Valdoxan, the First Melatonergic Antidepressant, Confirms its Efficacy in Preventing Relapse Whatever the Severity of the Depression

VIENNA, Austria, Oct. 15 /CNW/ - Valdoxan(R) (agomelatine), the first melatonergic antidepressant, is an effective, long-term treatment for Major Depressive Disorder (MDD) according to new data presented today at the European College of Neurospsychopharmacology (ECNP) annual congress. The new international study showed Valdoxan's efficacy in preventing relapse in out-patients with MDD over six-months, irrespective of the severity of depression(1).

"The short term efficacy of this novel antidepressant has already been demonstrated in several clinical studies", points out study investigator Professor Guy Goodwin from the Department of Psychiatry, University of Oxford, UK. "This new study demonstrated the long-term efficacy of Valdoxan in the prevention of depressive relapses, after an initial response to the drug, over a treatment period of six months. The results show that Valdoxan is a promising therapeutic agent for the short-and-long-term management of MDD, which offers remission to our depressed patients with very few adverse effects".

The multicentre, randomised, double-blind study involved nearly 500 (n=492) patients with recurrent MDD according to the DSM-IV classification. The primary outcome of the study was time to relapse (relapse defined as HAM-D17 score(3) 16 or any withdrawal for lack of efficacy according to the investigator's opinion during the randomised period).

Valdoxan: significantly lower relapse rate

Overall, Valdoxan was associated with a significantly lower relapse rate compared to placebo (p=0.0001). Nearly half of all patients who received placebo relapsed (46.6%) compared to just over fifth of patients who received Valdoxan (21.7%) over a six month treatment period, representing a 54% reduction of the risk of relapse for patients treated with Valdoxan. These results demonstrating the long-term antidepressant efficacy of Valdoxan were further confirmed in the more severely depressed subpopulation of the study. In patients with a baseline HAM-D17 score of greater than or equal to 25, Valdoxan was associated with a significantly fewer cumulative relapses (22.7%) than placebo (50.4%) over six months. Interestingly, the low number of early relapses (up to 6-8 weeks after randomisation) reported by patients switched from Valdoxan to placebo is an additional proof of absence of discontinuation symptoms when stopping Valdoxan treatment.

Valdoxan treatment was found to be well tolerated with the rate of treatment-emergent adverse events similar in patients receiving active treatment and placebo.

Valdoxan: efficacy in severely depressed patients

The antidepressant properties of Valdoxan have been demonstrated in several clinical trials, including large-scale phase III studies either versus placebo or other antidepressants(2-6). Efficacy has been shown to be superior in comparison to placebo and at least equal in comparison to selective serotonin reuptake inhibitors (SSRIs) and selective noradrenaline reuptake inhibitors (SNRIs), against which Valdoxan showed favorable trends in terms of response and remission rates. Valdoxan also demonstrated to be effective across clinical trials, whatever the severity of depression including in the subgroup of severely depressed patients. Results of placebo controlled studies showed that the greater the severity of depression, the greater the treatment efficacy of Valdoxan.

A reduction in sleep disruption, a core symptom of depression and a common problem in people with depression, without any sedation during the daytime, is one of the clinical benefits of Valdoxan treatment(5,7).

An innovative approach to the treatment of depression

Binding studies have shown that Valdoxan, the first melatonergic antidepressant, interacts with both melatonergic (agonist) receptors (MT1 and MT2), and with 5-HT2C (antagonist) receptors.(8) The antidepressant efficacy of Valdoxan involves joint actions on these receptors, possibly interacting synergistically. Valdoxan resynchronizes altered circadian rhythms of depressed patients, thus retaining antidepressant efficacy without the typical side effects such as sexual dysfunction(8,9) and drug discontinuation symptoms commonly seen with other antidepressants (SSRIs and SNRIs). Overall, Valdoxan possesses a pharmacological profile entirely distinct from SNRIs and SSRIs, making it an innovation and a significant advance in the treatment of depression.

Valdoxan was discovered and developed by Servier, France's leading independent pharmaceutical company. Novartis acquired exclusive rights to further develop and market agomelatine in the United States and several other countries. Servier retained the rights to develop and market the product in the rest of the world.

<< References

(1) G Goodwin, F Rouillon, R Emsley. Long-term efficacy of agomelatine, a novel antidepressant, in the prevention of relapse in out-patients with Major Depressive Disorder. ECNP presentation 2007

(2) Lôo H, Hale A & D'Haenen H. Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT(2C) antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study. Int Clin Psychopharmacol 2002; 17: 239-247.

(3) Kennedy SH, Emsley RA. Placebo-controlled trial of agomelatine in the treatment of major depressive disorder. Eur Neuropsychopharmacol 2006;16: 93-100.

(4) Olie J-P, and Kasper Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder. Int J Neuropsychopharmacol 2007 E-pub ahead of print

(5) Lemoine P, Guilleminault C and Alvarez E Improvement of subjective sleep in Major depressive disorder with a novel antidepressant agomelatine: randomized, double blind comparison with venlafaxine. J Clin Psychiatry. In Press

(6) S.H.Kennedy, C. Guilleminault. Antidepressant efficacy of agomelatine 25-50 mg versus venlafaxine 75-150 mg: two randomized, double blind studies. Eur Neuropsychopharmacol 2006, 16, S 319

(7) MA Quera-Salva, Vanier B, Laredo J, Chapotot F, Moulin C, Lofaso F and Guilleminault C. Major Depressive Disorder, Sleep EEG and Agomelatine: an open label study. Int J Neuropsychopharmacol 2007, Epub ahead of print

(8) M. Hamon, MJ Millan. Agomelatine, a novel pharmacological approach to treating depression. European College of Neuropsychopharmacology (ECNP) 2006. Eur Neuropsychopharmacol 2006, 16, S 337

(9) S.H. Kennedy. Favorable sexual profile of agomelatine in depressed patients Eur Neuropsychopharmacol 2006, 16, S 319 >>

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/For further information: Moira Gitsham, Tonic Life Communications, +33-5-46-00-08-20, moira.gitsham@toniclc.com; Leah Baldwin, Tonic Life Communications, +44-207-798-9923, leah.baldwin@toniclc.com/

Posted: October 2007

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