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Chapter 7 - Drugs to Treat Depression

from Part 2 - Psychopharmacology of the Main Psychotropic Drug Groups

Published online by Cambridge University Press:  29 May 2020

Peter M. Haddad
Hamad Medical Corporation, Qatar
David J. Nutt
Centre for Neuropsychopharmacology, Division of Psychiatry, Department of Brain Sciences, Imperial College London
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This chapter reviews the main drugs used in the treatment of unipolar depressive disorders. At the outset it should be noted that the term ‘antidepressant’ is problematic given that drugs traditionally regarded as ‘antidepressants’ are effective in treating psychiatric syndromes other than depression, most notably various anxiety disorders. Furthermore, some drugs not traditionally classified as ‘antidepressants’ are effective in treating depression either in monotherapy or as adjunctive agents to antidepressants. Examples of the former include lamotrigine and quetiapine, which have efficacy in treating bipolar depression, and lithium and some antipsychotics which are effective in augmenting the efficacy of reuptake inhibiting antidepressants in major depressive disorder. Despite these issues, the term ‘antidepressant’ is widely used and is likely to remain so.

Publisher: Cambridge University Press
Print publication year: 2020

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Aan Het Rot, M, Zarate, CA Jr, Charney, DS, Mathew, SJ (2012). Ketamine for depression: where do we go from here? Biol Psychiatry, 72(7), 537547. doi:10.1016/j.biopsych.2012.05.003.CrossRefGoogle Scholar
Aberg-Wistedt, A, Agren, H, Ekselius, L, Bengtsson, F, Akerblad, AC (2000). Sertraline versus paroxetine in major depression: clinical outcome after six months of continuous therapy. J Clin Psychopharmacol, 20, 645652.CrossRefGoogle ScholarPubMed
Adli, M, Baethge, C, Heinz, A, Langlitz, N, Bauer, M (2005). Is dose escalation of antidepressants a rational strategy after a medium-dose treatment has failed? A systematic review. Eur Arch Psychiatry Clin Neurosci, 255, 387400.CrossRefGoogle ScholarPubMed
Akerblad, AC, Bengtsson, F, von Knorring, L, Ekselius, L (2006). Response, remission and relapse in relation to adherence in primary care treatment of depression: a 2-year outcome study. Int Clin Psychopharmacol, 21, 117124.CrossRefGoogle ScholarPubMed
Alvarez, E, Perez, V, Artigas, F (2014). Pharmacology and clinical potential of vortioxetine in the treatment of major depressive disorder. Neuropsychiatr Dis Treat, 10, 12971307.CrossRefGoogle ScholarPubMed
American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington, VA: American Psychiatric Association.Google Scholar
Anderson, IM (2000). Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord, 58, 1936.Google Scholar
Anderson, IM (2001). Meta-analytical studies on new antidepressants. Br Med Bull, 57, 161178.Google Scholar
Anderson, IM (2003). Drug treatment of depression: reflections on the evidence. Adv Psychiatr Treat, 9, 1120.Google Scholar
Anglin, R, Yuan, Y, Moayyedi, P, et al. (2014). Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis. Am J Gastroenterol, 109(6), 811819. doi:10.1038/ajg.2014.82.Google Scholar
Angst, J, Scheidegger, P, Stabl, M (1993). Efficacy of moclobemide in different patient groups. Results of new subscales of the Hamilton Depression Rating Scale. Clin Neuropharmacol, 16(Suppl 2), S55S62.Google Scholar
Angst, J, Gamma, A, Bowden, CL, et al. (2012). Diagnostic criteria for bipolarity based on an international sample of 5,635 patients with DSM-IV major depressive episodes. Eur Arch Psychiatry Clin Neurosci, 262(1), 311. doi:10.1007/s00406-011-0228-0.CrossRefGoogle Scholar
Appelberg, BG, Syvalahti, EK, Koskinen, TE, et al. (2001). 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, 62, 448452.CrossRefGoogle ScholarPubMed
Aronson, R, Offman, HJ, Joffe, RT, Naylor, CD (1996). Triiodothyronine augmentation in the treatment of refractory depression. A meta-analysis. Arch Gen Psychiatry, 53, 842848.CrossRefGoogle ScholarPubMed
Bair, MJ, Robinson, RL, Eckert, GJ, et al. (2004). Impact of pain on depression treatment response in primary care. Psychosom Med, 66, 1722.Google Scholar
Baldessarini, RJ, Tondo, L, Ghiana, C, Lepri, B (2010). Illness risk following rapid versus gradual discontinuation of antidepressants. Am J Psychiatry, 167, 934994.Google Scholar
Baldwin, DS, Anderson, IM, Nutt, DJ, et al. (2005). Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J Psychopharmacol, 19, 567596.CrossRefGoogle ScholarPubMed
Barbee, JG, Thompson, TR, Jamhour, NJ, et al. (2011). A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression. J Clin Psychiatry, 72(10), 14051412. doi:10.4088/JCP.09m05355gre.Google Scholar
Barbosa, L, Berk, M, Vorster, M (2003). A double-blind, randomized, placebo-controlled trial of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes. J Clin Psychiatry, 64, 403407.Google Scholar
Bateman, DN (2003). Poisonous substances: antidepressants. Medicine, 31, 3234.Google Scholar
Bauer, M, Dell’osso, L, Kasper, S, et al. (2013). Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder. J Affect Disord, 151(1), 209219. doi:10.1016/j.jad.2013.05.079.CrossRefGoogle ScholarPubMed
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), 331342. doi:10.1007/s40263-014-0152-8.Google Scholar
