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Depressive Disorders: Mechanisms, Measurement and Management pp 201–217Cite as

Optimized Treatment Strategy for Depressive Disorder

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1180))

Abstract

Despite many advances in pharmacotherapy over the past half centurye, only a fraction of patients with Major Depressive Disorder (MDD) can achieve remission after the first or second trial of pharmacotherapy. Those who failed standard antidepressant treatment are termed as Treatment-Resistant Depression (TRD). Pharmacotherapy for TRD is more viable over past 15 years in part due to advances in clinical trials such as the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and the US Department of Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study. In general, optimizing pharmacotherapy consists of switching to different agents, combination with different antidepressants, or augmentation with different class of psychotropic medications, and the latter is preferred. Augmenting agents with strong evidence include Bupropion, Lithium, Triiodothyronine (T3), Aripiprazole, Brexpiprazole, Quetiapine, and Olanzapine in combination with Fluoxetine. Many works need to be done to further advance this field. These include (1) Establish agreement on a standardized, systematic, and feasible definition of TRD, (2) Establish safety and tolerability beyond acute treatment phase, (3) Establish individual psychosocial and neurobiological marks such as pharmacogenetic variance, and (4) Utilize multi-treatment modules such as combination of psychotherapy and pharmacotherapy in conjunction with brain stimulation therapy such as electroconvulsive therapy, vagus nerve stimulation and transcranial magnetic stimulation; as well as non-traditional therapy such as nutritional supplements, exercise and light therapy.

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References

  • Aronson R, Offman HJ, Joffe RT, Naylor CD (1996) Triiodothyronine augmentation in the treatment of refractory depression: a meta-analysis. Arch Gen Psychiatry 53:842–848

    CAS  PubMed  Google Scholar 

  • Barbee JG, Jamhour NJ (2002) Lamotrigine as an augmentation agent in treatment-resistant depression. J Clin Psychiatry 63:737–741

    CAS  PubMed  Google Scholar 

  • Bauer M, Dell’osso L, Kasper S, Pitchot W, Dencker Vansvik E, Köhler J, Jørgensen L, Montgomery SA (2013) J Affect Disord 151(1):209–219. Epub 27 Jun 2013

    Google Scholar 

  • Bauer M, Adli M, Ricken R, Severus E, Pilhatsch M (2014) Role of lithium augmentation in the management of major depressive disorder. CNS Drugs 28(4):331–342, Apr 2014

    CAS  PubMed  Google Scholar 

  • Bedson E, Bell D, Carr D, Carter B, Hughes D, Jorgensen A, Lewis H, Lloyd K, McCaddon A, Moat S, Pink J (2014) Folate augmentation of Treatment–Evaluation for Depression (FolATED): randomised trial and economic evaluation. Health Technol Assess 18:1–159

    Google Scholar 

  • Bennabi D, Aouizerate B, El-Hage W, Doumy O, Moliere F, Courtet P et al (2014) Risk factors for treatment resistance in unipolar depression: a systematic review. J Affect Disord 171C:137–141

    Google Scholar 

  • Berent D, Zboralski K, Orzechowska A, Gałecki P (2014) Thyroid hormones association with depression severity and clinical outcome in patients with major depressive disorder. Mol Biol Rep 41(4):2419–2425

    CAS  PubMed  PubMed Central  Google Scholar 

  • Blier P, Gobbi G, Turcotte JE, de Montigny C, Boucher N, Hébert C, Debonnel G (2009) Mirtazapine and paroxetine in major depression: a comparison of monotherapy versus their combination from treatment initiation. Eur Neuropsychopharmacol 19:457–465

    CAS  PubMed  Google Scholar 

  • Blier P, Ward HE, Tremblay P, Laberge L, Hébert C, Bergeron R (2010) Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. Am J Psychiatry 167:281–288

    PubMed  Google Scholar 

  • Brunner E, Tohen M, Osuntokun O, Landry J, Thase ME (2014) Efficacy and safety of olanzapine/fluoxetine combination vs. fluoxetine monotherapy following successful combination therapy of treatment-resistant major depressive disorder. Neuropsychopharmacology 39(11):2549–2559

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bschor T, Kern H, Henssler J, Baethge C (2018) Switching the antidepressant after nonresponse in adults with major depression: a systematic literature search and meta-analysis. J Clin Psychiatry 79(1):16r10749

