Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-22T08:45:28.885Z Has data issue: false hasContentIssue false
  • English
  • Français

Treating to target in major depressive disorder: response to remission to functional recovery

Published online by Cambridge University Press:  18 December 2015

Roger S. McIntyre ,
Yena Lee Open the ORCID record for Yena Lee [Opens in a new window]  and
Rodrigo B. Mansur
Roger S. McIntyre*
Affiliation:
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
Yena Lee
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Rodrigo B. Mansur
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
*
*Address for correspondence: Dr. Roger S. McIntyre, MD, FRCPC, Professor of Psychiatry and Pharmacology, University of Toronto, Head, Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Treating to target in chronic diseases [e.g. Major Depressive Disorder (MDD)] fosters precision, consistency, and appropriateness of treatment selection and sequencing. Therapeutic target definitions/endpoints in MDD should satisfy patient-, provider-, and societal expectations. Functional recovery in depression and return to both physical and mental health are the overarching therapeutic objectives. Treating to target in MDD implies multidimensional symptomatic remission, with a particular emphasis on cognitive function and aspects of positive mental health. Several atypical antipsychotic agents (i.e. brexpiprazole, aripiprazole, quetiapine) are FDA-approved as augmentation agents in MDD. Vortioxetine, duloxetine, and psychostimulants have evidence of independent, direct, and robust effects on cognitive function in MDD. Vortioxetine is the only agent that demonstrates efficacy across multiple cognitive domains in MDD associated with functional recovery. Measurement-based care, health information technology/systems, and integrated care models (e.g. medical homes) provide requisite tools and health environments for optimal health outcomes in MDD. Achieving remission in MDD does not equate to health. Return to positive mental health as well as full functioning provide the impetus to pivot away from traditional provider-defined outcomes toward an inclusive perspective involving patient- and society-defined outcomes (i.e. optimization of human capital). As in other chronic diseases, treating to target (e.g. cognitive function) further increases the probability of achieving optimal health outcomes.

Keywords

antidepressantcognition, depressiontargettreatment resistant
Type
CME Review Article
Information
CNS Spectrums , Volume 20 , Issue S1: CME SUPPLEMENT , December 2015 , pp. 17 - 31
Copyright
© Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

This activity is supported by an unrestricted educational grant from Takeda Pharmaceuticals U.S.A., Inc.

References

1.Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015; 386(9995): 743–800.CrossRefGoogle Scholar
2.Kessler, RC. The costs of depression. Psychiatr Clin North Am. 2012; 35(1): 1–14.CrossRefGoogle ScholarPubMed
3.McIntyre, RS, O’Donovan, C. The human cost of not achieving full remission in depression. Can J Psychiatry. 2004; 49(3 Suppl 1): 10S–16S.Google Scholar
4.Greenberg, PE, Fournier, AA, Sisitsky, T, Pike, CT, Kessler, RC. The economic burden of adults with major depressive disorder in the United States (2005 and 2010). J Clin Psychiatry. 2015; 76(2): 155–162.CrossRefGoogle ScholarPubMed
