. Author manuscript; available in PMC: 2017 Aug 10.

Published in final edited form as: Expert Rev Clin Pharmacol. 2017 Jan 16;10(2):153–166. doi: 10.1080/17512433.2017.1253472

Table 1. New agents in the treatment of mood disorders ranked by evidence of efficacy.

Evidence drawn from replicated double-blind (DB), randomized controlled trials (RCTs) that include a placebo arm, or from meta-analyses

	Target	Mechanism of Action

Ketamine	Glutamatergic system	Broad glutamatergic modulation
Esketamine	Glutamatergic system	Non-competitive and subtype non-selective activity-dependent NMDA receptor antagonism
Scopolamine	Cholinergic system	Anticholinergic
Dehydroepiandrosterone (DHEA)	Hormone regulation	Unknown
Pioglitazone	Metabolic pathways	PPAR-γ agonism
Evidence drawn from one double-blind, randomized controlled trial that includes a placebo arm or from a trial with an active comparator

	Target	Mechanism of Action

Nitrous oxide	Glutamatergic system	Non-competitive NMDA receptor inhibition
AZD6765	Glutamatergic system	Broad glutamatergic modulation
CP-101,606	Glutamatergic system	Subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonism
D-cycloserine (DCS)	Glutamatergic system	Glycine-site partial agonism
GLYX-13 (Rapastinel)	Glutamatergic system	Glycine-site partial agonism
Sarcosine	Glutamatergic system	Glycine transporter-I inhibition
Metyrapone	Glucocorticoid system	Glucocorticoid synthesis inhibition
Ketoconazole	Glucocorticoid system	Cortisol modulation
Celecoxib	Inflammation pathway	COX-2 inhibition
N-acetyl cysteine (NAC)	Oxidative stress	Increase in glutathione levels
Silexan	Serotonergic system	5-TH_1A receptor inhibition
Evidence from prospective, non-controlled trials with 10 or more subjects or secondary measures assessed in double-blind, randomized controlled trials

	Target	Mechanism of Action

Basimglurant (RO4917523 or RG7090)	Glutamatergic system	Metabotropic (mGluR5) glutamate receptor modulation
Biperiden	Cholinergic system	Anticholinergic
Mifepristone (RU-486)	Glucocorticoid system modulation	Non-selective glucocorticoid receptor antagonism
Pregnenolone	Glucocorticoid system modulation	Downstream hormone regulation
Erythropoietin (EPO)	Neurotrophins	Neurotrophism
Anecdotal reports or expert opinion

	Target	Mechanism of Action

Dextromethorphan	Glutamatergic system	Non-competitive NMDA receptor antagonism
MK-0657 (CERC-301)	Glutamatergic system	Subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonism
Donepezil	Cholinergic system	Cholinesterase inhibition