Skip to main content

Advertisement

SpringerLink
Log in

Update on augmentation of antidepressant response in resistant depression

  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

Abstract

Most patients in acute depression trials fail to achieve remission with antidepressant monotherapy. Many patients seem to require more than one medication to achieve remission or adequate response. Augmentation strategies are commonly used in clinical practice, but most have been poorly studied. In addition, better-studied strategies, such as the use of lithium and thyroid augmentation, have not been well investigated in combination with newer antidepressants. Various novel strategies are being investigated as augmenting agents, including selective dopamine agonists, sex steroids, norepinephrine reuptake inhibitors, glucocorticoid-specific agents, and newer anticonvulsants. We review the status of augmentation strategies in the treatment of depression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Thase ME, Entsuah AR, Rudolph RL: Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 2001, 178:234–241.

    Article  PubMed  CAS  Google Scholar 

  2. Thase ME: Therapeutic alternatives for difficult-to-treat depression: a narrative review of the state of the evidence. CNS Spectr 2004, 9:808–821. Excellent review of the current concept of treatment resistance.

    PubMed  Google Scholar 

  3. Khan A, Schwartz K: Study designs and outcomes in antidepressant clinical trials. Essent Psychopharmacol 2005, 6:221–226. Describes methodologic issues surrounding placebo response in antidepressant trials.

    PubMed  Google Scholar 

  4. Bagby RM, Ryder AG, Schuller DR, Marshall MB: The Hamilton Depression Rating Scale: has the gold standard become a lead weight? Am J Psychiatry 2004, 161:2163–2177.

    Article  PubMed  Google Scholar 

  5. Fredman SJ, Fava M, Kienke AS, et al.: Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: a survey of current "nextstep" practices. J Clin Psychiatry 2000, 61:403–408.

    Article  PubMed  CAS  Google Scholar 

  6. DeBattista C, Doghramji K, Menza MA, et al.: Modafinil in Depression Study Group. Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebocontrolled study. J Clin Psychiatry 2003, 64:1057–1064.

    Article  PubMed  CAS  Google Scholar 

  7. Bodkin JA, Lasser RA, Wines Jr JD, et al.: Combining serotonin reuptake inhibitors and bupropion in partial responders to antidepressant monotherapy. J Clin Psychiatry 1997, 58:137–145.

    PubMed  CAS  Google Scholar 

  8. Spier SA: Use of bupropion with SRIs and venlafaxine. Depress Anxiety 1998, 7:73–75.

    Article  PubMed  CAS  Google Scholar 

  9. Feinberg SS: Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication. J Clin Psychiatry 2004, 65:1520–1524.

    PubMed  CAS  Google Scholar 

  10. Masand PS, Anand VS, Tanquary JF: Psychostimulant augmentation of second generation antidepressants: a case series. Depress Anxiety 1998, 7:89–91.

    Article  PubMed  CAS  Google Scholar 

  11. Satel SL, Nelson JC: Stimulants in the treatment of depression: a critical overview. J Clin Psychiatry 1989, 50:241–249. One of the best available reviews of stimulant use in depression.

    PubMed  CAS  Google Scholar 

  12. DeBattista C, Lembke A, Solvason HB, et al.: A prospective trial of modafinil as an adjunctive treatment of major depression. J Clin Psychopharmacol 2004, 24:87–90.

    Article  PubMed  CAS  Google Scholar 

  13. DeBattista C, Doghramji K, Menza MA, et al.: Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. J Clin Psychiatry 2003, 64:1057–1064.

    Article  PubMed  CAS  Google Scholar 

  14. Fava M, Thase ME, DeBattista C: A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry 2005, 66:85–93.

    PubMed  CAS  Google Scholar 

  15. Nelson JC, Mazure CM, Jatlow PI, et al.: Combining norepinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a double-blind, randomized study. Biol Psychiatry 2004, 55:296–300.

    Article  PubMed  CAS  Google Scholar 

  16. Fava M, Alpert J, Nierenberg A, et al.: Double-blind study of high-dose fluoxetine versus lithium or desipramine augmentation of fluoxetine in partial responders and nonresponders to fluoxetine. J Clin Psychopharmacol 2002, 22:379–387.

    Article  PubMed  CAS  Google Scholar 

  17. Carpenter LL, Yasmin S, Price LH: A double-blind, placebocontrolled study of antidepressant augmentation with mirtazapine. Biol Psychiatry 2002, 51:183–188.

    Article  PubMed  CAS  Google Scholar 

  18. Nierenberg AA, Adler LA, Peselow E, et al.: Trazodone for antidepressant-associated insomnia. Am J Psychiatry 1994, 151:1069–1072.

    PubMed  CAS  Google Scholar 

  19. Nierenberg AA, Cole JO, Glass L: Possible trazodone potentiation of fluoxetine: a case series. J Clin Psychiatry 1992, 53:83–85.

