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

  • Roger S. McIntyre (a1) (a2), Yena Lee (a3) and Rodrigo B. Mansur (a3)
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.

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Corresponding author
*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: roger.mcintyre@uhn.ca)
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This activity is supported by an unrestricted educational grant from Takeda Pharmaceuticals U.S.A., Inc.

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References
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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): 743800.
2.Kessler, RC. The costs of depression. Psychiatr Clin North Am. 2012; 35(1): 114.
3.McIntyre, RS, O’Donovan, C. The human cost of not achieving full remission in depression. Can J Psychiatry. 2004; 49(3 Suppl 1): 10S16S.
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): 155162.
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): 123171.
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.
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.
8.Collins, PY, Patel, V, Joestl, SS, et al. Grand challenges in global mental health. Nature. 2011; 475(7354): 2730.
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): 796800.
10.McIntyre, RS, Fallu, A, Konarski, JZ. Measurable outcomes in psychiatric disorders: remission as a marker of wellness. Clin Ther. 2006; 28(11): 18821891.
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): 15011504.
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): 375380.
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): 14391445.
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): 851855.
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): 11651174.
16.Mojtabai, R. Residual symptoms and impairment in major depression in the community. Am J Psychiatry. 2001; 158(10): 16451651.
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): 19111913.
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): 633641.
19.McIntyre, RS. Using measurement strategies to identify and monitor residual symptoms. J Clin Psychiatry. 2013; 74(Suppl 2): 1418.
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): 515527.
21.Mitchell, AJ, Vaze, A, Rao, S. Clinical diagnosis of depression in primary care: a meta-analysis. Lancet. 2009; 374(9690): 609619.
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): 11361143.
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): 213214.
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): 2840.
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): 782788.
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): 344353.
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): 11781184.
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): 14781484.
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): S26S43.
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): 743750.
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): 751759.
32.Gelenberg, AJ. A review of the current guidelines for depression treatment. J Clin Psychiatry. 2010; 71(7): e15.
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): 19051917.
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: 8494.
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): 528534.
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): 125133.
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): 980991.
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.
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): 420.
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): 397414.
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): 169177.
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): 181186.
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): 118124.
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): 497521.
45.Kast, RE. Mirtazapine may be useful in treating nausea and insomnia of cancer chemotherapy. Support Care Cancer. 2001; 9(6): 469470.
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): 281288.
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): 689701.
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): 8794.
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): 561569.
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): 10571064.
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): 755759.
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): e487e498.
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): 11571164.
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): 409416.
55.Fournier, JC, DeRubeis, RJ, Hollon, SD, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010; 303(1): 4753.
56.Hollon, SD, Ponniah, K. A review of empirically supported psychological therapies for mood disorders in adults. Depress Anxiety. 2010; 27(10): 891932.
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): 123133.
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): 739752.
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): 1320.
60.Kellner, CH, Greenberg, RM, Murrough, JW, Bryson, EO, Briggs, MC, Pasculli, RM. ECT in treatment-resistant depression. Am J Psychiatry. 2012; 169(12): 12381244.
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): 410416.
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): 324331.
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): 314324.
64.Rasmussen, KG. Some considerations in choosing electroconvulsive therapy versus transcranial magnetic stimulation for depression. J ECT. 2011; 27(1): 5154.
65.Kennedy, SH, Giacobbe, P. Treatment resistant depression—advances in somatic therapies. Ann Clin Psychiatry. 2007; 19(4): 279287.
66.Thachil, AF, Mohan, R, Bhugra, D. The evidence base of complementary and alternative therapies in depression. J Affect Disord. 2007; 97(1–3): 2335.
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): 942948.
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): 12671274.
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.
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): 247252.
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): 533535.
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): 16051611.
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): 335343.
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: 119139.
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.
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.
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: 7280.
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.
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): 171183.
80.Papakostas, GI. Components of cognitive functioning and their measurement. J Clin Psychiatry. 2015; 76(6): e16.
81.Jaeger, J, Berns, S, Uzelac, S, Davis-Conway, S. Neurocognitive deficits and disability in major depressive disorder. Psychiatry Res. 2006; 145(1): 3948.
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): 451458.
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: 279282.
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): 577589.
85.Insel, TR. The NIMH Research Domain Criteria (RDoC) project: precision medicine for psychiatry. Am J Psychiatry. 2014; 171(4): 395397.
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): 748751.
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): 15571567.
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.
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): 12911304.
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): 215223.
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): 900909.
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): 13881398.
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): 243254.
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: 2230.
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: 164171.
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.
97.Liu, CS, Carvalho, AF, Mansur, RB, McIntyre, RS. Obesity and bipolar disorder: synergistic neurotoxic effects? Adv Ther. 2013; 30(11): 9871006.
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: 123126.
99.Rizvi, SJ, Grima, E, Tan, M, et al. Treatment-resistant depression in primary care across Canada. Can J Psychiatry. 2014; 59(7): 349357.
100.McCrimmon, RJ, Ryan, CM, Frier, BM. Diabetes and cognitive dysfunction. Lancet. 2012; 379(9833): 22912299.
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): e528e530.
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): 107116.
103.Masley, S, Roetzheim, R, Gualtieri, T. Aerobic exercise enhances cognitive flexibility. J Clin Psychol Med Settings. 2009; 16(2): 186193.
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): 510519.
105.Kubesch, S, Bretschneider, V, Freudenmann, R, et al. Aerobic endurance exercise improves executive functions in depressed patients. J Clin Psychiatry. 2003; 64(9): 10051012.
106.Shay, KA, Roth, DL. Association between aerobic fitness and visuospatial performance in healthy older adults. Psychol Aging. 1992; 7(1): 1524.
107.Shelton, RC, Trivedi, MH. Using algorithms and computerized decision support systems to treat major depression. J Clin Psychiatry. 2011; 72(12): e36.
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