. 2012 May 1;6:369–388. doi: 10.2147/PPA.S29716

Table 6.

Mechanism of action of agents used as augmentation for treatment-resistant depression

Augmentation agent	Mechanism of action
Lithium	Potentiate serotonergic neurotransmission, modulates phosphatidyl-inositol pathway
Triiodothyronine	Potentiate norepinephrine neurotransmission, corrects subclinical hypothyroidism that causes depression-like symptoms
Atypical antipsychotics	Improve frontal serotonin, norepinephrine, and dopamine functions, and other neurotransmitters such as glutamate
Psychostimulants	Improve norepinephrine and dopamine neurotransmission
Inositol	Precursor of diacylglycerol and inositol triphosphate
Estrogen	Affects gamma aminobutyric acid, serotonergic, noradrenergic and cholinergic neurotransmission
Omega-3 fatty acids	Normalize communication in nerve cells; lower tumor necrosis factor-α; lower interleukin-B; lower prostaglandins E 2, 3, 4; and increase brain-derived neurotrophic factor
Dopamine agonists	Increase dopamine tone
Herbal supplements	May impact monoaminergic neurotransmission
Lamotrigine	Blocks 5-hydroxytriptamine 3 receptors, potentiates dopamine
Tetraiodothyronine	Potentiates norepinephrine neurotransmission
Pindolol	Increases serotonergic tone