Pharmacologic approaches to treatment resistant depression: A re-examination for the modern era

Expert Opinion on Pharmacotherapy

Volumn 11, Issue 5, 2010, Pages 709-722

  Philip, Noah S ^a   Carpenter, Linda L ^a   Tyrka, Audrey R ^a   Price, Lawrence H ^a  

^a BROWN UNIVERSITY   (United States)

Author keywords

Atypical antipsychotics; Augmentation; Depression; Treatment resistant

Indexed keywords

AGOMELATINE; AMFEBUTAMONE; ARIPIPRAZOLE; ATOMOXETINE; ATYPICAL ANTIPSYCHOTIC AGENT; BUSPIRONE; CENTRAL STIMULANT AGENT; CITALOPRAM; FLUOXETINE; LAMOTRIGINE; LIOTHYRONINE; LITHIUM; MECAMYLAMINE; METHYLPHENIDATE; MIRTAZAPINE; OLANZAPINE; PINDOLOL; PLACEBO; QUETIAPINE; RISPERIDONE; SCOPOLAMINE; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; SEX HORMONE; TRANYLCYPROMINE; TRICYCLIC ANTIDEPRESSANT AGENT; UNINDEXED DRUG; VENLAFAXINE; ZIPRASIDONE;

ANXIETY; BIPOLAR DEPRESSION; BIPOLAR DISORDER; BRAIN DEPTH STIMULATION; CLINICAL FEATURE; CLINICAL PRACTICE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; COMORBIDITY; CONTROLLED CLINICAL TRIAL; DEPRESSION; DISEASE SEVERITY; DRUG BLOOD LEVEL; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG INHIBITION; DRUG MECHANISM; DRUG RELEASE; DRUG SAFETY; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; EXTRAPYRAMIDAL SYNDROME; HUMAN; LIFE STRESS; MAJOR DEPRESSION; MONOTHERAPY; NEUROLEPTIC MALIGNANT SYNDROME; NEUROTRANSMISSION; PERSONALITY DISORDER; REMISSION; REVIEW; RISK ASSESSMENT; SIDE EFFECT; TARDIVE DYSKINESIA; TRANSCRANIAL MAGNETIC STIMULATION; TREATMENT DURATION; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; VAGUS NERVE STIMULATION; WEIGHT GAIN;

ACETYLCHOLINE; ANTIDEPRESSIVE AGENTS; CLINICAL TRIALS AS TOPIC; DEPRESSIVE DISORDER, MAJOR; DRUG DELIVERY SYSTEMS; DRUG RESISTANCE; GLUTAMIC ACID; HUMANS; MELATONIN; SEROTONIN UPTAKE INHIBITORS; TREATMENT OUTCOME;

EID: 77949426913     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656561003614781     Document Type: Review

References (132)

