VALDOXAN® (AGOMELATINE), A NOVEL ANTIDEPRESSANT,
RECEIVES EUROPEAN MARKETING AUTHORISATION

Valdoxan: a novel approach to treating depression

Valdoxan® is now authorised by the European Commission for its use in the treatment of Major Depressive Episodes (MDE) in adults.1

Valdoxan is an innovative approach to the treatment of MDE and has demonstrated efficacy in depressed adult patients with moderate-severe depression2, offering a new option to many of the over 2.5 million adults in the UK suffering from depression at any one time3.

Data from the clinical development programme show that Valdoxan is effective against the core symptoms of depression, including depressed mood, anxiety, psychomotor retardation, sleep disturbances, and daytime fatigue.4-8

Valdoxan is the result of an extensive pharmacological research programme involving investigation centres all around the world (including the UK), and represents a different approach to the treatment of depression that goes a step beyond the monoamine hypothesis. Valdoxan is an MT1 & MT2 melatonergic receptor agonist with 5-HT2C receptor antagonist properties.9,10 As a result of this novel mode of action, Valdoxan has demonstrated antidepressant efficacy through circadian rhythm resynchronisation and the increase of dopamine and noradrenaline levels.11 This mechanism of action is unlike those of commonly prescribed antidepressants such as selective serotonin reuptake inhibitors (SSRIs), and serotonin and noradrenaline reuptake inhibitors (SNRIs), since Valdoxan has no impact on serotonin levels.12

In clinical trials Valdoxan has demonstrated efficacy at a once-daily dose of 25 - 50 mg in moderately and severely depressed adult patients (18-65 years old) presenting with a first or recurrent episode of Major Depressive Disorder (MDD).2, 4 - 8, 10

Short-term and long-term results from the extensive international development programme, including nearly 4,000 adult patients with MDD, were evaluated during the regulatory process. This programme supported the antidepressant efficacy of Valdoxan as compared with placebo, SSRI and SNRI treatments. This programme also showed that Valdoxan’s antidepressant efficacy was combined with a favourable tolerability profile. Indeed, most patients treated with Valdoxan did not present with any symptoms of sexual dysfunction.7 Furthermore, in double-blind placebo controlled trials patients treated with Valdoxan exhibited a body weight variation profile similar to that of placebo.13 Finally, studies indicate that Valdoxan has beneficial effects on disturbed sleep patterns in depression as early as the first week of treatment4 and is not associated with discontinuation symptoms upon cessation of treatment.14 As a precautionary measure liver function tests will be required during treatment with Valdoxan. In clinical trials an increase in serum transaminases (an indicator of liver function) was observed in some patients. When Valdoxan was discontinued in these patients, the serum transaminases usually returned to normal levels. Incidences of liver damage or pathology were rarely reported.15

Michael Sumpter, CEO of Servier UK said “I am delighted that this novel antidepressant treatment is now licensed for use in Europe. Valdoxan is an innovative approach to the treatment of Major Depressive Episodes in adults offering an additional treatment option to many of the over 2.5 million adults in the UK suffering from depression at any one time3.” Valdoxan will be fully available to patients in the UK in autumn 2009. The recommended dose is 25mg once daily taken orally at bedtime, which can be increased to 50mg if necessary. Valdoxan® was discovered and developed by Servier, France’s leading independent pharmaceutical company. Valdoxan was granted a positive opinion from the European Medicines Agency Committee for Medicinal Products for Human Use in November 2008.16

References
1. Marketing Authorisation, European Commission
2. Montgomery SA and Kasper S. Int Clin Psychopharmacol. 2007; 22: 283-291
3. Ohayon MM et al. Biol Psychiatry. 1999; 45: 300-307
4. Lemoine P et al. J Clin Psychiatry. 2007; 68: 1723-1732
5. Olié JP and Kasper S. Int J Neuropsychopharmacol. 2007; 10: 661-673
6. Kennedy SH and Emsley R. Eur Neuropsychopharmacol. 2006; 16(2): 93-100
7. Kennedy SH et al. J Clin Psychopharmacol. 2008; 28: 329-333
8. Kasper S et al. Eur Neuropsychopharmacol. 2008; 18(suppl4): S336. Abstract P2c022.
9. Chilman-Blair K et al. Drugs of the Future. 2003; 28(1): 7-13
10. Lôo H et al. Int Clin Psychopharmacol. 2002; 17: 239-247
11. Leproult R et al. Clin Endocrinol. 2005; 63: 298-304
12. Stahl S. Int Journal of Psychopharmacol. 2007; 10: 575-578
13. Data on File 07VADOF126
14. Montgomery Kennedy SH et al. Int Clin Psychopharmacol. 2004; 19: 271-280.
15. Data on File 08VAL0094
16. EMEA website www.emea.europa.eu/pdfs/human/opinion/Valdoxan_57541108en.pdf (Date Last
Accessed: 21 November 2008)
17. NICE depression guideline, Questions and Answers Depression and Anxiety
www.nice.org.uk/nicemedia/pdf/CG022%20and%20CG023_QandA.pdf
(Date Last Accessed: 20 November 2008)
18. Mind Information Booklet: Understanding Depression.
www.mind.org.uk/Information/Bookletes/Understanding/Understanding+depression.htm
(Date Last Accessed: 20 November 2008)
19. Quality and Outcomes Framework, Revisions to the GMS Contract 2006-7
www.bma.org.uk/ap.nsf/Content/revisionnGMSFeb20062
(Date Last Accessed: 20 November 2008)
20. Moussavi S et al. Lancet.. 2007; 370: 851–858
21. Scott J. British Medical Journal. .2006; 332: 985-986
22. Thomas C and Morris S. British Journal of Psychiatry. 2003; 183: 514-519.

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