Economic issues in access to medications: Schizophrenia treatment in England

International Journal of Law and Psychiatry 28 (2005) 514 – 531

Economic issues in access to medications: Schizophrenia treatment in England Martin KnappT, Panos Kanavos, Derek King, Hannah Monica Yesudian TU Darmstadt, Institute for Material Science, Petersenstrasse 23, 64287 Darmstadt, Germany

Abstract Mental health problems and the services to address them are currently receiving more attention in the UK than ever. Mental health care in England — indeed, across the UK — is experiencing a much needed transformation. It is therefore highly pertinent to examine the patterns of psychotropic medication use, given their intended links to recovery, rehabilitation, and reintegration, as well as to explore the economic and other factors that appear to influence those patterns. These are the aims of this paper. Our attention will be primarily focused on England. What this analysis shows is that given a higher profile by government, including additional funding (although not really benefiting differentially compared to other parts of the health service) and the first national service framework, it is possible to see changes in service patterns, access and (to a degree) outcomes. These changes are occurring at a time when new classes of psychotropic medication are being introduced in a range of therapeutic areas, contributing to the relatively rapid growth of take-up but also raising questions about appropriateness, effectiveness, cost-effectiveness and equity. D 2005 Elsevier Inc. All rights reserved.

1. Introduction Government mental health policy is focused on how to ensure that all those with mental ill health are able to access timely and effective, evidence-based services and receive any treatment and care they need. New investment has been directed towards the provision of new teams, staff and services. . . new money, clear targets and new structures and institutions have been put in place to ensure that all this happens (Robbins, 2004 p.1). T Corresponding author. Personal Social Services Research Unit, London School of Economics, Houghton Street, London, WC2A 2AE, United Kingdom. E-mail address: [email protected] (M. Knapp). 0160-2527/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ijlp.2005.08.007

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Mental health problems and the services to address them are currently receiving more attention in the UK than ever. Key elements of present day policy are to promote better health (drecoveryT), tackle social exclusion, support people with mental health problems in the community where possible, and use hospital admissions where necessary (and not seeing them as an indication of failure) in an integrated context. New specialist multidisciplinary teams are being put in place, more staff are being trained in evidence-based treatments, and more psychotropic medications are being dispensed. Developments of this kind have been made possible by a high-level policy commitment and substantial growth in expenditure. The UK spent 6.9% of its GDP on health in 2000, a percentage which had remained fairly constant since the early 1990s. But Tony Blair’s Labour government has pledged to increase that share to the dEuropean averageT of 8.5%. Public expenditure on health accounts for 85% of total health care spending. Within this overall total for public expenditure, mental health services have maintained a steady share of between 11% and 13% for the last decade. There have been undoubted successes: in England the suicide rate is the lowest since records began in the 1860s, positive experiences with care are expressed by a majority of service users and employment rates are up. But much remains to be done to help people with mental health problems gain better access to effective treatments. It is therefore highly pertinent to examine the patterns of psychotropic medication use, given their intended links to recovery, rehabilitation, and reintegration, as well as to explore the economic and other factors that appear to influence those patterns. These are the aims of this paper. Our attention will be primarily focused on England, as the health systems of the constituent parts of the UK are now governed by slightly different policies under recently devolved powers.

2. The UK health system The foundations for the UK’s health and social care systems were laid in the 1940s: universal, taxfunded systems were put in place which continue to dominate today. Treatment is available free at the point of use for all citizens, with the majority of services provided by the National Health Service (NHS) in the state sector. The NHS is financed mainly (94%) through central government general taxation, the remainder raised through user charges (2.1%; mainly for pharmaceutical prescriptions, ophthalmic services and dental care), repayments of interest-bearing debt (3.0%), and other miscellaneous sources (1.2%) such as capital repayments. The share of all health expenditure accounted for by private payments has ranged between 6% and 9% of total healthcare spending over recent years. Less than 10% of the population have private medical insurance cover, and the number has been falling for a few years. Private, out-of-pocket payments, or co-payments for private medical care, long-term care, pharmaceuticals, dental and ophthalmic services have not been insubstantial. Cost-sharing for pharmaceuticals in the UK comprises the prescription charge, which is a flat fee per prescription item, although patients with chronic conditions have the option of acquiring a (cost-reducing) prescription pre-payment certificate if they expect their drug costs to continue to be significant. Prescription charges are updated annually, although recent increases have been below the rate of general price inflation. Significant exemptions — applying to over 80% of the total number of prescriptions issued in any given year — are made on the basis of age, income, or diagnosis (NHS, 2004). However, mental illness is not a criterion for exemption, and some people on multiple medications find the out-of-pocket payments a barrier (Rethink, 2001).

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Private medical insurance takes two main forms: employment-based, company insurance (which represents 59% of the total) and individual insurance (which accounts for 31%). The remaining 10% is comprised of voluntary employee-paid groups where professional associations or trade unions act as umbrella organisations, but employees meet the costs of premiums themselves. It is also worth noting that in just under one-third of company schemes employees meet all or part of the premium costs. Health care is delivered through general practice, community health services, and the hospital network. Access to specialist care is through the general practice gate-keeping system. General practices are funded on a capitation basis with fee-for-service allowances for delivering specific care items. Hospitals and community trusts are now remunerated on the basis of healthcare resource groups, with health service purchasing now the responsibility of primary care trusts (covering populations of roughly 100,000), and will soon become largely the responsibility of individual primary care practices. The capitation funding formula for the NHS now includes a separate equation for mental health services, introduced in 1995/96, although expenditure is not hypothecated. Bindman, Glover, Goldberg, and Chisholm (2000) found that actual spending diverged significantly from allocation, with relative under-spending occurring more frequently in deprived areas. There has been a long-standing distinction between healthcare provided by the NHS, which is central government-controlled and overwhelmingly free at the point of use, and social care, which is commissioned by local government, and which is means-tested. Over time, central government policy has encouraged non-statutory sector provision of nursing homes, residential care homes, and home-based social care to replace state services. The public sector is now the minority provider of most social care services, including those for people with mental health problems.

