Skip to main content
×
×
Home

Aripiprazole Augmentation in Major Depressive Disorder: A Double-Blind, Placebo-Controlled Study in Patients with Inadequate Response to Antidepressants

Abstract

Introduction: Effective management of major depressive disorder (MDD) continues to be a challenging task for psychiatrists and primary care physicians. This trial evaluated the efficacy and safety of adjunctive aripiprazole versus antidepressant monotherapy in patients with MDD and independently replicated the positive findings of two similar trials.

Methods: Patients (N=1, 147) with MDD experiencing a major depressive episode and a history of inadequate response to antidepressant monotherapy were enrolled (week 0); 827 received single-blind adjunctive placebo plus open-label antidepressant (escitalopram, fluoxetine, paroxetine controlled release, sertraline, or venlafaxine extended release) for 8 weeks to confirm inadequate response to antidepressants; 349 patients with inadequate response were randomized (1:1) to double-blind, adjunctive placebo (n=172) or adjunctive aripiprazole (n=177; 2–20 mg/day). Primary outcome was the mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total score from baseline (week 8) to endpoint (week 14).

Results: Clinically significant improvements in depressive symptoms as assessed by decreases in the MADRS Total score were greater with adjunctive aripiprazole (−10.1) than placebo (−6.4; P<.001). Remission rates were greater for adjunctive aripiprazole than for adjunctive placebo (week 14, 36.8% vs 18.9%; P<.001). Completion rates with adjunctive aripiprazole and placebo were high (83% vs. 87%) and discontinuations due to adverse events were low (6.2% vs 1.7%).

Conclusion: For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and previous studies, have shown that discontinuations due to adverse events were low and completion rates were high, and has indicated that both antidepressant and aripiprazole in combination were relatively well-tolerated and safe. This is the third consecutive clinical trial, in the absence of a failed trial, to demonstrate that aripiprazole augmentation to antidepressants is an efficacious and well-tolerated treatment for patients with MDD who do not respond adequately to standard antidepressant monotherapy (ClinicalTrials.gov study NCT00105196).

Copyright
Corresponding author
Please direct all correspondence to: Robert M. Berman, MD, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492; Tel: 203-677-6914; Fax: 203-677-7695; E-mail: Robert.Berman@bms.com.
References
Hide All
1.Murray, CJ, Lopez, AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet. 1997;349:14981504.
2.Kessler, RC, Berglund, P, Demler, O, et al.The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289:30953105.
3.Moussavi, S, Chatterji, S, Verdes, E, Tandon, A, Patel, V, Ustun, B. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet. 2007;370:851858.
4.Regier, DA, Narrow, WE, Rae, DS, Manderscheid, RW, Locke, BZ, Goodwin, FK. The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective 1-year prevalence rates of disorders and services. Arch Gen Psychiatry. 1993;50:8594.
5.Greenberg, PE, Birnbaum, HG, Leong, SA. Cost of depression: current assessment and future direction. Expert Review of Pharmacoeconomics & Outcomes Research. 2001;1:6976.
6.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;163:2840.
7.Rush, AJ, Trivedi, MH, Wisniewski, SR, et al.Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163:19051917.
8.Gaynes, BN, Rush, AJ, Trivedi, MH, et al.Primary versus specialty care outcomes for depressed outpatients managed with measurement-based care: results from STAR*D. J Gen Intern Med. 2008;23:551560.
9.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;68:843853.
10.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;28:156165.
11.Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.
12.Fava, M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry. 2003;53:649659.
13.Montgomery, SA, Asberg, M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382389.
14.Leon, AC, Shear, MK, Portera, L, Klerman, GL. Assessing impairment in patients with panic disorder: the Sheehan Disability Scale. Soc Psychiatry Psychiatr Epidemiol. 1992;27:7882.
15.Guy, W. Clinical Global Impressions (CGI). ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: US Department of Health, Education, and Welfare Publication (ADM) 76-338. National Institute of Mental Health; 1976:218222.
16.Rush, AJ, Gullion, CM, Basco, MR, Jarrett, RB, Trivedi, MH. The Inventory of Depressive Symptomatology (IDS): psychometric properties. Psychol Med. 1996;26:477486.
17.Rush, A, Trivedi, M, Ibrahim, HM. 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;54:573583.
18.Endicott, J, Nee, J, Harrison, W, Blumenthal, R. Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure. Psychopharmacol Bull. 1993;29:321326.
19.Einarson, TR. Evidence based review of escitalopram in treating major depressive disorder in primary care. Int Clin Psychopharmacol. 2004;19:305310.
20.Gorwood, P, Weiller, E, Lemming, O, Katona, C. Escitalopram prevents relapse in older patients with major depressive disorder. Am J Geriatr Psychiatry. 2007;15:581593.
21.Mittmann, N, Mitter, S, Borden, EK, Herrmann, N, Naranjo, CA, Shear, NH. Montgomery-Asberg severity gradations. Am J Psychiatry. 1997;154:13201321.
22.Simpson, GM, Angus, JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl. 1970;212:1119.
23.Guy, W. Abnormal Involuntary Movement Scale (AIMS). In: ECDEU Assessment Manual for Psychopharmacology. Rockville, Md: US Department of Health, Education, and Welfare publication (ADM) 76-338. National Institute of Mental Health; 1976:534537.
24.Barnes, TR. A rating scale for drug-induced akathisia. Br J Psychiatry. 1989;154:672676.
25.Labbate, LA, Lare, SB. Sexual dysfunction in male psychiatric outpatients: validity of the Massachusetts General Hospital Sexual Functioning Questionnaire. Psychother Psychosom. 2001;70:221225.
26.Mojtabai, R. Increase in antidepressant medication in the US adult population between 1990 and 2003. Psychother Psychosom. 2008;77:8392.
27.Trivedi, MH, Fava, M, Wisniewski, SR, et al.Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006;354:12431252.
28.Trivedi, MH, Rush, AJ, Gaynes, BN, et al.Maximizing the adequacy of medication treatment in controlled trials and clinical practice: STAR(*)D measurement-based care. Neuropsychopharmacology. 2007;32:24792489.
29.Turner, EH, Matthews, AM, Linardatos, E, Tell, RA, Rosenthal, R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008;358:252260.
30.Fava, M, Evins, AE, Dorer, DJ, Schoenfeld, DA. The problem of the placebo response in clinical trials for psychiatric disorders: culprits, possible remedies, and a novel study design approach. Psychother Psychosom. 2003;72:115127.
31.Corruble, E, Legrand, JM, Zvenigorowski, H, Duret, C, Guelfi, JD. Concordance between self-report and clinician's assessment of depression. J Psychiatr Res. 1999;33:457465.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

CNS Spectrums
  • ISSN: 1092-8529
  • EISSN: 2165-6509
  • URL: /core/journals/cns-spectrums
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 71 *
Loading metrics...

Abstract views

Total abstract views: 1162 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 20th August 2018. This data will be updated every 24 hours.