Leveraging CAM to treat depression and anxiety

,; ,

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

PDF Download

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.

Response to EPA may be greater in patients with depression who have high levels of inflammatory biomarkers, such as interleuken (IL)-1 receptor antagonist (1Ra), IL-6, high-sensitivity C-reactive protein (hs-CRP), leptin, and adiponectin, than in patients with low levels. An 8-week trial randomly assigned patients with unipolar major depression (N = 155) to receive either EPA, DHA, or placebo and found that improvement for the 3 groups was comparable; however, in the subgroup of patients with high levels of inflammatory markers, improvement in depressive symptoms was significantly greater with EPA than with either DHA or placebo.³¹

If screening for vitamin D levels is indicated for another reason and low levels are confirmed, vitamin D replacement may improve anxiety and/ or depression symptoms.

It is unclear whether different sources of n-3 PUFA, such as whole fish vs fish oil vs prescription omega-3 acid ethyl esters (Lovaza), are more or less efficacious in the treatment of anxiety or depression. Furthermore, there is no standard dosing for n-3 PUFA in the treatment of mood disorders. Given that the US Food and Drug Administration recommends no more than 2 g/d of combined EPA and DHA supplementation, we recommend using 2 g/d if one decides to treat depression/anxiety with n-3 PUFA.³²

N-3 PUFA supplementation is fairly benign. There have been previous concerns about n-3 PUFA supplementation increasing patients’ risk for gastrointestinal bleeding, but a 2006 systematic review that included 9 trials (N = 2612) that looked at clinically significant bleeding episodes found that even patients at high risk for bleeding (ie, those taking aspirin or warfarin) had no increased bleeding risk from taking n-3 PUFA supplementation at up to 4 g/d.³³

Don’t underestimate exercise and meditation; consider acupuncture

Exercise. Multiple practice guidelines, including the American Psychiatric Association’s “Practice Guideline for the Treatment of Patients with Major Depressive Disorder,” and meta-analyses have supported the use of exercise to treat unipolar major depression and anxiety.^34-37 However, only about 26% of American men and 19% of American women met the US Department of Health and Human Services’ “Federal Physical Activity Guidelines for Americans” in 2016.³⁸

Exercise alone is a reasonable monotherapy, as long as patients are monitored closely for worsening symptoms. Additionally, exercise as an add-on treatment can be helpful for more severe depression or anxiety.³⁹The best type, duration, and frequency of exercise specifically for the treatment of depression or anxiety has yet to be determined, but physicians may base their exercise recommendations on the “Federal Physical Activity Guidelines for Americans” for general good health (TABLE).³⁸

Continue to: Meditation