, Volume 71, Issue 1, pp 43–64 | Cite as

If at First You Don’t Succeed

A Review of the Evidence for Antidepressant Augmentation, Combination and Switching Strategies
Review Article


Major depressive disorder is a common and disabling illness that leads to significant reductions in quality of life and considerable cost to society. Despite numerous advances in the pharmacological treatment of depression, many patients remain ill despite initial treatment. Beyond first-line treatment, current guidelines recommend either augmentation or switching of the initial antidepressant. In this narrative review, we summarize the data from randomized controlled trials and meta-analyses in order to concisely discuss how the impact of current research can be translated into clinical practice and, ultimately, into lasting improvements in patient outcomes. The augmentation strategies reviewed are lithium, thyroid hormone, pindolol, psychostimulants and second-generation antipsychotics. The data on switching from first-line antidepressants to other antidepressants are also reviewed, and include switching within the same class, switching to other first-line antidepressant classes and switching to less commonly prescribed antidepressants. Finally, the strategy of antidepressant combinations is examined. Overall, the strength of evidence supporting a trial of augmentation or a switch to a new agent is very similar, with remission rates between 25% and 50% in both cases.

Our review of the evidence suggests several conclusions. First, although it is true that adjunctive lithium and thyroid hormone have established efficacy, we can only be confident that this is true for use in combination with tricyclic antidepressants (TCAs), and the trials were done in less treatment-resistant patients than those who typically receive TCAs today. Of these two options, triiodothyronine augmentation seems to offer the best benefit/risk ratio for augmentation of modern antidepressants. After failure of a first-line selective serotonin reuptake inhibitor (SSRI), neither a switch within class nor a switch to a different class of antidepressant is unequivocally supported by the data, although switching from an SSRI to venlafaxine or mirtazapine may potentially offer greater benefits. Interestingly, switching from a newer antidepressant to a TCA after a poor response to the former is not supported by strong evidence. Of all strategies to augment response to new-generation antidepressants, quetiapine and aripiprazole are best supported by the evidence, although neither the cost effectiveness nor the longer-term benefit of these strategies has been established.

The data to guide later steps in the treatment of resistant depression are sparse. Given the wide variety of options for the treatment of major depressive disorder, and the demonstrated importance of truly adequate treatment to the long-term outcomes of patients facing this illness, it is clear that further well conducted studies are needed.



No sources of funding were used in the preparation of this article. Dr Thase has provided scientific consultation to Astra-Zeneca, Bristol-Myers Squibb Company, Eli Lilly & Company, Forest Pharmaceuticals, Inc., GlaxoSmithKline, MedAvante, Inc., Neuronetics, Inc., Novartis, Pfizer (formerly Wyeth-Ayerst Laboratories), Schering-Plough, Shire US Inc., Supernus Pharmaceuticals, Takeda and Transcept Pharmaceuticals. Dr Thase has been a member of the speakers’ bureaus for AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly & Company and Pfizer (formerly Wyeth-Ayerst Laboratories). He receives grant funding from Eli Lilly & Company, GlaxoSmithKline, National Institute of Mental Health and Sepracor, Inc. Dr Thase has equity holdings in MedAvante, Inc. and receives royalty income from American Psychiatric Publishing, Inc., Guilford Publications, Herald House, Oxford University Press and W.W. Norton & Company. His wife is employed as the senior medical director for Advogent.

Dr Connolly would like to thank the Philadelphia Veterans Affairs Medical Center’s Mental Illness Research Education and Clinical Center (MIRECC) for their support. Dr Connolly has no competing interests.


