Omega-3 Polyunsaturated Fatty Acids Supplementation Alleviate Anxiety Rather Than Depressive Symptoms Among First-Diagnosed, Drug-Naïve Major Depressive Disorder Patients: A Randomized Clinical Trial

Rong Yang, Lu Wang, Kun Jin, Song Cao, Chujun Wu, Jimin Guo, Jindong Chen, Hui Tang, Mimi Tang, Rong Yang, Lu Wang, Kun Jin, Song Cao, Chujun Wu, Jimin Guo, Jindong Chen, Hui Tang, Mimi Tang

Abstract

Background: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) augmentation of antidepressants has shown great potential in the prevention and treatment of major depressive disorders (MDD).

Objective: To investigate the effect of n-3 PUFAs plus venlafaxine in patients with first-diagnosed, drug-naïve depression.

Method: A total of 72 outpatients with first-diagnosed depression were recruited. The daily dose of 2.4 g/day n-3 PUFAs or placebo plus venlafaxine was used for over 12 weeks. The outcomes were assessed by the Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), Beck depression inventory (BDI), and Self-rating anxiety scale (SAS).

Results: Both groups exhibited improvement on clinical characteristics at week 4 and week 12 compared with baseline. The rate of responders for anxiety in n-3 PUFAs group (44.44%) was significantly higher than that in placebo group (21.21%) at week 4 (χ2 = 4.182, p = 0.041), while week 12 did not show a difference (χ2 = 0.900, p = 0.343). The rate of responders for depression at both week 4 (χ2 = 0.261, p = 0.609) and week 12 (χ2 = 1.443, p = 0.230) showed no significant difference between two groups. Further analysis found that Childhood Trauma Questionnaire (CTQ) had positive correlation with HAMA (r = 0.301, p = 0.012), SAS (r = 0.246, p = 0.015), HAMD (r = 0.252, p = 0.038) and BDI (r = 0.233, p = 0.022) with Pearson correlation analysis. Social Support Rating Scale (SSRS) had negative correlation with SAS (r = -0.244, p = 0.015) and BDI (r = -0.365, p = 0.000).

Conclusion: This trial found that n-3 PUFAs supplementation in favor of venlafaxine alleviated the anxiety symptoms rather than depressive symptoms at the early stage of treatment (4 weeks) for first-diagnosed, drug-naïve depressed patients. However, the advantage disappeared in long-term treatment. Furthermore, childhood abuse and social support are closely related to the clinical and biological characteristics of depression. Both childhood trauma and lack of social support might be predictors of poor prognosis in depression.

Clinical trial registration: [clinicaltrials.gov], identifier [NCT03295708].

Keywords: antidepressant; childhood abuse; major depressive disorders; nutrient intervention; omega-3 polyunsaturated fatty acids; social support.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Yang, Wang, Jin, Cao, Wu, Guo, Chen, Tang and Tang.

Figures

FIGURE 1
FIGURE 1
Flow of participants in the Trial. Non-compliance includes being unwilling to take medicine and taking medicine irregularly.
FIGURE 2
FIGURE 2
The scores on depression and anxiety questionnaires in n-3 PUFAs and placebo group. *significantly different compared with baseline, # significantly different compared with week 4, *p < 0.05, **p < 0.01, # p < 0.05, ## p < 0.01. n-3 PUFAs, Omega-3 polyunsaturated fatty acids; HAMD, Hamilton Depression Scale; BDI, Beck Depression Inventory; HAMA, Hamilton anxiety scale; SAS, Self-rating Anxiety Scale. For n-3 PUFAs group, n = 36, after week 4, n = 36, and after week 12, n = 21. For the placebo group, n = 36, after week 4, n = 33, and after week 12, n = 27.
FIGURE 3
FIGURE 3
The ROC curve analysis of CTQ, SSRS, and combined effect for the prognosis of patients. ROC, receiver operating curve; AUC, area under the curve; SD, Standard deviation; CI, confidence interval; SSRS, Social Support Rate Scale; CTQ, Childhood Trauma Questionnaire; HAMA, Hamilton anxiety scale; HAMD, Hamilton Depression Scale; n-3 PUFAs, Omega-3 polyunsaturated fatty acids. The N-3 and P in images represent n-3 PUFAs and placebo group separately.

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