Natural Remedies for Depression
Primary Recommendation
For adults with major depressive disorder, omega-3 fatty acids (EPA ≥1-2g daily with EPA:DHA ratio >2:1) should be used as adjunctive therapy to conventional antidepressants, not as monotherapy. 1, 2
Evidence-Based Natural Treatments
Tier 1: Strongest Evidence (Grade A)
Omega-3 Fatty Acids
- Use EPA ≥1-2g daily with EPA:DHA ratio >2:1 as add-on to antidepressants 1, 2
- Effect sizes range from 0.23-0.56, comparable to conventional antidepressants (0.30-0.47) 1
- Meta-analyses demonstrate clear benefit for adjunctive use but NOT for monotherapy 1
- Particularly beneficial in patients with elevated inflammatory markers or comorbid obesity 1, 2
- Safe for perinatal depression with no adverse fetal effects 2, 3
- Start at lower doses and titrate up over 2-4 weeks 1
S-Adenosyl-L-Methionine (SAMe)
- Dose: 1-2g daily, starting at 400-800mg/day and titrating up over 2 weeks 4
- Recognized by the American College of Physicians as effective CAM treatment 4
- Comparable efficacy to tricyclic antidepressants 4
- Mean reduction of 3.90 points on depression scales when added to SSRIs (95% CI -6.93 to -0.87; P = 0.01) 4
- Critical caveat: Do NOT combine with other serotonergic agents without careful monitoring due to serotonin syndrome risk 4
- Quality varies significantly between products; prescription formulations preferred 4
St. John's Wort
- Dose: 300-1800mg daily of standardized extract 2
- Grade B evidence for mild-to-moderate depression 2, 5
- Major caveat: Significant drug interactions with many medications including oral contraceptives, anticoagulants, and immunosuppressants 2
- Should only be considered when drug interactions can be avoided 2
Tier 2: Moderate Evidence (Grade B)
Saffron (Crocus sativus)
Rhodiola rosea
- Evidence supports use in mood disorders 3, 6
- May be particularly useful for stress-related depression 3
L-Methylfolate
- Moderate evidence as adjunctive therapy 5
- Consider in patients with folate deficiency or MTHFR polymorphisms 5
Special Populations
Perinatal Depression
- Omega-3 fatty acids (EPA 380-400mg + DHA 180-200mg) recommended by American College of Obstetricians and Gynecologists 2
- No adverse fetal effects documented 3
Childhood Depression
- Omega-3 fatty acids (EPA 380-400mg + DHA 180-200mg) recommended by American Academy of Pediatrics 2
Patients with Inflammation or Obesity
- Omega-3 fatty acids show enhanced efficacy in this subgroup 1, 2
- Effect sizes increase from -0.09 to -1.11 when inflammatory markers are elevated 1
Critical Implementation Points
Diagnostic Requirements
- Accurate DSM-defined major depressive disorder diagnosis required 1
- Measurement-based assessments should guide treatment decisions 1
Treatment Strategy
- Natural remedies should be adjunctive to standard care, NOT replacements for conventional treatment in moderate-to-severe depression 1, 2
- Acute treatment duration: 6-12 weeks minimum 4
- Titrate to maximum tolerated dose within 4-6 weeks if inadequate response 4
Common Pitfalls to Avoid
- Using omega-3s as monotherapy (insufficient evidence) 1, 2
- Combining SAMe with SSRIs/SNRIs without monitoring for serotonin syndrome 4
- Ignoring drug interactions with St. John's Wort 2
- Using low-quality supplements with variable content 4
- Expecting dramatic effects (effect sizes are small-to-moderate, similar to conventional antidepressants) 1
Quality Considerations
- Supplement quality varies significantly; prescription products preferred when available 4
- Evaluate product quality in non-responders before concluding treatment failure 4
Treatments with Insufficient Evidence
Vitamin D
- Despite widespread use, does NOT have evidence for treating depression 5
- Results equivocal in mood disorder trials 3
Vitamin B Complex
- Results equivocal in depression despite benefits in physical illness 3