UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Unipolar depression in adults and initial treatment: Investigational approaches

Author
Michael Gitlin, MD
Section Editor
Peter P Roy-Byrne, MD
Deputy Editor
David Solomon, MD

INTRODUCTION

Unipolar depression is highly prevalent, disabling, and recurrent. Community surveys in 14 countries have estimated that the lifetime prevalence of unipolar depressive disorders is 12 percent [1], and the World Health Organization ranks unipolar major depression as the 11th greatest cause of disability and mortality in the world, among 291 diseases and causes of injury [2]. Following recovery from one major depressive episode, the estimated rate of recurrence over two years is greater than 40 percent; after two episodes, the risk of recurrence within five years is approximately 75 percent [3].

In addition, initial treatment of unipolar major depression is often unsuccessful. The prospective, observational Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study initially treated 2876 outpatients with full doses of citalopram for up to 14 weeks, and found that remission occurred in only 33 percent [4].

As a result, many therapies (primarily medications) have been investigated for the initial treatment of depression, but have not been widely adopted due to limited evidence of their efficacy, safety, and tolerability. This topic reviews the evidence for these nonstandard treatments.

The general principles and prognosis for the initial treatment of depression are discussed separately, as are the choice of therapy for the initial treatment of depression and the evidence of efficacy of standard therapies, and the evidence for standard therapies that are used for initially treating depression in primary care patients and in patients with general medical illnesses. Continuation and maintenance treatment of major depression, the treatment of resistant depression and refractory depression, and the clinical manifestations and diagnosis of depression are also discussed separately.

(See "Unipolar depression in adults and initial treatment: General principles and prognosis".)

