title: Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder.
abstract: Depression is a devastating disorder that places a significant burden on both the individual and society. As such, the discovery of novel therapeutics and innovative treatments--especially for treatment-resistant depression (TRD)--are essential. Research into antidepressant therapies for TRD has evolved from explorations of antidepressants with primary mechanisms of action on the monoaminergic neurotransmitter system to augmentation agents with primary mechanisms both within and outside of the serotonin/norepinephrine system. Now the field of antidepressant research has changed trajectories yet again; this time, compounds with primary mechanisms of action on the glutamatergic, cholinergic and opioid systems are in the forefront of antidepressant exploration. In this review, we will discuss the most recent research surrounding these novel compounds. In addition, we will discuss novel device-based therapeutics, with a particular focus on transcranial magnetic stimulation. In many cases of antidepressant drug discovery, the role of serendipity coupled with meticulous clinical observation in drug development in medicine was crucial. Moving forward, we must look toward the combination of innovation plus improvements on the remarkable discoveries thus far to advance the field of antidepressant research.
authors.affiliation: Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: G I
authors.initials: GI
authors.lastname: Papakostas
authors.affiliation: Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Ionescu
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use; D018678:Cholinergic Agents / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000628:therapy; D018683:Excitatory Amino Acid Agents / Q000627:therapeutic use; D006801:Humans
chemical_list: D000701:Analgesics, Opioid; D018678:Cholinergic Agents; D018683:Excitatory Amino Acid Agents