5.Cashin, P, Sahay, R. Internal migration, center-state grants, and economic growth in the states of India. Staff Papers (International Monetary Fund). 1996; 43(1): 123–171.CrossRefGoogle ScholarPubMed
6.Sahakian, BJ, Bruhl, AB, Cook, J, et al. The impact of neuroscience on society: cognitive enhancement in neuropsychiatric disorders and in healthy people. Philos Trans R Soc Lond B Biol Sci. 2015; 370(1677): 20140214.CrossRefGoogle ScholarPubMed
7.Collins, PY, Insel, TR, Chockalingam, A, Daar, A, Maddox, YT. Grand challenges in global mental health: integration in research, policy, and practice. PLoS Med. 2013; 10(4): e1001434.CrossRefGoogle ScholarPubMed
8.Collins, PY, Patel, V, Joestl, SS, et al. Grand challenges in global mental health. Nature. 2011; 475(7354): 27–30.CrossRefGoogle ScholarPubMed
9.Prien, RF, Carpenter, LL, Kupfer, DJ. The definition and operational criteria for treatment outcome of major depressive disorder: a review of the current research literature. Arch Gen Psychiatry. 1991; 48(9): 796–800.CrossRefGoogle ScholarPubMed
10.McIntyre, RS, Fallu, A, Konarski, JZ. Measurable outcomes in psychiatric disorders: remission as a marker of wellness. Clin Ther. 2006; 28(11): 1882–1891.CrossRefGoogle ScholarPubMed
11.Judd, LL, Paulus, MJ, Schettler, PJ, et al. Does incomplete recovery from first lifetime major depressive episode herald a chronic course of illness? Am J Psychiatry. 2000; 157(9): 1501–1504.CrossRefGoogle Scholar
12.Judd, LL, Akiskal, HS, Zeller, PJ, et al. Psychosocial disability during the long-term course of unipolar major depressive disorder. Arch Gen Psychiatry. 2000; 57(4): 375–380.CrossRefGoogle ScholarPubMed
13.Gaynes, BN, Warden, D, Trivedi, MH, Wisniewski, SR, Fava, M, Rush, AJ. What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatr Serv. 2009; 60(11): 1439–1445.CrossRefGoogle ScholarPubMed
14.Frank, E, Prien, RF, Jarrett, RB, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder: remission, recovery, relapse, and recurrence. Arch Gen Psychiatry. 1991; 48(9): 851–855.CrossRefGoogle ScholarPubMed
15.Conradi, HJ, Ormel, J, de Jonge, P. Presence of individual (residual) symptoms during depressive episodes and periods of remission: a 3-year prospective study. Psychol Med. 2011; 41(6): 1165–1174.CrossRefGoogle ScholarPubMed
16.Mojtabai, R. Residual symptoms and impairment in major depression in the community. Am J Psychiatry. 2001; 158(10): 1645–1651.CrossRefGoogle ScholarPubMed
17.Zimmerman, M, Posternak, MA, Chelminski, I. Using a self-report depression scale to identify remission in depressed outpatients. Am J Psychiatry. 2004; 161(10): 1911–1913.CrossRefGoogle ScholarPubMed
18.Trivedi, MH, Morris, DW, Wisniewski, SR, et al. Increase in work productivity of depressed individuals with improvement in depressive symptom severity. Am J Psychiatry. 2013; 170(6): 633–641.CrossRefGoogle ScholarPubMed
19.McIntyre, RS. Using measurement strategies to identify and monitor residual symptoms. J Clin Psychiatry. 2013; 74(Suppl 2): 14–18.CrossRefGoogle ScholarPubMed
20.McIntyre, RS, Cha, DS, Soczynska, JK, et al. Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions. Depress Anxiety. 2013; 30(6): 515–527.CrossRefGoogle ScholarPubMed
21.Mitchell, AJ, Vaze, A, Rao, S. Clinical diagnosis of depression in primary care: a meta-analysis. Lancet. 2009; 374(9690): 609–619.CrossRefGoogle ScholarPubMed
22.Harding, KJ, Rush, AJ, Arbuckle, M, Trivedi, MH, Pincus, HA. Measurement-based care in psychiatric practice: a policy framework for implementation. J Clin Psychiatry. 2011; 72(8): 1136–1143.CrossRefGoogle ScholarPubMed