                        
To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Sep 2017. | This topic last updated: Jun 15, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. Kessler RC, Ormel J, Petukhova M, et al. Development of lifetime comorbidity in the World Health Organization world mental health surveys. Arch Gen Psychiatry 2011; 68:90.
  2. Murray CJ, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380:2197.
  3. Solomon DA, Keller MB, Leon AC, et al. Multiple recurrences of major depressive disorder. Am J Psychiatry 2000; 157:229.
  4. Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 2006; 163:28.
  5. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005; 353:487.
  6. Gallagher P, Malik N, Newham J, et al. Antiglucocorticoid treatments for mood disorders. Cochrane Database Syst Rev 2008; :CD005168.
  7. Lyoo IK, Yoon S, Kim TS, et al. A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. Am J Psychiatry 2012; 169:937.
  8. Wolkowitz OM, Reus VI, Keebler A, et al. Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry 1999; 156:646.
  9. Peixoto C, Devicari Cheda JN, Nardi AE, et al. The effects of dehydroepiandrosterone (DHEA) in the treatment of depression and depressive symptoms in other psychiatric and medical illnesses: a systematic review. Curr Drug Targets 2014; 15:901.
  10. Schmidt PJ, Daly RC, Bloch M, et al. Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry 2005; 62:154.
  11. Amann B, Born C, Crespo JM, et al. Lamotrigine: when and where does it act in affective disorders? A systematic review. J Psychopharmacol 2011; 25:1289.
  12. Abolfazli R, Hosseini M, Ghanizadeh A, et al. Double-blind randomized parallel-group clinical trial of efficacy of the combination fluoxetine plus modafinil versus fluoxetine plus placebo in the treatment of major depression. Depress Anxiety 2011; 28:297.
  13. Vaishnavi S, Gadde K, Alamy S, et al. Modafinil for atypical depression: effects of open-label and double-blind discontinuation treatment. J Clin Psychopharmacol 2006; 26:373.
  14. Fernandes BS, Dean OM, Dodd S, et al. N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis. J Clin Psychiatry 2016; 77:e457.
  15. Bloch MH, Hannestad J. Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. Mol Psychiatry 2012; 17:1272.
  16. Martins JG, Bentsen H, Puri BK. Eicosapentaenoic acid appears to be the key omega-3 fatty acid component associated with efficacy in major depressive disorder: a critique of Bloch and Hannestad and updated meta-analysis. Mol Psychiatry 2012; 17:1144.
  17. 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.
  18. Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry 2007; 68:1056.
  19. Sublette ME, Ellis SP, Geant AL, Mann JJ. Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry 2011; 72:1577.
  20. Martins JG. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr 2009; 28:525.
  21. Appleton KM, Sallis HM, Perry R, et al. Omega-3 fatty acids for depression in adults. Cochrane Database Syst Rev 2015; :CD004692.
  22. 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.
  23. 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.
  24. Portella MJ, de Diego-Adeliño J, Ballesteros J, et al. Can we really accelerate and enhance the selective serotonin reuptake inhibitor antidepressant effect? A randomized clinical trial and a meta-analysis of pindolol in nonresistant depression. J Clin Psychiatry 2011; 72:962.
  25. Whale R, Terao T, Cowen P, et al. Pindolol augmentation of serotonin reuptake inhibitors for the treatment of depressive disorder: a systematic review. J Psychopharmacol 2010; 24:513.
  26. American Psychiatric Association: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition, 2010. http://psychiatryonline.org/guidelines.aspx (Accessed on April 17, 2012).
  27. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder, third edition. Am J Psychiatry 2010; 167 (supplement):1.
  28. National Institute for Health & Clinical Excellence. The Treatment and Management of Depression in Adults (updated edition). National Clinical Practice Guideline 90, 2010. http://www.nice.org.uk/ (Accessed on December 09, 2012).
  29. Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database Syst Rev 2008; :CD000448.
  30. Cui YH, Zheng Y. A meta-analysis on the efficacy and safety of St John's wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults. Neuropsychiatr Dis Treat 2016; 12:1715.
  31. Hammerness P, Basch E, Ulbricht C, et al. St John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics 2003; 44:271.
  32. Huang CC, Wei IH, Huang CL, et al. Inhibition of glycine transporter-I as a novel mechanism for the treatment of depression. Biol Psychiatry 2013; 74:734.
  33. Mathew SJ. Glycine transporter-I inhibitors: a new class of antidepressant? Biol Psychiatry 2013; 74:710.
  34. Jaffe RJ, Novakovic V, Peselow ED. Scopolamine as an antidepressant: a systematic review. Clin Neuropharmacol 2013; 36:24.
  35. Furey ML, Zarate CA Jr. Pulsed intravenous administration of scopolamine produces rapid antidepressant effects and modest side effects. J Clin Psychiatry 2013; 74:850.
  36. Khajavi D, Farokhnia M, Modabbernia A, et al. Oral scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2012; 73:1428.
  37. 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.
  38. Candy M, Jones L, Williams R, et al. Psychostimulants for depression. Cochrane Database Syst Rev 2008; :CD006722.
  39. Lavretsky H, Reinlieb M, St Cyr N, et al. Citalopram, methylphenidate, or their combination in geriatric depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 2015; 172:561.
  40. Zarrouf FA, Artz S, Griffith J, et al. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract 2009; 15:289.
  41. Amanatkar HR, Chibnall JT, Seo BW, et al. Impact of exogenous testosterone on mood: a systematic review and meta-analysis of randomized placebo-controlled trials. Ann Clin Psychiatry 2014; 26:19.
  42. Almeida OP, Ford AH, Hirani V, et al. B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial. Br J Psychiatry 2014; 205:450.
  43. Martiny K, Lunde M, Undén M, et al. Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales. Acta Psychiatr Scand 2005; 112:117.
  44. Goel N, Terman M, Terman JS, et al. Controlled trial of bright light and negative air ions for chronic depression. Psychol Med 2005; 35:945.
  45. Lieverse R, Van Someren EJ, Nielen MM, et al. Bright light treatment in elderly patients with nonseasonal major depressive disorder: a randomized placebo-controlled trial. Arch Gen Psychiatry 2011; 68:61.
  46. Wirz-Justice A, Bader A, Frisch U, et al. A randomized, double-blind, placebo-controlled study of light therapy for antepartum depression. J Clin Psychiatry 2011; 72:986.
  47. Golden RN, Gaynes BN, Ekstrom RD, et al. The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry 2005; 162:656.
  48. Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of Bright Light Treatment, Fluoxetine, and the Combination in Patients With Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry 2016; 73:56.
  49. Güzel Özdemir P, Boysan M, Smolensky MH, et al. Comparison of venlafaxine alone versus venlafaxine plus bright light therapy combination for severe major depressive disorder. J Clin Psychiatry 2015; 76:e645.
  50. Hanusch KU, Janssen CH, Billheimer D, et al. Whole-body hyperthermia for the treatment of major depression: associations with thermoregulatory cooling. Am J Psychiatry 2013; 170:802.
  51. Janssen CW, Lowry CA, Mehl MR, et al. Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry 2016; 73:789.