Antidepressant side effects and their impact on treatment outcome in people with major depressive disorder: an iSPOT-D report

Taylor A Braund,Evian Gordon,Donna M Palmer,A John Rush,Anthony W F Harris,Gabriel Tillman

doi:10.1038/s41398-021-01533-1

Abstract

Side effects to antidepressant medications are common and can impact the prognosis of successful treatment outcome in people with major depressive disorder (MDD). However, few studies have investigated the severity of side effects over the course of treatment and their association with treatment outcome. Here we assessed the severity of side effects and the impact of treatment type and anxiety symptoms over the course of treatment, as well as whether side effects were associated with treatment outcome. Participants were N = 1008 adults with a current diagnosis of single-episode or recurrent, nonpsychotic MDD. Participants were randomised to receive escitalopram, sertraline, or venlafaxine-extended release with equal probability and reassessed at 8 weeks regarding Hamilton Rating Scale Depression (HRSD17) and Quick Inventory of Depressive Symptomatology (QIDS-SR16) remission and response. Severity of side effects were assessed using the Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) scale and assessed at day 4 and weeks 2, 4, 6, and 8. Frequency, intensity, and burden of side effects were greatest at week 2, then only frequency and intensity of side effects gradually decreased up to week 6. Treatment type and anxiety symptoms did not impact the severity of side effects. A greater burden—but not frequency or intensity—of side effects was associated with poorer treatment outcome and as early as 4 days post-treatment. Together, this work provides an informative mapping of the progression of side effects throughout the treatment course and their association with treatment outcome. Importantly, the burden of side effects that are present as early as 4 days post-treatment predicts poorer treatment outcome and should be monitored closely. iSPOT-D: Registry name: ClinicalTrials.gov. Registration number: NCT00693849.

Highlights

Selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) are firstline pharmacological treatments for people with major depressive disorder (MDD) [1] and anxiety disorders [2]
Treatment type and anxiety symptoms did not impact the severity of side effects
Anxious depression is present in approximately half of the MDD population and is commonly defined either syndromally or using 17-item Hamilton Rating Scale Depression (HRSD17) criteria

Summary

Introduction

Selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) are firstline pharmacological treatments for people with major depressive disorder (MDD) [1] and anxiety disorders [2]. Previous studies suggest that frequency, intensity, and burden of side effects are impacted by antidepressant treatment type, anxiety symptoms, and the presence of anxious depression (for a review, see Ionescu et al [8]). People with anxious depression were found to have a greater maximum frequency, intensity, and burden of side effects compared to people with non-anxious depression in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial [12]. A greater side effect severity has been found at various study endpoints in people with anxious depression compared to people with MDD only [13,14,15] These associations are not found in all definitions of anxious depression, with Gaspersz et al [14]. These associations are not found in all definitions of anxious depression, with Gaspersz et al [14]. finding no differences in the frequency of side effects between people with syndromal and non-syndromal anxious depression

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