Leveraging CAM to treat depression and anxiety

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doi:10.12788/jfp.0002

Applied Evidence

Leveraging CAM to treat depression and anxiety

J Fam Pract. 2020 June;69(5):221-227 | 10.12788/jfp.0002

By

Amanda E. Olagunju, DO

Heidi Gaddey, MD

Conventional medications and psychotherapy are still first-line treatments, but certain complementary and alternative strategies have value as adjunctive measures.

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PRACTICE RECOMMENDATIONS

› Consider standardized preparations of St. John’s wort for the treatment of mild to moderate depression in certain patients. A

› Encourage patients with depression or anxiety to engage in exercise and meditation to help with symptom management. A

› Consider methylfolate and S-adenosyl methionine as adjunctive treatments to improve depression. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

References

1. National Center for Health Statistics, Centers for Disease Control and Prevention. FastStats: Depression. Last reviewed October 7, 2015. www.cdc.gov/nchs/fastats/depression.htm. Accessed May 26, 2020.

2. National Institute of Mental Health. Mental health information—statistics: any anxiety disorder. Last updated November 2017. www.nimh.nih.gov/health/statistics/any-anxiety-disorder.shtml. Accessed May 26, 2020.

3. Hedegaard H, Curtin SC, Warner M. Increase in suicide mortality in the United States, 1999–2018. NCHS Data Brief, no 362. Hyattsville, MD: National Center for Health Statistics; 2020.

4. National Center for Complementary and Integrative Health. Complementary, alternative, or integrative health: what’s in a name? Last updated July 2018. www.nccih.nih.gov/health/complementary-alternative-or-integrative-health-whats-in-a-name. Accessed May 26, 2020.

5. Bennett DA Jr, Phun L, Polk JF, et al. Neuropharmacology of St. John’s wort (Hypericum). Ann Pharmacother. 1998;32:1201-1208.

6. Müller WE, Singer A, Wonnemann M, et al. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry. 1998;31(suppl 1):16-21.

7. Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database Syst Rev. 2008;CD000448.

8. Ng QX, Venkatanarayanan N, Ho CY. Clinical use of Hypericum perforatum (St John’s wort) in depression: a meta-analysis. J Affect Disord. 2017;210:211-221.

9. Kobak KA, Taylor LV, Bystritsky A, et al. St John’s wort versus placebo in obsessive-compulsive disorder: results from a double-blind study. Int Clin Psychopharmacol. 2005;20:299-304.

10. Kobak KA, Taylor LV, Warner G, et al. St. John’s wort versus placebo in social phobia: results from a placebo-controlled pilot study. J Clin Psychopharmacol. 2005;25:51-58.

11. Product reviews: St. John’s wort supplements review. ConsumerLab.com. September 23, 2016. www.consumerlab.com/reviews/St_Johns_Wort/stjohnswort/. Accessed May 26, 2020.

12. Simhan S. Serotonin syndrome. In: Abd-Elsayed A. (ed) Pain: A Review Guide. New York, NY: Springer; 2019.

13. Chrubasik-Hausmann S, Vlachojannis J, McLachlan A. Understanding drug interactions with St. John’s wort (Hypericum perforatum L.): impact of hyperforin content. J Pharm Pharmacol. 2019;71:129-138.

14. Knüppel L, Linde K. Adverse effects of St. John’s wort: a systematic review. J Clin Psychiatry. 2004;65:1470-1479.

15. Pan LA, Martin P, Zimmer T, et al. Neurometabolic disorders: potentially treatable abnormalities in patients with treatment-refractory depression and suicidal behavior. Am J Psychiatry. 2017;174:42-50.

16. Kandler C, Lam S. Methylenetetrahydrofolate reductase screening in treatment-resistant depression. Fed Pract. 2019;36:207-208.

17. Papakostas GI, Shelton RC, Zajecka JM, et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry. 2012;169:1267-1274.

18. Zajecka J, Fava M, Shelton R, et al. Long-term efficacy, safety, and tolerability of L-methylfolate calcium 15 mg as adjunctive therapy with selective serotonin reuptake inhibitors: a 12-month, open-label study following a placebo-controlled acute study. J Clin Psychiatry. 2016;77:654-660.