23.McIntyre, RS, Konarski, JZ, Gupta, S. Editorial: sharpening the focus in mood disorders: from disease models to individualized measurement-based care. Ann Clin Psychiatry. 2007; 19(4): 213–214.CrossRefGoogle ScholarPubMed
24.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(1): 28–40.CrossRefGoogle ScholarPubMed
25.Kudlow, PA, Cha, DS, McIntyre, RS. Predicting treatment response in major depressive disorder: the impact of early symptomatic improvement. Can J Psychiatry. 2012; 57(12): 782–788.CrossRefGoogle ScholarPubMed
26.Szegedi, A, Jansen, WT, Van Willigenburg, AP, van der Meulen, E, Stassen, HH, Thase, ME. Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry. 2009; 70(3): 344–353.CrossRefGoogle ScholarPubMed
27.Harmer, CJ, O’Sullivan, U, Favaron, E, et al. Effect of acute antidepressant administration on negative affective bias in depressed patients. Am J Psychiatry. 2009; 166(10): 1178–1184.CrossRefGoogle ScholarPubMed
28.Uher, R, Mors, O, Rietschel, M, et al. Early and delayed onset of response to antidepressants in individual trajectories of change during treatment of major depression: a secondary analysis of data from the Genome-Based Therapeutic Drugs for Depression (GENDEP) study. J Clin Psychiatry. 2011; 72(11): 1478–1484.CrossRefGoogle ScholarPubMed
29.Lam, RW, Kennedy, SH, Grigoriadis, S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord. 2009; 117(Suppl 1): S26–S43.CrossRefGoogle Scholar
30.Arnow, BA, Blasey, C, Williams, LM, et al. Depression subtypes in predicting antidepressant response: a report from the iSPOT-D Trial. Am J Psychiatry. 2015; 172(8): 743–750.CrossRefGoogle ScholarPubMed
31.Schatzberg, AF, DeBattista, C, Lazzeroni, LC, Etkin, A, Murphy, GM Jr, Williams, LM. ABCB1 genetic effects on antidepressant outcomes: a report from the iSPOT-D Trial. Am J Psychiatry. 2015; 172(8): 751–759.CrossRefGoogle ScholarPubMed
32.Gelenberg, AJ. A review of the current guidelines for depression treatment. J Clin Psychiatry. 2010; 71(7): e15.CrossRefGoogle ScholarPubMed
33.Rush, AJ, Trivedi, MH, Wisniewski, SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006; 163(11): 1905–1917.CrossRefGoogle ScholarPubMed
34.Han, C, Wang, SM, Kwak, KP, 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.CrossRefGoogle ScholarPubMed
35.Nelson, JC, Rahman, Z, Laubmeier, KK, et al. Efficacy of adjunctive aripiprazole in patients with major depressive disorder whose symptoms worsened with antidepressant monotherapy. CNS Spectr. 2014; 19(6): 528–534.CrossRefGoogle ScholarPubMed
36.Nelson, JC, Thase, ME, Bellocchio, EE, et al. Efficacy of adjunctive aripiprazole in patients with major depressive disorder who showed minimal response to initial antidepressant therapy. Int Clin Psychopharmacol. 2012; 27(3): 125–133.CrossRefGoogle ScholarPubMed
37.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.CrossRefGoogle ScholarPubMed
38.Zhou, X, Keitner, GI, Qin, BM, et al. Atypical antipsychotic augmentation for treatment-resistant depression: a systematic review and network meta-analysis. Int J Neuropsychopharmacol. 2015; 18(11): pyv060.CrossRefGoogle ScholarPubMed
39.McIntyre, RS, Cha, DS, Kim, RD, Mansur, RB. A review of FDA-approved treatment options in bipolar depression. CNS Spectr. 2013; 18(Suppl 1): 4–20.CrossRefGoogle ScholarPubMed
40.Citrome, L. Brexpiprazole: a new dopamine D2 receptor partial agonist for the treatment of schizophrenia and major depressive disorder. Drugs Today (Barc). 2015; 51(7): 397–414.CrossRefGoogle ScholarPubMed
