Research progress of non-monoamine antidepressants

Major depressive disorder (MDD) is a recurring mental illness that has brought severe physical and psychological burdens to people around the world and caused heavy medical and economic burdens on society. For many years, the monoamine hypothesis based on the first- and second-generation antidepressants have been developed and put into clinical use, but the traditional monoamine antidepressants have a series of problems, such as poor targeting, strong side effects, and slow onset. The emergence of non-monoamine antidepressants such as ketamine, scopolamine, and brexanolone has injected new impetus into the development of long-silent antidepressants. They have the characteristics of fast onset, low toxicity, fewer side effects, and a better response rate to treatment-resistant depression (TRD). This review will discuss the characteristics, mechanisms, advantages, and remaining problems of non-monoamine antidepressants, and provide recommendations for future clinical and scientific research.