    PubMed  CAS  Google Scholar 

  20. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for Study of Obesity: Consensus development conference on antipsychotic drugs and obesity and diabetes. J Clin Psychiatry 2004, 65:267–272.

    Google Scholar 

  21. Barbee JG, Conrad EJ, Jamhour NJ: Aripiprazole augmentation in treatm ent-resistant depression. Ann Clin Psychiatry 2004, 16:189–194.

    PubMed  Google Scholar 

  22. Worthington III JJ, Kinrys G, Wygant LE, Pollack MH: Aripiprazole as an augmenter of selective serotonin reuptake inhibitors in depression and anxiety disorder patients. Int Clin Psychopharmacol 2005, 20:9–11.

    Article  PubMed  Google Scholar 

  23. Shelton RC, Tollefson GD, Tohen M, et al.: A novel augmentation strategy for treating resistant major depression. Am J Psychiatry 2001, 158:131–134.

    Article  PubMed  CAS  Google Scholar 

  24. Papakostas GI: Augmentation of standard antidepressants with atypical antipsychotic agents for treatment-resistant major depressive disorder. Essent Psychopharmacol 2005, 6:209–220.

    PubMed  Google Scholar 

  25. Blier P: The pharmacology of putative early-onset antidepressant strategies. Eur Neuropsychopharmacol 2003, 13:57–66.

    Article  PubMed  CAS  Google Scholar 

  26. Artigas F, Perez V, Alvarez E: Pindolol induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors. Arch Gen Psychiatry 1994, 51:248–251.

    PubMed  CAS  Google Scholar 

  27. Segrave R, Nathan PJ: Pindolol augmentation of selective serotonin reuptake inhibitors: accounting for the variability of results of placebo-controlled double blind studies in patients with major depression. Hum Psychopharmacol 2005, 20:163–174.

    Article  PubMed  CAS  Google Scholar 

  28. Rabiner EA, Bhagwagar Z, Gunn RN, et al.: Pindolol augmentation of selective serotonin reuptake inhibitors: PET evidence that the dose used in clinical trials is too low. Am J Psychiatry 2001, 158:2080–2082.

    Article  PubMed  CAS  Google Scholar 

  29. Nierenberg AA: Treatment choice after one antidepressant fails: a survey of northeastern psychiatrists. J Clin Psychiatry 1991, 52:383–385.

    PubMed  CAS  Google Scholar 

  30. Fredman SJ, Fava M, Kienke AS, et al.: Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: a survey of current "nextstep" practices. J Clin Psychiatry 2000, 61:403–408.

    Article  PubMed  CAS  Google Scholar 

  31. Manji HK, Potter WZ, Lenox RH: Signal transduction pathways. Molecular targets for lithium’s actions. Arch Gen Psychiatry 1995, 52:531–543.

    PubMed  CAS  Google Scholar 

  32. Bauer M, Adli M, Baethge C, et al.: Lithium augmentation therapy in refractory depression: clinical evidence and neurobiological mechanisms. Can J Psychiatry 2003, 48:440–448.

    PubMed  Google Scholar 

  33. Nierenberg AA, Papakostas GI, Petersen T, et al.: Lithium augmentation of nortriptyline for subjects resistant to multiple antidepressants. J Clin Psychopharmacol 2003, 23:92–95.

    Article  PubMed  CAS  Google Scholar 

  34. Pies RW: Handbook of Essential Psychopharmacology. Washington, DC: American Psychiatric Press; 2005.

    Google Scholar 

  35. Fava M, Alpert J, Nierenberg A, et al.: Double-blind study of high-dose fluoxetine versus lithium or desipramine augmentation of fluoxetine in partial responders and nonresponders to fluoxetine. J Clin Psychopharmacol 2002, 22:379–387.

    Article  PubMed  CAS  Google Scholar 

  36. Zullino D, Baumann P: Lithium augmentation in depressive patients not responding to selective serotonin reuptake inhibitors. Pharmacopsychiatry 2001, 34:119–127.

    Article  PubMed  CAS  Google Scholar 

  37. Prange Jr AJ: Novel uses of thyroid hormones in patients with affective disorders. Thyroid 1996, 6:537–543.

    Article  PubMed  Google Scholar 

  38. Joffe RT, Sokolov ST: Thyroid hormone treatment of primary unipolar depression: a review. Int J Neuropsychopharmacol 2000, 3:143–147.

    Article  PubMed  CAS  Google Scholar 

  39. Gitlin MJ, Weiner H, Fairbanks L, et al.: Failure of T3 to potentiate tricyclic antidepressant response. J Affect Disord 1987, 13:267–272.

    Article  PubMed  CAS  Google Scholar 

  40. Altshuler LL, Bauer M, Frye MA, et al.: Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry 2001, 158:1617–1622.

    Article  PubMed  CAS  Google Scholar 

  41. Joffe RT, Singer W: A comparison of triiodothyronine and thyroxine in the potentiation of tricyclic antidepressants. Psychiatry Res 1990, 32:241–251.