3. Mental health policy in England 3.1. Reforms in 1990 Significant alterations to the structure of health and social care services were made by the 1990 National Health Service and Community Care Act. Major changes included creation of an dinternalT market within the NHS (separating purchasing and providing within the state system), the promotion of non-government provision and greater emphasis on needs-led rather than supply-led planning. The intention was to address some deep-rooted, pervasive problems of poor targeting, service fragmentation, and cost shifting: basically, unacceptable levels of inefficiency and inequity. These problems applied with at least equal force to mental health as to other areas (Kavanagh & Knapp, 1995). Long-term concerns that have proved hard to address include sub-therapeutic prescribing for depression (Donoghue & Tylee, 1996), poor schizophrenia care (Audit Commission, 1996; Kavanagh, 1997), inadequate targeting on serious mental illness (Lelliott & Audini, 1996), tensions between primary and secondary services (Gask, Sibbald, & Creed, 1997), and doubts about the ability of primary care doctors to identify mental health problems (Sainsbury Centre for Mental Health, 2002; NIMHE, 2003). However, it may well be that secondary mental health services are now being targeted better on more needy patients, and that the growing practice of providing specialist mental health services in primary care settings can divert more people away from secondary care (Kendrick, Burns, Garland, Greenwood, & Smith, 2004). Inequities also continue to be a widespread concern, with evidence confirming, among other things, the persistence of major disadvantage in London and other major cities (Johnson et al., 1997), marked

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differences in prevalence rates by socio-economic group (Melzer, Fryers, Jenkins, Brugha, & McWilliams, 2003), broader problems of social exclusion of people with mental health problems (ODPM, 2004), and — as we discuss in more detail later — continuing variations in access to treatments, including some medications. Another ongoing concern is whether England’s mental health services are dinstitutionally racistT, a charge levelled recently following the death of a black patient in care (NSCHA, 2003). The organisational changes introduced by the 1990 legislation raised some new challenges (Hadley & Goldman, 1995; Kavanagh & Knapp, 1995; Shepherd, Muijen, Hadley, & Goldman, 1996). Criticism was directed at some of the financial arrangements in what was seen as a fragmented, complicated set of new purchasing arrangements. Most of these difficulties have since been removed. The introduction of the NHS internal market made it necessary to be much more explicit about costs, expected effects of interventions, and criteria to be employed in rationing, thereby adding weight to other calls for an evidence-based-approach to practice. This was a welcome development, except that the mental health evidence base looked relatively thin. Commissioning of mental health services has been criticised for being poor quality, lacking strategic intent and insight, relying on limited and often uninformative data, and embodying perverse incentives. There is much coverage in the British media of the public risks associated with certain mental health problems, some of it undoubtedly stoking exaggerated public fears (Taylor & Gunn, 1999). Nevertheless, there clearly is a need to help service users maintain contact with services and to take their medications, and thereby lessen the rates of deliberate self-harm, suicide, and violent criminal acts. However, mental health policy in the period leading up to and following the 1990 legislation may have been over-concerned with this risk. Holloway (1996) described the dmoral panicT over community care since the early 1990s, leading to policies and practices dominated by minimisation of the risk of harm. One consequence has been the growth of coercion, close monitoring, and a rapid increase in compulsory inpatient admissions. The growth in the number of secure units has been labelled a return to dasylumdomT (Morrall & Hazelton, 2000), and Wolff (2002) has suggested that mental health policy in England dhas historically mismanaged the risk issue. . . and as such has set in motion the growing community care backlashT (p.801). 3.2. dModernisingT mental health Tony Blair’s Labour government came into power in 1997 and prioritised health policy. The mantra of mental health policy was that services should be dsafe, sound and supportiveT. The 1998 White Paper, Modernising Mental Health Services, set out a new strategy that promised dExtra investment and new systems to manage resources more effectively, well-integrated care processes, crossing professional and agency boundaries, legal powers which work with and underpin comprehensive local servicesT (Department of Health, 1998 p.8). Among the specific requirements were high quality senior leadership, clinical governance, commitment to education, training, recruitment and retention of staff, better information services, more research and development, and clearer lines of accountability. Specific service proposals for mental health care in England were announced with publication of the National Service Framework (NSF) in 1999. The NSF was evidence-based, set national standards, defined service models and suggested measures of performance and milestones to gauge progress over a ten-year programme. It was generally enthusiastically received as, in many respects, it reaffirmed long-standing and widely accepted principles. Seven standards spanned the areas of mental health promotion, primary care and access to services, effective services for people with severe mental illness, caring about carers, preventing suicide. Access to effective treatments, including medications, was central. As Beecham (2005) describes,

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recent intentions include expansions to the numbers of early intervention, assertive outreach and crisis resolution teams, expansion of the workforce in both primary and secondary care, development of new accommodation, and better services for prisoners and people leaving prison with mental health problems.