1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006, 311: e442.
2. Gaynes BN, Warden D, Trivedi MH, et al. 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
3. Rush AJ, Thase ME, Dube S. Research issues in the study of difficult-to-treat depression. Biol Psychiatry 2003;53(8):743-753
4. Souery D, Papakostas GI, Trivedi MH. Treatment-resistant depression. J Clin Psychiatry 2006;67(Suppl 6):16-22
5. Price L, Carpenter LL, Tyrka AH. Lithium augmentation for refractory depression: a critical reappraisal. Prim Psychiatry 2008;15(11):35-42
6. Joffe RT, Sokolov ST. Thyroid hormone treatment of primary unipolar depression: a review. Int J Neuropsychopharmacol 2000;3(2):143-147
7. Cuijpers P, Dekker J, Hollon SD, Andersson G. Adding psychotherapy to pharmacotherapy in the treatment of depressive disorders in adults: a meta-analysis. J Clin Psychiatry 2009;70(9):1219-1229
8. Merkl A, Heuser I, Bajbouj M. Antidepressant electroconvulsive therapy: mechanism of action, recent advances and limitations. Exp Neurol 2009;219(1):20-26
9. Rush AJ, Sackeim HA, Marangell LB, et al. Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry 2005;58(5):355-363
10. Lam RW, Chan P, Wilkins-Ho M, Yatham LN. Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and metaanalysis. Can J Psychiatry 2008;53(9):621-631
11. American Psychiatric Association. Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed. Washington, DC: American Psychiatric Association; 2000
12. O'Reardon JP. Pharmacologic and therapeutic strategies in treatment-resistant depression. Introduction and clinical presentations. CNS Spectr 2009;14(3 Suppl 4):4-6
13. Sackeim HA. The definition and meaning of treatment-resistant depression. J Clin Psychiatry 2001;62(Suppl 16):10-17
14. Howland RH, Rush AJ, Wisniewski SR, et al. Concurrent anxiety and substance use disorders among outpatients with major depression: clinical features and effect on treatment outcome. Drug Alcohol Depend 2009;99(1-3):248-260
15. 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
16. Amital D, Fostick L, Silberman A, et al. Serious life events among resistant and non-resistant MDD patients. J Affect Disord 2008;110(3):260-264
17. Lu W, Mueser KT, Rosenberg SD, Jankowski MK. Correlates of adverse childhood experiences among adults with severe mood disorders. Psychiatr Serv 2008;59(9):1018-1026
18. Ghaemi SN, Boiman EE, Goodwin FK. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry 2000;61(10):804-8; quiz 9
19. Petrides G, Fink M, Husain MM, et al. ECT remission rates in psychotic versus nonpsychotic depressed patients: a report from CORE. J ECT 2001;17(4):244-253
20. Rothschild AJ. Challenges in the treatment of depression with psychotic features. Biol Psychiatry 2003;53(8):680-690
21. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder. 2nd edition. Washington, DC., American Psychiatric Association; 2000
22. Nierenberg AA, Husain MM, Trivedi MH, et al. Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report. Psychol Med 2009;40(1):41-50
23. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62
24. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979;134:382-389
25. Trivedi MH, Rush AJ, Ibrahim HM, et al. The Inventory of Depressive Symptomatology, Clinician Rating (IDS-C) and Self-Report (IDS-SR), and the Quick Inventory of Depressive Symptomatology, Clinician Rating (QIDS-C) and Self-Report (QIDS-SR) in public sector patients with mood disorders: a psychometric evaluation. Psychol Med 2004;34(1):73-82
26. Rush AJ, Trivedi MH, Ibrahim HM, et al. The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry 2003;54(5):573-583
27. Keller MB, McCullough JP, Klein DN, et al. A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression (see comment). N Engl J Med 2000;342(20):1462-1470
28. Baumann P, Hiemke C, Ulrich S, et al. The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry 2004;37(6):243-265
29. Ruhe HG, Huyser J, Swinkels JA, Schene AH. Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review. J Clin Psychiatry 2006;67(12):1836-1855
30. Papakostas GI, Fava M, Thase ME. Treatment of SSRI-resistant depression: a meta-analysis comparing within-versus across-class switches. Biol Psychiatry 2008;63(7):699-704
31. McGrath PJ, Stewart JW, Fava M, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry 2006;163(9):1531-41; quiz 666
32. Nandagopal JJ, DelBello MP. Selegiline transdermal system: a novel treatment option for major depressive disorder. Expert Opin Pharmacother 2009;10(10):1665-1673
