Evidence-Based Reviews

Nontraditional therapies for treatment-resistant depression: Part 2

Current Psychiatry. 2021 October;20(10):32-38 | doi: 10.12788/cp.0179

References

1. Pittampalli S, Mekala HM, Upadhyayula, S, et al. Does vitamin D deficiency cause depression? Prim Care Companion CNS Disord. 2018;20(5):17l02263.

2. Parker GB, Brotchie H, Graham RK. Vitamin D and depression. J Affect Disord. 2017;208:56-61.

3. Berridge MJ. Vitamin D and depression: cellular and regulatory mechanisms. Pharmacol Rev. 2017;69(2):80-92.

4. 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.

5. Sarris J, Murphy J, Mischoulon D, et al. Adjunctive nutraceuticals for depression: a systematic review and meta-analyses. Am J Psychiatry 2016;173(6);575-587.

6. Liao Y, Xie B, Zhang H, et al. Efficacy of omega-3 PUFAs in depression: a meta-analysis. Transl Psychiatry. 2019;9(1):190.

7. Mocking RJT, Steijn K, Roos C, et al. Omega-3 fatty acid supplementation for perinatal depression: a meta-analysis. J Clin Psychiatry. 2020;81(5):19r13106.

8. Sharma A, Gerbarg P, Bottiglieri T, et al; Work Group of the American Psychiatric Association Council on Research. S-Adenosylmethionine (SAMe) for neuropsychiatric disorders: a clinician-oriented review of research. J Clin Psychiatry. 2017;78(6):e656-e667.

9. 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.

10. Huang R, Wang K, Hu J. Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2016;8(8):483.

11. Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: a systematic review and meta-analysis of controlled clinical trials. Neurosci Biobehav Rev. 2019;102:13-23.

12. Wallace CJK, Milev RV. The efficacy, safety, and tolerability of probiotics on depression: clinical results from an open-label pilot study. Front Psychiatry. 2021;12(132):618279.

13. Köhler-Forsberg O, N Lyndholm C, Hjorthøj C, et al. Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials. Acta Psychiatr Scand. 2019;139(5):404-419.

14. Jha MK. Anti-inflammatory treatments for major depressive disorder: what’s on the horizon? J Clin Psychiatry. 2019;80(6)18ac12630.

15. Salagre E, Fernandes BS, Dodd S, et al. Statins for the treatment of depression: a meta-analysis of randomized, double-blind, placebo-controlled trials. J Affect Disord. 2016;200:235-242.

16. Dichtel LE, Nyer M, Dording C, et al. Effects of open-label, adjunctive ganaxolone on persistent depression despite adequate antidepressant treatment in postmenopausal women: a pilot study. J Clin Psychiatry. 2020;81(4):19m12887.

17. Deligiannidis KM, Meltzer-Brody S, Gunduz-Bruce H, et al. Effect of zuranolone vs placebo in postpartum depression: a randomized clinical trial. JAMA Psychiatry. 2021;78(9):951-959.

18. Kalu UG, Sexton CE, Loo CK, et al. Transcranial direct current stimulation in the treatment of major depression: a meta-analysis. Psychol Med. 2012;42(9):1791-800.

19. Berlim MT, Van den Eynde F, Daskalakis ZJ. Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials. J Psychiatr Res. 2013;47(1):1-7.

20. Lefaucheur JP, Antal A, Ayache SS, et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017;128(1):56-92.

21. Singh SP, Singh V, Kar N. Efficacy of agomelatine in major depressive disorder: meta-analysis and appraisal. Int J Neuropsychopharmacol. 2012;15(3):417-428.

22. Norman TR, Olver JS. Agomelatine for depression: expanding the horizons? Expert Opin Pharmacother. 2019;20(6):647-656.

23. Ramirez-Mahaluf JP, Rozas-Serri E, Ivanovic-Zuvic F, et al. Effectiveness of sleep deprivation in treating acute bipolar depression as augmentation strategy: a systematic review and meta-analysis. Front Psychiatry. 2020;11:70.