Baumann, P, Ulrich, S, Eckermann, G, et al. (2005). The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants. Dialogues Clin Neurosci, 7, 231247.Google Scholar
Berman, RM, Marcus, RN, Swanink, R, et al. (2007). The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry, 68, 843853.CrossRefGoogle ScholarPubMed
Birkenhager, TK, van den Broek, WW, Moleman, P, Bruijn, JA (2006). Outcome of a 4-step treatment algorithm for depressed inpatients. J Clin Psychiatry, 67, 12661271.CrossRefGoogle ScholarPubMed
Blier, P, Gobbi, G, Turcotte, JE, et al. (2009). Mirtazapine and paroxetine in major depression: a comparison of monotherapy versus their combination from treatment initiation. Eur Neuropsychopharmacol, 19(7), 457465.CrossRefGoogle ScholarPubMed
Blier, P, Ward, HE, Tremblay, P, et al. (2010). Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. Am J Psychiatry, 167(3), 281288.Google Scholar
Bridge, JA, Iyengar, S, Salary, CB, et al. (2007). Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA, 297, 16831696.Google Scholar
Brown, WA (2007). Treatment response in melancholia. Acta Psychiatr Scand, 115(Suppl 433), 125129.CrossRefGoogle Scholar
Bryant, SG, Fisher, S, Kluge, RM (1987). Long-term versus short-term amitriptyline side effects as measured by a postmarketing surveillance system. J Clin Psychopharmacol, 7, 7882.Google Scholar
Buckley, NA, McManus, PR (2002). Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ, 325, 13321333.Google Scholar
Bukh, JD, Bock, C, Vinberg, M, Kessing, LV (2013). The effect of prolonged duration of untreated depression on antidepressant treatment outcome. J Affect Disord, 145(1), 4248. doi:10.1016/j.jad.2012.07.008.Google Scholar
Bump, GM, Mulsant, BH, Pollock, BG, et al. (2001). Paroxetine versus nortriptyline in the continuation and maintenance treatment of depression in the elderly. Depress Anxiety, 13, 3844.3.0.CO;2-7>CrossRefGoogle ScholarPubMed
Burke, WJ, Gergel, I, Bose, A (2002). Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry, 63, 331336.Google Scholar
Byrne, SE, Rothschild, AJ (1998). Loss of antidepressant efficacy during maintenance therapy: possible mechanisms and treatments. J Clin Psychiatry, 59, 279288.Google Scholar
Canuso, CM, Singh, JB, Fedgchin, M, et al. (2018). Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Am J Psychiatry, 175, 620630. doi:10.1176/appi.ajp.2018.17060720.CrossRefGoogle ScholarPubMed
Carpenter, LL, Yasmin, S, Price, LH (2002). A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine. Biol Psychiatry, 51, 183188.Google Scholar
Castro, VM, Clements, CC, Murphy, SN, et al. (2013). QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ, 346, f288. doi:10.1136/bmj.f288.Google Scholar
Cheeta, S, Schifano, F, Oyefeso, A, Webb, L, Ghodse, AH (2004). Antidepressant-related deaths and antidepressant prescriptions in England and Wales, 1998–2000. Br J Psychiatry, 184, 4147.Google Scholar
Cheng, YL, Hu, HY, Lin, XH, et al. (2015). Use of SSRI, but not SNRI, increased upper and lower gastrointestinal bleeding: a nationwide population-based cohort study in Taiwan. Medicine (Baltimore), 94(46), e2022. doi:10.1097/MD.0000000000002022.Google Scholar
Cipriani, A, Hawton, K, Stockton, S, Geddes, JR (2013). Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ, 346, f3646. ScholarPubMed
Cipriani, A, Furukawa, TA, Salanti, G, et al. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet, 391(10128), 13571366.Google Scholar
Cleare, A, Pariante, CM, Young, AH, et al. (2015). Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacology, 29(5), 459525.Google Scholar
Cramer, JA, Rosenheck, R (1998). Compliance with medication regimens for mental and physical disorders. Psychiatr Serv, 49, 196201.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, 935940.Google Scholar
Dawson, R, Lavori, PW, Coryell, WH, Endicott, J, Keller, MB (1998). Maintenance strategies for unipolar depression: an observational study of levels of treatment and recurrence. J Affect Disord, 49, 3144.CrossRefGoogle ScholarPubMed
de Abajo, FJ, Garcia-Rodriguez, LA (2008). Risk of upper gastrointestinal tract bleeding associated with selective serotonin reuptake inhibitors and venlafaxine therapy: interaction with nonsteroidal anti-inflammatory drugs and effect of acid-suppressing agents. Arch Gen Psychiatry, 65, 795803.Google Scholar
Delgado, PL (2004). Common pathways of depression and pain. J Clin Psychiatry, 65(Suppl 12), 1619.Google ScholarPubMed
Delgado, PL, Brannan, SK, Mallinckrodt, CH, et al. (2005). Sexual functioning assessed in 4 double-blind placebo- and paroxetine-controlled trials of duloxetine for major depressive disorder. J Clin Psychiatry, 66, 686692.CrossRefGoogle ScholarPubMed
Demyttenaere, K, Albert, A, Mesters, P, et al. (2005). What happens with adverse events during 6 months of treatment with selective serotonin reuptake inhibitors? J Clin Psychiatry, 66, 859863.Google Scholar
Detke, MJ, Wiltse, CG, Mallinckrodt, CH, et al. (2004). Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Neuropsychopharmacol, 14, 457470.Google Scholar
DeVeaugh-Geiss, AM, West, SL, Miller, WC, et al. (2010). The adverse effects of comorbid pain on depression outcomes in primary care patients: results from the ARTIST trial. Pain Med, 11(5), 732741. doi:10.1111/j.1526-4637.2010.00830.x.CrossRefGoogle ScholarPubMed
