Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors

Abstract

There is evidence of derangement of oxidant and antioxidant defense systems in depression. The present study examined the effects of fluoxetine and citalopram, standard selective serotonin re-uptake inhibitors, on lipid peroxidation, superoxide dismutase (SOD) activity and ascorbic acid concentrations. For this, a prospective open-labeled, randomized design was utilized. Patients with major depression (n = 62) were compared with age- and sex-matched healthy volunteers (n = 40). There was a significant increase in serum SOD, serum MDA and decrease in plasma ascorbic acid levels in patients of major depression as compared to control subjects. The trend reversed significantly after treatment with fluoxetine and citalopram. Results indicate a greater reduction in oxidative stress with citalopram than fluoxetine. The Hamilton Rating Scale for Depression (HRSD) score also improved with fluoxetine and citalopram treatment. These findings indicate that major depression is associated with increased levels of serum SOD, serum MDA and decreased levels of plasma ascorbic acid. Treatment with fluoxetine and citalopram reversed these biochemical parameters. This study can be used as a predictor of drug response by fluoxetine and citalopram in major depression.

Clinical correlation of alteration of endogenous antioxidant-uric acid level in major depressive disorder

“…Although, no literature is available regarding the direct effect of these SSRIs on serum uric acid levels, the rise could be due to decreased consumption of uric acid required for scavenging free radicals. SSRIs are known to decrease lipid peroxidation in major depression (2). Similarly, they also increase plasma ascorbic acid levels and up regulate SOD1 gene in depressive subjects and produce neuroprotective effects against free radical induced damage in major depression (20).…”

“…Abnormal levels of antioxidant enzymes and lipid peroxidation in major depression further substantiates the role of free radical in major depression (2,3). Neurons are especially vulnerable to free radical attacks.…”

Type 1 diabetes mellitus and major depressive disorder: evidence for a biological link

“…In rodent studies, experimental models of depression (chronic mild stress model) demonstrate that glucocorticoid hypersecretion causes oxidative stress, both by increasing lipid peroxidation in the brain cortex and medulla and by decreasing glutathione levels in the medulla [60]; this finding requires confirmation in humans. Furthermore, antidepressant treatment in humans and animals has been shown to alleviate oxidative stress [54,60]. The mechanism by which oxidative stress may cause depression is not known; however, one potential area of investigation is oxidative stress-induced mitochondrial dysfunction, which is characteristic of depression [61] and may induce altered neuronal activity or death [61].…”

“…Clinical studies have found depression to be characterised by elevated markers of oxidative stress, such as serum lipid peroxidation [54], and diminished antioxidant levels, such as serum vitamin E [55] and plasma vitamin C [54]. Correlations between increasing depression severity and the magnitude of superoxide dismutase (SOD) activity have also been reported, such that patients with severe MDD have been found to have greater SOD activity than those experiencing mild (p<0.001) or moderate (p <0.001) disease [56].…”

Mitochondria and the central nervous system: searching for a pathophysiological basis of psychiatric disorders

“…167,168 Some psychiatric medications already exhibit antioxidant activity. [169][170][171][172] To protect mitochondria and the cell against such damaging effects, several measures can be applied. One is to increase the intracellular glutathione content.…”