33. De Montigny C, Grunberg F, Mayer A, Deschenes JP. Lithium induces rapid relief of depression in tricyclic antidepressant drug non-responders. Br J Psychiatry 1981;138:252-256
34. Bschor T, Bauer M. Efficacy and mechanisms of action of lithium augmentation in refractory major depression. Curr Pharm Des 2006;12(23):2985- 2992
35. Crossley NA, Bauer M. Acceleration and augmentation of antidepressants with lithium for depressive disorders: two meta-analyses of randomized, placebo-controlled trials. J Clin Psychiatry 2007;68(6):935-940
36. Baumann P, Nil R, Souche A, et al. A double-blind, placebo-controlled study of citalopram with and without lithium in the treatment of therapy-resistant depressive patients: a clinical, pharmacokinetic, and pharmacogenetic investigation. J Clin Psychopharmacol 1996;16(4):307-314
37. Fava M, Rosenbaum JF, McGrath PJ, et al. Lithium and tricyclic augmentation of fluoxetine treatment for resistant major depression: a double-blind, controlled study. Am J Psychiatry 1994;151(9):1372-1374
38. Fava M, Alpert J, Nierenberg A, et al. Double-blind study of high-dose fluoxetine versus lithium or desipramine augmentation of fluoxetine in partial responders and nonresponders to fluoxetine. J Clin Psychopharmacol 2002;22(4):379-387
39. Bauer M, Dopfmer S. Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies. J Clin Psychopharmacol 1999;19(5):427-434
40. Aronson R, Offman HJ, Joffe RT, Naylor CD. Triiodothyronine augmentation in the treatment of refractory depression. A meta-analysis. Arch Gen Psychiatry 1996;53(9):842-848
41. Iosifescu DV, Bolo NR, Nierenberg AA, et al. Brain bioenergetics and response to triiodothyronine augmentation in major depressive disorder. Biol Psychiatry 2008;63(12):1127-1134
42. Altshuler LL, Bauer M, Frye MA, et al. Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry 2001;158(10):1617-1622
43. Cooper-Kazaz R, Apter JT, Cohen R, et al. Combined treatment with sertraline and liothyronine in major depression: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry 2007;64(6):679-688
44. Posternak M, Novak S, Stern R, et al. A pilot effectiveness study: placebo-controlled trial of adjunctive L-triiodothyronine (T3) used to accelerate and potentiate the antidepressant response. Int J Neuropsychopharmacol 2008;11(1):15-25
45. Appelhof BC, Brouwer JP, van Dyck R, et al. Triiodothyronine addition to paroxetine in the treatment of major depressive disorder. J Clin Endocrinol Metab 2004;89(12):6271-6276
46. Iosifescu DV, Nierenberg AA, Mischoulon D, et al. An open study of triiodothyronine augmentation of selective serotonin reuptake inhibitors in treatment-resistant major depressive disorder. J Clin Psychiatry 2005;66(8):1038-1042
47. Abraham G, Milev R, Stuart Lawson J. T3 augmentation of SSRI resistant depression. J Affect Disord 2006;91(2-3):211-215
48. Kelly TF, Lieberman DZ. Long term augmentation with T3 in refractory major depression. J Affect Disord 2009;115(1-2):230-233
49. Joffe RT, Sokolov ST, Levitt AJ. Lithium and triiodothyronine augmentation of antidepressants. Can J Psychiatry 2006;51(12):791-793
50. Nierenberg AA, Fava M, Trivedi MH, et al. A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry 2006;163(9):1519-30; quiz 665
51. Trivedi MH, Fava M, Wisniewski SR, et al. Medication augmentation after the failure of SSRIs for depression. N Engl J Med 2006;354(12):1243-1252
52. Zimmerman M, Posternak MA, Attiullah N, et al. Why isn't bupropion the most frequently prescribed antidepressant? J Clin Psychiatry 2005;66(5):603-610
53. Landen M, Bjorling G, Agren H, Fahlen T. A randomized, double-blind, placebo-controlled trial of buspirone in combination with an SSRI in patients with treatment-refractory depression. J Clin Psychiatry 1998;59(12):664-668
54. Appelberg BG, Syvalahti EK, Koskinen TE, et al. Patients with severe depression may benefit from buspirone augmentation of selective serotonin reuptake inhibitors: results from a placebo-controlled, randomized, double-blind, placebo wash-in study. J Clin Psychiatry 2001;62(6):448-452
55. Carpenter LL, Jocic Z, Hall JM, et al. Mirtazapine augmentation in the treatment of refractory depression. J Clin Psychiatry 1999;60(1):45-49
56. Carpenter LL, Yasmin S, Price LH. A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine. Biol Psychiatry 2002;51(2):183-188