19. Kakar MS, Jehangir S, Mustafa M, et al. Therapeutic efficacy of combination therapy of L-methylfolate and escitalopram in depression. Pakistan Armed Forces Med J. 2017;67:976-981.

20. Papakostas GI, Mischoulon D, Shyu I, et al. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry. 2010;167:942-948.

21. Sakurai H, Carpenter L, TyrkaA, et al. Dose increase of S-adenosyl-methionine and escitalopram in a randomized clinical trial for major depressive disorder. J Affect Disord. 2020;262:118-125.

22. Sarris J, Murphy J, Mischoulon D, et al. Adjunctive nutraceuticals for depression: a systematic review and meta-analyses. Am J Psychiatry. 2016;173:575-587.

23. Anglin RE, Samaan Z, Walter SD, et al. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013;202:100-107.

24. Eid A, Khoja S, AlGhamdi S, et al. Vitamin D supplementation ameliorates severity of generalized anxiety disorder (GAD). Metab Brain Dis. 2019;34:1781-1786.

25. Li G, Mbuagbaw L, Samaan Z, et al. Efficacy of vitamin D supplementation in depression in adults: a systematic review. J Clin Endocrinol Metab. 2014;99:757-767.

26. Hennebelle M, Champeil-Potokar G, Lavialle M, et al. Omega-3 polyunsaturated fatty acids and chronic stress-induced modulations of glutamatergic neurotransmission in the hippocampus. Nutr Rev. 2014;72:99-112.

27. Kiecolt-Glaser JK, Belury MA, Andridge R, et al. Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial. Brain Behav Immun. 2011;25:1725-1734.

28. Buydens-Branchey L, Branchey M, Hibbeln JR. Associations between increases in plasma n-3 polyunsaturated fatty acids following supplementation and decreases in anger and anxiety in substance abusers. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:568-575.

29. Lin PY, Mischoulon D, Freeman MP, et al. Are omega-3 fatty acids antidepressants or just mood-improving agents? The effect depends upon diagnosis, supplement preparation, and severity of depression. Mol Psychiatry 2012;17:1161-1163.

30. Hallahan B, Ryan T, Hibbeln JR, et al. Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. Br J Psychiatry. 2016;209:192-201.

31. Rapaport MH, Nierenberg AA, Schettler PJ, et al. Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-concept study. Mol Psychiatry. 2016;21:71-79.

32. National Institutes of Health Office of Dietary Supplements. Omega-3 fatty acids. Updated October 17, 2019. https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional. Accessed May 26, 2020.

33. Wang C, Harris WS, Chung M, et al. n-3 fatty acids from fish or fish-oil supplements, but not alpha-linoleic acid, benefit cardiovascular disease outcomes in primary- and secondary- prevention studies: a systematic review. Am J Clin Nutr. 2006;84:5-17.

34. American Psychiatric Association Practice. Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd Edition. 2010. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed May 26, 2020.

35. Gordon B, McDowell C, Lyons M, et al. The effects of resistance exercise training on anxiety: a meta-analysis and meta-regression analysis of randomized controlled trials. Sports Med. 2017;47:2521-2532.

36. Stubbs B, Vancampfort D, Rosenbaum S, et al. An examination of the anxiolytic effects of exercise for people with anxiety and stress-related disorders: a meta-analysis. Psychiatry Res. 2017;249:102-108.

37. Rethorst CD, Trivedi MH. Evidence-based recommendations for the prescription of exercise for major depressive disorder. J Psychiatr Pract. 2013;19:204-212.

38. US Department of Health and Human Services. Physical Activity Guidelines for Americans. 2nd edition. Washington, DC: US Department of Health and Human Services; 2018.

39. Cooney GM, Dwan K, Greig CA, et al. Exercise for depression. Cochrane Database Syst Rev. 2013;CD004366.

40. Merriam-Webster Dictionary. "Mindfulness." www.merriam-webster.com/dictionary/mindfulness. Accessed May 26, 2020.

41. Goyal M, Singh S, Sibinga EM, et al. Meditation programs for psychological stress and well-being: a systematic review and meta-analysis. JAMA Intern Med. 2014;174:357-368.