    Google Scholar 

  • Carpenter LL, Yasmin S, Price LH (2002) A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine. Biol Psychiatry 51:183–188

    CAS  PubMed  Google Scholar 

  • Cheon EJ, Lee KH, Park YW, Lee JH, Koo BH, Lee SJ, Sung HM (2017) Comparison of the efficacy and safety of aripiprazole versus bupropion augmentation in patients with major depressive disorder unresponsive to selective serotonin reuptake inhibitors: a randomized, prospective, open-label study. J Clin Psychopharmacol 37(2):193

    CAS  PubMed  Google Scholar 

  • Citrome L (2010) Adjunctive aripiprazole, olanzapine, or quetiapine for major depressive disorder: an analysis of number needed to treat, number needed to harm, and likelihood to be helped or harmed. Postgrad Med 122:39–48

    PubMed  Google Scholar 

  • Citrome L (2015) Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Int J Clin Pract 69:978–997

    CAS  PubMed  Google Scholar 

  • Cowen PJ (2017) Backing into the future: pharmacological approaches to the management of resistant depression. Psychol Med 47(15):2569–2577

    CAS  PubMed  PubMed Central  Google Scholar 

  • Crossley NA, Bauer M (2007) Acceleration and augmentation of antidepressants with lithium for depressive disorders: two meta-analyses of randomized, placebo-controlled trials. J Clin Psychiatry 68:935–940

    CAS  PubMed  Google Scholar 

  • Demyttenaere K, Van Duppen Z (2019) The impact of (the concept of) treatment-resistant depression: an opinion review. Int J Neuropsychopharmacol 22(2):85–92

    PubMed  Google Scholar 

  • Fava M, Rush AJ, Wisniewski SR et al (2006) A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report. Am J Psychiatry 163(7):1161–1172

    PubMed  Google Scholar 

  • Fornaro M, Martino M, Mattei C, et al (2014) Duloxetine-bupropion combination for treatment-resistant atypical depression: a double-blind, randomized, placebo-controlled trial. Eur Neuropsychopharmacol. 24(8):1269

    CAS  PubMed  Google Scholar 

  • Gaynes BN, Dusetzina SB, Ellis AR, Hansen RA, Farley JF, Miller WC, Stürmer T (2012) Treating depression after initial treatment failure: directly comparing switch and augmenting strategies in STAR*D. J Clin Psychopharmacol 32(1):114–119

    PubMed  Google Scholar 

  • Ge W, Jakobsson E (2018) Systems biology understanding of the effects of lithium on affective and neurodegenerative disorders. Front Neurosci 12:933

    PubMed  PubMed Central  Google Scholar 

  • Goss AJ, Kaser M, Costafreda SG, Sahakian BJ, Fu CH (2013) Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry 74:1101–1107

    CAS  PubMed  Google Scholar 

  • Greden JF (2001) The burden of disease for treatment-resistant depression. J Clin Psychiatry 62(Suppl 16):26–31

    PubMed  Google Scholar 

  • Gulrez G, Badyal DK, Deswal RS, Sharma A (2012) Bupropion as an augmenting agent in patients of depression with partial response. Basic Clin Pharmacol Toxicol 110(3):227–230

    Google Scholar 

  • Hobart M, Skuban A, Zhang P et al (2018a) A randomized, placebo-controlled study of the efficacy and safety of fixed-dose brexpiprazole 2 mg/d as adjunctive treatment of adults with major depressive disorder. J Clin Psychiatry 79(4):17m12058

    Google Scholar 

  • Hobart M, Zhang P, Weiss C, Meehan SR, Eriksson H (2018b) Adjunctive brexpiprazole and functioning in major depressive disorder: a pooled analysis of six randomized studies using the Sheehan disability scale. Int J Neuropsychopharmacol 22(3):173–179

    Google Scholar 

  • Kautzky A, Dold M, Bartova L, Spies M, Kranz GS, Souery D et al (2019) Clinical factors predicting treatment resistant depression: affirmative results from the European multicenter study. Acta Psychiatr Scand 139:78–88

