Which nutritional therapies are safe and effective for depression?

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Clinical Inquiries

Which nutritional therapies are safe and effective for depression?

J Fam Pract. 2011 February;60(2):99-100c

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References

1. Linde K, Bemer MM, Kriston L. St. John’s wort for major depression. Cochrane Database Syst Rev. 2008;(4):CD000448.-

2. Sarris J. Herbal medicines in the treatment of psychiatric disorders: a systematic review. Phytother Res. 2007;21:703-716.

3. Akhondzadeh Basti A, Moshiri E, Noorbala AA, et al. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients. Prog Neuropsychopharmacol Biol Psychiatry. 2006;31:439-442.

4. Akhondzadeh S, Kashani L, Fotouhi A, et al. Comparison of Lavandula angustifolia Mill. tincture and imipramine in the treatment of mild to moderate depression. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:123-127.

5. Taylor MJ, Carney S, Geddes J, et al. Folate for depressive disorders. Cochrane Database Syst Rev. 2003;(2):CD003390.-

6. Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepres-sant. Acta Neurol Scand Suppl. 1994;154:7-14.

7. Williams AL, Girard C, Jui D, et al. S-adenosylmethionine (SAMe) as treatment for depression. Clin Invest Med. 2005;28:132-139.

8. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxy-tryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198.-

9. Taylor MJ, Wilder H, Bhagwager Z, et al. Inositol for depressive disorders. Cochrane Database Syst Rev. 2004;(2):CD004049.-

10. Williams AL, Katz D, Ali A, et al. Do essential fatty acids have a role in the treatment of depression? J Affect Disord. 2006;93:117-123.

11. Appleton KM, Hayward RC, Gunnell D, et al. Effects of n-3 longchain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr. 2006;84:1308-1316.

12. Akhondzadeh S, Fallah-Pour H, Afkham K, et al. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression. BMC Complement Altern Med. 2004;4:12.-

13. Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, et al. Crocus sativus L. in the treatment of mild to moderate depression. Phytother Res. 2005;19:148-151.

14. Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, et al. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression. J Ethnopharmacol. 2005;97:281-284.

15. Moshiri E, Basti AA, Noorbala AA, et al. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression. Phytomedicine. 2006;13:607-611.

16. Sayyah M, Sahhah M, Kamalinejad M. A preliminary randomized double blind clinical trial on the efficacy of aqueous extract of Echium amoenum in the treatment of mild to moderate major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:166-169.

17. Schulz V Safety of St. John’s wort extract compared to synthetic antidepressants. Phytomedicine. 2006;13:199-204.

18. Lee S, Gura KM, Kim S, et al. Current clinical applications of ome-ga-6 and omega-3 fatty acids. Nutr Clin Pract. 2006;21:323-341.

19. Bauer M, Bschor T, Pfennig A, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders in primary care. World J Biol Psychiatry. 2007;8:67-104.

St. John’s wort does have pharmacokinetic interactions and should not be taken concurrently with other antidepressants, immunosuppressants, anti-HIV drugs, cou-marin-type anticoagulants, or certain antineoplastic agents.¹⁷

Reviews of meta-analyses, case reports, population studies, RCTs, and other literature have reported virtually no adverse effects for PUFAs; ¹⁸ trials investigating saffron, lavender, borage, dan zhi xiao yao, folate, SAMe, and inositol also reported no safety concerns. However, the size and duration of these studies limit their ability to detect significant problems.^2,5,6,9 As previously noted, concerns exist regarding an association between tryptophan and eosinophilia-myalgia syndrome.⁸

Recommendations

The World Federation of Societies of Biological Psychiatry doesn’t recommend St. John’s wort for moderate to severe depression, but suggests it can be considered for treating mild to moderate depressive episodes provided the prescriber considers potential pharmacokinetic interactions with other medications and understands possible variations in purity and potency of extracts.¹⁹ The Federation also states that St. John’s wort is an alternative for patients reluctant to take traditional antidepressants.