41.Mojtabai, R, Olfson, M. National trends in long-term use of antidepressant medications: results from the U.S. National Health and Nutrition Examination Survey. J Clin Psychiatry. 2014; 75(2): 169–177.CrossRefGoogle ScholarPubMed
42.Kennedy, SH, McCann, SM, Masellis, M, et al. Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects. J Clin Psychiatry. 2002; 63(3): 181–186.CrossRefGoogle ScholarPubMed
43.Cooper, JA, Tucker, VL, Papakostas, GI. Resolution of sleepiness and fatigue: a comparison of bupropion and selective serotonin reuptake inhibitors in subjects with major depressive disorder achieving remission at doses approved in the European Union. J Psychopharmacol. 2014; 28(2): 118–124.CrossRefGoogle ScholarPubMed
44.Soczynska, JK, Kennedy, SH, Goldstein, BI, Lachowski, A, Woldeyohannes, HO, McIntyre, RS. The effect of tumor necrosis factor antagonists on mood and mental health-associated quality of life: novel hypothesis-driven treatments for bipolar depression? Neurotoxicology. 2009; 30(4): 497–521.CrossRefGoogle ScholarPubMed
45.Kast, RE. Mirtazapine may be useful in treating nausea and insomnia of cancer chemotherapy. Support Care Cancer. 2001; 9(6): 469–470.CrossRefGoogle ScholarPubMed
46.Blier, P, Ward, HE, Tremblay, P, Laberge, L, Hebert, C, Bergeron, R. Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. Am J Psychiatry. 2010; 167(3): 281–288.CrossRefGoogle ScholarPubMed
47.Rush, AJ, Trivedi, MH, Stewart, JW, t al. Combining medications to enhance depression outcomes (CO-MED): acute and long-term outcomes of a single-blind randomized study. Am J Psychiatry. 2011; 168(7): 689–701.CrossRefGoogle ScholarPubMed
48.Ravindran, AV, Kennedy, SH, O’Donovan, MC, Fallu, A, Camacho, F, Binder, CE. 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.CrossRefGoogle ScholarPubMed
49.Lavretsky, H, Reinlieb, M St, Cyr, N, Siddarth, P, Ercoli, LM, Senturk, D. Citalopram, methylphenidate, or their combination in geriatric depression: a randomized, double-blind, placebo-controlled trial 1. Am J Psychiatry. 2015; 172(6): 561–569.CrossRefGoogle ScholarPubMed
50.DeBattista, C, Doghramji, K, Menza, MA, Rosenthal, MH, Fieve, RR. 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(9): 1057–1064.CrossRefGoogle ScholarPubMed
51.Rizvi, SJ, Geraci, J, Ravindran, A, Kennedy, SH. Predictors of response to adjunctive osmotic-release methylphenidate or placebo in patients with major depressive disorder: effects of apathy/anhedonia and fatigue. J Clin Psychopharmacol. 2014; 34(6): 755–759.CrossRefGoogle ScholarPubMed
52.Zhou, X, Ravindran, AV, Qin, B, et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry. 2015; 76(4): e487–e498.CrossRefGoogle ScholarPubMed
53.Hollon, SD, DeRubeis, RJ, Fawcett, J, et al. Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2014; 71(10): 1157–1164.CrossRefGoogle ScholarPubMed
54.DeRubeis, RJ, Hollon, SD, Amsterdam, JD, et al. Cognitive therapy vs medications in the treatment of moderate to severe depression. Arch Gen Psychiatry. 2005; 62(4): 409–416.CrossRefGoogle ScholarPubMed
55.Fournier, JC, DeRubeis, RJ, Hollon, SD, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010; 303(1): 47–53.CrossRefGoogle ScholarPubMed
56.Hollon, SD, Ponniah, K. A review of empirically supported psychological therapies for mood disorders in adults. Depress Anxiety. 2010; 27(10): 891–932.CrossRefGoogle ScholarPubMed
