Are neuropeptides relevant for the mechanism of action of SSRIs?

• Published in: Neuropeptides (Edinburgh) 2019-06, Vol.75, p.1-17
• Main Authors: Gołyszny, Miłosz, Obuchowicz, Ewa
• Format: Article
• Language: English
• Subjects: Animal studies; Animals; Antidepressants; Anxiety; Anxiety disorders; Brain - drug effects; Brain - metabolism; Clinical research; Corticotropin-releasing hormone; Depressive disorders; Galanin; Humans; Mental depression; Mood; Neuromodulation; Neurons - drug effects; Neurons - metabolism; Neuropeptide Y; Neuropeptides; Neuropeptides - metabolism; Orexins; Oxytocin; Serotonin uptake inhibitors; Serotonin Uptake Inhibitors - pharmacology; SSRIs; Vasopressin
• ISSN: 0143-4179; 1532-2785
• DOI: 10.1016/j.npep.2019.02.002

Selective serotonin reuptake inhibitors (SSRIs) are drugs of first choice in the therapy of moderate to severe depression and anxiety disorders. Their primary mechanism of action is via influence of the serotonergic (5-HT) system, but a growing amount of data provides evidence for other non-monoaminergic players in SSRI effects. It is assumed that neuropeptides, which play a role as neuromodulators in the CNS, are involved in their mechanism of action. In this review we focus on six neuropeptides: corticotropin-releasing factor – CRF, galanin – GAL, oxytocin – OT, vasopressin – AVP, neuropeptide Y – NPY, and orexins – OXs. First, information about their roles in depression and anxiety disorders are presented. Then, findings describing their interactions with the 5-HT system are summarized. These data provide background for analysis of the results of published preclinical and clinical studies related to SSRI effects on the neuropeptide systems. We also report findings showing how modulation of neuropeptide transmission influences behavioral and neurochemical effects of SSRIs. Finally, future research necessary for enriching our knowledge of SSRI mechanisms of action is proposed. Recognition of new molecular targets for antidepressants will have a significant effect on the development of novel therapeutic strategies for mood-related disorders. •Until now mechanism of action of SSRIs has not been elucidated exactly.•Some neuropeptides are involved in the neurobiology of stress-related mood diseases.•Interaction of some neuropeptides with serotonergic system has been evidenced.•Influence of SSRIs on six neuropeptide systems has been presented.•Changes in neuropeptides may be relevant to therapeutic and side effects of SSRIs.