Reimbursement of acetilcholinesterase inhibitors for Alzheimer's Disease in Europe

Delaying the onset and progression of Alzheimer's disease (AD) is a tremendously relevant issue in western countries. It has been estimated that delaying the onset of AD-related disability by 6 months might lead to 100,000 fewer persons with AD-related disability after 10 years in the United States (population 300 million) (Brookmeyer et al., 1998). Such a ®gure can be projected to 125,000 in the European Union (population of about 380 million). Eective antidementia drugsÐacetilcholinesterase inhibitors (AChI) such as donepezil and rivastigmineÐare available in most European countries that can provide symptomatic relief. Randomized clinical trials in mild to moderate AD patients have shown detectable but modest bene®ts on cognition (Rogers et al., 1998; Burns et al., 1999; Rosler et al., 1999) and authoritative reviews and guidelines either discourage their use or emphasize their limitations rather than their bene®ts (American Psychiatric Association, 1997; Lovestone et al., 1997; Birks and Melzer, 1998; Eccles et al., 1998; Birks et al., 1999; Mayeux and Sano, 1999). Reimbursement policies of the national health authorities are extremely variable across European countries, varying from 0 to 100%. Perhaps as a consequence of the nihilistic attitude of part of the scienti®c literature, reimbursement tends to be proportional to aordability, as shown in Figure 1 (Pearson's r0.43). This approach contrasts with a number of reports on the ecacy of AChI drugs on cognitive and non-cognitive symptoms (for example, agitation, psychosis, and apathy) (Mega et al., 1999; Wengel et al., 1999; Dallocchio et al., 2000) in AD and other neurodegenerative disorders (such as Levy body dementia patients) (Kaufer et al., 1998; Shea et al., 1998; Fergusson and Howard, 2000; Lanctot and Herrman, 2000; McKeith et al., 2000). Moreover, it contrasts also with clinical practice, in that a recent survey among 150 Alzheimer's specialists in the US found that 71% of respondents reported that an AChI was used in association with vitamin E by at least half of their AD patients (Morris, personal communication). The global picture that seems to emerge is that (a) `shower' treatment of AD patients with AChI drugs does not bring about, at a population level, signi®cantly relevant bene®ts, but (b) some diagnostic or non-cognitive symptom subgroups might be particularly sensitive to the treatment. Unfortunately, the ®rst statement is supported by strong evidence, while the second by more feeble evidence, and only the ®rst ®nds room in the available guidelines on AChI treatment of AD. Although the use of drugs with poor evidence of ecacy should obviously not be endorsed, attention should be drawn to the dangers of a too strict use of evidence to inform policy. Black and colleagues have stated that `even in the long term, some aspects [of clinical practice] will not be amenable to scienti®c study' (Black et al., 1999), since for a number of clinical issues randomized clinical trials will never be available. The need for evidence of the intervention's bene®t to the patient might be integrated through (a) the formulation and adoption of guidelines that avoid general statements (American Psychiatric Association, 1997; Lovestone et al., 1997; Birks and Melzer, 1998; Eccles et al., 1998; Birks et al., 1999; Mayeux and Sano, 1999), while strictly formalizing the intervention on the single patient (Norheim, 1999), (b) inclusion of interventions with relatively weak LETTERS TO THE EDITOR 233