57. Blier P, Szabo ST. Potential mechanisms of action of atypical antipsychotic medications in treatment-resistant depression and anxiety. J Clin Psychiatry 2005;66(Suppl 8):30-40
58. Bersani G, Pozzi F, Marini S, et al. 5-HT2 receptor antagonism in dysthymic disorder: a double-blind placebo-controlled study with ritanserin. Acta Psychiatr Scand 1991;83(4):244-248
59. Bakish D, Lapierre YD, Weinstein R, et al. Ritanserin, imipramine, and placebo in the treatment of dysthymic disorder. J Clin Psychopharmacol 1993;13(6):409-414
60. Nemeroff CB. Use of atypical antipsychotics in refractory depression and anxiety. J Clin Psychiatry 2005;66(Suppl 8):13-21
61. Berman RM, Marcus RN, Swanink R, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2007;68(6):843-853
62. Marcus RN, McQuade RD, Carson WH, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 2008;28(2):156-165
63. Berman RM, Fava M, Thase ME, et al. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectr 2009;14(4):197-206
64. Leon AC, Olfson M, Portera L, et al. Assessing psychiatric impairment in primary care with the Sheehan Disability Scale. Int J Psychiatry Med 1997;27(2):93-105
65. Boulton D, Balch A, Royzman K, et al. The pharmacokinetics of standard antidepressants with aripiprazole as adjunctive therapy: studies in healthy subjects and in patients with major depressive disorder. J Psychopharmacol 2008
66. Trivedi MH, Thase ME, Fava M, et al. Adjunctive aripiprazole in major depressive disorder: analysis of efficacy and safety in patients with anxious and atypical features. J Clin Psychiatry 2008;69(12):1928-1936
67. Shelton RC, Tollefson GD, Tohen M, et al. A novel augmentation strategy for treating resistant major depression. Am J Psychiatry 2001;158(1):131-134
68. Thase ME, Corya SA, Osuntokun O, et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. J Clin Psychiatry 2007;68(2):224-236
69. Shelton RC, Williamson DJ, Corya SA, et al. Olanzapine/fluoxetine combination for treatment-resistant depression: a controlled study of SSRI and nortriptyline resistance. J Clin Psychiatry 2005;66(10):1289-1297
70. Corya SA, Williamson D, Sanger TM, et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, fluoxetine, and venlafaxine in treatment-resistant depression. Depress Anxiety 2006;23(6):364-372
71. Trivedi MH, Thase ME, Osuntokun O, et al. An integrated analysis of olanzapine/fluoxetine combination in clinical trials of treatment-resistant depression. J Clin Psychiatry 2009;70(3):387-396
72. Bobo WV, Shelton RC. Fluoxetine and olanzapine combination therapy in treatment-resistant major depression: review of efficacy and safety data. Expert Opin Pharmacother 2009;10(13):2145-2159
73. El-Khalili NJM, Atkinson S, Buynak R, et al. Adjunctive extended-release quetiapine fumarate (quetiapine-extended release) in patients with major depressive disorder and inadequate antidepressant response. American Psychiatric Association 2008 Annual Meeting: New Research Abstracts 3-8 May 2008, Washington, DC, APA; 2008
74. Earley WMA, Bauer M, Pretorius HW, et al. Efficacy and tolerability of extended release quetiapine fumarate (quetiapine extended release) as add-on to antidepressants in patients with major depressive disorder (MDD): results from a double-blind, randomized, phase III study. Annual Meeting Abstracts 9-13 December 2007, Boca Raton, Fla
75. Nashville, TN, ACNP 2007. Am Coll Neuropsychopharmacol 2007
76. McIntyre A, Gendron A. Quetiapine adjunct to selective serotonin reuptake inhibitors or venlafaxine in patients with major depression, comorbid anxiety, and residual depressive symptoms: a randomized, placebo-controlled pilot study. Depress Anxiety 2007;24(7):487-494
77. Mahmoud RA, Pandina GJ, Turkoz I, et al. Risperidone for treatment-refractory major depressive disorder: a randomized trial. Ann Intern Med 2007;147(9):593-602
78. Keitner GI, Garlow SJ, Ryan CE, et al. A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression. J Psychiatr Res 2009;43(3):205-214
79. Reeves H, Batra S, May RS, et al. Efficacy of risperidone augmentation to antidepressants in the management of suicidality in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. J Clin Psychiatry 2008;69(8):1228-1336
80. Rapaport MH, Gharabawi GM, Canuso CM, et al. Effects of risperidone augmentation in patients with treatment-resistant depression: results of open-label treatment followed by double-blind continuation. Neuropsychopharmacology 2006;31(11):2505-2513