  1. 1.
    Kessler RC, Sonnega A, Bromet E, et al. Posttraumatic stress disorder in the national comorbidity survey. Arch Gen Psychiatry 1995; 52: 1048–60PubMedCrossRefGoogle Scholar
  2. 2.
    Narasimhan M, Raynor JD, Jones AB. Depression in the medically ill: diagnostic and therapeutic implications. Curr Psychiatry Rep 2008; 10: 272–9PubMedCrossRefGoogle Scholar
  3. 3.
    Fava M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry 2003; 53: 649–59PubMedCrossRefGoogle Scholar
  4. 4.
    Rush AJ, Trivedi MH, Wisniewski SR, et al., STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med 2006; 354: 1231–42PubMedCrossRefGoogle Scholar
  5. 5.
    Tranter R, O’Donovan C, Chandarana P, et al. Prevalence and outcome of partial remission in depression. J Psychiatry Neurosci 2002; 27: 241–7PubMedGoogle Scholar
  6. 6.
    American Psychiatric Association practice guideline for treatment of patients with major depressive disorder, third edition [online]. Available from URL: http://www.psychiatryonline.com/pracGuide/pracGuideTopic_7.aspx [Accessed 2010 Feb 26]
  7. 7.
    Malhi GS, Adams D, Porter R, et al., Northern Sydney Central Coast Mental Health Drug & Alcohol, NSW Health Clinical Redesign Program, CADE Clinic, University of Sydney. Clinical practice recommendations for depression. Acta Psychiatr Scand Suppl 2009; 119(439): 8–26CrossRefGoogle Scholar
  8. 8.
    Lam RW, Kennedy SH, Grigoriadis S, et al., Canadian Network for Mood and Anxiety Treatments (CANMAT). Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III: pharmacotherapy. J Affect Disord 2009; 117 Suppl. 1: S26–43PubMedCrossRefGoogle Scholar
  9. 9.
    Institute for Clinical Systems Improvement (ICSI) healthcare guideline for major depression in adults in primary care [online]. Available from URL: http://www.icsi.org/guidelines_and_more/gl_os_prot/behavioral_health/depression_5/depression__major__in_adults_in_primary_care_4.html [Accessed 2010 Feb 26]
  10. 10.
    Zall H, Therman PG, Myers JM. Lithium carbonate: a clinical study. Am J Psychiatry 1968; 125: 549–55PubMedGoogle Scholar
  11. 11.
    Bauer M, Dopfmer S. Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies. J Clin Psychopharmacol 1999; 19: 427–34PubMedCrossRefGoogle Scholar
  12. 12.
    De Montigny C, Cournoyer G, Morissette R, et al. Lithium carbonate addition in tricyclic antidepressant-resistant unipolar depression: correlations with the neurobiologic actions of tricyclic antidepressant drugs and lithium ion on the serotonin system. Arch Gen Psychiatry 1983; 40: 1327–34PubMedCrossRefGoogle Scholar
  13. 13.
    Bschor T, Lewitzka U, Sasse J, et al. Lithium augmentation in treatment-resistant depression: clinical evidence, serotonergic and endocrine mechanisms. Pharmacopsychiatry 2003; 36 Suppl. 3: S230–4PubMedGoogle Scholar
  14. 14.
    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: 935–40PubMedCrossRefGoogle Scholar
  15. 15.
    Stein G, Bernadt M. Lithium augmentation therapy in tricyclic-resistant depression: a controlled trial using lithium in low and normal doses. Br J Psychiatry 1993; 162: 634–40PubMedCrossRefGoogle Scholar
  16. 16.
    Nierenberg AA, Papakostas GI, Petersen T, et al. Lithium augmentation of nortriptyline for subjects resistant to multiple antidepressants. J Clin Psychopharmacol 2003; 23: 92–5PubMedCrossRefGoogle Scholar
  17. 17.
    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: 307–14PubMedCrossRefGoogle Scholar
  18. 18.
    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: 1372–4PubMedGoogle Scholar
  19. 19.
    Delgado PL, Price LH, Charney DS, et al. Efficacy of fluvoxamine in treatment-refractory depression. J Affect Disord 1988; 15: 55–60PubMedCrossRefGoogle Scholar
  20. 20.
    Ontiveros A, Fontaine R, Elie R. Refractory depression: the addition of lithium to fluoxetine or desipramine. Acta Psychiatr Scand 1991; 83: 188–92PubMedCrossRefGoogle Scholar
