Pharmacopsychiatry 2021; 54(05): 225-231
DOI: 10.1055/a-1385-0263
Original Paper

Impacts on Quality of Life with Escitalopram Monotherapy and Aripiprazole Augmentation in Patients with Major Depressive Disorder: A CAN-BIND Report

Emma Morton
1   Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
,
Venkat Bhat
2   Department of Psychiatry, University of Toronto, Toronto, ON, Canada
,
Peter Giacobbe
2   Department of Psychiatry, University of Toronto, Toronto, ON, Canada
,
Wendy Lou
3   Dalla Lane School of Public Health, University of Toronto, ON, Canada
,
Erin E. Michalak
1   Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
,
Trisha Chakrabarty
1   Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
,
Benicio N. Frey
4   Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada
,
Roumen V. Milev
5   Departments of Psychiatry and Psychology, Queen’s University, Kingston, ON, Canada
,
Daniel J. Müller
2   Department of Psychiatry, University of Toronto, Toronto, ON, Canada
,
Sagar V. Parikh
6   Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA
,
Susan Rotzinger
2   Department of Psychiatry, University of Toronto, Toronto, ON, Canada
,
Sidney H. Kennedy
2   Department of Psychiatry, University of Toronto, Toronto, ON, Canada
,
Raymond W. Lam
1   Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
,
on behalf of the CAN-BIND Investigator Team › Author Affiliations
Funding: CAN-BIND is an Integrated Discovery Program carried out in partnership with and receiving financial support from the Ontario Brain Institute, an independent non-profit corporation, funded partially by the Ontario government. The opinions, results, and conclusions are those of the authors, and no endorsement by the Ontario Brain Institute is intended or should be inferred. Additional funding was provided by the Canadian Institutes of Health Research, Lundbeck, Bristol Myers Squibb, and Servier. Funding and/or in-kind support was also provided by the investigators’ academic institutions.

ABSTRACT

Introduction Many individuals with major depressive disorder (MDD) do not respond to initial antidepressant monotherapy. Adjunctive aripiprazole is recommended for treatment non-response; however, the impacts on quality of life (QoL) for individuals who receive this second-line treatment strategy have not been described.

Methods We evaluated secondary QoL outcomes in patients with MDD (n=179). After 8 weeks of escitalopram, non-responders (<50% decrease in clinician-rated depression) were treated with adjunctive aripiprazole for 8 weeks (n=97); responders continued escitalopram (n=82). A repeated-measures ANOVA evaluated change in Quality of Life Enjoyment and Satisfaction Short Form scores. QoL was described relative to normative benchmarks.

Results Escitalopram responders experienced the most QoL improvements in the first treatment phase. For non-responders, QoL improved with a large effect during adjunctive aripiprazole treatment. At the endpoint, 47% of patients achieving symptomatic remission still had impaired QoL.

Discussion Individuals who were treated with adjunctive aripiprazole after non-response to escitalopram experienced improved QoL, but a substantial degree of QoL impairment persisted. Since QoL deficits may predict MDD recurrence, attention to ways to support this outcome is required.