Dombrovski, AY, Mulsant, BH, Houck, PR, et al. (2007). Residual symptoms and recurrence during maintenance treatment of late-life depression. J Affect Disord, 103, 7782.CrossRefGoogle ScholarPubMed
Dornseif, BE, Dunlop, SR, Potvin, JH, Wernicke, JF (1989). Effect of dose escalation after low-dose fluoxetine therapy. Psychopharmacol Bull, 25, 7179.Google Scholar
Dotoli, D, Spagnolo, C, Bongiorno, F, et al. (2006). Relapse during a 6-month continuation treatment with fluvoxamine in an Italian population: the role of clinical, psychosocial and genetic variables. Prog Neuropsychopharmacol Biol Psychiatry, 30, 442448.Google Scholar
Dubini, A, Bosc, M, Polin, V (1997). Noradrenaline-selective versus serotonin-selective antidepressant therapy: differential effects on social functioning. J Psychopharmacol, 11, S17S23.Google Scholar
Edwards, JG, Anderson, I (1999). Systematic review and guide to selection of selective serotonin reuptake inhibitors. Drugs, 57(4), 507533.Google Scholar
El-Khalili, N, Joyce, M, Atkinson, S, et al. (2010). Extended-release quetiapine fumerate (quetiapine XR) as adjunctive therapy in major depressive disorder (MDD) in patients with an inadequate response to ongoing antidepressant treatment: a multicentre, randomized, double-blind, placebo-controlled study. Int J Neuropsychopharmacol, 13, 917932.CrossRefGoogle Scholar
Ezquiaga, E, Garcia, A, Bravo, F, Pallares, T (1998). Factors associated with outcome in major depression: a 6-month prospective study. Soc Psychiatry Psychiatr Epidemiol, 33, 552557.Google Scholar
Fava, GA, Ruini, C, Rafanelli, C, Grandi, S (2002). Cognitive behavior approach to loss of clinical effect during long-term antidepressant treatment: a pilot study. Am J Psychiatry, 159, 20942095.Google Scholar
Fava, M, Rappe, SM, Pava, JA, et al. (1995). Relapse in patients on long-term fluoxetine treatment: response to increased fluoxetine dose. J Clin Psychiatry, 56, 5255.Google Scholar
Fava, M, Uebelacker, LA, Alpert, JE, et al. (1997). Major depressive subtypes and treatment response. Biol Psychiatry, 42, 568576.Google Scholar
Fava, M, Detke, MJ, Balestrieri, M, et al. (2006). Management of depression relapse: re-initiation of duloxetine treatment or dose increase. J Psychiatr Res, 40, 328336.Google Scholar
Fava, M, Thase, ME, DeBattista, C, et al. (2007). Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness. Ann Clin Psychiatry, 19, 153159.Google Scholar
Fekadu, A, Wooderson, S, Donaldson, C, et al. (2009). A multidimensional tool to quantify treatment resistance in depression: the Maudsley staging method. J Clin Psychiatry, 70, 177184.CrossRefGoogle ScholarPubMed
Fekadu, A, Donocik, J, Cleare, AJ (2018). Standardisation framework for the Maudsley staging method for treatment resistance in depression. BMC Psychiatry, 18, 100. Available at: Scholar
Fergusson, D, Doucette, S, Glass, KC, et al. (2005). Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ, 330, 396.Google Scholar
Ferreri, M, Lavergne, F, Berlin, I, Payan, C, Puech, AJ (2001). Benefits from mianserin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone. Acta Psychiatr Scand, 103, 6672.Google Scholar
Flint, AJ, Rifat, SL (1998). Two-year outcome of psychotic depression in late life. Am J Psychiatry, 155, 178183.Google Scholar
Fond, G, Loundou, A, Rabu, C, et al. (2014). Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology (Berl), 231(18), 36633676. doi:10.1007/s00213-014-3664-5.Google Scholar
Franchini, L, Gasperini, M, Zanardi, R, Smeraldi, E (2000a). Four-year follow-up study of sertraline and fluvoxamine in long-term treatment of unipolar subjects with high recurrence rate. J Affect Disord, 58, 233236.Google Scholar
Franchini, L, Rossini, D, Bongiorno, F, et al. (2000b). Will a second prophylactic treatment with a higher dosage of the same antidepressant either prevent or delay new depressive episodes? Psychiatry Res, 96, 8185.Google Scholar
Frank, E, Kupfer, DJ, Perel, JM, et al. (1990). Three-year outcomes for maintenance therapies in recurrent depression. Arch Gen Psychiatry, 47, 10931099.Google Scholar
Frank, E, Kupfer, DJ, Perel, JM, et al. (1993). Comparison of full-dose versus half-dose pharmacotherapy in the maintenance treatment of recurrent depression. J Affect Disord, 27, 139145.CrossRefGoogle ScholarPubMed
Furukawa, TA, McGuire, H, Barbui, C (2002). Meta-analysis of effects and side effects of low dosage tricyclic antidepressants in depression: systematic review. BMJ, 325, 991.Google Scholar
Geddes, JR, Carney, SM, Davies, C, et al. (2003). Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet, 361, 653661.Google Scholar
Ghaziuddin, M, Ghaziuddin, N, Stein, GS (1990). Life events and the recurrence of depression. Can J Psychiatry, 35, 239242.Google Scholar
Gibbons, RD, Brown, CH, Hur, K, et al. (2007). Early evidence on the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry, 164, 13561363.Google Scholar
Gijsman, HJ, Geddes, JR, Rendell, JM, et al. (2004). Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry, 161 15371547.Google Scholar
Goldstein, DJ, Lu, Y, Detke, MJ, et al. (2004). Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol, 24, 389399.CrossRefGoogle ScholarPubMed
Goodwin, GM, Haddad, PM, Ferrier, IN, et al. (2016). Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol, 30(6), 495553.CrossRefGoogle ScholarPubMed
Greden, JF (1993). Antidepressant maintenance medications: when to discontinue and how to stop. J Clin Psychiatry, 54 Suppl, 3945.Google ScholarPubMed