  21. 21.
    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: 1519–30PubMedCrossRefGoogle Scholar
  22. 22.
    Aronson R, Offman HJ, Joffe RT, et al. Triiodothyronine augmentation in the treatment of refractory depression: a meta-analysis. Arch Gen Psychiatry 1996; 53: 842–8PubMedCrossRefGoogle Scholar
  23. 23.
    Joffe RT, Sokolov ST, Levitt AJ. Lithium and triiodothyronine augmentation of antidepressants. Can J Psychiatry 2006; 51: 791–3PubMedGoogle Scholar
  24. 24.
    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: 1617–22PubMedCrossRefGoogle Scholar
  25. 25.
    Prange Jr AJ, Wilson IC, Rabon AM, et al. Enhancement of imipramine antidepressant activity by thyroid hormone. Am J Psychiatry 1969; 126: 457–69PubMedGoogle Scholar
  26. 26.
    Cooper-Kazaz R, Lerer B. Efficacy and safety of triiodothyronine supplementation in patients with major depressive disorder treated with specific serotonin reuptake inhibitors. Int J Neuropsychopharmacol 2008; 11: 685–99PubMedCrossRefGoogle Scholar
  27. 27.
    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: 679–88PubMedCrossRefGoogle Scholar
  28. 28.
    Papakostas GI, Shelton RC. Use of atypical antipsychotics for treatment-resistant major depressive disorder. Curr Psychiatry Rep 2008; 10: 481–6PubMedCrossRefGoogle Scholar
  29. 29.
    Papakostas GI, Shelton RC, Smith J, et al. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry 2007; 68: 826–31PubMedCrossRefGoogle Scholar
  30. 30.
    Nemeroff CB. Use of atypical antipsychotics in refractory depression and anxiety. J Clin Psychiatry 2005; 66 Suppl. 8: 13–21PubMedGoogle Scholar
  31. 31.
    Goodwin G, Fleischhacker W, Arango C, et al. Advantages and disadvantages of combination treatment with antipsychotics ECNP consensus meeting, March 2008, Nice. Eur Neuropsychopharmacol 2009; 19(7): 520–32PubMedCrossRefGoogle Scholar
  32. 32.
    Shelton RC, Tollefson GD, Tohen M, et al. A novel augmentation strategy for treating resistant major depression. Am J Psychiatry 2001; 158: 131–4PubMedCrossRefGoogle Scholar
  33. 33.
    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: 1289–97PubMedCrossRefGoogle Scholar
  34. 34.
    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: 364–72PubMedCrossRefGoogle Scholar
  35. 35.
    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: 224–36PubMedCrossRefGoogle Scholar
  36. 36.
    Bauer M, Pretorius HW, Constant EL, et al. Extended-release quetiapine as adjunct to an antidepressant in patients with major depressive disorder: results of a randomized, placebo-controlled, double-blind study. J Clin Psychiatry 2009; 70: 540–9PubMedCrossRefGoogle Scholar
  37. 37.
    El-Khalili N, Joyce M, Atkinson S, et al. Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in major depressive disorder (MDD) in patients with an inadequate response to ongoing antidepressant treatment: a multi-centre, randomized, double-blind, placebo-controlled study. Int J Neuropsychopharmacol 2010; 13: 917–32PubMedCrossRefGoogle Scholar
  38. 38.
    Garakani A, Martinez JM, Marcus S, et al. A randomized, double-blind, and placebo-controlled trial of quetiapine augmentation of fluoxetine in major depressive disorder. Int Clin Psychopharmacol 2008; 23: 269–75PubMedCrossRefGoogle Scholar
  39. 39.
    Chaput Y, Magnan A, Gendron A. The co-administration of quetiapine or placebo to cognitive-behavior therapy in treatment refractory depression: a preliminary trial. BMC Psychiatry 2008; 8: 73PubMedCrossRefGoogle Scholar
  40. 40.
    Mahmoud RA, Pandina GJ, Turkoz I, et al. Risperidone for treatment-refractory major depressive disorder: a randomized trial. Ann Intern Med 2007; 147: 593–602PubMedGoogle Scholar
  41. 41.
    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: 205–14PubMedCrossRefGoogle Scholar
  42. 42.
