An antidepressant developed by France’s Servier Laboratories could represent the first effective treatment for severe depression, according to results of Phase III clinical trials.
The drug, known as Valdoxan (agomelatine), is a melanotergic antidepressant that has a different mechanism of action to the established drug classes, including the selective serotonin reuptake inhibitors, serotonin/noradrenaline reuptake inhibitors and tricyclic antidepressants.
The clinical data suggest that Servier’s drug is at least as effective as these other drug classes – even in severe depression – but has a more favourable side effect profile, according to Professor Stuart Montgomery, emeritus professor of psychiatry at Imperial College School of Medicine in London, UK.
Prof Montgomery told Pharma Times NewsOnline that studies have shown Valdoxan has a similar efficacy in severe depression to Wyeth’s SNRI drug Effexor (venlafaxine), which has been shown to be more effective in these patients than the SSRIs and TCAs. But Servier’s drug seems to avoid some of the debilitating side effects with these classes, including nausea, restlessness and sexual dysfunction.
Moreover, it seems to improve the sleep problems experienced by up to 80% of all depressed patients - which can be exacerbated by the SSRIs and SNRIs - without the sedative properties of current antidepressants, such as paroxetine, that can linger after dosing.
Studies have suggested that, overall, 30%-40% of all patients treated with antidepressants discontinue treatment because of side effects, said Prof Montgomery. A drug that combined efficacy with a good tolerability profile could be expected to quickly come into very broad usage, he suggested.
He also noted that Valdoxan also seems to have a calming effect in patients whose depression is accompanied by anxiety. Separate studies are underway of the drug in anxiety disorders, as well as in biopolar depression.
On the downside, psychiatrists are still waiting for an antidepressant that can provide an early onset of action. Valdoxan takes effect at around two weeks, better than the four weeks required by some other antidepressants, but there is still an urgent need for an agent that can provide an improvement in mood within days, said Prof Montgomery.
Valdoxan, which acts as a melanotergic MT1and MT2 receptor agonist, as well as an antagonist at serotonin 5-HT2C receptors, has already been submitted for approval in Europe on the basis of Phase III trials in patients with moderate-to-severe depression.