Greist, J, McNamara, RK, Mallinckrodt, CH, Rayamajhi, JN, Raskin, J (2004). Incidence and duration of antidepressant-induced nausea: duloxetine compared with paroxetine and fluoxetine. Clin Ther, 26, 14461455.Google Scholar
Gunnell, D, Saperia, J, Ashby, D (2005). Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA’s safety review. BMJ, 330, 385.Google Scholar
Guo, T, Xiang, YT, Xiao, L, et al. (2015). Measurement-based care versus standard care for major depression: a randomized controlled trial with blind raters. Am J Psychiatry, 172(10), 10041013.Google Scholar
Gusmao, R, Quintao, S, McDaid, D, et al. (2013). Antidepressant utilization and suicide in Europe: an ecological multi-national study. PLoS One, 8, e66455.Google Scholar
Haddad, PM, Anderson, IM (2002). Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs, 62, 16491671.CrossRefGoogle ScholarPubMed
Halperin, D, Reber, G (2007). Influence of antidepressants on hemostasis. Dialogues Clin Neurosci, 9, 4759.Google Scholar
Hammerlein, A, Derendorf, H, Lowenthal, DT (1998). Pharmacokinetic and pharmacodynamic changes in the elderly. Clinical implications. Clin Pharmacokinet, 35, 4964.Google Scholar
Hansen, R, Gaynes, B, Thieda, P, et al. (2008). Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants. Psychiatr Serv, 59(10), 11211130. doi:10.1176/ Scholar
Hawton, K, Bergen, H, Simkin, S, et al. (2010). Toxicity of antidepressants: rates of suicide relative to prescribing and non-fatal overdose. Br J Psychiatry, 196(5), 354358. doi:10.1192/bjp.bp.109.070219.Google Scholar
Healy, D, McMonagle, T (1997). The enhancement of social functioning as a therapeutic principle in the management of depression. J Psychopharmacol, 11, S25S31.Google Scholar
Henkel, V, Mergl, R, Allgaier, AK, et al. (2006). Treatment of depression with atypical features: a meta-analytic approach. Psychiatry Res, 141, 89101.Google Scholar
Hoffman, L, Enders, J, Luo, J, et al. (2003). Impact of an antidepressant management program on medication adherence. Am J Manag Care, 9, 7080.Google ScholarPubMed
Howland, RH (2010). Potential adverse effects of discontinuing psychotropic drugs: part 2: antidepressant drugs. J Psychosoc Nurs Ment Health Serv, 48, 912. doi:10.3928/02793695-20100527-98.Google ScholarPubMed
Iosifescu, DV, Nierenberg, AA, Alpert, JE, et al. (2004). Comorbid medical illness and relapse of major depressive disorder in the continuation phase of treatment. Psychosomatics, 45, 419425.Google Scholar
Isbister, GK, Bowe, SJ, Dawson, A, Whyte, IM (2004). Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol, 42, 277285.Google Scholar
Jacobsen, PL, Mahableshwarkar, AR, Palo, WA, et al. (2016). Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis. CNS Spectr, 21, 367378.Google Scholar
Jick, H, Kaye, JA, Jick, SS (2004). Antidepressants and the risk of suicidal behaviors. JAMA, 292, 338343.Google Scholar
Joint Formulary Committee (2018). British National Formulary, 75th ed. London: BMJ Group and Pharmaceutical Press.Google Scholar
Kanai, T, Takeuchi, H, Furukawa, TA, et al. (2003). Time to recurrence after recovery from major depressive episodes and its predictors. Psychol Med, 33, 839845.Google Scholar
Karp, JF, Scott, J, Houck, P, et al. (2005). Pain predicts longer time to remission during treatment of recurrent depression. J Clin Psychiatry, 66, 591597.CrossRefGoogle ScholarPubMed
Katz, MM, Tekell, JL, Bowden, CL, et al. (2004). Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression. Neuropsychopharmacology, 29, 566579.Google Scholar
Kessing, LV (1998). Recurrence in affective disorder. II. Effect of age and gender. Br J Psychiatry, 172, 2934.Google Scholar
Kessing, LV (2003). Subtypes of depressive episodes according to ICD-10: prediction of risk of relapse and suicide. Psychopathology, 36, 285291.Google Scholar
Kessing, LV (2007). Epidemiology of subtypes of depression. Acta Psychiatr Scand, 433 Suppl, 8589.Google Scholar
Kessing, LV, Andersen, PK (2005). Predictive effects of previous episodes on the risk of recurrence in depressive and bipolar disorders. Curr Psychiatry Rep, 7, 413420.Google Scholar
Kessler, D, Burns, A, Tallon, D, et al. (2018). Combining mirtazapine with SSRIs or SNRIs for treatment-resistant depression: the MIR RCT. Health Technol Assess, 22(63), 1136.Google Scholar
Köhler-Forsberg, O, Lydholm, N, Hjorthøj, C, et al. (2019). Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials. Acta Psychiatr Scand, 139, 404419.Google Scholar
Lader, M (1983). Combined use of tricyclic antidepressants and monoamine oxidase inhibitors. J Clin Psychiatry, 44, 2024.Google Scholar
Lam, RW, Gorman, CP, Michalon, M, et al. (1995). Multicenter, placebo-controlled study of fluoxetine in seasonal affective disorder. Am J Psychiatry, 152, 17651770.Google Scholar
Landen, M, Bjorling, G, Agren, H, Fahlen, T (1998). A randomized, double-blind, placebo-controlled trial of buspirone in combination with an SSRI in patients with treatment-refractory depression. J Clin Psychiatry, 59, 664668.Google Scholar
Lee, P, Shu, L, Xu, X, et al. (2007). Once-daily duloxetine 60 mg in the treatment of major depressive disorder: multicenter, double-blind, randomized, paroxetine-controlled, non-inferiority trial in China, Korea, Taiwan and Brazil. Psychiatry Clin Neurosci, 61, 295307.Google Scholar