    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: 2505–13PubMedCrossRefGoogle Scholar
  43. 43.
    Papakostas GI, Petersen TJ, Nierenberg AA, et al. Ziprasi-done augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant major depressive disorder. J Clin Psychiatry 2004; 65: 217–21PubMedCrossRefGoogle Scholar
  44. 44.
    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: 1071–7PubMedCrossRefGoogle Scholar
  45. 45.
    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: 843–53PubMedCrossRefGoogle Scholar
  46. 46.
    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: 156–65PubMedCrossRefGoogle Scholar
  47. 47.
    Thase ME, Trivedi MH, Nelson JC, et al. Examining the efficacy of adjunctive aripiprazole in major depressive disorder: a pooled analysis of 2 studies. Prim Care Companion J Clin Psychiatry 2008; 10: 440–7PubMedCrossRefGoogle Scholar
  48. 48.
    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: 197–206PubMedGoogle Scholar
  49. 49.
    Redrobe JP, Bourin M. Dose-dependent influence of buspirone on the activities of selective serotonin reuptake inhibitors in the mouse forced swimming test. Psychopharmacology (Berl) 1998; 138: 198–206CrossRefGoogle Scholar
  50. 50.
    Landen M, Bjorling G, Agren H, et al. 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: 664–8PubMedCrossRefGoogle Scholar
  51. 51.
    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: 448–52PubMedCrossRefGoogle Scholar
  52. 52.
    Trivedi MH, Fava M, Wisniewski SR, et al., STAR *D Study Team. Medication augmentation after the failure of SSRIs for depression. N Engl J Med 2006; 354: 1243–52PubMedCrossRefGoogle Scholar
  53. 53.
    Fava M, Rush AJ, Alpert JE, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry 2008; 165: 342–51PubMedCrossRefGoogle Scholar
  54. 54.
    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: 137–47PubMedCrossRefGoogle Scholar
  55. 55.
    Brunton LB, Lazo JS, Parker KL, editors. Goodman & Gilman’s the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill, 2005Google Scholar
  56. 56.
    Candy M, Jones L, Williams R, et al. Psychostimulants for depression. Cochrane Database Syst Rev 2008; (2): CD006722Google Scholar
  57. 57.
    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: 653–6PubMedCrossRefGoogle Scholar
  58. 58.
    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: 87–94PubMedCrossRefGoogle Scholar
  59. 59.
    Minzenberg MJ, Carter CS. Modafinil: a review of neuro-chemical actions and effects on cognition. Neuropsycho-pharmacology 2008; 33: 1477–502CrossRefGoogle Scholar
  60. 60.
    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: 85–93PubMedCrossRefGoogle Scholar
  61. 61.
    DeBattista C, Doghramji K, Menza MA, et al., Modafinil in Depression Study Group. 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: 1057–64PubMedCrossRefGoogle Scholar
  62. 62.
    Fava M, Thase ME, DeBattista C, et al. Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness. Ann Clin Psychiatry 2007; 19: 153–9PubMedCrossRefGoogle Scholar
  63. 63.
    Baldomero EB, Ubago JG, Cercos CL, et al. Venlafaxine extended release versus conventional antidepressants in the remission of depressive disorders after previous antidepressant failure: ARGOS study. Depress Anxiety 2005; 22: 68–76PubMedCrossRefGoogle Scholar
  64. 64.
    Thase ME, Entsuah AR, Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 2001; 178: 234–41PubMedCrossRefGoogle Scholar
  65. 65.
    Nemeroff CB, Entsuah R, Benattia I, et al. Comprehensive analysis of remission (COMPARE) with venlafaxine versus SSRIs. Biol Psychiatry 2008; 63: 424–34PubMedCrossRefGoogle Scholar
  66. 66.
    Bauer M, Tharmanathan P, Volz HP, et al. The effect of venlafaxine compared with other antidepressants and placebo in the treatment of major depression: a meta-analysis. Eur Arch Psychiatry Clin Neurosci 2009; 259: 172–85PubMedCrossRefGoogle Scholar
  67. 67.
