Even though there are many drugs for the treatment of gastric ulcers, these 
drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been 
used for several non-psychiatric indications. A lot of antidepressant drugs have 
been shown experimentally to produce antiulcer activity in various ulcer models. 
This study aimed to investigate the antiulcer effects of mirtazapine and to 
determine its relationship with antioxidant mechanisms. The antiulcer activities 
of 15, 30, and 60 mg/kg mirtazapine have been investigated on 
indomethacin-induced ulcers in rats, and the results have been compared with 
that of the control group. Mirtazapine decreased the indomethacin-induced ulcers 
significantly at all doses used. Mirtazapine significantly increased the 
glutathione (GSH) level, which decreased in the control group given only 
indomethacin. All doses of mirtazapine significantly decreased the catalase 
(CAT) level in stomach tissue compared to the control. Additionally, all doses 
of mirtazapine reversed the decrease in the superoxide dismutase (SOD) level in 
the stomach tissue of control rats. And finally, all doses of mirtazapine 
decreased malondialdehyde (MDA) and myeloperoxidase (MPO) levels significantly 
compared to the control. In conclusion, the activation of enzymatic and 
non-enzymatic antioxidant mechanisms and the inhibition of some toxic oxidant 
mechanisms play a role in the antiulcer effect mechanism of mirtazapine. This 
new indication of mirtazapine will make it the first-choice drug in depressive 
patients with gastric ulcers.