Leinonen, E, Skarstein, J, Behnke, K, Agren, H, Helsdingen, JT (1999). Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group. Int Clin Psychopharmacol, 14, 329337.Google Scholar
Leucht, S, Hierl, S, Kissling, W, Dold, M, Davis, JM (2012). Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses. Br J Psychiatry, 200(2), 97106. doi:10.1192/bjp.bp.111.096594.Google Scholar
Leuchter, AF, Husain, MM, Cook, IA, et al. (2010). Painful physical symptoms and treatment outcome in major depressive disorder: a STAR*D (Sequenced Treatment Alternatives to Relieve Depression) report. Psychol Med, 40(2), 239251. doi:10.1017/S0033291709006035.Google Scholar
Licht, RW, Qvitzau, S (2002). Treatment strategies in patients with major depression not responding to first-line sertraline treatment. A randomised study of extended duration of treatment, dose increase or mianserin augmentation. Psychopharmacology (Berl), 161, 143151.Google Scholar
Lonnqvist, J, Sihvo, S, Syvalahti, E, et al. (1995). Moclobemide and fluoxetine in the prevention of relapses following acute treatment of depression. Acta Psychiatr Scand, 91, 189194.Google Scholar
Maes, M, Libbrecht, I, van Hunsel, F, Campens, D, Meltzer, HY (1999). Pindolol and mianserin augment the antidepressant activity of fluoxetine in hospitalized major depressed patients, including those with treatment resistance. J Clin Psychopharmacol, 19, 177182.Google Scholar
Maidment, R, Livingston, G, Katona, C (2002). Just keep taking the tablets: adherence to antidepressant treatment in older people in primary care. Int J Geriatr Psychiatry, 17(8), 752757.Google Scholar
Masand, PS, Gupta, S (2002). Long-term side effects of newer-generation antidepressants: SSRIs, venlafaxine, nefazodone, bupropion, and mirtazapine. Ann Clin Psychiatry, 14, 175182.CrossRefGoogle ScholarPubMed
Mazure, CM, Bruce, ML, Maciejewski, PK, Jacobs, SC (2000). Adverse life events and cognitive-personality characteristics in the prediction of major depression and antidepressant response. Am J Psychiatry, 157, 896903.Google Scholar
McAllister-Williams, RH, Christmas, D, Cleare, AJ, et al. (2018). Multiple-therapy-resistant-major depressive disorder: a clinically important concept. Br J Psychiatry, 212(5), 274278. doi:10.1192/bjp.2017.33.Google Scholar
McGirr, A, Berlim, MT, Bond, DJ, et al. (2015). A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med, 45(4), 693704. doi:10.1017/S0033291714001603.Google Scholar
McGrath, PJ, Stewart, JW, Fava, M, et al. (2006a). Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry, 163, 15311541.Google Scholar
McGrath, PJ, Stewart, JW, Quitkin, FM, et al. (2006b). Predictors of relapse in a prospective study of fluoxetine treatment of major depression. Am J Psychiatry, 163, 15421548.Google Scholar
McLaughlin, T, Hogue, SL, Stang, PE (2007). Once-daily bupropion associated with improved patient adherence compared with twice-daily bupropion in treatment of depression. Am J Ther, 14, 221225.Google Scholar
Medhus, A, Heskestad, S, Tjemsland, L (1994). Mianserin added to tricyclic antidepressant in depressed patients not responding to a tricyclic antidepressant alone. A randomised, placebo-controlled, double-blind trial. Nord J Psychiatry, 48, 355358.Google Scholar
Medicines and Healthcare products Regulatory Agency (2011). Citalopram and escitalopram: QT interval prolongation (online). Available at: (last accessed 16.10.19).Google Scholar
Melander, H, Salmonson, T, Abadie, E, et al. (2008). A regulatory Apologia – a review of placebo-controlled studies in regulatory submissions of new-generation antidepressants. Eur Neuropsychopharmacol, 18(9), 623627.CrossRefGoogle ScholarPubMed
Modell, JG, Rosenthal, NE, Harriett, AE, et al. (2005). Seasonal affective disorder and its prevention by anticipatory treatment with bupropion XL. Biol Psychiatry, 58, 658667.Google Scholar
Montgomery, SA, Reimitz, PE, Zivkov, M (1998). Mirtazapine versus amitriptyline in the long-term treatment of depression: a double-blind placebo-controlled study. Int Clin Psychopharmacol, 13, 6367.Google Scholar
Morgan, ML, Cook, IA, Rapkin, AJ, Leuchter, AF (2005). Estrogen augmentation of antidepressants in perimenopausal depression: a pilot study. J Clin Psychiatry, 66, 774780.Google Scholar
Morgan, O, Griffiths, C, Baker, A, Majeed, A (2004). Fatal toxicity of antidepressants in England and Wales, 1993–2002. Health Stat Q, 23, 1824.Google Scholar
Moscovitch, A, Blashko, CA, Eagles, JM, et al. (2004). A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder. Psychopharmacology (Berl), 171, 390397.Google Scholar
Mueller, TI, Leon, AC, Keller, MB, et al. (1999). Recurrence after recovery from major depressive disorder during 15 years of observational follow-up. Am J Psychiatry, 156, 10001006.Google Scholar
Murrough, JW, Iosifescu, DV, Chang, LC, et al. (2013a). Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry, 170(10), 11341142. doi:10.1176/appi.ajp.2013.13030392.Google Scholar
Murrough, JW, Perez, AM, Pillemer, S, et al. (2013b). Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry, 74(4), 250256. doi:10.1016/j.biopsych.2012.06.022.Google Scholar
National Institute for Clinical Excellence (2004). Depression: the management of depression in primary and secondary care. Clinical guideline [CG23]. Available at: (last accessed 20.10.19).Google Scholar