42. Sharma A, Barrett MS, Cucchiara AJ, et al. A breathing-based meditation intervention for patients with major depressive disorder following inadequate response to antidepressants: a randomized pilot study. J Clin Psychiatry. 2017;78:e59-e63.

43. Smith CA, Armour M, Soo Lee M, et al. Acupuncture for depression. Cochrane Database Syst Rev. 2018;CD004046.

44. Li M, Xing X, Yao L, et al. Acupuncture for treatment of anxiety, an overview of systematic reviews. Complement Ther Med. 2019;43:247-252.

45. Brennan J. Service animals and emotional support animals. ADA National Network Information Guidance and Training on the Americans with Disabilities Act. Last updated April 2020. adata.org/publication/service-animals-booklet. Accessed May 26, 2020.

46. Clay RA. Is that a pet or therapeutic aid? Monitor on Psychology. 2016;47:38.

47. Brooks HL, Rushton K, Lovell K, et al. The power of support from companion animals for people living with mental health problems: a systematic review and narrative synthesis of the evidence. BMC Psychiatry. 2018;18:31.

48. Kamioka H, Okada S, Tsutani K, et al. Effectiveness of animal-assisted therapy: a systematic review of randomized controlled trials. Complement Ther Med. 2014;22:371-390.

Almost 8% of Americans ages ≥ 12 years have depression and 19.1% of Americans ages ≥ 18 years have experienced an anxiety disorder in the past year.^1,2 Furthermore, suicide, which can result from depression and anxiety, is the 10th leading cause of death in the United States, claiming about 40,000 to 49,000 lives per year since 2012, with increasing yearly rates.³ While multiple conventional medication and therapy treatments are available, patients remain interested in complementary and alternative medicine (CAM) options. According to the National Center for Complementary and Integrative Health, more than 30% of American adults use CAM treatments.⁴

This article provides an overview of the evidence for commonly used CAM treatments for unipolar depression and anxiety in adults. It is designed to serve as a useful resource when patients are interested in looking beyond conventional medications.

St. John’s wort: ‘Yes’ for depression; ‘no’ for anxiety

Hypericum perforatum, more commonly known as St. John’s wort, is a widely used antidepressant, especially in Europe where it is prescribed, rather than offered over the counter as it is here. Its mechanism of action is not completely understood because its various constituents have different neuropharmacologic activities.^5,6

A 2008 Cochrane review evaluated 29 randomized, double-blind studies (N = 5489) that compared St. John’s wort with placebo or standard antidepressants in the treatment of depression.⁷ St. John’s wort was found to be superior to placebo and comparable to standard antidepressants. More recently, a 2017 meta-analysis of 27 studies (N = 3808) had similar findings.⁸ In patients with mild-to-moderate depression, St. John’s wart produced rates of remission that were comparable to those produced by selective serotonin reuptake inhibitors (SSRIs) but with a lower discontinuation rate.

Mood disorders other than depression. Studies do not support a role for St. John’s wort in the treatment of anxiety disorders. There are no trials that assess the efficacy of St. John’s wort for the reduction of symptoms of general anxiety disorder as a primary outcome of treatment. Some small clinical trials have investigated the efficacy of St. John’s wort in obsessive-compulsive disorder and social anxiety disorder. In those studies, St. John’s wort performed no better than placebo.^9,10

A few words of caution. Preparations of St. John’s wort in the United States are not standardized, so St. John’s wort should be used in America with caution. Furthermore, long-term use of St. John’s wort for depression is questionable given that most studies have evaluated only up to 12 weeks of use.⁸

In patients with mildto-moderate depression, St. John’s wort produced rates of remission that were comparable to those produced by SSRIs— with a lower discontinuation rate.

If used, studies indicate that the St. John’s wort extract that should be used is 0.3% hypericin or 5% hyperforin administered in a dosage of 300 to 400 mg tid.^7,8,11 Physicians and patients can use www.consumerlabs.com to find St. John’s wort brands that have met specified quality criteria based on independent laboratory studies. This Web site can also be used to investigate the quality of the brands available for the other supplements discussed in this article.

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