Publication History

Received: 23 September 2020
Received: 03 February 2021

Accepted: 03 February 2021

Article published online:
02 March 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Ferrari AJ, Charlson FJ, Norman RE. et al. Burden of depressive disorders by country, sex, age, and year: Findings from the Global Burden of Disease Study 2010. PLoS Medicine 2013; 10: e1001547
  • 2 Ishak WW, Balayan K, Bresee C. et al. A descriptive analysis of quality of life using patient-reported measures in major depressive disorder in a naturalistic outpatient setting. Qual Life Res 2013; 22: 585-596
  • 3 IsHak WW, Greenberg JM, Balayan K. et, al. Quality of life: The ultimate outcome measure of interventions in major depressive disorder. Harv Rev Psychiatry 2011; 19: 229-239
  • 4 Kennedy SH, Lam RW, McIntyre RS. et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: Section 3. Pharmacological treatments. Can J Psychiatry 2016; 61: 540-560
  • 5 Gelenberg A, Freeman M, Markowitz J. et al. American Psychiatric Association practice guidelines for the treatment of patients with major depressive disorder. 2010: Retrieved from http://psychiatryonline.org/guidelines.aspx
  • 6 Cleare A, Pariante CM, Young AH. et al. Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol 2015; 29: 459-525
  • 7 Kolovos S, van Tulder MW, Cuijpers P. et al. The effect of treatment as usual on major depressive disorder: A meta-analysis. J Affect Disord 2017; 210: 72-81
  • 8 Warden D, Rush AJ, Trivedi MH. et al. The STAR* D Project results: A comprehensive review of findings. Curr Psychiatry Rep 2007; 9: 449-459
  • 9 Knoth RL, Bolge SC, Kim E. et al. Effect of inadequate response to treatment in patients with depression. Am J Manag Care 2010; 16: e188-e196
  • 10 Trivedi MH, Morris DW, Wisniewski SR. et al. Increase in work productivity of depressed individuals with improvement in depressive symptom severity. Am J Psychiatry 2013; 170: 633-641
  • 11 Mauskopf JA, Simon GE, Kalsekar A. et al. Nonresponse, partial response, and failure to achieve remission: Humanistic and cost burden in major depressive disorder. Depress Anxiety 2009; 26: 83-97
  • 12 Johnston KM, Powell LC, Anderson IM. et al. The burden of treatment-resistant depression: A systematic review of the economic and quality of life literature. J Affect Disord 2019; 242: 195-210
  • 13 Dennehy EB, Marangell LB, Martinez J. et al. Clinical and functional outcomes of patients who experience partial response to citalopram: secondary analysis of STAR*D. J Psychiatr Pract 2014; 20: 178-187
  • 14 Measuring success: the problem with primary outcomes The Lancet Psychiatry 2020; 7: 1
  • 15 Cohen RM, Greenberg JM, IsHak WW. Incorporating multidimensional patient-reported outcomes of symptom severity, functioning, and quality of life in the Individual Burden of Illness Index for Depression to measure treatment impact and recovery in MDD. JAMA Psychiatry 2013; 70: 343-350
  • 16 IsHak WW, Mirocha J, James D. et al. Quality of life in major depressive disorder before/after multiple steps of treatment and one-year follow-up. Acta Psychiatr Scand 2015; 131: 51-60
  • 17 Morton E, Michalak EE, Levitt A. et al. Quality of life impacts of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: A randomized clinical trial. Can J Psychiatry. 2020: 0706743720936470
  • 18 Demyttenaere K, Andersen HF, Reines EH. Impact of escitalopram treatment on Quality of Life Enjoyment and Satisfaction Questionnaire scores in major depressive disorder and generalized anxiety disorder. Int Clin Psychopharmacol 2008; 23: 276-286
  • 19 Lam RW, Parikh SV, Michalak EE. et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) consensus recommendations for functional outcomes in major depressive disorder. Ann Clin Psychiatry 2015; 27: 142-149
  • 20 Luan S, Wan H, Zhang L. et al. Efficacy, acceptability, and safety of adjunctive aripiprazole in treatment-resistant depression: A meta-analysis of randomized controlled trials. Neuropsychiatr Dis Treat 2018; 14: 467-477
  • 21 Zhou X, Ravindran AV, Qin B. et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: Systematic review and network meta-analysis. J Clin Psychiatry 2015; 76: e487-e498
  • 22 Pae C-U, Patkar AA. Clinical issues in use of atypical antipsychotics for depressed patients. CNS Drugs 2013; 27: 39-45
  • 23 Spielmans GI, Berman MI, Linardatos E. et al. Adjunctive atypical antipsychotic treatment for major depressive disorder: A meta-analysis of depression, quality of life, and safety outcomes. PLoS Med 2013; 10: e1001403
  • 24 Kalsekar I, Wagner JS, Di Bonaventura M. et al. 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 Qual Life Outcomes 2012; 10: 81
  • 25 Weiller E, Weiss C, Watling CP. et al. Functioning outcomes with adjunctive treatments for major depressive disorder: A systematic review of randomized placebo-controlled studies. Neuropsychiatr Dis Treat 2018; 14: 103-115
  • 26 Kennedy SH, Lam RW, Rotzinger S. et al. Symptomatic and functional outcomes and early prediction of response to escitalopram monotherapy and sequential adjunctive aripiprazole therapy in patients with major depressive disorder: A CAN-BIND-1 report. J Clin Psychiatry 2019; 80: 18m12202
