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BACKGROUND: Depression is one of the most common mental disorders and is associated with a significant increase in the risk of mental and somatic comorbidities. The chronobiological theory of the pathogenesis of depression explains the relationship between the symptoms of depression and disturbance of circadian rhythm regulation. Disrupted circadian rhythms are also observed in other disorders such as alcohol use disorder, anxiety disorders, epilepsy, and Parkinson’s disease. Therefore, there is a growing interest in the use of medications with a melatoninergic mechanism of action in the treatment of depression comorbid with the aforementioned disorders.

AIM: This review aims to systematically examine the evidence for the use of melatoninergic antidepressants (agomelatine and fluvoxamine) in the treatment of depression comorbid with alcohol abuse, anxiety disorders (including phobic anxiety, panic, and generalized anxiety disorders), or neuropsychiatric disorders (such as epilepsy and Parkinson’s disease).

METHODS: This systematic review included experimental studies, systematic reviews, and meta-analyses published in English and Russian, which examined the use of fluvoxamine and agomelatine in adult patients with recurrent depressive disorder (ICD-10) or major depressive disorder (DSM-5) comorbid with alcohol abuse, anxiety or neuropsychiatric disorders. The search was conducted in the PubMed, Cochrane Library and eLIBRARY scientific databases. The quality of the selected studies was assessed using the Cochrane Risk of Bias tool, which is used to evaluate the risk of systematic errors in clinical studies. The results were presented as a narrative synthesis and grouped by the comorbidities evaluated.

RESULTS: A total of 20 articles were reviewed (with a pooled sample size of n=1,833 participants). The results suggest that melatoninergic antidepressants might help in reducing depressive and anxiety symptoms, improve sleep, decrease alcohol cravings, and alleviate the severity of motor symptoms in Parkinson’s disease. Moreover, the use of pharmacogenetic testing to select the medication and dosage may enhance its therapeutic effectiveness.

CONCLUSION: The review demonstrates a significant lack of clinical data and guidelines on the use of melatoninergic medications for the treatment of depression comorbid with other disorders. In this regard, it is currently difficult to draw a definitive conclusion regarding the efficacy and safety of agomelatine and fluvoxamine in the treatment of these comorbidities. Available studies suggest an improvement in the clinical manifestations of the comorbidities. Future research directions might include the development and implementation of double-blind, randomized clinical trials to study the use of melatoninergic medications in patients with depression comorbid with other disorders.