Abstract

Treatment-resistant depression (TRD) is a lack of satisfactory response to standard antidepressant therapy, and poses a formidable challenge for both patients and clinicians, underscoring the constant need for innovative therapeutic strategies. This article delves into the therapeutic modalities for TRD, with a focal point on personalized treatment paradigms. We will describe a new cohort of antidepressants, such as esketamine and the dextromethorphan-bupropion combination, spotlighting their efficacy in targeting the cerebral glutamate system. Gepirone ER, a selective medication for serotonin 1A receptors, emerges as a promising therapeutic avenue for patients with TRD. In addition to pharmacological therapy, neuromodulation methodologies such as electroconvulsive therapy (ECT), light therapy and transcranial magnetic stimulation (TMS), have yielded promising results in the treatment of TRD. Furthermore, hormone therapy, including the utilization of triiodothyronine (T3) in tandem with other pharmacotherapies, alongside exogenous oxytocin, emerge as prospective therapeutic options. Upon reviewing the available literature, it is evident that continued research is required in this domain. This review underscores new insights into the treatment landscape of treatment-resistant depression, including a new class of medications, neuromodulation techniques, hormone therapy and other substances, as promising modalities in the battle against TRD.