Pretreatment anxious depression as a predictor of side effect frequency and severity in escitalopram and aripiprazole adjunctive therapy

Caroline W Espinola; Yuelee Khoo; Roohie Parmar; Ilya Demchenko; Benicio N Frey; Roumen V Milev; Arun V Ravindran; Sagar V Parikh; Keith Ho; Susan Rotzinger; Wendy Lou; Raymond W Lam; Sidney H Kennedy; Venkat Bhat; CAN-BIND Investigator Team

doi:10.1002/brb3.2555

Pretreatment anxious depression as a predictor of side effect frequency and severity in escitalopram and aripiprazole adjunctive therapy

Brain Behav. 2022 May;12(5):e2555. doi: 10.1002/brb3.2555. Epub 2022 Mar 25.

Authors

Caroline W Espinola^{1

2}, Yuelee Khoo¹, Roohie Parmar¹, Ilya Demchenko¹, Benicio N Frey^{3

4}, Roumen V Milev⁵, Arun V Ravindran^{2

6}, Sagar V Parikh⁷, Keith Ho¹, Susan Rotzinger¹, Wendy Lou⁸, Raymond W Lam⁹, Sidney H Kennedy^{1

2

6

10}, Venkat Bhat^{1

2

6

10}; CAN-BIND Investigator Team¹

Affiliations

¹ Interventional Psychiatry Program, St. Michael's Hospital, Toronto, Ontario, Canada.
² Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
³ Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
⁴ Mood Disorders Program and Women's Health Concerns Clinic, St. Joseph's Healthcare, Hamilton, Ontario, Canada.
⁵ Departments of Psychiatry and Psychology, Queen's University, Providence Care, Kingston, Ontario, Canada.
⁶ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA.
⁸ Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁹ Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁰ Li Ka Shing Knowledge Institute, St. Michael's Hospital & Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

Abstract

Objective: To report side effect frequency and severity in patients with major depressive disorder (MDD) receiving escitalopram and aripiprazole adjunctive therapy and to examine whether pretreatment anxious depression is associated with the number and presence of specific side effects.

Methods: 188 of the 211 trial participants provided information on side effects during treatment with escitalopram (10-20 mg) for 8 weeks, and nonresponders received further augmentation on aripiprazole (2-10 mg) adjunctive therapy for another 8 weeks, whereas responders remained on escitalopram. Participants completed the Toronto Side Effects Scale at weeks 2, 4, 10, and 12. Covariate-adjusted negative binomial regression and Wilcoxon tests examined the association between anxious depression (GAD-7 ≥ 10) and number of side effects. Covariate-adjusted logistic regression and chi-square tests explored the association between anxious depression and specific side effects.

Results: For both therapies, the most frequent side effects were also the most severe. They mostly related to the central nervous system (CNS) (i.e., drowsiness and nervousness). Between baseline and week 2, the number of side effects participants experienced (incidence rate ratio [IRR] = 1.38, p = .010) or had trouble with (IRR = 1.34, p = .026) was significantly higher among those with anxious depression for escitalopram but not adjunctive aripiprazole. Further, odds of experiencing and having trouble with nervousness and agitation were also significantly higher in anxious depression for escitalopram only (p < .05).

Conclusion: Patients on escitalopram and aripiprazole adjunctive therapy may experience and have trouble with CNS side effects. Pretreatment anxious depression may predispose escitalopram recipients with MDD to developing side effects, especially those related to anxiety.

Keywords: aripiprazole; depressive disorder; drug-related effects and adverse reactions; escitalopram; serotonin uptake inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aripiprazole / adverse effects
Depression
Depressive Disorder, Major* / complications
Depressive Disorder, Major* / drug therapy
Drug Therapy, Combination
Drug-Related Side Effects and Adverse Reactions*
Escitalopram
Humans
Treatment Outcome

Substances

Escitalopram
Aripiprazole