National Institute for Health and Clinical Excellence (NICE) (2009). Depression in adults: the treatment and management of depression in adults (update). Clinical guideline [CG90]. London: National Institute for Health and Care Excellence. Available at: (last accessed 16.10.19).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), 980991. doi:10.1176/appi.ajp.2009.09030312.Google Scholar
Nelson, JC, Portera, L, Leon, AC (2005a). Are there differences in the symptoms that respond to a selective serotonin or norepinephrine reuptake inhibitor? Biol Psychiatry, 57, 15351542.Google Scholar
Nelson, JC, Portera, L, Leon, AC (2005b). Residual symptoms in depressed patients after treatment with fluoxetine or reboxetine. J Clin Psychiatry, 66, 14091414.Google Scholar
Nierenberg, AA, McLean, NE, Alpert, JE, et al. (1995). Early nonresponse to fluoxetine as a predictor of poor 8-week outcome. Am J Psychiatry, 152, 15001503.Google Scholar
Nierenberg, AA, Farabaugh, AH, Alpert, JE, et al. (2000). Timing of onset of antidepressant response with fluoxetine treatment. Am J Psychiatry, 157, 14231428.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, 15191530.Google Scholar
Nurnberg, H, Hensley, PL, Heiman, JR, et al. (2008). Sildenafil treatment of women with antidepressant-associated sexual dysfunction: a randomized controlled trial. JAMA, 300, 395404.Google Scholar
Ohayon, MM, Schatzberg, AF (2003). Using chronic pain to predict depressive morbidity in the general population. Arch Gen Psychiatry, 60, 3947.Google Scholar
Okuda, A, Suzuki, T, Kishi, T, et al. (2010). Duration of untreated illness and antidepressant fluvoxamine response in major depressive disorder. Psychiatry Clin Neurosci, 64(3), 268273. doi:10.1111/j.1440-1819.2010.02091.x.Google Scholar
Pacchiarotti, I, Bond, DJ, Baldessarini, RJ, et al. (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. Am J Psychiatry, 170(11), 12491262. doi:10.1176/appi.ajp.2013.13020185.CrossRefGoogle ScholarPubMed
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), 699704.CrossRefGoogle ScholarPubMed
Parker, G (2000). Classifying depression: should paradigms lost be regained? Am J Psychiatry, 157, 11951203.Google Scholar
Partonen, T, Lonnqvist, J (1996). Moclobemide and fluoxetine in treatment of seasonal affective disorder. J Affect Disord, 41, 9399.Google Scholar
Paykel, ES, Tanner, J (1976). Life events, depressive relapse and maintenance treatment. Psychol Med, 6, 481485.Google Scholar
Paykel, ES, Ramana, R, Cooper, Z, et al. (1995). Residual symptoms after partial remission: an important outcome in depression. Psychol Med, 25, 11711180.Google Scholar
Perahia, DG, Wang, F, Mallinckrodt, CH, Walker, DJ, Detke, MJ (2006). Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Psychiatry, 21, 367378.Google Scholar
Perahia, DG, Pritchett, YL, Kajdasz, DK, et al. (2008). A randomized, double-blind comparison of duloxetine and venlafaxine in the treatment of patients with major depressive disorder. J Psychiatr Res, 42, 2234.Google Scholar
Petersen, I, Gilbert, RE, Evans, SJ, Man, SL, Nazareth, I (2011). Pregnancy as a major determinant for discontinuation of antidepressants: an analysis of data from The Health Improvement Network. J Clin Psychiatry, 72(7), 979985. doi:10.4088/JCP.10m06090blu.Google Scholar
Pope, HG Jr, Cohane, GH, Kanayama, G, Siegel, AJ, Hudson, JI (2003). Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry, 160(1), 105111.Google Scholar
Pope, HG, Amiaz, R, Brennan, BP, et al. (2010). Parallel-group placebo-controlled trial of testosterone gel in men with major depressive disorder displaying an incomplete response to standard antidepressant treatment. J Clin Psychopharmacol, 30(2), 126134. doi:10.1097/JCP.0b013e3181d207ca.Google Scholar
Posternak, MA, Zimmerman, M (2005). Is there a delay in the antidepressant effect? A meta-analysis. J Clin Psychiatry, 66, 148158.Google Scholar
Posternak, MA, Zimmerman, M (2007). Therapeutic effect of follow-up assessments on antidepressant and placebo response rates in antidepressant efficacy trials: meta-analysis. Br J Psychiatry, 190, 287292.Google Scholar
Posternak, MA, Solomon, DA, Leon, AC, et al. (2006). The naturalistic course of unipolar major depression in the absence of somatic therapy. J Nerv Ment Dis, 194, 324329.Google Scholar
Quitkin, FM, Petkova, E, McGrath, PJ, et al. (2003). When should a trial of fluoxetine for major depression be declared failed? Am J Psychiatry, 160, 734740.Google Scholar
Raison, CL, Rutherford, RE, Woolwine, BJ, et al. (2013). A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry, 70(1), 3141. doi:10.1001/2013.jamapsychiatry.4.Google Scholar
Ramana, R, Paykel, ES, Cooper, Z, et al. (1995). Remission and relapse in major depression: a two-year prospective follow-up study. Psychol Med, 25, 11611170.CrossRefGoogle ScholarPubMed
Reimherr, FW, Amsterdam, JD, Quitkin, FM, et al. (1998). Optimal length of continuation therapy in depression: a prospective assessment during long-term fluoxetine treatment. Am J Psychiatry, 155, 12471253.Google Scholar
Reimherr, FW, Strong, RE, Marchant, BK, Hedges, DW, Wender, PH (2001). Factors affecting return of symptoms 1 year after treatment in a 62-week controlled study of fluoxetine in major depression. J Clin Psychiatry, 62(Suppl 22), 1623.Google Scholar
Reis, M, Aamo, T, Spigset, O, Ahlner, J (2009). Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database. Ther Drug Monit, 31(1), 4256. doi:10.1097/FTD.0b013e31819114ea.Google Scholar