4. Pharmaceutical policy in England Pharmaceuticals account for a significant share of total health care expenditure in the UK (nearly 17% in 2003). Both the supply- and the demand-side are subjected to regulation. Among the key features of UK pharmaceutical policy are the following:

! a system of free pricing of medicines at launch subject to profit control on the basis of return on capital regulation, through the Pharmaceutical Price Regulation Scheme (PPRS); ! the absence of a restrictive national reimbursement formulary for medicines reimbursed by the National Health Service; ! the establishment of the National Institute for Clinical Excellence as a means of assessing clinical- and cost-effectiveness for innovative treatments (drugs, devices and procedures) and thus, determining the extent to which new therapies can be prescribed in general practice or inpatient care; ! the explicit determination of capped budgets (including prescribing budgets) in primary care; ! limited cost-sharing with extensive exemptions; and ! an attempt to make pharmacy practice more competitive and responsive to patient needs. Many of these elements of medicines’ policy have major implications for access to and utilisation of treatments for mental health problems. 4.1. Pharmaceutical Price Regulation Scheme (PPRS) The PPRS is a voluntary, non-statutory scheme that indirectly controls the prices of medicines used within the NHS by regulating the profits that companies can make from these sales (Department of Health, 2003). It covers all licensed, branded, prescription medicines sold to the NHS, but not products without a brand name (generics) nor branded products available without prescription (OTC medicines) except when prescribed by a doctor. The PPRS covers around 80% by value of the medicines used in the NHS; the scheme was recently re-negotiated for a further 5-year term (2005–2010). The objectives of the 2005–2010 PPRS are that it should continue to: (a) secure the provision of safe and effective medicines for the NHS at reasonable prices; (b) promote a strong and profitable pharmaceutical industry capable of such sustained research and development expenditure as should lead to the future availability of new and improved medicines; and (c) encourage the efficient and competitive development and supply of medicines to pharmaceutical markets in this and other countries (Department of Health, 2004a,b,c,d). There is a common profit target, usually expressed as a return on capital (ROC; currently set at 21%). The allowable return is associated with a margin of tolerance, and makes allowance for research and

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development, and marketing expenditure. Companies cannot be granted price increases unless they are forecasting profits less than 40% of the ROC target. The PPRS allows free pricing of medicines at launch, subject to the above rates of return. The new five-year agreement is associated with a 7% price reduction from January 2005 on NHS list prices for all products on the market for a year and without the possibility of increasing prices during that period. In imposing this reduction, the aim is to effect a corresponding reduction in the NHS expenditure on branded medicines. Scheme members may opt to deliver the price cut by modulating the prices of some or all of their products covered by the PPRS. The PPRS has been criticized, among others, for being non-transparent and encouraging regulatory capture. It has been characterized as inefficient, leading to over-investment in physical capital (Mossialos, 1997) in order to support high drug prices. On the other hand, periodic price assessments suggest that UK prices are not higher than prices in comparable countries (Department of Health, 2003), and that it provides a clear incentive for the industry to conduct R and D in the UK and export a significant proportion of its UK output. 4.2. National Institute for Clinical Excellence (NICE) In the UK as in other countries, new drugs must demonstrate efficacy, safety and quality of manufacture before they receive a product licence. (The procedures for ensuring safety have recently been called into question over the way that the Medicines and Healthcare Products Regulatory Agency handled evidence on the SSRIs, amid allegations of inappropriate links with industry; see Brook, 2004.) The establishment in 1999 of the National Institute for Clinical Excellence (NICE) — an independent organisation within the NHS — formalised what is effectively the dfourth hurdleT of cost-effectiveness. The aim of NICE is to promote clinical excellence and the effective use of resources within the NHS. Guidance has been issued on a wide range of treatments and technologies. In 2001 the government announced that the NHS would be compelled to implement guidance issued by NICE, but made no additional money available to fund the provision of recommended drugs and other treatments. Not surprisingly, NICE has generated much debate. It has been criticised for slow decision making (for example in relation to whether trastuzumab should be offered to breast cancer patients, and concerning the use of beta interferon for multiple sclerosis), and the results of its appraisals have often been contested (House of Commons, 2002). However, a review by the World Health Organization (WHO) Regional Office for Europe reached more positive conclusions about the process of appraisal (Hill, Garattini, van Loenhout, O’Brien, & de Joncheere, 2003). The WHO team commented that, in a limited space of time, NICE had developed a well-deserved reputation for innovation and methodological developments that represent an important model for technology appraisals internationally. Achievements included the transparency in the technology assessment, the intensive participation of different stakeholders (especially service users, apparently very influential in the mental health area; see Walley, 2004), a generally inclusive approach, and a commitment to using the best available evidence for decision-making. These plaudits have not all been offered by other commentators, as we discuss later. A recent assessment of the implementation of NICE guidance reveals what many people have suggested: it has certainly not yet eradicated the wide variations in practice across the country. Some guidance has had almost no apparent impact. Guidance is bmore likely to be adopted when there is strong professional support, a stable and convincing evidence base, and no increased or unfunded costs, in organisations that have established good systems for tracking guidance implementation and where the professionals involved are not isolatedQ (Sheldon et al., 2004; p.999).

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4.3. Prescribing and prescribing budgets in general practice Prescribing in general practice is assisted by the evidence base and practice guidelines, and benefits from monitoring and follow-up by the Prescription Pricing Authority. The Department of Health issues guidance to inform primary care trusts (PCTs) in making decisions about their unified budget allocations; this also includes prescribing. In calculating the resources for prescribing, the factors taken into consideration by the Department include the current rate of growth of the drugs bill, guidance issued by NICE, the financial implications of national service frameworks (such as that published in 1999 for mental health), the scope for prescribing newly licensed drugs prior to their evaluation by NICE, and the need to ensure consistency between primary and secondary care in treatment pathways for discharged patients as well as savings to the NHS that accrue by hospital pharmacy services supplying more medicines on discharge. (Hospitals receive medicines directly from manufacturers at a significant discount, therefore the same medicine costs significantly less to the NHS if prescribed in the in-patient setting than elsewhere.) 4.4. Community pharmacy and dispensing In 2000 the Department of Health announced modernisation of the national contractual framework for community pharmacy to establish minimum standards and to promote and reward high quality services, no longer funding on the basis of volume of prescriptions. The new contract for community pharmacists takes effect in 2005 (Department of Health, 2004c,d). The objective is to widen the range of services provided by local pharmacists, thereby offering a more convenient service to patients and creating a more flexible, choice-orientated health service. For example, community services will be reimbursed for checking blood pressure, monitoring blood glucose levels, offering smoking cessation advice, and promoting healthy lifestyles. Pharmacists will also be able to dispense repeat prescriptions without the patient needing to revisit their doctor for up to a year at a time, subject to the prior agreement of both the GP and the pharmacist. The expectation is that the contract should gradually develop over time to meet the needs of patients, the NHS and the pharmacy profession.

