Objective:
Amantadine blocks
N-methyl-D-aspartate (
NMDA) receptors and has dopaminergic and noradrenergic action, a neurochemical profile that suggests its potential as an
antidepressant drug. We conducted a
systematic review of preclinical and clinical studies addressing the effects of
amantadine in
animal models of
depression and in
patients with
depression.
Methods:
PubMed,
Science Direct, and Web of
Science were searched up to September 1, 2017 to identify clinical and preclinical studies. The following search terms were used "
amantadine AND depress*"; "
amantadine AND
mood"; "
amantadine AND
animal models AND antidepres*"; and "
amantadine AND (forced swim,
learned helplessness,
reserpine, chronic mild stress,
anhedonia,
sucrose preference)."
Results:
Amantadine had
antidepressant-like effects in
animal models and appeared to potentiate the
antidepressant effects of other
antidepressants. These preclinical findings have received some support from the results of small open-label clinical trials, suggesting that
amantadine can reduce depressive symptomatology and potentiate the
antidepressant effects of monoaminergic
drugs. In addition to its glutamatergic and
dopaminergic effects, the potential
antidepressant-like effects of
amantadine have been linked to molecular and cellular actions, such as increased expression of
neurotrophic factors (e.g.,
brain-derived neurotrophic factor), activation of σ1 receptors, decreased
corticosterone levels, and decreased inflammatory response to stress.
Conclusion:
Amantadine is an interesting candidate as new
antidepressant drug for the
treatment of
depression.