Reynolds, CF, III, Perel, JM, Frank, E, et al. (1999). Three-year outcomes of maintenance nortriptyline treatment in late-life depression: a study of two fixed plasma levels. Am J Psychiatry, 156, 11771181.Google Scholar
Reynolds, CF, III, Dew, MA, Pollock, BG, et al. (2006). Maintenance treatment of major depression in old age. N Engl J Med, 354, 11301138.Google Scholar
Robinson, P, Katon, W, Von Korff, M, et al. (1997). The education of depressed primary care patients: what do patients think of interactive booklets and a video?J Fam Pract, 44, 562571.Google Scholar
Rojo, JE, Ros, S, Aguera, L, de la Gandara, J, de Pedro, JM (2005). Combined antidepressants: clinical experience. Acta Psychiatr Scand Suppl, 428, 2531.Google Scholar
Ronalds, C, Creed, F, Stone, K, Webb, S, Tomenson, B (1997). The outcome of anxiety and depressive disorders in general practice. Br J Psychiatry, 171, 427433.Google Scholar
Rouillon, F, Serrurier, D, Miller, HD, Gerard, MJ (1991). Prophylactic efficacy of maprotiline on unipolar depression relapse. J Clin Psychiatry, 52, 423431.Google ScholarPubMed
Rudolph, RL, Fabre, LF, Feighner, JP, et al. (1998). A randomized, placebo-controlled, dose-response trial of venlafaxine hydrochloride in the treatment of major depression. J Clin Psychiatry, 59, 116122.Google Scholar
Ruhe, HG, Huyser, J, Swinkels, JA, Schene, AH (2006). Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review. J Clin Psychiatry, 67, 18361855.Google Scholar
Rush, AJ, Trivedi, MH, Wisniewski, SR, et al. (2006a). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry, 163, 19051917.Google Scholar
Rush, AJ, Trivedi, MH, Wisniewski, SR, et al. (2006b). Bupropion-SR, sertraline or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med, 354, 12311242.Google Scholar
Rush, AJ, Trivedi, MH, Stewart, JW, 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, 689701.Google Scholar
Sachs, GS, Nierenberg, AA, Calabrese, JR, et al. (2007). Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med, 356(17), 17111722.Google Scholar
Sansone, RA, Sansone, LA (2012). Antidepressant adherence: are patients taking their medications? Innov Clin Neurosci, 9(5–6), 4146.Google Scholar
Schindler, F, Anghelescu, IG (2007). Lithium versus lamotrigine augmentation in treatment resistant unipolar depression: a randomized, open-label study. Int Clin Psychopharmacol, 22, 179182.Google Scholar
Schmidt, ME, Fava, M, Zhang, S, et al. (2002). Treatment approaches to major depressive disorder relapse. Part 1: dose increase. Psychother Psychosom, 71, 9094.Google Scholar
Schueler, Y-B, Koesters, M, Wieseler, B, et al. (2011). A systematic review of duloxetine and venlafaxine in major depression, including unpublished data. Acta Psychiatr Scand, 123, 247265.Google Scholar
Schweizer, E, Rynn, M, Mandos, LA, et al. (2001). The antidepressant effect of sertraline is not enhanced by dose titration: results from an outpatient clinical trial. Int Clin Psychopharmacol, 16, 137143.Google Scholar
Servier Laboratories Limited (2012). SPC for Valdoxan.Google Scholar
Simon, GE, Savarino, J (2007). Suicide attempts among patients starting depression treatment with medications or psychotherapy. Am J Psychiatry, 164, 10291034.Google Scholar
Simon, GE, Savarino, J, Operskalski, B, Wang, PS (2006). Suicide risk during antidepressant treatment. Am J Psychiatry, 163, 4147.Google Scholar
Solomon, DA, Keller, MB, Leon, AC, et al. (2000). Multiple recurrences of major depressive disorder. Am J Psychiatry, 157, 229233.Google Scholar
Solomon, DA, Leon, AC, Mueller, TI, et al. (2005). Tachyphylaxis in unipolar major depressive disorder. J Clin Psychiatry, 66, 283290.Google Scholar
Spielmans, GI, Berman, MI, Linardatos, E, et al. (2013). Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS Med, 10(3), e1001403.Google Scholar
Spina, E, Santoro, V, D’Arrigo, C (2008). Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update. Clin Ther, 30(7), 12061227.Google Scholar
Stassen, HH, Angst, J, Delini-Stula, A (1996). Delayed onset of action of antidepressant drugs? Survey of results of Zurich meta-analyses. Pharmacopsychiatry, 29, 8796.Google Scholar
Strawbridge, R, Carter, B, Marwood, L, et al. (2019). Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis. Br J Psychiatry, 214(1), 4251. doi:10.1192/bjp.2018.233.Google Scholar
Suppes, T, Silva, R, Cucchiaro, J, et al. (2016). Lurasidone for the treatment of major depressive disorder with mixed features: a randomized, double-blind, placebo-controlled study. Am J Psychiatry, 173, 400407.Google Scholar
Szegedi, A, Muller, MJ, Anghelescu, I, et al. (2003). Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression. J Clin Psychiatry, 64, 413420.Google Scholar
Targownik, LE, Bolton, JM, Metge, CJ, Leung, S, Sareen, J (2009). Selective serotonin reuptake inhibitors are associated with a modest increase in the risk of upper gastrointestinal bleeding. Am J Gastroenterol, 104(6), 14751482. doi:10.1038/ajg.2009.128.Google Scholar
Taylor, D, Cornelius, V, Smith, L, Young, AH (2014). Comparative efficacy and acceptability of drug treatments for bipolar depression: a multiple-treatments meta-analysis. Acta Psychiatr Scand, 130(6), 452469. doi:10.1111/acps.12343.Google Scholar
Taylor, D, Barnes, TRE, Young, A (2018). The Maudsley Prescribing Guidelines in Psychiatry, 13th ed. Wiley-Blackwell.Google Scholar
