The heterogeneity of symptoms within major depressive disorder poses significant challenges for treatment and it is likely that current pharmacotherapies do not target all symptoms equally, although they have similar efficacy rates. While there is still continuing interest in understanding monoamine interactions and consequent downstream effects, the limited efficacy and tolerability achieved with classical antidepressants provides a compelling argument to move beyond the monoamines. Several lines of biological research in depression exploring immune function, neurotrophins, amino acid and neuropeptide neurotransmitters, neuroanatomical function and circadian rhythms, may lead to novel therapeutic targets and enhance depression outcomes. This review will evaluate the evidence for emerging treatments as well as recommendations from current international guidelines regarding antidepressant management.
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