5. Trends in schizophrenia treatment 5.1. Expenditure As total NHS expenditure has increased so has the absolute amount going to mental health. In real terms, NHS mental health spending was 60% higher in 2000/01 than in 1990/91. The main change in component spending was on community health services, growing from 10% to 20% of total mental health expenditure over this period. Meanwhile the proportion accounted for by hospital inpatient services has fallen from 78% to 60%, although, interestingly, actual expenditure on inpatient services grew in (priceadjusted) volume from o1855 million to o2303 million over the decade despite a policy emphasis on reducing the use of inpatient admissions. This expenditure increase has been heavily influenced by the rapidly growing use of secure provision, consistent with the emphasis on risk minimisation. Local government social care spending on mental health has grown hugely over recent years, particularly growing responsibilities for funding non-hospitals accommodation services.

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The chronicity and disabling effects of schizophrenia have contributed to its high impact on total NHS expenditure; estimated as 2.8% in 1992/93 (Knapp, 1997). But, of course, the economic impact of schizophrenia ranges much wider, with substantial impacts on the social care, housing, criminal justice and employment sectors, and with high lost productivity costs and economic repercussions for families (Knapp, Mangalore, & Simon, 2004). 5.2. In-patient trends The most prominent trend in mental health care over five decades has undoubtedly been the shift away from hospital towards community-based care. The development of improved drug and psychosocial therapies were among a number of contributory factors in that shifting balance, at least in the period prior to 1990, although expectations of cost saving undoubtedly played their part (Whitaker, 2004). In England, hospital closures have not proved to be cost saving. A more recent trend has been the shifting balance between the public and independent sectors. Both trends have quite long histories, and both were given greater emphasis in the 1980s and 1990s. Psychiatric inpatient bed numbers peaked in absolute terms at around 155,000 for the UK as a whole in 1954, around 100,000 in 1975 and had fallen to 38,000 in England by 2000 and to 32,750 by 2002/03. Relatively few of the large hospitals closed until the late 1980s, gradually releasing valuable capital resources. Much of the remaining hospital estate is in poor condition. Admission rates, on the other hand, increased in the 1980s and early 1990s, representing a substantial increase in hospital throughout (Ford, Durcan, Warner, Hardy, & Muijen, 1998). More recent hospital episode statistics (for the period 1998/99 to 2002/03) show a fall in the number of admissions for people with dementia, substance misuse, mood disorders and neuroses, but not really any change in relation to people with schizophrenia. On the other hand, mean length of completed stay for people with schizophrenia has fallen slightly, although it is still around 100 days. 5.3. Community care There is clearly a relationship between the rate of hospital bed closure and the rate of opening of replacement accommodation and other community facilities. What is not at all clear is whether enough or appropriate community facilities were opened in advance of the closure processes. The closure of some inpatient facilities without adequate replacement with community accommodation has been a concern to many. It led — it was argued — to drevolving doorT patterns of service use, homelessness, increases in custodial detention of people with mental health problems, and generally impoverished quality of life. The 1999 National Service Framework identified a number of accommodation settings that could be suitable for mental health service users, including — as well as fully independent settings — supported living options such as individual tenancies, short- or medium-term hostel accommodation with residential staff support, 24-h staffed accommodation for people with a high level of need, inpatient hospital beds, alternatives to acute admission such as crisis houses, day hospitals or home treatment, and a range of secure provision. Subsequent government policy announcements have put greater emphasis on supported living options such as tenancies and shared housing, with less emphasis on staffed accommodation in the community.

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UK Germany France Italy The Netherlands

100000

packs

80000

60000

40000

20000

0 q1- q1- q3 - q4 - q1- q2- q3- q4 - q1- q2- q3- q4 - q1- q2- q3- q4 - q1 - q2- q3- q4- q1 - q2- q3- q4- q1 - q2- q3- q496 96 96 96 97 97 97 97 98 98 98 98 99 99 99 99 00 00 00 00 01 01 01 01 02 02 02 02

Source: The authors from IMS.

Fig. 1. Trend in sales of atypical antipsychotics, 1996–2002; retail and hospital markets.

5.4. Antipsychotic medications Globally, sales of antipsychotics grew from less than $500 m in 1991 to around $5 bn by the end of the decade (source: IMS website). The uptake of atypical antispychotics has been the reason, and the UK has matched the global trend. The UK market essentially increased tenfold in volume terms from early 1996 until 2002, for example, with double-digit year-on-year growth rates. Similar rises, but not as robust, are observed in other European countries of roughly similar size, as illustrated by Fig. 1, which shows trends in pack sales of atypicals over the 1996–2002. Prescribing data for primary care (and therefore excluding drugs prescribed by hospitals — a complication we discuss later) show rapid increases in the use of atypicals in a number of local studies: for instance, a 28% growth in prescriptions in Scotland in 1994–97 (Stark, Jones, Agnew, & Hepburn, 2000); a sixfold volume increase in the West Midlands between 1996/7 and 2000/01 (Ashcroft, Frischer, Lockett, & Chapman, 2002); a twenty-fold rise in expenditure over a similar period in Greater Manchester (Hayhurst, Brown, & Lewis, 2003). Overall, although antipsychotics account for only about 10% of all mental health drugs prescribed by general practitioners in England, a proportion that has grown slightly since 1998, they represent about 21% of spending on mental health drugs in primary care, up from around 12% in 1998 (source: PACT data). The rise is entirely due to switching from low price atypicals to the much more expensive atypicals (even though prices for the latter have dropped over time). Kaye, Bradbury, and Jick (2003) calculated that antipsychotic use increased from 10.5 people per 1000 population in 1991 to 12.2 per 1000 in 2000, with most of the increase — and indeed most of the use — to treat non-psychotic disorders (anxiety, depression, panic disorders, agitation in dementia). The

