Potential antidepressant effect of amantadine: a review of preclinical studies and clinical trials

Raupp-Barcaro, I. F. and Vital, M. A. and Galduróz, J. C. and Andreatini, R.

Braz J Psychiatry (2018) 40: 449–458

DOI: 10.1590/1516-4446-2017-2393

Abstract

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.

Citation

Raupp-Barcaro, I. F., Vital, M. A., Galduróz, J. C., & Andreatini, R. (2018). Potential antidepressant effect of amantadine: a review of preclinical studies and clinical trials. Braz J Psychiatry, 40(4), 449–458. https://doi.org/10.1590/1516-4446-2017-2393 Animals, Disease Models, Animal, Humans, Drug Evaluation, Preclinical, Clinical Trials as Topic, Amantadine/*therapeutic use, Antidepressive Agents/*therapeutic use, Biogenic Monoamines, Depressive Disorder/*drug therapy

Keywords

• Animals
• Disease Models
• Animal
• Humans
• Drug Evaluation
• Preclinical
• Clinical Trials as Topic
• Amantadine/*therapeutic use
• Antidepressive Agents/*therapeutic use
• Biogenic Monoamines
• Depressive Disorder/*drug therapy