Abstract
About 30%-50% of patients experience inadequate response to antidepressant therapy, and treatment choices for these patients include augmenting the antidepressant with another therapy, increasing the dose, switching to a different antidepressant, or combining antidepressants. Clinicians should tailor treatment strategies based on patients’ response, tolerability, and disease severity. In this activity, augmentation and adjunctive strategies involving atypical antipsychotics, as well as off-label options including buspirone, stimulants, thyroid hormone, and lithium, are reviewed.
Free Access: Please Log In
This content is completely free—but you need to be logged in to read the full article. If you already have an account, please log in below. Otherwise, register for free to unlock instant access.
References (28)
- Fleurence R, Williamson R, Jing Y, et al. A systematic review of augmentation strategies for patients with major depressive disorder. Psychopharmacol Bull. 2009;42(3):57–90. PubMed
- Barowsky J, Schwartz TL. An evidence-based approach to augmentation and combination strategies for treatment-resistant depression. Psychiatry (Edgmont). 2006;3(7):42–61. PubMed
- Philip NS, Carpenter LL, Tyrka AR, et al. Pharmacologic approaches to treatment resistant depression: a re-examination for the modern era. Expert Opin Pharmacother. 2010;11(5):709–722. PubMed CrossRef
- Kurian BT, Greer TL, Trivedi MH. Strategies to enhance the therapeutic efficacy of antidepressants: targeting residual symptoms. Expert Rev Neurother. 2009;9(7):975–984. PubMed CrossRef
- Nemeroff CB. Prevalence and management of treatment-resistant depression. J Clin Psychiatry. 2007;68(suppl 8):17–25. Pubmed
- Jackson E, Endow-Eyer RA. A review of the evidence supporting the use of lithium augmentation therapy for the reduction of suicidal behavior in patients with unipolar depression: revisiting an overlooked benefit of an older medication. Ment Health Clin. 2014;4(5):221–225. CrossRef
- Landén M, Björling G, Agren H, et al. A randomized, double-blind, placebo-controlled trial of buspirone in combination with an SSRI in patients with treatment-refractory depression. J Clin Psychiatry. 1998;59(12):664–668. Pubmed CrossRef
- Appelberg BG, Syvälahti EK, Koskinen TE, et al. Patients with severe depression may benefit from buspirone augmentation of selective serotonin reuptake inhibitors: results from a placebo-controlled, randomized, double-blind, placebo wash-in study. J Clin Psychiatry. 2001;62(6):448–452. Pubmed CrossRef
- Patkar AA, Masand PS, Pae C-U, et al. A randomized, double-blind, placebo-controlled trial of augmentation with an extended release formulation of methylphenidate in outpatients with treatment-resistant depression. J Clin Psychopharmacol. 2006;26(6):653–656. Pubmed CrossRef
- Ravindran AV, Kennedy SH, O’Donovan MC, et al. Osmotic-release oral system methylphenidate augmentation of antidepressant monotherapy in major depressive disorder: results of a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry. 2008;69(1):87–94. Pubmed
- Pary R, Scarff JR, Jijakli A, et al. A review of psychostimulants for adults with depression. Fed Pract. 2015;32(suppl 3):30S–37S. Pubmed
- Fava M, Thase ME, DeBattista C, et al. Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness. Ann Clin Psychiatry. 2007;19(3):153–159. Pubmed CrossRef
- Joffe RT, Singer W, Levitt AJ, et al. A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression. Arch Gen Psychiatry. 1993;50(5):387–393. Pubmed CrossRef
- Bauer M, Adli M, Bschor T, et al. Lithium’s emerging role in the treatment of refractory major depressive episodes: augmentation of antidepressants. Neuropsychobiology. 2010;62(1):36–42. Pubmed CrossRef
- Cipriani A, Hawton K, Stockton S, et al. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ. 2013;346(jun27 4):f3646–f3646. Pubmed CrossRef
- Wang S-M, Han C, Lee S-J, et al. Second generation antipsychotics in the treatment of major depressive disorder: an update. Chonnam Med J. 2016;52(3):159–172. Pubmed CrossRef
- Berman RM, Marcus RN, Swanink R, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2007;68(6):843–853. Pubmed CrossRef
- Marcus RN, McQuade RD, Carson WH, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol. 2008;28(2):156–165. Pubmed CrossRef
- Berman RM, Fava M, Thase ME, et al. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectr. 2009;14(4):197–206. Pubmed CrossRef
- Han C, Wang S-M, Kwak K-P, et al. Aripiprazole augmentation versus antidepressant switching for patients with major depressive disorder: A 6-week, randomized, rater-blinded, prospective study. J Psychiatr Res. 2015;66-67:84–94. Pubmed CrossRef
- Mohamed S, Johnson GR, Chen P, et al; and the VAST-D Investigators. Effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder unresponsive to antidepressant treatment: the VAST-D randomized clinical trial. JAMA. 2017;318(2):132–145. Pubmed CrossRef
- Chaput Y, Magnan A, Gendron A. The co-administration of quetiapine or placebo to cognitive-behavior therapy in treatment refractory depression: a preliminary trial. BMC Psychiatry. 2008;8(1):73. Pubmed CrossRef
- Shelton RC, Tollefson GD, Tohen M, et al. A novel augmentation strategy for treating resistant major depression. Am J Psychiatry. 2001;158(1):131–134. Pubmed CrossRef
- Thase ME, Corya SA, Osuntokun O, et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. J Clin Psychiatry. 2007;68(2):224–236. Pubmed CrossRef
- Brunner E, Tohen M, Osuntokun O, et al. Efficacy and safety of olanzapine/fluoxetine combination vs fluoxetine monotherapy following successful combination therapy of treatment-resistant major depressive disorder. Neuropsychopharmacology. 2014;39(11):2549–2559. Pubmed CrossRef
- Thase ME, Zhang P, Weiss C, et al. Efficacy and safety of brexpiprazole as adjunctive treatment in major depressive disorder: overview of four short-term studies. Expert Opin Pharmacother. 2019;20(15):1907–1916. Pubmed CrossRef
- Papakostas GI, Shelton RC, Smith J, Fava M. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry. 2007;68(6):826–831. Pubmed CrossRef
- Nelson JC, Papakostas GI. Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. Am J Psychiatry. 2009;166(9):980–991. Pubmed CrossRef
Save
Share
Cite