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publication of positive NICE guidance in July 2002, favouring the use of atypical antipsychotics as a first line treatment for patients with schizophrenia, may further provide a boost to growth (Walley, 2004), although the early indications do not point to much of an impact. One peculiarity is that depot medication has been used for a larger proportion of people with schizophrenia and for longer in the UK than in the US. In 2001, for example, about a third of patients on antipsychotics in the South London and Maudsley Trust were on depot medication, and this was probably lower than the national average. Depot antipsychotics have been argued to improve adherence with medication (Moore, Kelly, Herr, Love, & Conley, 1998) and reduce the rate of relapse (Dencker & Axelsson, 1996). They also eliminate the risk of deliberate or inadvertent overdose, an important consideration given the high risk of suicide in people with schizophrenia. Improved patient care and follow up may follow from the regular clinical contact necessitated by depot administration. On the other hand, depot injections may give rise to a higher incidence of extrapyramidal side effects than oral preparations, and there can be difficulties with titrating the dosage, with the risk of drug accumulation (Dencker & Axelsson, 1996). Despite these adverse properties, depot antipsychotics were widely seen as appropriate treatments by clinicians in the UK for quite some time. Even though there were few studies of efficacy, and none of cost-effectiveness (Adams, Fenton, Quraishi, & David, 2001; Knapp, Ilson, & David, 2002), doctors were often reluctant to move from a stable depot treatment regime to an uncertain oral atypical. Schizophrenia generates many concerns because it is a fairly common severe mental health problem with often appalling consequences. The first acute episode can have a devastating impact on someone with a disorder, and many people find it difficult to come to terms with the symptoms. Relapses are similarly very distressing. Around one quarter of first episode patients will make a full recovery, but for the majority there will continue to be periods of acute illness and remission. For some patients acute episodes occur with such frequency that it becomes impossible to lead a normal life. Suicide rates are high. The disorder can also have major implications for families and is also sometimes seen as a societal concern because of the association often made with violent crime (Taylor & Gunn, 1999). In this challenging personal, clinical and societal context, the atypical antipsychotics were seen as important new treatment options for people with schizophrenia because they appear better able to tackle the symptoms of the illness, whilst having fewer side effects. Of course, they are not without their side effects, with weight gain being one that has particularly attracted recent attention. Nevertheless, patient groups express strong preferences for atypical over typical antipsychotics (Hogman, 2001; Rethink, 2001).

6. Patterns of use of atypical antipsychotics 6.1. Efficacy, effectiveness, and cost-effectiveness Davis, Chen, and Glick (2003) carried out a thorough meta-analysis of clinical trials of atypical antipsychotic treatment for people with schizophrenia, including 124 RCTs that compared typicals with atypicals, and another 18 that made comparisons between different atypicals. They concluded that clozapine, amisulpride, risperidone and olanzapine are significantly more efficacious than typicals, but there was not evidence that other atypicals had this same advantage, which strongly argues against seeing the atypicals as a homogeneous group. They also concluded that some atypicals produced ba better functional recovery than [typicals] and are cost-effective because reduction of other costs (particularly

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hospitalisation) offsets these much greater medication costsQ (p.559). They went on to argue that bif efficacy differences are da mythT (as some authors have argued), it is a myth that reproduces costsQ (p.559). Other views have been expressed. Basu (2004) found 17 studies of the cost-effectiveness of pharmacological treatments that met a carefully specified set of study criteria. Very few were based on UK data. Clozapine appeared to produce cost savings and better outcomes, although there is uncertainty in the estimates of both that may prevent decision makers from making optimal decisions based on existing results. For chronic schizophrenia patients who are not dtreatment resistantT, Basu concluded dthat the cost-effectiveness results do not unambiguously lead to the choice of one pharmacological treatment over another. Both olanzapine and risperidone seem to produce incremental benefits over haloperidol and other standard neuroleptics across all studies. . . . However, due to the variety of measures used to assess clinical outcomes in these studies, an effect size and common measure is not possible to ascertain. Olanzapine seems to produce cost savings over haloperidol, but again the extent of cost savings varies widely. Finally, a study based on an experimental setting that compares risperidone to haloperidol finds risperidone to cost more than haloperidol presumably because only drug expenditures are considered on the costs sideT (pp. 456–457). Further cost-effectiveness studies are clearly needed, adopting a wider perspective than just an insurance company or hospital given the broad societal impact of an illness such as schizophrenia (Knapp, 1997). Basu (2004) argued for more consistency in methodology, and the US Panel recommendation to include a reference case has been taken up by NICE. In this area, as in others, there has been criticism of industry-funded trials: bThe majority of recent psychotropic drug trials are business rather than scientific exercises, constructed for the purposes of achieving regulatory approval and thereafter market penetrationQ (Healy, 2001 p.290). Whether doubts about these trials would warrant a return to greater use of conventional antipsychotics, with their unattractive side-effect profiles, is another matter. 6.2. Guidelines In 2002, NICE issued clinical guidelines on schizophrenia, seeing antipsychotic drugs as ban indispensable treatment option for most people in the recovery phaseQ (NICE, 2002). It recommended that five oral atypical antipsychotic drugs (amisulpride, olanzapine, quetiapine, risperidone, zotepine) should be considered as first-line treatments for people with newly diagnosed schizophrenia. Patients already receiving typical antipsychotics who, despite adequate symptom control, are experiencing unacceptable side-effects, and people in relapse who have previously experienced unsatisfactory management or unacceptable side-effects with typical antipsychotics should also be offered atypical antipsychotics. Choice of medication should follow informed discussion between patient, carer and doctor. NICE also recommended that, where more than one atypical antipsychotic drug is considered appropriate, the drug with the lowest purchase cost, taking into account daily required dose and product price per dose, should be prescribed. It also made clear that atypical and typical antipsychotic drugs should not be prescribed concurrently except for short periods to cover changeover of medication. Although the National Service Framework encourages use of evidence-based treatments, it is not government policy to recommend specific treatments. As Rosie Winterton, minister with responsibility for mental health care, stated in Parliament in December 2004: bThe Department [of Health] has not made any forecasts or set targets relating to atypical antipsychotics. Responsibility for implementing guidance published by NICE is devolved within the NHS to local [provider] trusts, supported and performance-managed by strategic health authoritiesQ (Hansard, 13 Dec 2004, column 945W).