    CAS  PubMed  Google Scholar 

  • Kessler D, Burns A, Tallon D, Lewis G, MacNeill S, Round J et al (2018) Combining mirtazapine with SSRIs or SNRIs for treatment-resistant depression: the MIR RCT. Health Technol Assess 22(63)

    PubMed  Google Scholar 

  • Lewitzka U, Severus E, Bauer R, Ritter P, Müller-Oerlinghausen B, Bauer M (2015) The suicide prevention effect of lithium: more than 20 years of evidence-a narrative review. Int J Bipolar Disord 3(1):32. https://doi.org/10.1186/s40345-015-0032-2

    Article  CAS  PubMed  Google Scholar 

  • Luan S, Wan H, Wang S, Li H, Zhang B (2017) Efficacy and safety of olanzapine/fluoxetine combination in the treatment of treatment-resistant depression: a meta-analysis of randomized controlled trials. Neuropsychiatr Dis Treat 13:609–620

    CAS  PubMed  PubMed Central  Google Scholar 

  • Luan S, Wan H, Zhang L, Zhao H (2018) Efficacy, acceptability, and safety of adjunctive aripiprazole in treatment-resistant depression: a meta-analysis of randomized controlled trials. Neuropsychiatr Dis Treat 14:467–477

    CAS  PubMed  PubMed Central  Google Scholar 

  • McAllister-Williams RH, Anderson IM, Finkelmeyer A, Gallagher P, Grunze HC, Haddad PM, Hughes T, Lloyd AJ, Mamasoula C, McColl E, Pearce S (2016) Antidepressant augmentation with metyrapone for treatment-resistant depression (the ADD study): a double-blind, randomised, placebo-controlled trial. Lancet Psychiatry 3:117–127

    PubMed  Google Scholar 

  • McIntyre RS, Filteau MJ, Martin L, Patry S, Carvalho A, Cha DS et al (2014) Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord 156:1–7

    CAS  PubMed  Google Scholar 

  • Mohamed S, Johnson GR, Chen P, et al (2017) 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 318:132–145

    Google Scholar 

  • Mulder R, Hamilton A, Irwin L, Boyce P, Morris G, Porter RJ, Malhi GS (2018) Treating depression with adjunctive antipsychotics. Bipolar Disord (Suppl 2):17–24. https://doi.org/10.1111/bdi.12701

    PubMed  Google Scholar 

  • Nelson JC, Papakostas GI (2009) Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. Am J Psychiatry 166(9):980–991

    PubMed  Google Scholar 

  • Nelson JC, Baumann P, Delucchi K, Joffe R, Katona C (2014) A systematic review and meta-analysis of lithium augmentation in tricyclic and second generation antidepressants in major depression. J Affect Disord 156:269–275

    Google Scholar 

  • Nelson JC, Zhang P, Skuban A et al (2016) Overview of short-term and long-term safety of brexpiprazole in patients with major depressive disorder and inadequate response to antidepressant treatment. Curr Psychiatry Rev 12(3):278–290

    CAS  Google Scholar 

  • Nemets B, Stahl Z, Belmaker RH (2002) Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am J Psychiatry 159:477–479

    PubMed  Google Scholar 

  • Nierenberg AA, Fava M, Trivedi MH et al (2006) A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry 163:1519–1530

    PubMed  Google Scholar 

  • Papakostas GI, Shelton RC, Smith J, Fava M (2007) Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry 68:826–831

    CAS  PubMed  Google Scholar 

  • Papakostas GI, Fava M, Thase ME (2008) Treatment of SSRI-resistant depression: a meta-analysis comparing within- versus across-class switches. Biol Psychiatry 63(7):699–704

    CAS  PubMed  Google Scholar 

  • Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M (2010) 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 167:942–948

    PubMed  Google Scholar 

  • Papakostas GI, Shelton RC, Zajecka JM, Etemad B, Rickels K, Clain A, Baer L, Dalton ED, Sacco GR, Schoenfeld D, Pencina M (2012) L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry 169:1267–1274

    PubMed  Google Scholar 

  • Papakostas GI, Ionescu DF (2015) Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder. Mol Psychiatry 20:1142–1150

    CAS  PubMed  Google Scholar 

  • Patel K, Allen S, Haque MN, Angelescu I, Baumeister D, Tracy DK (2016) Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant. Ther Adv Psychopharmacol 6(2):99–144. https://doi.org/10.1177/2045125316629071. Epub 18 Feb 2016

