Mirtazapine revisited: new therapeutic perspectives and formulation advances

Mirtazapine (MTZ) is a Food and Drug Administration-approved medication used primarily for the treatment of severe depression. It is a BCS class II drug having poor aqueous solubility (0.092 mg/mL), low oral bioavailability (50%), and high first-pass metabolism. This narrative review summarizes the ongoing research for the development of MTZ's novel formulations, keeping in view its physicochemical properties and its pharmacokinetic limitations. Owing to its novel pharmacodynamics, MTZ offers considerable potential for the management of various diseases, including schizophrenia, Alzheimer's disease, Parkinson's disease, epilepsy, post-traumatic stress disorder, diabetes, irritable bowel syndrome, and infertility, in addition to its widely established utility in depression. Nevertheless, the literature findings on the usage of MTZ in the aforementioned diseases remain contentious, which can be attributed to the inconsistencies in the research evidence and variable study outcomes. However, promising results of therapeutic effectiveness of MTZ against pruritus, cancer-induced nausea, emesis, and anorexia have been reported from preliminary investigations. Lastly, the present review provides a worthwhile overview of clinical trials and patents, which together put forward substantial evidence suggesting the potential repurposing of MTZ beyond from its use in depression, thereby accelerating advancements in drug delivery technologies.