title: Mood Therapeutics: Novel Pharmacological Approaches for Treating Depression.
abstract: Real-world effectiveness trials suggest that antidepressant efficacy is limited in many patients with mood disorders, underscoring the urgent need for novel therapeutics to treat these disorders. Areas covered: Here, we review the clinical evidence supporting the use of novel modulators for the treatment of mood disorders, including specific glutamate modulators such as: 1) high-trapping glutamatergic modulators; 2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists; 3) NMDA receptor glycine-site partial agonists; and 4) metabotropic glutamate receptor (mGluR) modulators. We also discuss other promising, non-glutamatergic targets for potential rapid antidepressant effects in mood disorders, including the cholinergic system, the glucocorticoid system, and the inflammation pathway, as well as several additional targets of interest. Clinical evidence is emphasized, and non-pharmacological somatic treatments are not reviewed. In general, this paper only explores agents available in the United States. Expert commentary: Of these novel targets, the most promising - and the ones for whom the most evidence exists - appear to be the ionotropic glutamate receptors. However, moving forward will require us to fully embrace the goal of personalized medicine and will require health professionals to pre-emptively identify potential responders.
authors: a Experimental Therapeutics and Pathophysiology Branch , NIMH-NIH , Bethesda , Maryland , USA.
authors: Ioline D
authors: ID
authors: Henter
authors: a Experimental Therapeutics and Pathophysiology Branch , NIMH-NIH , Bethesda , Maryland , USA.
authors: Rafael T
authors: RT
authors: de Sousa
authors: a Experimental Therapeutics and Pathophysiology Branch , NIMH-NIH , Bethesda , Maryland , USA.
authors: Philip W
authors: PW
authors: Gold
authors: b Laboratory of Neuroscience, LIM- 27, Institute and Department of Psychiatry , University of São Paulo , São Paulo , Brazil.
authors: Andre R
authors: AR
authors: Brunoni
authors: a Experimental Therapeutics and Pathophysiology Branch , NIMH-NIH , Bethesda , Maryland , USA.
authors: Carlos A
authors: CA
authors: Zarate
authors: a Experimental Therapeutics and Pathophysiology Branch , NIMH-NIH , Bethesda , Maryland , USA.
authors: Rodrigo
authors: R
authors: Machado-Vieira
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D018680:Cholinergic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000928:Antidepressive Agents; D000975:Antioxidants; D018680:Cholinergic Antagonists; D018683:Excitatory Amino Acid Agents
keywords: AMPA receptor; N-methyl-D-aspartate (NMDA); bipolar disorder; depression; glutamate; major depressive disorder (MDD); mood; treatment