TABLE W1
What the studies say about nutritional therapies for depression

Supplement	Study type	Number of subjects	Comparison group	Outcome measure	Results	Conclusion	SOR
Borage (Echium amoenum)	1 small RCT	35^2,16	Placebo	HAM-D	Improved HAM-D scores significantly at week 4 (borage 18. 3±3. 9 vs placebo 21. 9±3. 9; t=2. 51; P=. 02); no significant difference at Week 6^2,16	Superior to placebo in reducing symptoms of depression	B
Dan zhi xiao yao	1 small RCT	63²	Maprotiline	HAM-D, SDS, SAS, scale for traditional Chinese medicine syndrome and symptom differentiation	87% depression reduction (dan zhi xiao yao) vs 84% depression reduction (maprotiline)	As effective as maprotiline in treating depression	B
Folate	Cochrane review of 3 RCTs	247⁵	Studies 1 and 2: folate vs folate + other treatment (Study 1: low folate levels; Study 2: normal folate levels) Study 3: folate vs trazodone (normal folate levels)	HAM-D	Superior to placebo (NNT=5, defined as 50% reduction in HAM-D); comparable to trazodone (RR=0. 97; 95% CI, 0. 14-2. 01)⁷	May have role as supplement to other treatments for depression Efficacy unclear in patients with normal folate levels	A
Inositol	Cochrane review of 4 RCTs	141⁹	Studies 1-3: placebo plus conventional antidepressants Study 4: placebo only	HAM-D, MADRS	Pooled estimate of effect of all 3 studies (SMD= -0. 08; 95% CI, -0. 45 to 0. 30)	No clear evidence of therapeutic benefit	A
Lavender (Lavandula angustifolia)	1 small RCT	45⁴	Imipramine	HAM-D	Imipramine plus lavender showed significant effect compared with imipramine alone (f=26. 87; Df=3. 01; P<. 0001)	Synergistic effect suggested when used with imipramine	B
n-3 long-chain polyunsaturated fatty acids	Systematic review including 3 RCTs; ¹⁰ meta-analysis of 12 RCTs¹¹	102¹⁰ 1032¹¹	Various comparison groups included	Serum SFAs, MUFAs, PUFAs; RBC membrane levels n-3 PUFAs² HAM-D, BDI³	Systematic review:¹⁰ Study 1: n=30; ES=3. 61 Study 2: n=24; ES=1. 2 Study 3: n=48; ES=2. 43 Meta-analysis:¹¹ Pooled ES=0. 13; 95% CI, 0. 01-0. 25	Significantly higher RBC membrane levels of n-3 PUFAs in nondepressed vs depressed patients¹⁰ No significant effect for supplementation¹¹ Larger trials with adequate power needed²,³	A
S-adenosyl-methionine (SAMe)	Meta-analysis of 13 RCTs,⁶ systematic review including 2 RCTs⁷	399⁶ 78⁷	Placebo and conventional antidepressants	HAM-D	NNT=2. 5 for HAM-D decrease of >25%; ⁶ NNT=6. 25 for HAM-D decrease of >50%⁶	May have role in treatment of major depression Further trials are needed to address unanswered questions about absorption, mechanism of action, and bioavailability⁷	A
Saffron (Crocus sativus)	Systematic review of 4 small RCTs, 1 later RCT	30¹² 40¹³ 40¹⁴ 40¹⁵ 40³	Imipramine¹² Placebo^13,¹⁵ Fluoxetine^5,14	HAM-D	Systematic review: Study 1: imipramine and saffron equally efficacious (f=2. 91; P=. 09)¹² Study 2: Improved HAM-D scores: -12. 20±4. 67 (saffron) vs -5. 10±4. 71 (placebo) (P<. 0001)¹³ Study 3: Improved HAM-D scores: saffron petal -12. 00±4. 10; fluoxetine -13. 50±4. 91; difference between 2 treatments not significant (P=. 27)¹⁴ Study 4: Improved HAM-D scores: -14. 01±5. 53 (saffron petal) vs -5. 05±4. 63 (placebo) (P<. 0001)¹⁵ Study 5:⁵ NNT=10	Efficacy of extract and petal suggested to treat mild to moderate depression Large-scale trials are warranted	B
St. John’s wort (Hypericum perforatum L. )	Cochrane review of 29 RCTs	5489¹	SSRIs, tri/tetracyclic antidepressants, placebo	Responder rate ratio	St. John’s wort vs placebo: 9 larger trials: RR=1. 28; 95% CI, 1. 10-1. 49¹ 9 smaller trials: RR=1. 87; 95% CI, 1. 22-2. 87¹ St. John’s wort vs SSRIs: 12 trials: RR=1. 00; 95% CI, 0. 90-1. 11¹ St. John’s wort vs tricyclics: 5 trials: RR=1. 02; 95% CI, 0. 90-1. 15¹	Effective for treating mild to moderate depression	A
Tryptophan and 5-hydroxy-tryptophan (5-HTP)	Cochrane review of 2 RCTs	64⁸	Placebo	HAM-D	NNT=2. 78 vs placebo (OR=4. 1; 95% CI, 1. 28-13. 15	Superior to placebo Insufficient evidence regarding safety	A
BDI, Beck Depression Inventory; CI, confidence interval; DF, degrees of freedom; ES, effect size; F, F statistic; HAM-D, Hamilton Depression Rating Scale; MADRS, Mont-gomery-Asberg Depression Rating Scale; MUFAs, monounsaturated fatty acids; n-3 PUFAs, n-3 long-chain polyunsaturated fatty acids; NNT, number needed to treat; OR, odds ratio; PUFAs, polyunsaturated fatty acids; RBC, red blood cell; RCT, randomized controlled trial; RR, relative risk; SAS, self-rating anxiety scale; SDS, self-rating depression scale; SFAs, saturated fatty acids; SMD, standard weighted mean difference; SOR, strength of recommendation; SSRI, selective serotonin reuptake inhibitor.

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