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These guidelines on schizophrenia treatment have been widely welcomed. Other guidelines are being issued, the most recent on treatment and care of people with depression and anxiety (December 2004). The evidence base for such guidelines is eclectic and inclusive — certainly the best RCTs but also the experiential insights of patients, their families and the professionals who treat and support them (Adams & Gilbody, 2001). Until publication of the NICE guidelines the most widely cited prescribing recommendations were from the Maudsley Hospital (Taylor, McConnell, McConnell, & Kerwin, 2001). 6.3. Under- and mistreatment A common phenomenon in the UK, not dissimilar to the situation in many other countries, is that people with mental health problems do not access treatment. This appears to be particularly problematic in relation to neurotic disorders, as evidence by, for example, Bebbington et al., (2000), who found that bonly a small proportion of people diagnosed as having a neurotic disorder in Britain actually consult their family doctor for treatment. Even if an appreciable number of these people where not in need of treatment, our findings are so dramatic that one must conclude that they represent a large reservoir of untreated psychiatric disordersQ (p.1365). Britain is certainly not alone in this respect: under-recognition and undertreatment of mental illness is a global phenomenon (Kohn, Saxena, Levav, & Saraceno, 2003). Improving the recognition and treatment rates in primary care — at least of neurotic disorders — need not be unaffordable, and more importantly might eventually pay for itself in terms of reduced morbidity costs downstream. The treatment itself should be evidence-based, and conform to established guidelines. In a searching analysis of rich Australian data Andrews, Sanderson, Corry, and Lapsley (2004) compared actual treatment to that recommended by guidelines, found an enormous discrepancy (in what is widely acknowledged to be a very well resourced mental health system) and costed the action necessary to close the gap. The discrepancy was less marked for schizophrenia than for more common disorders. For the UK there is no shortage of evidence of substantial departures from accepted treatment guidelines, whether produced (recently) by NICE or by the Royal College of Psychiatrists or by other groups. Particular problems appear to be excessive dosages, inappropriate combinations of typical and atypical agents, delays in moving to clozapine for treatment refractory patients, higher frequency of depot administration than needed, and delegation of important administration decisions to nurses by inexperienced junior doctors (Campbell, Bateman, Smith, & Thomas, 1998; Holmes, Milliard, Greer, & Silcock, 2003; Newton, Murthy, & Qureshi, 1996; Paton et al., 2003; Taylor, Mace, Mir, & Kerwin, 2000, Taylor, Young, & Paton, 2003). 6.4. Postcode prescribing Guidelines guide but doctors prescribe. Although, as noted, there has been fairly rapid growth in the prescribing of atypicals nationally, the picture is very varied locally. Looking at hospital prescribing, Taylor et al., (2000) and Paton et al., (2003) point to the wide variations in practice, and Purcell and Lewis (2000) found a 34-fold variation in rates of clozapine provision between twelve mental health provider units in one English county. The variation did not narrow over a two-year period. The evidence on primary care prescribing is perhaps even more telling. Although local differences in the links between, and respective responsibilities of primary and secondary care providers add bnoiseQ to the data, the sheer scale of variance is vast. Ashcroft et al., (2002) found a four-fold variation in primary care prescribing of all atypicals in 1996/97 in one region, narrowing slightly to a three-fold difference

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four years later. In both years they adjusted for need using a mental health-specific indicator. A similar adjustment was made by Hayhurst et al., (2003), using a different need indicator, when examining data for all 99 English health authorities in 1999 (shortly before their abolition under one of many NHS reorganisations of recent years). Per capital expenditure on atypicals varied nine-fold across the country, and was significantly positively correlated with need (r = 0.49).1 Need was also correlated with expenditure on typicals (r = 0.33) and all antipsychotics (r = 0.51). The establishment of NICE was intended to help address this problem of postcode prescribing. As we have seen, the general influence if NICE guidance has been variable (Sheldon et al., 2004). Performance indicators for primary care trusts collected by the Commission for Health Improvement for 2002/03 show that atypicals as a proportion of all antipsychotics prescribed ranged from 71% in one Southwest London PCT to 20% in one part of the Trent region. 6.5. Individual treatment differences Beneath these locality variations are marked differences in the experiences of individual patients. Some such variation is absolutely appropriate: people react in different ways to particular medications, and the bscience of matchingQ in schizophrenia treatment is not at all well developed. Moreover, there should always be plenty of scope for patient choice. Schizophrenia treatment is a question of trade-offs: effectiveness in one symptom dimension versus another; symptom relief but perhaps at the cost of worsened side-effects such as elevated prolactin or weight gain. Patient advocacy groups such as Rethink (2001) have been pressing — with some success, it should be noted — for patients’ views to be taken into account in prescription decisions. The NICE schizophrenia guidance issued in 2002 formalised this, and choice is at the heart of government health policy. However, not all inter-individual variation is so rational or so preference-based. It has been suggested by British authors, for example, that receipt of an atypical rather than a typical antipsychotic is linked to gender, history or risk of noncompliance, ethnicity, previous treatment history, whether being treated in hospital or the community, and symptom severity (Mortimer, 2001; Patel, Nikolaou, & David, 2003; Taylor et al., 2000; Hogman, 1996). Some of these associations, if supported by evidence, might be deemed appropriate; others not. In reaching treatment decisions, psychiatrists are to some extent influenced by evidence (as processed and summarised by the British National Formulary, the Royal College of Psychiatrists and NICE), but also by the extent of their postgraduate education, the views of local colleagues, staff shortages (encouraging, it has been argued, wider use of depot medications), pharmaceutical company advertising, the requests of patients and budgetary constraints (Babor, Ballinger, & Fenton, 1996; Bebbington, 2001; Hayhurst et al., 2003; Hogman, 1996; Walley, 2004). We return to the question of budgetary restrictions and cost-based rationing in a moment, but first offer some new evidence on individual treatment experiences. 6.6. New empirical evidence We conducted two series of analysis to examine factors associated with the prescription choice between typical and atypical antipsychotics in the treatment of patients with schizophrenia. We employed data from

