own feelings of helplessness. That is to say, because there is no straightforward solution to this multifaceted problem,we choose to ignore or at least sidestep the issue. It is precisely because of the creeping, insidious nature of these obesity-related problems, that we are allowing them to develop in to an "epidemic" of suchproportions.

We must ask ourselves if it is morally acceptable to treat chronic and enduring mental illness at the expense of inflicting chronic and enduring physical illnesses. As the authors elude to, if we actually bothered to ask our patients, particularly the younger ones, what it is they would be most distressed by-continued mental illness or aggressive weight gain, would it really be so surprising that a sizeable (no pun intended) proportion would prefer to remain distressed (or learn to cope with) by their psychiatric symptoms than become morbidly obese? Should this really come as a shock to us, given the ever increasingly body-conscious world I which we live? I suspect that our priorities as psychiatrists may not be entirely aligned with those of many of our patients. Is there a doctor-patient risk-benefit analysis mismatch at playhere?

But are we really improving our patients' quality of life and promoting social inclusion by treating one stigmatising condition for another, which arguably carries even greater prejudice? After all, most ofthe population view morbidly obese individuals not only as a repulsive eyesore, but tend to apportion blame. Many view obesity a self-inflicted condition, borne purely out of laziness and gluttony, and tend to make extremely pejorative judgments.

Notwithstanding this, whilst these drugs are the only truly effectiveweapons in our armament against chronic psychotic disorders, it is incumbent upon us to make prescribing decisions which genuinely take the potential ramifications of such physically and socially disabling adverse effects into account from the outset.

At the end of the day, if I was a patient, I would not be happy to learn I had developed a serious, chronic, physical disorder with many potential multi-system complications (such as diabetes), as a result of taking a drug which I probably wasn't keen to take in the first place anyway, and further, was never fully appraised of the risks. We must neverbe economical with the truth about the drugs we are all too happy to dish out.

References

1) Kahn, R.S., et al (2007) "Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomized clinical trial." Lancet, 371, 1085-97.

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Conflict of interest: None declared

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