Intended for healthcare professionals

Rapid response to:

Analysis

Getting better value from the NHS drug budget

BMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c6449 (Published 17 December 2010) Cite this as: BMJ 2010;341:c6449

Rapid Response:

Getting Better Value from the NHS Drug Budget

The article by Moon (BMJ Jan 2011; 342:30-32) presents options for
reducing the NHS prescribing budget and lists, amongst others, the
switching of the antidepressant Cipralex (escitalopram) to generic
citalopam as an example of substituting an active enantiomer for the
racemic mixture. Lundbeck developed and currently markets escitalopram
and we believe that the data do not support this strategy it would
certainly not be in the best interests of patients.

Citalopram exists as a racemate (equimolar mixture of S(+) and R(-)
stereoisomers). The S(+) stereoisomer, escitalopram (Cipralex), is the
pharmacologically active component of the parent compound1. In non-
clinical studies, the R(-) stereoisomer is about 150 times less potent
than escitalopram in serotonin reuptake inhibition in vitro, and
counteracts the activity of escitalopram in vivo2. Moreover, escitalopram
demonstrates more than twice the potency than an equivalent dose of the
racemate, citalopram, eliciting more than twice the effect on brain
serotonin levels in microdialysis studies3.

Escitalopram shows important differences from citalopram in clinical
studies. Independent meta-analysis of clinical studies in major depressive
disorder has shown that escitalopram is more efficacious than citalopram,
offering significantly greater acute response and remission rates4. In
patients with major depressive disorder, escitalopram treatment has also
been shown to
be more effective than citalopram in improving MADRS,CGI-S and CGI-I
scores and improving response and remission rates5. A meta-analysis of
four RCTs also demonstrated statistically significant higher response
rates
and mean change from baseline in MADRS with escitalopram compared to
citalopram over 8 weeks6, and in severe depression, significantly greater
efficacy of escitalopram compared to citalopram in the acute phase has
also been shown7.

The National Institute for Health and Clinical Excellence (NICE)
recognises that the advantage of escitalopram when considering changing
treatment "may be large enough to be clinically worthwhile in those who
have not benefited from treatment with a first or second antidepressant",
and found escitalopram to be one of the most cost-effective new generation
antidepressants8.

In a recent publication, the Department of Health advises that the
decision to initiate or change a patient's treatment regime should be
based on up-to-date best clinical evidence or guidance, (eg, from NICE or
other authoritative sources) and that health professionals should base
their prescribing decisions on individual assessments of their patients'
clinical circumstances, eg, patients whose clinical history suggests they
need a particular treatment should continue to receive it. Prescribers
should be able to make their choice of medicinal products on the basis of
clinical suitability, risk assessment and value for money.

Lundbeck believes that the evidence supports clinically relevant
differences between escitalopram and citalopram. Patients who are
receiving benefit from escitalopram may not continue to receive benefit if
switched to citalopram, and such a strategy is inconsistent with evidence,
NICE guidance and the Department of Health's position on cost-effective
prescribing.

Andrew Jones

Medical Director

Lundbeck UK

1. Hyttel, J et al. J Neural Transm 1992; 88: 157-162.

2. Sanchez C et al. Behav Pharmacol 2003; 14: 465-470.

3. Sanchez C et al. Basic Clin Pharmacol Toxicol 2006; 99: 91-9

4. Cipriani A et al. Cochrane database of Systematic Reviews 2009; Issue
2. Art. No: CD006532. DOI: 10.1002/14651858.CD006532.pub2.

5. Yevtushenko VY et al. Clin Ther 2007; 29(11): 2319-2332.

6. Auquier P et al. Int J Psych Clin Pract 2003; 7: 259-268.

7. Moore N et al. Int Clin Psychopharmacol 2005; 20: 131-137.

8. NICE Clinical Guideline 90, 2009. Available at:
http://guidance.nice.org.uk/CG90
(accessed November 2010).

Competing interests: I am a full time salaried employee of Lundbeck Ltd

18 January 2011
Andrew P Jones
Medical Director
Lundbeck Ltd