Agomelatine, the first melatonergic antidepressant, has been widely recognized as a true innovation since its launch in Europe one year ago. Agomelatine has a unique pharmacological profile: an agonist at MT1/MT2 melatonergic receptors and antagonist at 5-HT2C receptors, it resynchronizes altered circadian rhythms in depression.

Agomelatine has already become a first-line treatment option for patients with a first depressive episode, as well as those with recurrent depression. In daily practice, agomelatine can be used in all depressed patients, and is particularly indicated in patients complaining of sleep difficulties. Agomelatine ensures unimpaired daytime vigilance, cognition, gastrointestinal transit, and sexual functioning. Feedback to date from both inpatients and outpatients with major depression is positive: beyond the antidepressant effect, patients frequently report improvement in sleep-wake rhythms and daily functioning, as early as by the first week (mostly within the first 3 days), which differentiates agomelatine from other antidepressants. Most patients report improvement in mood and other symptoms after 2/3 weeks and satisfactory tolerability. The most frequently noted side effects are dizziness, headache, and nausea; liver function tests at initiation of treatment are not considered to be an issue. Because agomelatine, unlike conventional antidepressants, does not affect serotonin levels, in case of switch the initial antidepressant should be progressively downtitrated to avoid discontinuation symptoms, which risk masking the benefits of agomelatine.

In summary, the early effects of agomelatine shown in controlled studies are also experienced by the majority of patients in daily practice and reflect its ability to resynchronize circadian rhythms.