57.Hirschfeld, RM, Dunner, DL, Keitner, G, et al. Does psychosocial functioning improve independent of depressive symptoms? A comparison of nefazodone, psychotherapy, and their combination. Biol Psychiatry. 2002; 51(2): 123–133.CrossRefGoogle ScholarPubMed
58.Thase, ME, Friedman, ES, Biggs, MM, et al. Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report. Am J Psychiatry. 2007; 164(5): 739–752.CrossRefGoogle ScholarPubMed
59.Pagnin, D, de QueirozV, V V, V, Pini, S, Cassano, GB. Efficacy of ECT in depression: a meta-analytic review. J ECT. 2004; 20(1): 13–20.CrossRefGoogle ScholarPubMed
60.Kellner, CH, Greenberg, RM, Murrough, JW, Bryson, EO, Briggs, MC, Pasculli, RM. ECT in treatment-resistant depression. Am J Psychiatry. 2012; 169(12): 1238–1244.CrossRefGoogle ScholarPubMed
61.Schulze-Rauschenbach, SC, Harms, U, Schlaepfer, TE, Maier, W, Falkai, P, Wagner, M. Distinctive neurocognitive effects of repetitive transcranial magnetic stimulation and electroconvulsive therapy in major depression. Br J Psychiatry. 2005; 186(5): 410–416.CrossRefGoogle ScholarPubMed
62.Grunhaus, L, Schreiber, S, Dolberg, OT, Polak, D, Dannon, PN. A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression. Biol Psychiatry. 2003; 53(4): 324–331.CrossRefGoogle ScholarPubMed
63.Grunhaus, L, Dannon, PN, Schreiber, S, et al. Repetitive transcranial magnetic stimulation is as effective as electroconvulsive therapy in the treatment of nondelusional major depressive disorder: an open study. Biol Psychiatry. 2000; 47(4): 314–324.CrossRefGoogle ScholarPubMed
64.Rasmussen, KG. Some considerations in choosing electroconvulsive therapy versus transcranial magnetic stimulation for depression. J ECT. 2011; 27(1): 51–54.CrossRefGoogle ScholarPubMed
65.Kennedy, SH, Giacobbe, P. Treatment resistant depression—advances in somatic therapies. Ann Clin Psychiatry. 2007; 19(4): 279–287.CrossRefGoogle ScholarPubMed
66.Thachil, AF, Mohan, R, Bhugra, D. The evidence base of complementary and alternative therapies in depression. J Affect Disord. 2007; 97(1–3): 23–35.CrossRefGoogle ScholarPubMed
67.Papakostas, GI, Mischoulon, D, Shyu, I, Alpert, JE, Fava, M. 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. 2010; 167(8): 942–948.CrossRefGoogle ScholarPubMed
68.Papakostas, GI, Shelton, RC, Zajecka, JM, et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry. 2012; 169(12): 1267–1274.CrossRefGoogle ScholarPubMed
69.Grosso, G, Pajak, A, Marventano, S, et al. Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS One. 2014; 9(5): e96905.CrossRefGoogle ScholarPubMed
70.Wan, LB, Levitch, CF, Perez, AM, et al. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015; 76(3): 247–252.CrossRefGoogle ScholarPubMed
71.Aligeti, S, Quinones, M, Salazar, R. Rapid resolution of suicidal behavior and depression with single low-dose ketamine intravenous push even after 6 months of follow-up. J Clin Psychopharmacol. 2014; 34(4): 533–535.CrossRefGoogle ScholarPubMed
72.Diazgranados, N, Ibrahim, LA, Brutsche, NE, et al. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry. 2010; 71(12): 1605–1611.CrossRefGoogle ScholarPubMed
73.Price, RB, Iosifescu, DV, Murrough, JW, et al. Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. Depress Anxiety. 2014; 31(4): 335–343.CrossRefGoogle ScholarPubMed
74.Niciu, MJ, Henter, ID, Luckenbaugh, DA, Zarate, CA Jr, Charney, DS. Glutamate receptor antagonists as fast-acting therapeutic alternatives for the treatment of depression: ketamine and other compounds. Annu Rev Pharmacol Toxicol. 2014; 54: 119–139.CrossRefGoogle ScholarPubMed
