Researchers are constantly looking for new, faster-acting, more effective antidepressants with fewer side-effects. And one new antidepressant in particular is starting to look pretty promising. It's called agomelatine (brand name Valdoxan) and it isn't quite like any other antidepressant on the market, because it doesn't affect the uptake of serotonin, noradrenaline or dopamine.
Agomelatine is a specific agonist of MT1 and MT2 melatonin, and to some extent it is also an antagonist at serotonin 5HT-2C receptors (as are SSRIs). Melatonin is a hormone produced by the pineal gland, which has an important role in the sleep-wake cycle ('circadian rhythm'). Abnormalities in circadian rhythms are highly prevalent in mood disorders, including depression, so agomelatine has many potential advantages for treating depression, because it may help regulate the sleep-wake cycle. This means it helps you sleep better, without sedating you and causing daytime sleepiness. Which is a big deal, considering many SSRI's and SNRI's cause insomnia, and therefore make sleeping problems worse.
But the really big thing which makes agomelatine exciting is the lack of side effects. Unlike SSRI's and SNRI's, it does not cause weight gain, sexual dysfunction or withdrawal symptoms. It has no discontinuation syndrome. That is a big deal. Weight gain and sexual side-effects are the two main complaints people seem to have about SSRI's, and it's a big reason some people stop taking them. And trying to come of an SSRI can really suck. Not to mention how bad the discontinuation can get for venlafaxine.
As with any new antidepressant, its efficiacy is questionable. It has, however, demonstrated superior efficacy to sertraline in one study, and fluoxetine in another. In other studies, it had a higher efficiacy than placebo, especially for treating severe depression, and a lower rate of relapse. As with many antidepressants, some studies showed no difference between agomelatine and placebo. It's worth noting that those studies also showed no difference between the active controls (paroxetine and sertraline) and placebo.
If agomelatine really works, with such a good level of tolerability, it's definitely a very exciting step forward in antidepressant treatment. It was released in the UK in July this year, so watch this space.