81. Westerink BH, Kawahara Y, De Boer P, et al. Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum. Eur J Pharmacol 2001;412(2):127-138
82. Papakostas GI, Petersen TJ, Nierenberg AA, et al. Ziprasidone augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant major depressive disorder. J Clin Psychiatry 2004;65(2):217-221
83. Dunner DL, Amsterdam JD, Shelton RC, et al. Efficacy and tolerability of adjunctive ziprasidone in treatment-resistant depression: a randomized, open-label, pilot study. J Clin Psychiatry 2007;68(7):1071-1077
84. Papakostas GI, Shelton RC, Smith J, Fava M. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry 2007;68(6):826-831
85. 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
86. Atypical Antipsychotic Drug Information. Available from: http://fda.gov/cder/drug/infopage/antipsychotics/default.htm [Last accessed November 2009]
87. Philip NS, Carpenter LL, Tyrka AR, Price LH. Augmentation of antidepressants with atypical antipsychotics: a review of the current literature. J Psychiatr Pract 2008;14(1):34-44
88. Shelton RC, Papakostas GI. Augmentation of antidepressants with atypical antipsychotics for treatment-resistant major depressive disorder. Acta Psychiatr Scand 2008;117(4):253-259
89. Patkar AA, Masand PS, Pae CU, et al. A randomized, double-blind, placebo-controlled trial of augmentation with an extended release formulation of methylphenidate in outpatients with treatment-resistant depression. J Clin Psychopharmacol 2006;26(6):653-656
90. Ravindran AV, Kennedy SH, O'Donovan MC, et al. Osmotic-release oral system methylphenidate augmentation of antidepressant monotherapy in major depressive disorder: results of a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry 2008;69(1):87-94
91. Kollins SH. Abuse liability of medications used to treat attention-deficit/hyperactivity disorder (ADHD). Am J Addict 2007;16(Suppl 1):35-42; quiz 3-4
92. Michelson D, Adler LA, Amsterdam JD, et al. Addition of atomoxetine for depression incompletely responsive to sertraline: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2007;68(4):582-587
93. Dunlop BW, Crits-Christoph P, Evans DL, et al. Coadministration of modafinil and a selective serotonin reuptake inhibitor from the initiation of treatment of major depressive disorder with fatigue and sleepiness: a double-blind, placebo-controlled study. J Clin Psychopharmacol 2007;27(6):614-619
94. Fava M, Thase ME, DeBattista C. A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry 2005;66(1):85-93
95. Perez V, Gilaberte I, Faries D, et al. Randomised, double-blind, placebo-controlled trial of pindolol in combination with fluoxetine antidepressant treatment. Lancet 1997;349(9065):1594-1597
96. Perez V, Soler J, Puigdemont D, et al. A double-blind, randomized, placebo-controlled trial of pindolol augmentation in depressive patients resistant to serotonin reuptake inhibitors. Grup de Recerca en Trastorns Afectius. Arch Gen Psychiatry 1999;56(4):375-379
97. Perry EB, Berman RM, Sanacora G, et al. Pindolol augmentation in depressed patients resistant to selective serotonin reuptake inhibitors: a double-blind, randomized, controlled trial. J Clin Psychiatry 2004;65(2):238-243
98. Geretsegger C, Bitterlich W, Stelzig R, et al. Paroxetine with pindolol augmentation: a double-blind, randomized, placebo-controlled study in depressed in-patients. Eur Neuropsychopharmacol 2008;18(2):141-146
99. Sokolski KN, Conney JC, Brown BJ, DeMet EM. Once-daily high-dose pindolol for SSRI-refractory depression. Psychiatry Res 2004;125(2):81-86
100. Ballesteros J, Callado LF. Effectiveness of pindolol plus serotonin uptake inhibitors in depression: a meta-analysis of early and late outcomes from randomised controlled trials. J Affect Disord 2004;79(1-3):137-147
101. Segrave R, Nathan PJ. Pindolol augmentation of selective serotonin reuptake inhibitors: accounting for the variability of results of placebo-controlled double-blind studies in patients with major depression. Hum Psychopharmacol 2005;20(3):163-174
102. Geddes JR, Calabrese JR, Goodwin GM. Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. Br J Psychiatry 2009;194(1):4-9
103. Gutierrez RL, McKercher RM, Galea J, Jamison KL. Lamotrigine augmentation strategy for patients with treatment-resistant depression. CNS Spectr 2005;10(10):800-805
104. Barbee JG, Jamhour NJ. Lamotrigine as an augmentation agent in treatment-resistant depression. J Clin Psychiatry 2002;63(8):737-741
