Background: In treated patients with major depressive disorder (MDD), residual symptoms are common and challenging to disentangle from possible antidepressant side effects. Our objective was to prospectively differentiate between rates of residual symptoms and treatment-emergent side effects.
Methods: Participants in an episode of MDD were enrolled in a 6-week trial of an antidepressant. Assessments occurred at baseline and after 6 weeks of treatment, using the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) and the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH CPFQ). Among treatment responders, residual symptoms were those that remained the same or improved. Side effects were defined as newly emergent or worsening symptoms.
Results: Of 403 participants, 284 completed (70.5%) the trial; 93 (32.7%) were treatment responders. Residual symptoms were common and represented a substantially greater burden than side effects at end point. This was true across symptoms of depression broadly, as captured by items with the QIDS-SR and the MGH CPFQ.
Conclusions: Prospective assessment is crucial to discriminate between residual symptoms and side effects during antidepressant treatment. This study demonstrated that after 6 weeks of active treatment, symptoms are likely to persist despite response to treatment and are much less likely to represent side effects of medication treatment.