1

Pearson correlation coefficient.

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the General Practice Research Database (GPRD) for the UK for 1993 to 1999, and baseline observations from the more recent European Schizophrenia Outpatient Health Outcomes (SOHO) study. The GPRD is a computerised database of anonymous patient records that now contains over 30 million patient years of information commencing in 1987. Currently, the database collects information on approximately 3 million patients, approximately 4.7% of the UK population. Data are provided by contributing general practices from across the UK. Information is recorded by GPs on demographics, medical diagnosis, all prescriptions, referrals to hospitals, hospital discharge reports where patients are referred to hospital for treatment, and treatment outcomes (crudely measured) (Wood and Coulson, 2001). Other than academic and policy-related research, the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) also uses the database, primarily for better understanding of drug safety issues, brought to its attention by GPs submitting adverse drug reaction reports. The high quality and completeness of these data for research have been confirmed elsewhere (Walley & Mantgani, 1997). A panel logistic regression model (random effects) was run on all 4391 patients in the database for 1993 to 1999 who had a diagnosis of schizophrenia and received at least one antipsychotic medication prescription in each year that they contributed data to GPRD. The panel design allowed us to adjust for within-subject variation as we looked for associations between individual characteristics and the choice between atypical and typical antipsychotic. Significant associations ( p b 0.001) were observed between choice of atypical medication and age, having an inpatient stay in the previous year and having a high number of primary care visits. Age was associated with being prescribed an atypical. Patients who had an inpatient stay in the previous year were over 1.5 times as likely to receive atypicals, as were patients who had visited their GP six or more times in the previous year. Gender and time since first diagnosis of schizophrenia were not associated with higher or lower odds of being prescribed an atypical antipsychotic. Our other analyses used baseline data from the European SOHO study, which is a three-year, prospective, observational study of the treatment of schizophrenia in ten West European countries. Over 10,000 people with schizophrenia were initially recruited in outpatient settings at the point of either initiation or change of medication. Inclusion criteria were purposely wide and the research instrumentation purposely brief so as to interfere as little as possible with routine practice (Haro et al., 2003). SOHO is funded by Eli Lilly and Company, who provided the data for our (unrestricted) analysis. We first focused on those patients receiving their first ever antipsychotic, and therefore probably (but not necessarily) experiencing their first episode of psychosis. Although less data were collected than in a clinical trial, the SOHO study still offers a range of factors potentially associated with prescription choice. There were 1033 patients initiating antipsychotic treatment in the dataset, of which 783 had complete data as required. A logistic regression model was fitted to explore the prescription choice between typicals versus atypicals. Dummy variables to account for each patient’s country of residence were included. Only two factors were found to be associated with being treated with an atypical as opposed to typical as first-line medication: the negative symptoms score increased the likelihood of treatment with an atypical, while the cognitive symptoms score reduced the likelihood. There were quite marked differences by country, however. Focussing only on those countries with sufficiently large subsamples some other significant associations were observed. In Greece, a prior attempt at suicide was associated with higher odds of receipt of typicals, while more severe positive symptoms, and the (previous) prescription of concomitant medication were associated with the receipt of atypicals. In Italy, an inpatient stay in the previous six months was associated with initiated on a typical, while men were significantly more likely to receive atypicals than females. And in Spain, the greater the severity of depressive symptoms, the more likely that the patient would be started on an atypical.

