New Melatonergic Antidepressant Combines Efficacy With Very Favourable Side-Effe

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New Melatonergic Antidepressant Combines Efficacy With Very

Favourable Side-Effect Profile

http://www.medicalnewstoday.com/medicalnews.php?newsid=32653

The first melatonergic antidepressant, Valdoxan® (agomelatine),

offers an innovative new approach to the treatment of depression.

Valdoxan combines antidepressant efficacy, even in severely depressed

patients, with an extremely favourable side-effect profile and has

the additional benefit of sleep regulation in depressive patients,

according to new data presented at the 18th Congress of the European

College of Neuropsychopharmacology (ECNP) today. The ability of

Valdoxan to relieve depressive patients' sleep disruption without

affecting daytime vigilance is a key advantage for an antidepressant

medicine as sleep complaints are a very common and disabling feature

of depression.

Antidepressant efficacy and additional clinical benefits

Valdoxan was shown to be an effective antidepressant, by reducing the

initial HAMD score to a similar extent to that of the selective

serotonin reuptake inhibitor (SSRI) paroxetine and significantly

greater than placebo1. Results from two other clinical trials

presented in Amsterdam show that Valdoxan also has a similar efficacy

to the serotonin noradrenergic reuptake inhibitor (SNRI) venlafaxine,

but not the often observed side-effects associated with the SNRI.

Preliminary results of a specific study comparing Valdoxan (25 - 50

mg / day) with venlafaxine (75 - 150 mg / day) in depressed patients

showed that Valdoxan had a similar antidepressant effect. However,

Valdoxan treatment resulted in significantly better and earlier

improvement in initiating sleep (p<0.001). In addition, a

polysomnography study in depressed patients showed that Valdoxan 25

mg had a beneficial effect on sleep architecture.

" In addition to its effective antidepressant properties, Valdoxan is

the only antidepressant to have a specific action on circadian

rhythms " , says Dr Lam from the Department of Psychiatry,

University of British Columbia, Canada. " It can relieve sleep

complaints in depressed patients without residual impairment and thus

appears to be an innovative, new pharmacological treatment for

depression. "

Further studies versus placebo and comparators have confirmed the

antidepressant efficacy of Valdoxan in adults of all ages, including

elderly depressed patients.1, 2 In addition, Valdoxan has shown

particularly interesting results in severely depressed patients; its

antidepressant efficacy increased as the severity of the depression

increased, including in patients with a HAMD>30, therefore providing

clear patient benefits.

Excellent side-effect profile

Valdoxan has an innovative pharmacological profile; it is the first

melatonergic antidepressant acting as a MT1 and MT2 receptor agonist

with additional 5-HT2C receptor antagonist properties. Due to this

unique mode of action, it does not show the typical side effects

found with SSRIs and SNRIs, in particular sexual dysfunction and drug

discontinuation symptoms*, two common side-effects that patients find

particularly troubling.

A trial comparing Valdoxan with venlafaxine showed comparable

antidepressant efficacy of both treatments, but significantly less

sexual dysfunction with Valdoxan. In addition, a placebo-controlled,

double-blind study comparing Valdoxan with paroxetine showed that,

after one week of treatment discontinuation, no signs of

discontinuation symptoms were seen in the Valdoxan group compared to

significant discontinuation symptoms in the paroxetine group.3

A new and effective approach to depression treatment

Patient acceptability of antidepressants is a major concern and is

still one of the unmet needs in treating depression. Special emphasis

has been given to the acceptability of Valdoxan throughout its

clinical development programme, in particular its effect on sexual

dysfunction and drug discontinuation symptoms.

Valdoxan was discovered and developed by Servier. The drug is

currently in Phase III trials and a registration dossier for an

indication in major depressive disorder (MDD) was submitted to the

European Regulatory Agency (EMEA) in 2005.

*Discontinuation symptoms occur when treatment with certain

antidepressants (mainly SSRIs and SNRIs) is stopped. They can include

nausea, headache, dizziness, sleep disturbances, anxiety and

irritability.

References

1. Lôo H, Hale A, D'haenen H. Int Clin Psychopharmacol. 2002; 17:239-

247

2. Emsley, CINP 2004; Int.J.Neuropsychopharm. 2004; Vol 7; suppl 1:

P02.174

3. Montgomery SA, Kennedy SH, Burrows GD, Lejoyeux M, Hindmarch I.

Int Clin Psychopharmacol. 2004; 19 :271-280

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