105. Barbosa L, Berk M, Vorster M. 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 2003;64(4):403-407
106. Santos MA, Rocha FL, Hara C. Efficacy and safety of antidepressant augmentation with lamotrigine in patients with treatment-resistant depression: a randomized, placebo-controlled, double-blind study. Prim Care Companion J Clin Psychiatry 2008;10(3):187-190
107. Pope HG Jr, Cohane GH, Kanayama G, et al. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry 2003;160(1):105-111
108. Orengo CA, Fullerton L, Kunik ME. Safety and efficacy of testosterone gel 1% augmentation in depressed men with partial response to antidepressant therapy. J Geriatr Psychiatry Neurol 2005;18(1):20-24
109. Seidman SN, Rabkin JG. Testosterone replacement therapy for hypogonadal men with SSRI-refractory depression. J Affect Disord 1998;48(2-3):157-161
110. Rasgon NL, Altshuler LL, Fairbanks LA, et al. Estrogen replacement therapy in the treatment of major depressive disorder in perimenopausal women. J Clin Psychiatry 2002;63(Suppl 7):45-48
111. Morgan ML, Cook IA, Rapkin AJ, Leuchter AF. Estrogen augmentation of antidepressants in perimenopausal depression: a pilot study. J Clin Psychiatry 2005;66(6):774-780
112. Dias RS, Kerr-Correa F, Moreno RA, et al. Efficacy of hormone therapy with and without methyltestosterone augmentation of venlafaxine in the treatment of postmenopausal depression: a double-blind controlled pilot study. Menopause 2006;13(2):202-211
113. Lewy AJ, Bauer VK, Cutler NL, Sack RL. Melatonin treatment of winter depression: a pilot study. Psychiatry Res 1998;77(1):57-61
114. Goodwin GM, Emsley R, Rembry S, Rouillon F. Agomelatine prevents relapse in patients with major depressive disorder without evidence of a discontinuation syndrome: a 24-week randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2009;70(8):1128-1137
115. Kennedy SH, Rizvi S, Fulton K, Rasmussen J. A double-blind comparison of sexual functioning, antidepressant efficacy, and tolerability between agomelatine and venlafaxine XR. J Clin Psychopharmacol 2008;28(3):329-333
116. Olie JP, Kasper S. Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder. Int J Neuropsychopharmacol 2007;10(5):661-673
117. Kennedy SH, Emsley R. Placebo-controlled trial of agomelatine in the treatment of major depressive disorder. Eur Neuropsychopharmacol 2006;16(2):93-100
118. Furey ML, Drevets WC. Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Arch Gen Psychiatry 2006;63(10):1121-1129
119. George TP, Sacco KA, Vessicchio JC, et al. Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: a preliminary study. J Clin Psychopharmacol 2008;28(3):340-344
120. Bacher I, Wu B, Shytle DR, George TP. Mecamylamine-a nicotinic acetylcholine receptor antagonist with potential for the treatment of neuropsychiatric disorders. Expert Opin Pharmacother 2009;10(16):2709-2721
121. TC-5214 as add-on the Treatment of Major Depressive Disorder. Available from: http://www.clinicaltrials.gov [Last accessed November 2009]
122. Philip NS, Carpenter LL, Tyrka AR, et al. Varenicline augmentation in depressed smokers: an 8-week, open-label study. J Clin Psychiatry 2009;70(7):1026-1031
123. Zarate CA Jr, Singh JB, Quiroz JA, et al. A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am J Psychiatry 2006;163(1):153-155
124. Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006;63(8):856-864
125. Ongoing trials of ketamine for major depression. Available from: http:// clinicaltrials.gov [Last accessed November 2009]
126. Preskorn SH, Baker B, Kolluri S, et al. An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. J Clin Psychopharmacol 2008;28(6):631-637
127. Sanacora G, Kendell SF, Levin Y, et al. Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms. Biol Psychiatry 2007;61(6):822-825
128. Mathew SJ, Murrough JW, Aan Het Rot M, et al. Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial. Int J Neuropsychopharmacol 2009;13(1):71-82
129. Fava M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry 2003;53(8):649-659
130. Fekadu A, Wooderson S, Donaldson C, et al. A multidimensional tool to quantify treatment resistance in depression: the Maudsley staging method. J Clin Psychiatry 2009;70(2):177-184
131. Berlim MT, Turecki G. Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can J Psychiatry 2007;52(1):46-54
132. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 2009;65(9):732-741