Clinical Inquiries

Which nutritional therapies are safe and effective for depression?

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ST. JOHN’S WORT is effective for short-term relief of mild to moderate depression (strength of recommendation [SOR]: A; 1 systematic review). Its safety profile is superior to older antidepressants; data comparing it with newer antidepressants (such as selective serotonin reuptake inhibitors) are limited (SOR: A, 1 systematic review).

A small but statistically significant clinical benefit has been demonstrated for saffron, lavender, borage, dan zhi xiao yao (SOR: B, 1 systematic review and 3 randomized controlled trials), folate (SOR: A, 1 systematic review), and S-adenosylmethionine (SAMe) (SOR: A, 1 meta-analysis and 1 systematic review). Most trials of these preparations were short and small, limiting the ability to detect adverse effects.

Tryptophan (SOR: A, 1 systematic review) and 5-hydroxytryptophan (5-HTP) (SOR: A, 1 systematic review) have demonstrated superiority over placebo in alleviating symptoms of depression, but concerns exist about their safety.

N-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) and omega-3 fatty acids don’t appear effective in treating major depressive disorder (SOR: A, 1 systematic review.)

Evidence summary

TABLE W1 summarizes study results and recommendations for nutritional therapies for depression.1-16

St. John’s wort works as well as standard antidepressants
A recent Cochrane review suggested that St. John’s wort is more effective than placebo in patients with mild to moderate depression and as effective as standard antidepressants.1

Other supplements also have benefits
A systematic review of 4 small randomized controlled trials (RCTs) suggested that saffron (30 mg) is superior to placebo in treating short-term depression (6 weeks). Treatment and outcomes were equivalent to fluoxetine and imipramine.2 A later RCT yielded results consistent with the systematic review.3

Combined lavender tincture (60 drops per day) and imipramine were more effective than imipramine alone in 1 small RCT.4

Borage, a traditional Persian medicine, was superior to placebo in reducing depressive symptoms in 1 small RCT.2

Dan zhi xiao yao, a traditional Chinese medicine, was as effective as the tricyclic anti-depressant maprotiline in 1 small RCT.2

Three RCTs suggested that folate may be used to supplement conventional treatments for depression, but it isn’t clear whether this would help patients with normal folate levels.5

A meta-analysis of 13 controlled clinical trials and a later systematic review of 11 articles including 2 RCTs concluded that SAMe is more effective than placebo and as efficacious as tricyclic antidepressants in treating major depression in adults. However, further trials are needed to answer questions about absorption, mechanism of action, and bioavailability.6,7

Tryptophan’s benefit comes with risk
In a Cochrane review of 2 RCTs, tryptophan and 5-HTP were superior to placebo in alleviating symptoms of depression. However, some published case reports have linked tryptophan use to potentially fatal eosinophilia-myalgia syndrome.8

No clear evidence for inositol or n-3 PUFAs
A Cochrane review of 4 small double-blind RCTs investigating inositol as a nutritional supplement in depression treatment failed to find clear evidence of therapeutic benefit.9

Three RCTs demonstrated significantly higher red blood cell membrane levels of n-3 PUFAs in nondepressed patients compared with depressed patients.10 However, a systematic review of 12 RCTs failed to demonstrate any benefit of n-3 PUFA supplementation over placebo in treating depressed mood.11 The authors concluded that larger trials are needed to demonstrate efficacy because of marked heterogeneity among the RCTs.

Safety issues. A recent Cochrane review found fewer adverse effects for St. John’s wort than tricyclic antidepressants.1 The most common adverse reactions were sensitivity to light, skin symptoms, gastrointestinal symptoms, and agitation. Data comparing St. John’s wort with newer antidepressants are lacking.

Evidence-based answers from the Family Physicians Inquiries Network

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