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. 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

Copyright © 2005, MBL Communications. Adapted with permission from Gotto J, Rapaport MH. Treatment options in treatment-resistant depression. Prim Psychiatry. 2005;12:42–50.46