    Article  PubMed  CAS  Google Scholar 

  42. Iosifescu DV, Nierenberg AA, Mischoulon D, et al.: An open study of triiodothyronine augmentation of selective serotonin reuptake inhibitors in treatment-resistant major depressive disorder. J Clin Psychiatry 2005, 66:1038–1042.

    PubMed  CAS  Google Scholar 

  43. Ahokas A, Aito M, Rimon R: Positive treatment effect of estradiol in postpartum psychosis: a pilot study. J Clin Psychiatry 2000, 61:166–169.

    Article  PubMed  CAS  Google Scholar 

  44. Rasgon NL, Altshuler LL, Fairbanks LA, et al.: Estrogen replacement therapy in the treatment of major depressive disorder in perimenopausal women. J Clin Psychiatry 2002, 63(Suppl 7):45–48.

    PubMed  CAS  Google Scholar 

  45. Soares CN, Almeida OP, Joffe H, Cohen LS: Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 2001, 58:529–534.

    Article  PubMed  CAS  Google Scholar 

  46. Schmidt PJ, Daly RC, Bloch M, et al.: Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry 2005, 62:154–162.

    Article  PubMed  CAS  Google Scholar 

  47. Orengo CA, Fullerton L, Kunik ME: Safety and efficacy of testosterone gel 1% augmentation in depressed men with partial response to antidepressant therapy. J Geriatr Psychiatry Neurol 2005, 18:20–24.

    Article  PubMed  Google Scholar 

  48. Schatzberg AF, Posener JA, DeBattista C, et al.: Neuropsychological deficits in psychotic versus nonpsychotic major depression and no mental illness. Am J Psychiatry 2000, 157:1095–1100.

    Article  PubMed  CAS  Google Scholar 

  49. Schatzberg AF: New approaches to managing psychotic depression. J Clin Psychiatry 2003, 64(Suppl 1):19–23.

    PubMed  CAS  Google Scholar 

  50. Dinan TG, Lavelle E, Cooney J, et al.: Dexamethasone augmentation in treatment-resistant depression. Acta Psychiatr Scand 1997, 95:58–61.

    PubMed  CAS  Google Scholar 

  51. DeBattista C, Posener JA, Kalehzan BM, Schatzberg AF: Acute antidepressant effects of intravenous hydrocortisone and CRH in depressed patients: a double-blind, placebo-controlled study. Am J Psychiatry 2000, 157:1334–1337.

    Article  PubMed  CAS  Google Scholar 

  52. Arana GW, Santos AB, Laraia MT, et al.: Dexamethasone for the treatment of depression: a randomized, placebo-controlled, double-blind trial. Am J Psychiatry 1995, 152:265–267.

    PubMed  CAS  Google Scholar 

  53. Jahn H, Schick M, Kiefer F, et al.: Metyrapone as additive treatment in major depression: a double-blind and placebocontrolled trial. Arch Gen Psychiatry 2004, 61:1235–1244.

    Article  PubMed  CAS  Google Scholar 

  54. Belanoff JK, Flores BH, Kalezhan M, et al.: Rapid reversal of psychotic depression using mifepristone. J Clin Psychopharmacol 2001, 21:516–521.

    Article  PubMed  CAS  Google Scholar 

  55. Belanoff JK, Rothschild AJ, Cassidy F, et al.: An open label trial of C-1073 (mifepristone) for psychotic major depression. Biol Psychiatry 2002, 52:386–392.

    Article  PubMed  CAS  Google Scholar 

  56. Simpson GM, El Sheshai A, Loza N, et al.: An 8-week openlabel trial of a 6-day course of mifepristone for the treatment of psychotic depression. J Clin Psychiatry 2005, 66:598–602.

    Article  PubMed  CAS  Google Scholar 

  57. Young AH, Gallagher P, Watson S, et al.: Improvements in neurocognitive function and mood following adjunctive treatment with mifepristone (RU-486) in bipolar disorder. Neuropsychopharmacology 2004, 29:1538–1545.

    Article  PubMed  CAS  Google Scholar 

  58. DeBattista C, Belanoff J: A double-blind, placebo controlled trial of C-1073 (Mifepristone) in the treatment of psychotic major depression. Paper presented at ACNP 43rd Annual Meeting. San Juan, Puerto Rico; December 12–16, 2004.

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, 94305, Stanford, CA, USA

    Charles DeBattista MD

Authors
  1. Charles DeBattista MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Lembke MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

DeBattista, C., Lembke, A. Update on augmentation of antidepressant response in resistant depression. Curr Psychiatry Rep 7, 435–440 (2005). https://doi.org/10.1007/s11920-005-0064-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11920-005-0064-x

Keywords

Search

Navigation