The Efficacy of Saffron in the Treatment of Mild to Moderate Depression: A Meta-analysis

Abstract

Herbal products, especially extracts, have been widely used as first-line treatments for mild to moderate depression. Recently, several randomized, controlled clinical trials have been conducted to evaluate the efficacy of another plant, saffron (), in mild to moderate depression. We have carried out a literature review of currently available published randomized, controlled clinical trials to give an up-to-date evaluation of the efficacy of saffron in mild to moderate depression, compared to placebo or routinely used antidepressants. The meta-analysis is reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines using the PICO (patients, intervention, comparison, outcome) format and was conducted using the statistical programs Comprehensive Meta-analysis and RevMan. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for relevant studies. Only placebo or active controlled, randomized clinical studies involving patients suffering from mild to moderate depression and using pharmacological doses of saffron were included. Hedges' g was used to calculate effect sizes. Risk of bias was assessed using the Cochrane Collaboration tool, and heterogeneity was tested by both performing the Cochran's test and calculating Higgins' indicator. Eleven randomized trials were included in the qualitative analysis, and nine were pooled for statistical analysis. According to the present meta-analysis, saffron has a significant effect on the severity of depression. Available data from randomized, controlled clinical trials support that saffron is significantly more effective than placebo (g = 0.891; 95% CI: 0.369 - 1.412, p = 0.001), and non-inferior to tested antidepressant drugs (g = - 0.246; 95% CI: - 0.495 - 0.004, p = 0.053).

Antianhedonic and Antidepressant Effects of Affron®, a Standardized Saffron (Crocus Sativus L.) Extract

“…Additionally, repeated oral administration reduced anhedonic behavior, assessed in the sucrose preference test—an effect that was not observed under ip administration. Overall, these results are congruent with reports describing the beneficial effects of saffron extract consumption in patients suffering from anxiety or depression [ 41 , 42 ].…”

“…Additionally, there is also growing evidence supporting the antidepressant and anxiolytic effects of saffron in humans suffering from depression and anxiety. Thus, saffron extracts can relieve the severity of symptoms of depression and the effect of saffron extracts resemble those of tricyclic (TCA), Selective Serotonin Reuptake Inhibitors (SSRI) and Selective Noradrenaline Reuptake Inhibitors antidepressants in depressed patients [ 41 , 42 ]. Saffron extracts, when administered in combination with pharmacological antidepressants, were also shown to improve some scores related to depression, even in subjects who had been using the antidepressants with no improvement [ 43 ].…”

Saffron (Crocus sativus L.) in Ocular Diseases: A Narrative Review of the Existing Evidence from Clinical Studies

“…Finally, an increasing body of RCTs indicate that saffron may improve the effects and symptoms of depression [47,66,67,68]. As depression may often affect patients with chronic diseases (e.g., with AMD, diabetic retinopathy, or glaucoma) [35,69,70] in whom it may also reduce treatment adherence (e.g., potentially lower adherence to glaucoma treatment, and, hence increase the glaucoma progression risk) [70], it seems plausible to hypothesize that some of the benefits of oral saffron supplementation in patients with ocular diseases may also have a component relating to the potential anti-depressive effects of saffron and/or its constituents [35].…”

Bioaccessibility and Pharmacokinetics of a Commercial Saffron (Crocus sativus L.) Extract

“…Nowadays, the clinical evidences of saffron extracts have been accumulated and has been postulated as a complementary therapy in several medical conditions. In particular, to delay the occurrence of the symptoms and effects of degenerative ocular diseases [8] and to prevent and treat mood disorders and mild-to-severe depression without side-effects, even in people with unremitted depression treated with antidepressant medication [12][13][14][15][16]. In depression, different mechanisms of actions have been proposed to explain the functional properties of saffron such as reuptake inhibitors of monoamines, N-methyl-Daspartate receptor (NMDA) antagonism, and gamma-aminobutyric acid (GABA) agonism [17,18].…”