Taylor, MJ, Freemantle, N, Geddes, JR, Bhagwagar, Z (2006). Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Arch Gen Psychiatry, 63, 12171223.Google Scholar
Taylor, MJ, Rudkin, L, Bullemor-Day, P, et al. (2013). Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database Syst Rev, (5), CD003382. doi:10.1002/14651858.CD003382.pub3.Google Scholar
Thanacoody, HK, Thomas, SH (2005). Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev, 24, 205214.Google Scholar
Thase, ME (2006). Preventing relapse and recurrence of depression: a brief review of therapeutic options. CNS Spectr, 11, 1221.Google Scholar
Thase, ME, Trivedi, MH, Rush, AJ (1995). MAOIs in the contemporary treatment of depression. Neuropsychopharmacology, 12, 185219.Google Scholar
Thase, ME, Shelton, RC, Khan, A (2006). Treatment with venlafaxine extended release after SSRI nonresponse or intolerance: a randomized comparison of standard- and higher-dosing strategies. J Clin Psychopharmacol, 26, 250258.Google Scholar
Thase, ME, Larsen, KG, Reines, E, Kennedy, SH (2013). The cardiovascular safety profile of escitalopram. Eur Neuropsychopharmacol, 23(11), 13911400. doi:10.1016/j.euroneuro.2013.05.011.Google Scholar
Thase, ME, Mahableshwarkar, AR, Dragheim, M, Loft, H, Vieta, E (2016). A meta-analysis of randomized, placebo-controlled trials of vortioxetine for the treatment of major depressive disorder in adults. Eur Neuropsychopharmacol, 26, 979993.Google Scholar
Tint, A, Haddad, PM, Anderson, IM (2008). The effect of rate of antidepressant tapering on the incidence of discontinuation symptoms: a randomised study. J Psychopharmacol, 22(3), 330332.Google Scholar
Tomaszewska, W, Peselow, ED, Barouche, F, Fieve, RR (1996). Antecedent life events, social supports and response to antidepressants in depressed patients. Acta Psychiatr Scand, 94, 352357.Google Scholar
Trivedi, MH, Fava, M, Wisniewski, SR, et al. (2006a). Medication augmentation after the failure of SSRIs for depression. N Engl J Med, 354, 12431252.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, 2840.Google Scholar
Uher, R, Maier, W, Hauser, J, et al. (2009). Differential efficacy of escitalopram and nortriptyline on dimensional measures of depression. Br J Psychiatry, 194, 252259. doi:10.1192/bjp.bp.108.057554.Google Scholar
Vallejo, J, Gasto, C, Catalan, R, Bulbena, A, Menchon, JM (1991). Predictors of antidepressant treatment outcome in melancholia: psychosocial, clinical and biological indicators. J Affect Disord, 21, 151162.Google Scholar
Vergouwen, AC, Bakker, A, Katon, WJ, Verheij, TJ, Koerselman, F (2003). Improving adherence to antidepressants: a systematic review of interventions. J Clin Psychiatry, 64, 14151420.Google Scholar
Vieta, E, Bauer, M, Montgomery, S, et al. (2013). Pooled analysis of sustained response rates for extended release quetiapine fumarate as monotherapy or adjunct to antidepressant therapy in patients with major depressive disorder. J Affect Disord, 150(2), 639643. doi:10.1016/j.jad.2013.01.052.Google Scholar
Walsh, BT, Seidman, SN, Sysko, R, Gould, M (2002). Placebo response in studies of major depression: variable, substantial, and growing. JAMA, 287, 18401847.Google Scholar
Walters, G, Reynolds, CF, III, Mulsant, BH, Pollock, BG (1999). Continuation and maintenance pharmacotherapy in geriatric depression: an open-trial comparison of paroxetine and nortriptyline in patients older than 70 years. J Clin Psychiatry, 60(Suppl 20), 2125.Google Scholar
Walther, A, Breidenstein, J, Miller, R (2019). Association of testosterone treatment with alleviation of depressive symptoms in men: a systematic review and meta-analysis. JAMA Psychiatry, 76(1), 3140. doi:10.1001/jamapsychiatry.2018.2734.Google Scholar
Warden, D, Rush, AJ, Trivedi, MH, Fava, M, Wisniewski, SR (2007). The STAR*D Project results: a comprehensive review of findings. Curr Psychiatry Rep, 9(6), 449459.Google Scholar
Wijkstra, J, Lijmer, J, Balk, JF, Geddes, JR., Nolen, WA (2006). Pharmacological treatment for unipolar psychotic depression: systematic review and meta-analysis. Br J Psychiatry, 188(5), 410415.Google Scholar
Wohlreich, MM, Mallinckrodt, CH, Watkin, JG, et al. (2005). Immediate switching of antidepressant therapy: results from a clinical trial of duloxetine. Ann Clin Psychiatry, 17, 259268.Google Scholar
Yildiz, A, Pauler, DK, Sachs, GS (2004). Rates of study completion with single versus split daily dosing of antidepressants: a meta-analysis. J Affect Disord, 78, 157162.Google Scholar
Yyldyz, A, Sachs, GS (2001). Administration of antidepressants. Single versus split dosing: a meta-analysis. J Affect Disord, 66, 199206.Google Scholar
Zarrouf, FA, Artz, S, Griffith, J, Sirbu, C, Kommor, M (2009). Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract, 15(4), 289305. doi:10.1097/01.pra.0000358315.88931.fc.Google Scholar
Zheng, W, Li, X-H, Zhu, X-M, et al. (2019). Adjunctive ketamine and electroconvulsive therapy for major depressive disorder: a meta-analysis of randomized controlled trials. J Affective Disord, 250, 123131.Google Scholar
Zhou, X, Ravindran, AV, Qin, B, et al. (2015). Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. Clin Psychiatry, 76(4), e487e498. doi:10.4088/JCP.14r09204.Google Scholar
Zivin, K, Pfeiffer, PN, Bohnert, AS, et al. (2013). Evaluation of the FDA warning against prescribing citalopram at doses exceeding 40 mg. Am J Psychiatry, 170(6), 642650. doi:10.1176/appi.ajp.2013.12030408.Google Scholar