75.Yang, C, Shirayama, Y, Zhang, JC, et al. R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects. Transl Psychiatry. 2015; 5: e632.CrossRefGoogle ScholarPubMed
76.Pots, WT, Fledderus, M, Meulenbeek, PA, Ten Klooster, PM, Schreurs, KM, Bohlmeijer, ET. Acceptance and commitment therapy as a web-based intervention for depressive symptoms: randomised controlled trial. Br J Psychiatry In press. DOI: 10.1192/bjp.bp.114.146068.Google Scholar
77.Kelders, SM, Bohlmeijer, ET, Pots, WT, van Gemert-Pijnen, JE. Comparing human and automated support for depression: Fractional factorial randomized controlled trial. Behav Res Ther. 2015; 72: 72–80.CrossRefGoogle ScholarPubMed
78.Renton, T, Tang, H, Ennis, N, et al. Web-based intervention programs for depression: a scoping review and evaluation. J Med Internet Res. 2014; 16(9): e209.CrossRefGoogle ScholarPubMed
79.IsHak, WW, Mirocha, J, Pi, S, et al. Patient-reported outcomes before and after treatment of major depressive disorder. Dialogues Clin Neurosci. 2014; 16(2): 171–183.CrossRefGoogle ScholarPubMed
80.Papakostas, GI. Components of cognitive functioning and their measurement. J Clin Psychiatry. 2015; 76(6): e16.CrossRefGoogle Scholar
81.Jaeger, J, Berns, S, Uzelac, S, Davis-Conway, S. Neurocognitive deficits and disability in major depressive disorder. Psychiatry Res. 2006; 145(1): 39–48.CrossRefGoogle ScholarPubMed
82.Buist-Bouwman, MA, Ormel, J, de Graaf, R, et al. Mediators of the association between depression and role functioning. Acta Psychiatr Scand. 2008; 118(6): 451–458.CrossRefGoogle ScholarPubMed
83.McIntyre, RS, Soczynska, JZ, Woldeyohannes, HO, et al. The impact of cognitive impairment on perceived workforce performance: Results from the International Mood Disorders Collaborative Project. Compr Psychiatry. 2015; 56: 279–282.CrossRefGoogle ScholarPubMed
84.McIntyre, RS, Xiao, HX, Syeda, K, et al. The prevalence, measurement, and treatment of the cognitive dimension/domain in major depressive disorder. CNS Drugs. 2015; 29(7): 577–589.CrossRefGoogle ScholarPubMed
85.Insel, TR. The NIMH Research Domain Criteria (RDoC) project: precision medicine for psychiatry. Am J Psychiatry. 2014; 171(4): 395–397.CrossRefGoogle ScholarPubMed
86.Insel, T, Cuthbert, B, Garvey, M, et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 2010; 167(7): 748–751.CrossRefGoogle Scholar
87.McIntyre, RS, Lophaven, S, Olsen, CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol. 2014; 17(10): 1557–1567.CrossRefGoogle ScholarPubMed
88.Rosenblat, JD, Kakar, R, McIntyre, RS. The cognitive effects of antidepressants in major depressive disorder: a systematic review and meta-analysis of randomized clinical trials. Int J Neuropsychopharmacol In press. DOI: 10.1093/ijnp/pyv082.Google Scholar
89.Al-Sukhni, M, Maruschak, NA, McIntyre, RS. Vortioxetine: a review of efficacy, safety and tolerability with a focus on cognitive symptoms in major depressive disorder. Expert Opin Drug Saf. 2015; 14(8): 1291–1304.CrossRefGoogle ScholarPubMed
90.Katona, C, Hansen, T, Olsen, CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. Int Clin Psychopharmacol. 2012; 27(4): 215–223.CrossRefGoogle ScholarPubMed
91.Raskin, J, Wiltse, CG, Siegal, A, et al. Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: an 8-week, double-blind, placebo-controlled trial. Am J Psychiatry. 2007; 164(6): 900–909.CrossRefGoogle ScholarPubMed
