Experimental and pilot clinical trials suggest the role of melatoninergic systems in the pathogenesis of migraine and the treatment effect of drugs acting on melatonin receptors. Authors studied the efficacy of the MT1- and MT2 agonist and selective 5-HT2C receptor antagonist agomelatine in the migraine prevention. Twenty patients with migraine, aged from 23 to 45 years, were treated with agomelatin in dose 25 mg per day during 3 months. The frequency of migraine attacks decreased from 7.4±2.4 to 3.8±1.4 (p=0.025), the duration and intensity of attacks decreased from 38.0±14.10 h to 24.0±6.1 h (p=0.018). The increase of treatment efficacy index, the decrease of headache impact on the general state measured with the VAS (from 8.1±1.8 to 7.2±1.6; p=0.01) and quality of life (HIT-6 index) as well as the duration of disability caused by headache (HALT index) were seen. The reduction of depression severity and normalization of night sleep were found in patients treated with agomelatin.