Depression Worse After Treatment in Few With MDD

Man with depression, profile
Man with depression, profile
Researchers found data that showed in a small number of patients with depressive disorder, antidepressants might worsen depression.

A small proportion of patients with major depressive disorder (MDD) experience worsening depression after acute-phase antidepressant treatment, according to a study published by the Journal of Affective Disorders.

Using data drawn from a previous multicenter, open-label, assessor-blinded, practical randomized controlled clinical trial (RCT), researchers evaluated the deterioration of depression symptom severity in patients who were not responding to first-line treatment with sertraline (either 50 mg/d or 100 mg/d) after 3 weeks (N=1647). Patients were individually randomized to continue receiving sertraline (n=551), or were switched to sertraline augmented with mirtazapine (n=538), or were switched to mirtazapine (n=558). At weeks 1, 3, and 9, researchers used telephone interviews to administer the Patient Health Questionnaire (PHQ-9) and the Frequency, Intensity and Burden of Side Effects Rating (FIBSER).

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During the acute phase of antidepressant treatment, 99 of 1647 patients (95% CI, 5%-7%) exhibited deterioration of depression, which was smaller when the reliable change index (RCI) criteria were applied. There were no significant differences among the patients exhibiting deterioration of depression between the 3 treatment groups.

Limitations of this study included a lack of clarity as to whether the results would differ if antidepressants other than sertraline augmenting with or switching to a drug other than mirtazapine were used. The follow-up duration of 9 weeks after initiation of pharmacotherapy might not have been sufficient. Because there was no placebo arm of this study, researchers were unable to compare worsening cases with a control cohort. Potentially relevant predictors might not have been comprehensively investigated because this study was a secondary analysis of a previous study.

A significant predictor of subsequent deterioration of depression was the worsening of PHQ-9 scores between week 0 and week 3, which suggests that it may be possible to predict responses to antidepressants somewhat earlier than the commonly applied duration of 6 to 8 weeks. Two age-related factors (young age at onset of first episode of MDD and current older age) may be useful predictors of subsequent deterioration of depression. When researchers applied the RCI, both of these factors were not found to be significant predictors. More rigorously designed studies are needed to clarify the association between age-related factors and worsening depression.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Akechi T, Sugishita K, Chino B, et al. Whose depression deteriorates during acute phase antidepressant treatment? [published online September 9, 2019]. J Affect Disord. doi: 10.1016/j.jad.2019.09.052