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According to the World Health Organization (WHO), depression is a common mental disorder and includes complex interaction between social and psychological behaviour affecting 264 million people worldwide. The review aims to highlight the role and importance of nitrogen-based heterocyclics in the development of antidepressant compounds. Many research groups have attempted to design drug candidates capable of binding within the receptors. The commonest drug design strategy includes the incorporation of different structural features widely recognized as an antidepressant in the synthesized derivatives to enhance their CNS antidepressant effects. In this review, we have shed light on nitrogenous heterocyclic moieties such as quinazoline, pyridine, pyrimidine, pyrrolidine, imidazole, pyrazole, piperidine, oxadiazole, benzimidazole, benzothiazole, piperazine, triazine, purine, benzoxazole, and isoxazole …