The first melatonergic antidepressant to offer a new approach to the treatment of depression is just over the horizon after new data demonstrated positive efficacy with marked improvements in sleep with no effect on daytime vigilance.
Current treatments for depression, suffer from patient acceptability, having an unwelcome reputation of causing unbearable side effects.
Indeed, acceptance of antidepressants of all drug classes is a major concern and is still one of the unmet needs in treating depression.
This approach aims to relieve depressive patients' sleep disruption without affecting daytime vigilance - a key advantage for an antidepressant medicine, as sleep complaints are common and a major disabling feature of depression.
Valdoxan (agomelatine), 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.
Valdoxan has a similar efficacy to the serotonin noradrenergic reuptake inhibitor (SNRI) venlafaxine, but not the often observed side-effects associated with the SNRI.
Data presented at the 18th Congress of the European College of Neuropsychopharmacology (ECNP), showed preliminary results of a specific study, which compared Valdoxan (25 - 50 mg / day) with venlafaxine (75 - 150 mg / day) in depressed patients.
Treatment with Valdoxan, discovered and developed by Servier, resulted in significantly better and earlier improvement in initiating sleep (p<0.001).
A polysomnography study in depressed patients showed that Valdoxan 25 mg had a beneficial effect on sleep patterns.
"In addition to its effective antidepressant properties, Valdoxan is the only antidepressant to have a specific action on circadian rhythms," says Dr Raymond Lam, 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," he added.
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.
There are many issues with current therapies for these disorders, particularly for depression. Selective Serotonin Reuptake Inhibitors (SSRI) are the current choice.
However, there is a 3-week gap for the drug to take effect. During this period the person becomes anxious for the drug to work and then more depressed because they feel the drug isn't working.
Depression is the single largest CNS drug market with global antidepressant sales of $19.5 billion in 2003. The WHO estimates that about 340 million people suffer from depression worldwide but only 20 per cent of patients with clinical depression receive treatment.
Many patients are underserved by or do not respond to currently available treatments and existing therapies, such as the selective serotonin reuptake inhibitor class, have a number of limitations such as delayed onset of anti-depressant activity and side effects.
Accordingly, there is great demand from physicians and patients for new types of therapies that work via new mechanism of actions and do not share these side effects.