24. Cooney GM, Dwan K, Greig CA, et al. Exercise for depression. Cochrane Database Syst Rev. 2013;(9):CD004366.

25. Kvam S, Kleppe CL, Nordhus IH, et al. Exercise as a treatment for depression: a meta-analysis. J Affect Disord. 2016;202:67-86.

26. Schuch FB, Vancampfort D, Richards J, et al. Exercise as a treatment for depression: a meta-analysis adjusting for publication bias. J Psychiatr Res. 2016;77:42-51.

27. Seshadri A, Adaji A, Orth SS, et al. Exercise, yoga, and tai chi for treatment of major depressive disorder in outpatient settings: a systematic review and meta-analysis. Prim Care Companion CNS Disord. 2020;23(1):20r02722.

28. Cramer H, Lauche R, Langhorst J, et al. Yoga for depression: a systematic review and meta-analysis. Depress Anxiety. 2013;30(11):1068-1083.

29. Mota-Pereira J, Silverio J, Carvalho S, et al. Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder. J Psychiatr Res. 2011;45(8):1005-1011.

30. Pilu A, Sorba M, Hardoy MC, et al. Efficacy of physical activity in the adjunctive treatment of major depressive disorders: preliminary results. Clin Pract Epidemiol Ment Health. 2007;3:8.

31. Strauss C, Cavanagh K, Oliver A, et al. Mindfulness-based interventions for people diagnosed with a current episode of an anxiety or depressive disorder: a meta-analysis of randomised controlled trials. PLoS One. 2014;9(4):e96110.

32. Shonin E, Van Gordon W, Griffiths MD. Are there risks associated with using mindfulness for the treatment of psychopathology? Clinical Practice. 2014;11(4):389-392.

In a systematic review and meta-analysis of 7 studies that included a total of 311 patients with bipolar depression²³:

TSD plus medications resulted in a significant decrease in depressive symptoms at 1 week compared with medications alone
higher response rates were maintained after 3 months with lithium.

Adverse effects commonly include general fatigue and headaches; possible switch into mania with bipolar depression; and rarely, seizures or other unexpected medical conditions (eg, acute coronary syndrome). Presently, this approach is limited to research laboratories with the appropriate sophistication to safely conduct such trials.

Other nontraditional strategies

Cardiovascular exercise, resistance training, mindfulness, and yoga have been shown to decrease severe depressive symptoms when used as adjuncts for patients with treatment-resistant depression, or as monotherapy to treat patients with milder depression.

Exercise. The significant benefits of exercise in various forms as treatment for mild to moderate depression are well described in the literature, but it is less clear if it is effective for treatment-resistant depression. A 2013 Cochrane report²⁴ (39 studies with 2,326 participants total) and 2 meta-analyses undertaken in 2015 (Kvam et al²⁵ included 23 studies with 977 participants, and Schuh et al²⁶ included 25 trials with 1,487 participants) reported that various types of exercise ameliorate depression of differing subtypes and severity, with effect sizes ranging from small to large. Schuh et al²⁶ found that publication bias underestimated effect size. Also, not surprisingly, separate analysis of only higher-quality trials decreased effect size.^24-26 A meta-analysis that included tai chi and yoga in addition to aerobic exercise and strength training (25 trials with 2,083 participants) found low to moderate benefit for exercise and yoga.²⁷ Finally, a meta-analysis by Cramer et al²⁸ that included 12 RCTs (N = 619) supported the use of yoga plus controlled breathing techniques as an ancillary treatment for depression.

Two small exercise trials specifically evaluated patients with treatment-resistant depression.^29,30 Mota-Pereira et al²⁹ compared 22 participants who walked for 30 to 45 minutes, 5 days a week for 12 weeks in addition to pharmacotherapy with 11 patients who received pharmacotherapy only. Exercise improved all outcomes, including HDRS score (both compared to baseline and to the control group). Moreover, 26% of the exercise group went into remission. Pilu et al³⁰ evaluated strength training as an adjunctive treatment. Participants received 1 hour of strength training twice weekly for 8 months (n = 10), or pharmacotherapy only (n = 20). The adjunct strength training group had a statistically significant (P < .0001) improvement in HDRS scores at the end of the 8 months, whereas the control group did not (P < .28).

Continue to: Adverse effects...