# Prophylactic effect of omega-3 polyunsaturated fatty acids monotherapy in preventing recurrent major depressive disorder: A randomized controlled trial

**Authors:** Ikbal Andrian Malau, Cheng-Ho Chang, Wei-Jen Chen, Wen-Chun Liu, Halliru Zailani, Hsien-Feng Liao, Jane Pei-Chen Chang, Wei-Che Chiu, Kuan-Pin Su

PMC · DOI: 10.37796/2211-8039.1667 · BioMedicine · 2025-12-01

## TL;DR

This study found that omega-3 fatty acids as a standalone treatment may help prevent the recurrence of major depressive disorder.

## Contribution

The study is the first to show the prophylactic effect of omega-3 monotherapy in preventing MDD recurrence.

## Key findings

- Omega-3 monotherapy reduced MDD recurrence compared to placebo at 6 months.
- Kaplan-Meier analysis confirmed omega-3's superiority in preventing MDD recurrence.
- EPA levels were significantly higher in the omega-3 group, but not DHA.

## Abstract

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have demonstrated efficacy as adjunctive treatment for MDD. In fact, fewer studies assessed the prophylactic properties of n-3 PUFAs as monotherapy on the recurrence of MDD.

This study aimed to assess the prophylactic effect of n-3 PUFAs monotherapy against recurrent MDD.

We conducted a 6-month randomized controlled trial to assess the prophylactic effect of n-3 in preventing recurrent MDD. We assigned 60 remitted MDD patients to the n-3 group (n = 30) and placebo (n = 30). Furthermore, we assessed the difference in depression severity and MDD recurrence based on the 21-item Hamilton Rating Scale for Depression (HRSD) at months 1, 2, 3, 4, and 6 between groups. The recurrent event of MDD was defined as an HRSD score >20. Furthermore, biochemical parameters in plasma were assessed as the secondary outcomes.

There was no significant difference in the HRSD score between the n-3 group and placebo each month ( p-value >0.05). However, our findings have implicated that omega-3 monotherapy for MDD contributed to a lower recurrence rate compared to the placebo group at month 6 ( p-value = 0.035). Omega-3 supplementation was superior to placebo to preventing recurrent MDD analyzed using Kaplan–Meier survival analysis over a 6-month study period ( p-value = 0.041). In comparison, the eicosapentaenoic acid (EPA) plasma level of the n-3 group at the end point of study was significantly higher than the placebo ( p-value = 0.023), but not for docosahexaenoic acid (DHA) ( p-value = 0.119).

Our study concluded that n-3 PUFAs monotherapy demonstrated a prophylactic effect on the recurrence of MDD.

## Linked entities

- **Chemicals:** eicosapentaenoic acid (PubChem CID 5282847), docosahexaenoic acid (PubChem CID 445580)
- **Diseases:** major depressive disorder (MONDO:0002009)

## Full-text entities

- **Diseases:** Depression (MESH:D003866), MDD (MESH:D003865)
- **Chemicals:** EPA (MESH:D015118), Omega-3 (MESH:D015525), DHA (MESH:D004281)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12788876/full.md

## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12788876/full.md

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Source: https://tomesphere.com/paper/PMC12788876