Skip to main content Accessibility help
×
Home

Efficacy of adjunctive aripiprazole in patients with major depressive disorder whose symptoms worsened with antidepressant monotherapy

  • J. Craig Nelson (a1), Zia Rahman (a2), Kimberly K. Laubmeier (a3), James M. Eudicone (a4), Robert D. McQuade (a5), Robert M. Berman (a6), Ronald N. Marcus (a7), Ross A. Baker (a8) and John J. Sheehan (a9)...

Abstract

Introduction

Efficacy of depression treatments, including adjunctive antipsychotic treatment, has not been explored for patients with worsening symptoms after antidepressant therapy (ADT).

Methods

This post-hoc analysis utilized pooled data from 3 similarly designed, randomized, double-blind, placebo-controlled trials that assessed the efficacy, safety, and tolerability of adjunctive aripiprazole in patients with major depressive disorder with inadequate response to ADT. The studies had 2 phases: an 8-week prospective ADT phase and 6-week adjunctive (aripiprazole or placebo) treatment phase. This analysis focused on patients whose symptoms worsened during the prospective 8-week ADT phase (worsening defined as >0% increase in Montgomery–Åsberg Depressive Rating Scale [MADRS] Total score). During the 6-week, double-blind, adjunctive phase, response was defined as ≥50% reduction in MADRS Total score and remission as ≥50% reduction in MADRS Total score and MADRS score ≤10.

Results

Of 1065 patients who failed to achieve a response during the prospective phase, 160 exhibited worsening of symptoms (ADT-Worseners), and 905 exhibited no change/reduction in MADRS scores (ADT-Non-worseners). Response rates for ADT-Worseners at endpoint were 36.6% (adjunctive aripiprazole) and 22.5% (placebo). Similarly, response rates at endpoint for ADT-Non-worseners were 37.5% (adjunctive aripiprazole) and 22.5% (placebo). Remission rates at endpoint for ADT-Worseners were 25.4% (adjunctive aripiprazole) and 12.4% (placebo). For ADT-Non-worseners, remission rates were 29.9% (adjunctive aripiprazole) and 17.4% (placebo).

Conclusion

These results suggest that adjunctive aripiprazole is an effective intervention for patients whose symptoms worsen during antidepressant monotherapy. The results challenge the view that benefits of adjunctive therapy with aripiprazole are limited to partial responders to ADT.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Efficacy of adjunctive aripiprazole in patients with major depressive disorder whose symptoms worsened with antidepressant monotherapy
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Efficacy of adjunctive aripiprazole in patients with major depressive disorder whose symptoms worsened with antidepressant monotherapy
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Efficacy of adjunctive aripiprazole in patients with major depressive disorder whose symptoms worsened with antidepressant monotherapy
      Available formats
      ×

Copyright

The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence . The written permission of Cambridge University Press must be obtained for commercial re-use.

Corresponding author

*Address for correspondence: J. Craig Nelson, Department of Psychiatry, University of California, San Francisco, 401 Parnassus Ave., San Francisco, CA 94143, USA. (Email: CraigN@lppi.ucsf.edu)

Footnotes

Hide All

This study was supported by Bristol-Myers Squibb (Princeton, NJ, USA) and Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan). Editorial support for the preparation of this manuscript was provided by Ogilvy Healthworld Medical Education (London, UK); funding was provided by Bristol-Myers Squibb.

A poster of this article was presented at the American College of Neuropsychopharmacology (ACNP) Annual Meeting, December 4–8, 2011, Waikaloa Beach, HI, USA.

