A Retrospective Analysis of the Impact of Electroconvulsive Therapy on Anxiety Symptoms in Patients With Treatment-Resistant Depression
Authors: Laszcz Julia , Wang Chenyang , Riva-Posse Patricio , Kim Jonathan , Tsygankova Valeriya , Mandell Ally , Rice Hanna , Hermida Adriana , Kitay Brandon M. , Crowell Andrea , McDonald William M. , Hershenberg Rachel 
Published: January 2025

Highlights
–Patients with treatment-resistant depression (TRD) referred for ECT may experience anxiety.
– Little is known about anxiety symptom changes during an ECT course.
– Retrospective data was analyzed for 117 TRD patients during an acute ECT course.
– Anxiety symptoms improved but not as robustly as depressive symptoms.
– More anxiety during treatment predicted worse antidepressant outcomes.
Major depressive disorder (MDD) is one of the most common psychiatric disorders in both specialist and general medical practice.
1
Symptoms of depression and anxiety are likely to co-occur, with 40%–60% of MDD patients experiencing anxiety symptoms.
2,3
Importantly, the presence of co-occurring anxiety is a negative prognostic factor. Indeed, the co-occurrence of anxiety symptoms or disorders has significant implications for MDD disease course and burden. For example, when anxiety is comorbid with MDD, the progression of the disease is more refractory to standard antidepressant treatment.
4,5
Coexisting anxiety symptoms make treating MDD more difficult than MDD without anxiety symptoms,
6
and individuals with depression and co-morbid anxiety disorders or symptoms are at greater risk of suicide.
7
Consistent with this, anxiety symptoms in patients with MDD are associated with increased use of healthcare resources.
8
Residual anxiety symptoms following improvements in depressive symptoms place patients at greater risk for relapse or recurrence of another depressive episode.
9,10

Approximately 30% of MDD patients are considered “treatment resistant,” typically defined as a failure to respond to at least 2 separate antidepressant trials of adequate dose and duration in the current depressive episode.
11
TRD contributes disproportionately to the cost and functional burden of MDD. Direct and indirect healthcare resource utilization costs are nearly double for TRD patients versus non-TRD MDD patients and quadruple in comparison to non-MDD patients.
12
Individuals with TRD demonstrate functional impairment equal to or above that associated with other severe chronic medical conditions such as diabetes and congestive heart failure.
13
As such, it is critical to improve personalized treatment recommendations for TRD patients when considering the armamentarium of advanced treatment options such as electroconvulsive therapy (ECT). ECT is a robustly efficacious antidepressant treatment, for patients with severe symptoms of depression, including in patients who do not respond to antidepressants or psychotherapy.
14,15

Despite the well-documented antidepressant effects of ECT for TRD patients, very little is known about the potential anxiolytic effects of ECT for TRD patients. Although there is a strong co-occurrence between depression and anxiety symptoms, the wealth of ECT studies primarily examine the extent to which ECT improves depression symptoms. ECT is a treatment for depression and not for anxiety; at the same time, an empirical question remains if anxiety symptoms will improve for TRD patients for whom ECT is indicated.
16,17
This understanding is critical to understanding the anticipated real-world impact on a broader range of symptoms in TRD patients referred for ECT. In one study of patients receiving a course of bitemporal (BT) ECT that modeled anxiety symptoms as an outcome variable, anxiety symptoms improved less than depression symptoms.
18
When anxiety is considered as a pretreatment variable, initial evidence suggests that anxiety may lower the response rate to ECT but that its presence should not be an exclusionary factor for receiving ECT.
19
In a study of 70 bipolar patients in a depressed or mixed episode who received a bilateral course of ECT twice weekly, ECT was shown to be an effective depression treatment, but patients with anxiety disorders relapsed in a shorter time.
10,19
In another study, ECT patients with primary anxiety disorders and mixed psychopathology including depression demonstrated clinical improvement.
20
Taken together, there is a dearth in the literature considering anxiety as an outcome variable in TRD patients receiving an acute course of ECT. Related but distinct lines of inquiry suggest that anxiety itself is not a contraindication for the receipt of ECT but may negatively impact either initial response or time to relapse.
The goal of the present study was to primarily consider the trajectory of change in anxiety symptoms. More specifically, the goal was to examine the extent to which anxiety symptom severity improves, relative to improvements in depressive symptoms, in TRD patients receiving an acute course of ECT, drawing from the finding that anxiety symptoms may not improve as robustly as symptoms of depression.
18
Data from a naturalistic cohort of TRD outpatients seeking a course of ECT were analyzed with the hypothesis that anxiety symptoms would decrease in an acute ECT course but that this change would be less robust than changes in symptoms of depression.

Background
Electroconvulsive therapy (ECT) is an effective treatment for treatment-resistant depression (TRD). There are limited data on the improvement of anxiety symptoms in patients receiving ECT for TRD.

Objective
The aim of the study was to examine the extent to which anxiety symptom severity improves, relative to improvements in depressive symptoms, in TRD patients receiving an acute course of ECT.

Methods
A retrospective chart review of 117 TRD patients who received an acute ECT course in a naturalistic outpatient setting was conducted. Symptomatic response was measured using the Beck Depression Inventory II and Generalized Anxiety Disorder 7 Scale. Two generalized estimating equation models assessed the degree of change in anxious symptoms relative to the change in depressive symptoms.

Results
Both depression (−0.09, P < 0.001) and anxiety (−0.08, P < 0.001) improved after ECT treatment, with a greater standardized decrease for symptoms of depression. Higher levels of anxiety over the treatment (−0.42, P < 0.001) were associated with smaller antidepressant improvements.

Conclusions
ECT may improve symptoms of anxiety in patients with TRD. Anxiety symptoms show a favorable trajectory of improvement, though to a lesser extent, relative to changes in symptoms of depression. Higher symptoms of anxiety throughout the treatment course may be a negative predictor of antidepressant response in ECT.