  • 27 Lam RW, Milev R, Rotzinger S. et al. Discovering biomarkers for antidepressant response: Protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort. BMC Psychiatry 2016; 16: 105
  • 28 Dzevlan A, Redzepagic R, Hadzisalihovic M. et al. Quality of life assessment in antidepressant treatment of patients with depression and/or anxiety disorder. Mater Sociomed 2019; 31: 14-18
  • 29 Kennedy SH, Downar J, Evans KR. et al. The Canadian Biomarker Integration Network in Depression (CAN-BIND): Advances in response prediction. Curr Pharm Des 2012; 18: 5976-5989
  • 30 Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134: 382-389
  • 31 Sheehan DV, Lecrubier Y, Sheehan KH. et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998; 59: 22-33
  • 32 Vaccarino AL, Dharsee M, Strother S. et al. Brain-CODE: A secure neuroinformatics platform for management, federation, sharing and analysis of multi-dimensional neuroscience data. Front Neuroinform 2018; 12: 28
  • 33 Stevanovic D. Quality of Life Enjoyment and Satisfaction Questionnaire – short form for quality of life assessments in clinical practice: A psychometric study. J Psychiatr Ment Health Nurs 2011; 18: 744-750
  • 34 Endicott J, Nee J, Harrison W. et al. Quality of life enjoyment and satisfaction questionnaire: A new measure. Psychopharmacol Bull 1993; 29: 321-326
  • 35 Hamilton CM, Strader LC, Pratt JG. et al. The PhenX Toolkit: get the most from your measures. Am J Epidemiol 2011; 174: 253-260
  • 36 Fayers PM, Machin D. Quality of Life: The Assessment, Analysis and Interpretation of Patient-reported Outcomes. 2nd ed.. West Sussex: Wiley; 2007
  • 37 Williams JB, Kobak KA. Development and reliability of a structured interview guide for the Montgomery Asberg Depression Rating Scale (SIGMA). Br J Psychiatry 2018; 192: 52-58
  • 38 European Medicines Agency (EMA). Guideline on missing data in confirmatory clinical trials. 2011. CPMP/EWP/1776/99 CPMP/EWP/1776/99
  • 39 Cohen J, Cohen R, Adad J. et al. Statistical power analysis for the behavioral sciences. J Am Stat Assoc 1988; 1096-1097
  • 40 Schechter D, Endicott J, Nee J. Quality of life of “normal” controls: Association with lifetime history of mental illness. Psychiatry Res 2007; 152: 45-54
  • 41 IsHak WW, Steiner AJ, Klimowicz A. et al. Major depression comorbid with medical conditions: analysis of quality of life, functioning, and depressive symptom severity. Psychopharmacol Bull 2018; 48: 8-25
  • 42 Papakostas GI, Petersen T, Mahal Y. et al. Quality of life assessments in major depressive disorder: A review of the literature. Gen Hosp Psychiatry 2004; 26: 13-17
  • 43 Rapaport MH, Clary C, Fayyad R. et al. Quality-of-life impairment in depressive and anxiety disorders. Am J Psychiatry 2005; 162: 1171-1178
  • 44 Daly EJ, Trivedi MH, Wisniewski SR. et al. Health-related quality of life in depression: A STAR*D report. Ann Clin Psychiatry 2010; 22: 43-55
  • 45 Kolovos S, Kleiboer A, Cuijpers P. Effect of psychotherapy for depression on quality of life: Meta-analysis. Br J Psychiatry 2016; 209: 460-468
  • 46 Kamenov K, Twomey C, Cabello M. et al. The efficacy of psychotherapy, pharmacotherapy and their combination on functioning and quality of life in depression: A meta-analysis. Psychol Med 2016; 47: 414-425
  • 47 Zimmerman M, McGlinchey JB, Posternak MA. et al. How should remission from depression be defined? The depressed patient's perspective. Am J Psychiatry 2006; 163: 148-150
  • 48 Ishak WW, Greenberg JM, Cohen RM. Predicting relapse in major depressive disorder using patient-reported outcomes of depressive symptom severity, functioning, and quality of life in the Individual Burden of Illness Index for Depression (IBI-D). J Affect Disord 2013; 151: 59-65
  • 49 Solomon DA, Leon AC, Endicott J. et al. Psychosocial impairment and recurrence of major depression. Compr Psychiatry 2004; 45: 423-430
  • 50 Berlim MT, Fleck MPA. Quality of life and major depression. In Ritsner MS, Awad AG. Quality of Life Impairment in Schizophrenia, Mood and Anxiety Disorders: New Perspectives on Research and Treatment. Dordrecht: Springer Netherlands; 2007: p 241-p 252
  • 51 Duckworth AL, Tsukayama E, May H. Establishing causality using longitudinal hierarchical linear modeling: An illustration predicting achievement from self-control. Soc Psychol Personal Sci 2010; 1: 311-317
  • 52 Bauer D, Preacher K, Gil K. Conceptualizing and testing random indirect effects and moderated mediation in multilevel models: New procedures and recommendations. Psychol Methods 2006; 11: 142-163
  • 53 Eickhoff JC. Placebo effect-adjusted assessment of quality of life in placebo-controlled clinical trials. Stat Med 2008; 27: 1387-1402
  • 54 Pae C-U, Seo H-J, Lee BC. et al. A meta-analysis comparing open-label versus placebo-controlled clinical trials for aripiprazole augmentation in the treatment of major depressive disorder: Lessons and promises. Psychiatry Investig 2014; 11: 371-379
  • 55 McKnight PE, Kashdan TB. The importance of functional impairment to mental health outcomes: A case for reassessing our goals in depression treatment research. Clin Psychol Rev 2009; 29: 243-259 Financial Support