Footnotes

References

Hide All
1.Fava, M, Davidson, KG. Definition and epidemiology of treatment-resistant depression. Psychiatr Clin North Am. 1996; 19(2): 179200.
2.Rush, AJ, Trivedi, MH, Wisniewski, SR, etal. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006; 163(11): 19051917.
3.Nemeroff, CB. Prevalence and management of treatment-resistant depression. J Clin Psychiatry. 2007; 68(Suppl 8): 1725.
4.American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder. Am J Psychiatry. 2010; 167(10): A34.
5.Nelson, JC, Papakostas, GI. Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. Am J Psychiatry. 2009; 166(9): 980991.
6.Nutt, DJ, Davidson, JR, Gelenberg, AJ, etal. International consensus statement on major depressive disorder. J Clin Psychiatry. 2010; 71(Suppl E1): e08.
7.Baghai, TC, Blier, P, Baldwin, DS, etal. General and comparative efficacy and effectiveness of antidepressants in the acute treatment of depressive disorders: a report by the WPA section of pharmacopsychiatry. Eur Arch Psychiatry Clin Neurosci. 2011; 261(Suppl 3): 207245.
8.Nelson, JC. Augmentation strategies in the treatment of major depressive disorder: recent findings and current status of augmentation strategies. CNS Spectr. 2007; 12(Suppl 22): 69.
9.Nelson, J, Thase, M, Bellocchio, E, etal. Efficacy of adjunctive aripiprazole in patients with major depressive disorder who showed minimal response to initial antidepressant therapy. Int Clin Psychopharmacol. 2012; 27(3): 125133.
10.Marcus, RN, McQuade, RD, Carson, WH, etal. 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): 156165.
11.Berman, R, Fava, M, Thase, M, etal. Aripiprazole augmentation in major depression: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectr. 2009; 14(4): 197206.
12.Berman, RM, Marcus, RN, Swanink, R, etal. 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): 843853.
13.Chernoloz, O, El Mansari, M, Blier, P. Electrophysiological studies in the rat brain on the basis for aripiprazole augmentation of antidepressants in major depressive disorder. Psychopharmacology (Berl). 2009; 206(2): 335344.
14.Lakoski, JM, Aghajanian, GK. Effects of ketanserin on neuronal responses to serotonin in the prefrontal cortex, lateral geniculate and dorsal raphe nucleus. Neuropharmacology. 1985; 24(4): 265273.
15.Thase, ME, Corya, SA, Osuntokun, O, etal. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. J Clin Psychiatry. 2007; 68(2): 224236.
16.McElroy, SL, Guerdjikova, A, Mori, N, Keck, PE Jr. Therapeutic potential of new second generation antipsychotics for major depressive disorder. Expert Opin Investig Drugs. 2010; 19(12): 15271544.
17.Blier, P, Blondeau, C. Neurobiological bases and clinical aspects of the use of aripiprazole in treatment-resistant major depressive disorder. J Affect Disord. 2011; 128(Suppl 1): S3S10.
18.Fava, GA. Do antidepressant and antianxiety drugs increase chronicity in affective disorders? Psychother Psychosom. 1994; 61(3–4): 125131.
19.Fava, GA. Can long-term treatment with antidepressant drugs worsen the course of depression? J Clin Psychiatry. 2003; 64(2): 123133.
20.Sheehan, KH, Sheehan, DV. Assessing treatment effects in clinical trials with the Discan metric of the Sheehan Disability Scale. Int Clin Psychopharmacol. 2008; 23(2): 7083.
21.Lam, RW, Kennedy, SH, Grigoriadis, S, etal. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord. 2009; 117(Suppl 1): S26S43.
22.Muzina, DJ, Chambers, J, Camacho, T, etal. Adjunctive aripiprazole for depression: predictive value of early assessment. Am J Manag Care. 2011; 17(12): 793801.
23.Casey, D, Laubmeier, K, Marler, S, Forbes, R, Baker, R. Efficacy of adjunctive aripiprazole in major depressive disorder: a pooled response quartile analysis and the predictive value of week 2 early response. Prim Care Comp for CNS Disorders. 2012; 14(3):pii: PCC.11m01251. doi: 10.4088/PCC.4011m01251.
24.Papakostas, GI. Managing partial response or nonresponse: switching, augmentation, and combination strategies for major depressive disorder. J Clin Psychiatry. 2009; 70(Suppl 6): 1625.
25.Nelson, JC, Papakostas, GI. Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. Am J Psychiatry. 2009; 166(9): 980991.
26.Berman, RM, Fava, M, Thase, ME, etal. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectr. 2009; 14(4): 197206.
27.Berman, RM, Marcus, RN, Swanink, R, etal. 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): 843853.
28.Marcus, RN, McQuade, RD, Carson, WH, etal. 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): 156165.
29.Nelson, JC, Thase, ME, Bellocchio, EE, etal. Efficacy of adjunctive aripiprazole in patients with major depressive disorder who showed minimal response to initial antidepressant therapy. Int Clin Psychopharmacol. 2012; 27(3): 125133.
30. Abilify® (aripiprazole). Full prescribing information. Tokyo, Japan: Otsuka Pharmaceutical Co., Ltd.; 2013.

Keywords

Efficacy of adjunctive aripiprazole in patients with major depressive disorder whose symptoms worsened with antidepressant monotherapy

  • J. Craig Nelson (a1), Zia Rahman (a2), Kimberly K. Laubmeier (a3), James M. Eudicone (a4), Robert D. McQuade (a5), Robert M. Berman (a6), Ronald N. Marcus (a7), Ross A. Baker (a8) and John J. Sheehan (a9)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed