OJD  Vol.2 No.4 , November 2013
Cognitive and Psychosocial Improvements Following Aripiprazole Augmentation of SSRI Antidepressant Therapy in Treatment Refractory Depression: A Pilot Study
Abstract: Functional impairments are a common concern for individuals with major depressive disorder (MDD) that does not resolve with initial antidepressant treatment. Such concerns include cognitive difficulties, such as impaired executive functions, which can be particularly disruptive to daily function. There is a need to evaluate potential augmentation strategies for depressed individuals who do not adequately respond to initial antidepressant treatment. Aripiprazole is an FDA-approved adjunctive treatment to antidepressants for MDD, and because of its effect on both dopaminergic and serotonergic systems, may be of particular benefit to cognitive functioning. This study evaluated depressive symptom severity, cognitive function, and psychosocial function before and after six weeks of open-label aripiprazole augmentation treatment in patients with MDD who did not fully respond to selective serotonin reuptake inhibitor treatment. Participants endorsed difficulty with concentration and decision-making at study entry. Significant decreases were observed for depressive symptoms, and significant increases were found in executive function measures and measures of psychosocial function and quality of life. These preliminary data suggest that aripiprazole augmentation may yield functional benefits when used as an adjunctive treatment in MDD, and support the need for further investigation of aripiprazole and other augmentation strategies to specifically evaluate functional outcomes in MDD.
Cite this paper: Greer, T. , Sunderajan, P. , Grannemann, B. & Trivedi, M. (2013). Cognitive and Psychosocial Improvements Following Aripiprazole Augmentation of SSRI Antidepressant Therapy in Treatment Refractory Depression: A Pilot Study. Open Journal of Depression, 2, 45-53. doi: 10.4236/ojd.2013.24010.

[1]   Berman, R. M., Fava, M., Thase, M. E., Trivedi, M. H., Swanink, R., McQuade, R. D. et al. (2009). Aripiprazole augmentation in major depressive disorder: A double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectrums, 14, 197-206.

[2]   Berman, R. M., Thase, M. E., Trivedi, M. H., Hazel, J. A., Marler, S. V., McQuade, R. D. et al. (2011). Long-term safety and tolerability of open-label aripiprazole augmentation of antidepressant therapy in major depressive disorder. Neuropsychiatric Disease and Treatment, 7, 303-312.

[3]   Blair, J. R., & Spreen, O. (1989). Predicting premorbid IQ: A revision of the national adult reading test. The Clinical Neuropsychologist, 3, 129-136.

[4]   Burdick, K. E., Braga, R. J., Nnadi, C. U., Shaya, Y., Stearns, W. H., & Malhotra, A. K. (2012). Placebo-controlled adjunctive trial of pramipexole in patients with bipolar disorder: Targeting cognitive dysfunction. Journal of Clinical Psychiatry, 73, 103-112.

[5]   Burris, K. D., Molski, T. F., Xu, C., Ryan, E., Tottori, K., Kikuchi, T. et al. (2002). Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. The Journal of Pharmacology and Experimental Therapeutics, 302, 381-389.

[6]   Bymaster, F. P., Calligaro, D. O., Falcone, J. F., Marsh, R. D., Moore, N. A., Tye, N. C. et al. (1996). Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology, 14, 87-96.

[7]   Cambridge Cognition Limited (2004). CANTABeclipse test administration guide.

[8]   Cuijpers, P., Beekman, A. T., & Reynolds 3rd, C.F. (2012). Preventing depression: A global priority. The Journal of the American Medical Association, 307, 1033-1034.

[9]   Davidson, J. R. (2010). Major depressive disorder treatment guidelines in America and Europe. The Journal of Clinical Psychiatry, 71, e04.

[10]   Endicott, J., & Nee, J. (1993). Quality of life experience & satisfaction questionnaire: A new scale. Psychopharmacology Bulletin, 29, 321-326.

[11]   Greer, T. L., Kurian, B. T., & Trivedi, M. H. (2010). Defining and measuring functional recovery from depression. CNS Drugs, 24, 267-284.

[12]   Hamilton, M. (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry, 23, 56-62.

[13]   Insel, T., Cuthbert, B., Garvey, M., Heinssen, R., Pine, D. S., Quinn, K. et al. (2010). Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders. The American Journal of Psychiatry, 167, 748-751.

[14]   Jaeger, J., Berns, S., Uzelac, S., & Davis-Conway, S. (2006). Neurocognitive deficits and disability in major depressive disorder. Psychiatry Research, 145, 39-48.

[15]   Kalsekar, I., Wagner, J. S., DiBonaventura, M., Bates, J., Forbes, R., & Hebden, T. (2012). Comparison of health-related quality of life among patients using atypical antipsychotics for treatment of depression: Results from the National Health and Wellness Survey. Health and Quality of Life Outcomes, 10, 81.

[16]   Keller, M. B. (2003). Past, present, and future directions for defining optimal treatment outcome in depression: Remission and beyond. The Journal of the American Medical Association, 289, 3152-3160.

[17]   Kurian, B. T., Greer, T. L., & Trivedi, M. H. (2009). Strategies to enhance the therapeutic efficacy of antidepressants: Targeting residual symptoms. Expert Review of Neurotherapeutics, 9, 975-984.

[18]   Landro, N. I., Stiles, T. C., & Sletvold, H. (2001). Neuropsychological function in nonpsychotic unipolar major depression. Neuropsychiatry, Neuropsychology, & Behavioral Neurology, 14, 233-240.

[19]   Levkovitz, Y., Alpert, J. E., Brintz, C. E., Mischoulon, D., & Papakostas, G. I. (2012). Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder. Journal of Affective Disorders, 136, 1174-1178.

[20]   Mathers, C. D., & Loncar, D. (2006). Projections of global mortality and burden of disease from 2002 to 2030. PLoS Medicine, 3, e442.

[21]   McClintock, S. M., Husain, M. M., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Trivedi, M. H. et al. (2011). Residual symptoms in depressed outpatients who respond by 50% but do not remit to antidepressant medication. Journal of Clinical Psychopharmacology, 31, 180-186.

[22]   McDermott, C. L., & Gray, S. L. (2012). Cholinesterase inhibitor adjunctive therapy for cognitive impairment and depressive symptoms in older adults with depression. The Annals of Pharmacotherapy, 46, 599-605.

[23]   McIntyre, R. S., Fallu, A., & Konarski, J. Z. (2006). Measurable outcomes in psychiatric disorders: Remission as a marker of wellness. Clinical Therapeutics, 28, 1882-1891.

[24]   Mundt, J. C., Marks, I. M., Shear, M. K., & Griest, J. H. (2002). The work and social adjustment scale: A simple measure of impairment in functioning. The British Journal of Psychiatry, 180, 461-464.

[25]   Nelson, J. C., Pikalov, A., & Berman, R. M. (2008). Augmentation treatment in major depressive disorder: Focus on aripiprazole. Neuropsychiatric Disease and Treatment, 4, 937-948.

[26]   Nelson, J. C., Thase, M. E., Bellocchio, E. E., Rollin, L. M., Eudicone, J. M., McQuade, R. D. et al. (2012). Efficacy of adjunctive aripiprazole in patients with major depressive disorder who showed minimal response to initial antidepressant therapy. International Clinical Psychopharmacology, 27, 125-133.

[27]   Nierenberg, A. A., Husain, M. M., Trivedi, M. H., Fava, M., Warden, D., Wisniewski, S. R. et al. (2010). Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: A STAR*D report. Psychological Medicine, 40, 41-50.

[28]   Reimherr, F. W., Martin, M. L., Eudicone, J. M., Marchant, B. K., Tran, Q. V., Pikalov, A. et al. (2010). A pooled MADRS/IDS cross-correlation analysis: Clinician and patient self-report assessment of improvement in core depressive symptoms with adjunctive aripiprazole. Journal of Clinical Psychopharmacology, 30, 300-305.

[29]   Reynolds 3rd, C. F., Butters, M. A., Lopez, O., Pollock, B. G., Dew, M. A., Mulsant, B. H. et al. (2011). Maintenance treatment of depression in old age: A randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy. Archives of General Psychiatry, 68, 51-60.

[30]   Rush, A. J., Giles, D. E., Schlesser, M. A., Fulton, C. I., Weissenburger, J., & Burns, C. (1986). The inventory for depressive symptomatology (IDS): Preliminary findings. Psychiatry Research, 18, 65-87.

[31]   Sanislow, C. A., Pine, D. S., Quinn, K. J., Kozak, M. J., Garvey, M. A., Heinssen, R. K. et al. (2010). Developing constructs for psychopathology research: Research domain criteria. Journal of Abnormal Psychology, 119, 631-639.

[32]   Seeger, T. F., Seymour, P. A., Schmidt, A. W., Zorn, S. H., Schulz, D. W., Lebel, L. A. et al. (1995). Ziprasidone (CP-88,059): A new antipsychotic with combined dopamine and serotonin receptor antagonist activity. The Journal of Pharmacology and Experimental Therapeutics, 275, 101-113.

[33]   Tadori, Y., Forbes, R. A., McQuade, R. D., & Kikuchi, T. (2008). Characterization of aripiprazole partial agonist activity at human dopamine D3 receptors. European Journal of Pharmacology, 597, 27-33.

[34]   Thase, M. E., Trivedi, M. H., Nelson, J. C., Fava, M., Swanink, R., Tran, Q. V. et al. (2008). Examining the efficacy of adjunctive aripiprazole in major depressive disorder: A pooled analysis of 2 studies. Primary Care Companion to the Journal of Clinical Psychiatry, 10, 440-447.

[35]   Veiel, H. O. (1997). A preliminary profile of neuropsychological deficits associated with major depression. Journal of Clinical and Experimental Neuropsychology, 19, 587-603.

[36]   Ware, J. E., & Snow, K. K. (1993). SF-36 health survey manual and information guide. Boston, MA: Health Institute, New England Medical Center.

[37]   Zimmerman, M., Martinez, J., Attiullah, N., Friedman, M., Toba, C., & Boerescu, D. A. (2012). How should residual symptoms be defined in depressed patients who have remitted? Comprehensive Psychiatry, 54, 91-96.