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These analyses — all tentative and exploratory, but carried out very carefully — suggest significant differences in a patient’s chances of being offered an atypical rather than a typical drug. Why does this matter? It matters because it is government policy in England to increase the proportion of atypicals to all antipsychotics, based on the evidence synthesis and consultations that underpinned, first, the National Service Framework and latterly the NICE review and guidance. Together with our earlier description of postcode prescribing, these analyses point to continuing inequities in access to evidence-based treatments. 6.7. Budgets and rationing Reports from the advocacy group Rethink (formerly the National Schizophrenia Fellowship) in 1996 and 1999 pointed to the widespread rationing of atypical antipsychotics (Hogman, 1996; Taylor, 1999). The reports’ authors argued that the high cost of the drugs relative to the costs of the (then) generic typical antipsychotics were the main reason for national variations in prescribing. Fifty-seven health authorities were surveyed, 40% of which provided no funding for the use of atypical antipsychotics in secondary care. Of those that did provide funding, one quarter had a fixed allocated budget or fixed number of patients who could be treated. The reports rightly noted that the cost of medication represented a small part of the overall cost of treatment (less than 5% of health care cost; e.g., see Knapp et al., 2004), and that an effective medication could substantially reduce inpatient service use for patients treated. The survey got responses from 761 UK psychiatrists, critically in 1995, most of whom reported restrictions on the use of atypicals, and half of whom described the restrictions as cost-related (Hogman, 1996). Follow-up work a few years later showed that health authorities were often still not providing a budget for atypicals (Taylor, 1999). Many factors were at play here: tight budgets (particularly until almost the end of the decade), lack of evidence of cost-effectiveness (particularly on whether expensive new medications could reduce inpatient utilisation), inability to move money between budgets even when such cost-effectiveness evidence emerged, and the age-old problem that mental health services have low priority in resource allocation processes. This is precisely why NICE was set up: to endeavour to place treatment decisions on a sounder footing, drawing on the best research and other evidence, and to iron out much of the variability across the country. But budgetary limitations do still play their part, as they must. There is no logic in arguing for the abolition of rationing, for there will always be scarcity and so always a need for tough decisions about which treatments to fund and which not. What is logical, however, is to argue for transparent, evidence-based, consistently applied criteria for that rationing. That must be the aspiration for NICE, of course and it has undoubtedly improved matters in its short existence. But doubts have also been voiced about its real impact on clinical practice, its independence from the pharmaceutical industry and the government, its accountability to the public and the consistency of its decision-making (Devlin & Parkin, 2004; Freemantle, 2004; Sheldon et al., 2004). There is also the problem that NICE has not necessarily greatly eased the rationing challenge since it does not itself have to juggle the competing demands on what remain fixed local treatment budgets (Maynard, Bloor, & Freemantle, 2004).

7. Conclusions Mental health care in England — indeed, across the UK — is experiencing a much needed transformation. Given a higher profile by government, including additional funding (although not really

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benefiting differentially compared to other parts of the health service) and the first national service framework, it is already possible to see changes in service patterns, access and (to a degree) outcomes. These changes are occurring at a time when new classes of psychotropic medication are being introduced in a range of therapeutic areas, contributing to the relatively rapid growth of take-up but also raising questions about appropriateness, effectiveness, cost-effectiveness and equity. At the national level there is no lack of commitment to these goals, nor to encouraging the research that can provide the necessary guidance. But it is clear from our review of the UK evidence and our new analyses of existing data that inconsistencies remain. Nevertheless, it would be unhelpful — indeed absurd — to rail against rationing procedures, or to moan about the existence of barriers to better treatment. So long as it retains its current responsibilities, the National Institute for Clinical Evidence has a pivotal role to play in ensuring that the economic barriers are the right ones. This means using costeffectiveness rather than cost criteria, societal rather than professional perspectives, participative rather than exclusive decision making. The economic bissuesQ in access to psychotropic medication will never go away, and nor should they. References Adams, C., & Gilbody, S. (2001). Nobody ever expects the Spanish Inquisition (Paython 1991). Psychiatric Bulletin, 25, 291 – 292. Adams, C., Fenton, M., Quraishi, S., & David, A. (2001). Systematic meta-review of depot antipsychotic drugs for people with schizophrenia. British Journal of Psychiatry, 179, 290 – 299. Andrews, G., Sanderson, K., Corry, J., & Lapsley, H. (2004). Utilising survey data to inform public policy: Comparison of the cost-effectiveness of treatment of ten mental disorders. British Journal of Psychiatry, 184, 526 – 533. Ashcroft, D., Frischer, M., Lockett, J., & Chapman, S. (2002). Variations in prescribing atypical antipsychotic drugs in primary care: Cross-sectional study. Pharmacoepidemiology and Drug Safety, 11, 285 – 289. Audit Commission. (1996). By accident or design. London7 The Stationary Office. Babor, E., Ballinger, B., & Fenton, G. (1996). Influences on psychiatric drug prescription in psychiatric service. Psychiatric Bulletin, 20, 406 – 409. Basu, A. (2004). Cost-effectiveness analysis of pharmacological treatments in schizophrenia: Critical review of results and methodological issues. Schizophrenia Research, 71, 445 – 462. Bebbington, P. (2001). Choosing antipsychotic drugs in schizophrenia. Psychiatric Bulletin, 25, 284 – 286. Bebbington, P., Meltzer, H., Brugha, T., Farrell, M., Jenkins, J., Ceresa, C., et al. (2000). Unequal access and unmet need: Neurotic disorders and the use of primary care services. Psychological Medicine, 30, 1359 – 1367. Beecham, J. (2005). in this issue. Bindman, J., Glover, G., Goldberg, D., & Chisholm, D. (2000). Expenditure on mental health care by English health authorities: A potential cause of inequity. British Journal of Psychiatry, 177, 267 – 274. Brook, R. (2004). Medicines regulation in the UK: The case for reform. Journal of Mental Health, 30, 431 – 438. Campbell, M., Bateman, D., Smith, J., & Thomas, S. (1998). The use of atypicals in the management of schizophrenia. British Journal of Pharmacology, 47, 13 – 22. Davis, J., Chen, N., & Glick, I. (2003). A meta-analysis of the efficacy of second-generation anti-psychotics. Archive of General Psychiatry, 60, 553 – 564. Dencker, S., & Axelsson, R. (1996). Optimising the use of depot antipsychotics. CNS Drugs, 6, 367 – 381. Department of Health. (1998). Modernising mental health services. London7 Department of Health. Department of Health. (2003). PPRS: 5th report to parliament. London7 UK Department of Health, PPRS Branch. Department of Health. (2004). Primary care prescribing and budget setting. London7 Department of Health. Department of Health. (2004). The Pharmaceutical Price Regulation Scheme (PPRS). London7 Department of Health (http://www.dh.gov.uk/pprs). Department of Health. (2004a). A sweet pill for pharmacists. Media release 25 October. London7 Department of Health.

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