Treatment-resistant depression (TRD) is a complex and challenging psychiatric condition. The selective serotonin reuptake inhibitors (SSRIs) and the serotonin and norepinephrine reuptake inhibitors (SNRIs) are considered first-line antidepressants treatment of TRD. Switching between various antidepressants and augmentation strategies of adding other pharmacological or non-pharmacological interventions to the first-line antidepressants treatment are usually implemented for the management of TRD. This review is a brief summary of the currently available therapeutic interventions that could be implemented to eventually improve TRD treatment outcomes.