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pérez V, Gilaberte I, Faries D, Alvarez E, Artigas F (1997) Randomised, double-blind, placebo-controlled trial of pindolol in combination with fluoxetine antidepressant treatment. Lancet 349:1594–1597

    Google Scholar 

  • Pérez V, Salavert A, Espadaler J et al (2017) Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial. BMC Psychiatry 17(1):250

    PubMed  PubMed Central  Google Scholar 

  • Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME et al (2006a) STAR*D study team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med 354(12):1231–1242

    Google Scholar 

  • Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, et al (2006b) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR* D report. Am J Psychiatry 163:1905–1917

    PubMed  Google Scholar 

  • Rush AJ, Wisniewski SR, Warden D, Luther JF, Davis LL, Fava M et al (2008) Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features. Arch Gen Psychiatry 65(8):870–880

    CAS  PubMed  Google Scholar 

  • Rush AJ, Trivedi MH, Stewart JW, Nierenberg AA, Fava M, Kurian BT et al (2011) Combining medications to enhance depression outcomes (CO-MED): acute and long-term outcomes of a single-blind randomized study. Am J Psychiatry 168:689–701

    PubMed  Google Scholar 

  • Simon GE, Khandker RK, Ichikawa L, Operskalski BH (2006) Recovery from depression predicts lower health services costs. J Clin Psychiatry 67:1226–1231

    PubMed  Google Scholar 

  • Smith KA, Cipriani A. Lithium and suicide in mood disorders: updated meta-review of the scientific literature.Bipolar Disord. 2017 Nov;19(7):575–586

    Google Scholar 

  • Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC (2013) Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS Med 10:e1001403

    PubMed  PubMed Central  Google Scholar 

  • Tansey KE, Guipponi M, Hu X, Domenici E, Lewis G, Malafosse A et al (2013) Contribution of common genetic variants to antidepressant response. Biol Psychiatry 73(7):679–682. https://doi.org/10.1016/j.biopsych.2012.10.030

    Article  CAS  PubMed  Google Scholar 

  • Thase ME, Zhang P, Skuban A, Hobart M, Weiss C, Weiller E, Nelson JC (2016) Efficacy of adjunctive brexpiprazole in patients with major depressive disorder: a clinical overview. Curr Psychiatry Rev 12:291–301

    CAS  Google Scholar 

  • Trivedi MH, Fava M, Wisniewski SR, Thase ME, Quitkin F, Warden D, Ritz L, Nierenberg AA, Lebowitz BD, Biggs MM, Luther JF, Shores-Wilson K, Rush AJ (2006a) STAR*D study team. Medication augmentation after the failure of SSRIs for depression. N Engl J Med 354(12):1243–1252

    CAS  PubMed  Google Scholar 

  • Trivedi MH, Rush AJ, Wisniewski SR et al (2006b) Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 163(1):28–40

    PubMed  Google Scholar 

  • Wang SM, Han C, Lee SJ et al (2016) Second generation antipsychotics in the treatment of major depressive disorder: an update. Chonnam Med J. 52(3):159–172

    PubMed  PubMed Central  Google Scholar 

  • WHO (2018) Depression fact sheet. https://www.who.int/en/news-room/fact-sheets/detail/depression. Accessed 17 Mar 2019

  • Zisook S, Johnson GR, Tal I, Hicks P, Chen P, Davis L et al (2019) General predictors and moderators of depression remission: a VAST-D report. Am J Psychiatry Published online 4 May 2019

    Google Scholar 

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Authors and Affiliations

  1. VA Northeast Ohio Healthcare System, Cleveland VA Medical Center, Case Western Reserve University School of Medicine, Cleveland, USA

    Peijun Chen

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Correspondence to Peijun Chen .

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  1. Division of Mood Disorders, Shanghai Mental Health Center, Shanghai, China

    Yiru Fang

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Chen, P. (2019). Optimized Treatment Strategy for Depressive Disorder. In: Fang, Y. (eds) Depressive Disorders: Mechanisms, Measurement and Management. Advances in Experimental Medicine and Biology, vol 1180. Springer, Singapore. https://doi.org/10.1007/978-981-32-9271-0_11

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