    Poirier MF, Boyer P. Venlafaxine and paroxetine in treatment-resistant depression: double-blind, randomised comparison. Br J Psychiatry 1999; 175: 12–6PubMedCrossRefGoogle Scholar
  68. 68.
    Lenox-Smith AJ, Jiang Q. Venlafaxine extended release versus citalopram in patients with depression unresponsive to a selective serotonin reuptake inhibitor. Int Clin Psychopharmacol 2008; 23: 113–9PubMedCrossRefGoogle Scholar
  69. 69.
    Perahia DG, Quail D, Desaiah D, et al. Switching to duloxetine in selective serotonin reuptake inhibitor non- and partial-responders: effects on painful physical symptoms of depression. J Psychiatr Res 2009 Feb; 43(5): 512–8PubMedCrossRefGoogle Scholar
  70. 70.
    Schatzberg AF. Pharmacological principles of antidepressant efficacy. Hum Psychopharmacol 2002; 17 Suppl. 1: S17–22PubMedCrossRefGoogle Scholar
  71. 71.
    Thase ME, Kremer C, Rodrigues H. Mirtazapine versus sertraline after SSRI non-response [abstract]. The Annual Meeting of the New Clinical Drug Evaluation Unit (NCDEU) of the National Institute of Mental Health; 2001 May 28–31; Phoenix (AZ)Google Scholar
  72. 72.
    Fava M, Rush AJ, Wisniewski SR, et al. A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report. Am J Psychiatry 2006; 163: 1161–72PubMedCrossRefGoogle Scholar
  73. 73.
    Ferreri M, Lavergne F, Berlin I, et al. Benefits from mian-serin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone. Acta Psychiatr Scand 2001; 103: 66–72PubMedCrossRefGoogle Scholar
  74. 74.
    Nierenberg AA, Papakostas GI, Petersen T, et al. Nortriptyline for treatment-resistant depression. J Clin Psychiatry 2003; 64: 35–9PubMedCrossRefGoogle Scholar
  75. 75.
    Thase ME, Rush AJ, Howland RH, et al. Double-blind switch study of imipramine or sertraline treatment of antidepressant-resistant chronic depression. Arch Gen Psychiatry 2002; 59: 233–9PubMedCrossRefGoogle Scholar
  76. 76.
    Krishnan KR. Revisiting monoamine oxidase inhibitors. J Clin Psychiatry 2007; 68 Suppl. 8: 35–41PubMedGoogle Scholar
  77. 77.
    McGrath PJ, Stewart JW, Harrison W, et al. Treatment of tricyclic refractory depression with a monoamine oxidase inhibitor antidepressant. Psychopharmacol Bull 1987; 23: 169–72PubMedGoogle Scholar
  78. 78.
    Thase ME, Frank E, Mallinger AG, et al. Treatment of imipramine-resistant recurrent depression, III: efficacy of monoamine oxidase inhibitors. J Clin Psychiatry 1992; 53: 5–11PubMedGoogle Scholar
  79. 79.
    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 Sep; 163(9): 1531–41; quiz 1666PubMedCrossRefGoogle Scholar
  80. 80.
    Carpenter LL, Yasmin S, Price LH. A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine. Biol Psychiatry 2002; 51: 183–8PubMedCrossRefGoogle Scholar
  81. 81.
    Blier P, Gobbi G, Turcotte JE, et al. Mirtazapine and paroxetine in major depression: a comparison of monotherapy versus their combination from treatment initiation. Eur Neuropsychopharmacol 2009; 19: 457–65PubMedCrossRefGoogle Scholar
  82. 82.
    Blier P, Ward HE, Tremblay P, et al. Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. Am J Psychiatry 2010; 167: 281–8PubMedCrossRefGoogle Scholar
  83. 83.
    Maes M, Libbrecht I, van Hunsel F, et al. Pindolol and mian-serin augment the antidepressant activity of fluoxetine in hospitalized major depressed patients, including those with treatment resistance. J Clin Psychopharmacol 1999; 19: 177–82PubMedCrossRefGoogle Scholar
  84. 84.
    Nelson JC, Mazure CM, Jatlow PI, et al. Combining nor-epinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a double-blind, randomized study. Biol Psychiatry 2004; 55: 296–300PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.University of Pennsylvania School of Medicine, MIRECC - Rm 228B, Philadelphia VA Medical CenterPittsburghUSA
  2. 2.University of Pittsburgh Medical CenterPittsburghUSA

Personalised recommendations