92.Madhoo, M, Keefe, RS, Roth, RM, et al. Lisdexamfetamine dimesylate augmentation in adults with persistent executive dysfunction after partial or full remission of major depressive disorder. Neuropsychopharmacology. 2014; 39(6): 1388–1398.CrossRefGoogle ScholarPubMed
93.Moskal, JR, Burch, R, Burgdorf, JS, et al. GLYX-13, an NMDA receptor glycine site functional partial agonist enhances cognition and produces antidepressant effects without the psychotomimetic side effects of NMDA receptor antagonists. Expert Opin Investig Drugs. 2014; 23(2): 243–254.CrossRefGoogle ScholarPubMed
94.Lennox, R, Porter, DW, Flatt, PR, Holscher, C, Irwin, N, Gault, VA. Comparison of the independent and combined effects of sub-chronic therapy with metformin and a stable GLP-1 receptor agonist on cognitive function, hippocampal synaptic plasticity and metabolic control in high-fat fed mice. Neuropharmacology. 2014; 86: 22–30.CrossRefGoogle Scholar
95.McIntyre, RS, Powell, AM, Kaidanovich-Beilin, O, et al. The neuroprotective effects of GLP-1: possible treatments for cognitive deficits in individuals with mood disorders. Behav Brain Res. 2013; 237: 164–171.CrossRefGoogle ScholarPubMed
96.Goldstein, BI, Carnethon, MR, Matthews, KA, et al. Major depressive disorder and bipolar disorder predispose youth to accelerated atherosclerosis and early cardiovascular disease: a scientific statement from the American Heart Association. Circulation In press. DOI: 10.1161/CIR.0000000000000229.Google Scholar
97.Liu, CS, Carvalho, AF, Mansur, RB, McIntyre, RS. Obesity and bipolar disorder: synergistic neurotoxic effects? Adv Ther. 2013; 30(11): 987–1006.CrossRefGoogle ScholarPubMed
98.Lin, CH, Chen, CC, Wong, J, McIntyre, RS. Both body weight and BMI predicts improvement in symptom and functioning for patients with major depressive disorder. J Affect Disord. 2014; 161: 123–126.CrossRefGoogle ScholarPubMed
99.Rizvi, SJ, Grima, E, Tan, M, et al. Treatment-resistant depression in primary care across Canada. Can J Psychiatry. 2014; 59(7): 349–357.CrossRefGoogle ScholarPubMed
100.McCrimmon, RJ, Ryan, CM, Frier, BM. Diabetes and cognitive dysfunction. Lancet. 2012; 379(9833): 2291–2299.CrossRefGoogle ScholarPubMed
101.Nierenberg, AA, Sylvia, L, Doederlein, A, et al. Improving the care of patients who have treatment-resistant depression: the promise of the PCORnet Mood Network. J Clin Psychiatry. 2015; 76(4): e528–e530.CrossRefGoogle ScholarPubMed
102.Kucyi, A, Alsuwaidan, MT, Liauw, SS, McIntyre, RS. Aerobic physical exercise as a possible treatment for neurocognitive dysfunction in bipolar disorder. Postgrad Med. 2010; 122(6): 107–116.CrossRefGoogle ScholarPubMed
103.Masley, S, Roetzheim, R, Gualtieri, T. Aerobic exercise enhances cognitive flexibility. J Clin Psychol Med Settings. 2009; 16(2): 186–193.CrossRefGoogle ScholarPubMed
104.Davis, CL, Tomporowski, PD, Boyle, CA, et al. Effects of aerobic exercise on overweight children’s cognitive functioning: a randomized controlled trial. Res Q Exerc Sport. 2007; 78(5): 510–519.Google ScholarPubMed
105.Kubesch, S, Bretschneider, V, Freudenmann, R, et al. Aerobic endurance exercise improves executive functions in depressed patients. J Clin Psychiatry. 2003; 64(9): 1005–1012.CrossRefGoogle ScholarPubMed
106.Shay, KA, Roth, DL. Association between aerobic fitness and visuospatial performance in healthy older adults. Psychol Aging. 1992; 7(1): 15–24.CrossRefGoogle ScholarPubMed
107.Shelton, RC, Trivedi, MH. Using algorithms and computerized decision support systems to treat major depression. J Clin Psychiatry. 2011; 72(12): e36.CrossRefGoogle ScholarPubMed