Potential strategies to optimize the efficacy of antidepressants: Beyond the monoamine theory

Depression is characterized by a feeling of sadness and lack pleasure, with impaired daily functioning poor quality life. The neurobiology the pathogenesis depression are not fully understood yet. Several hypotheses have been discussed including, monoamine theory, neurotransmission, oxidation, inflammation, glutamatergic transmission, neurotrophic factors, others. Reviewing three decades randomized controlled trials antidepressants revealed that response rate about 54% compared to placebo 37%. Treatment-resistant (TRD) could be defined as an inadequate two different antidepressants. In TRD, combination strategy using FDA-approved used, which may predispose patients adverse effects. Therefore, there compelling need explore potential “out box” adjuvants provide higher consistent rates high tolerability. These medications available for other indications, food supplements, or even experimental drugs. This review will highlight potentially beneficial such nitric oxide modulators, NMDA antagonists, anti-inflammatory, antioxidants, mitochondrial insulin sensitizers, opioids, probiotics, GABA agonists.