Few studies have investigated the proportion of patients with depression who experience worsening of depression symptoms during adequate antidepressant treatment. The current study aimed to investigate the proportion and predictors of worsening depression during antidepressant treatment in a multi-center randomized trial involving patients with major depression.We defined the deterioration of depression using depression symptom severity evaluated by total Patient Health Questionnaire (PHQ-9) score increases from week 0 to week 9 during acute phase antidepressant treatment. Patients' baseline demographic and clinical data, change in PHQ-9 scores from week 0 to week 3, and side effects at week 3 were evaluated as potential predictors of subsequent deterioration of depression.Of 1,647 patients, 99 (6.0%) exhibited deterioration of depression, and this proportion was smaller when reliable change index criteria were applied. Logistic regression analysis revealed that the following factors were significantly associated with deterioration of depression: younger age at onset of first episode of major depressive disorder, current older age, and greater increase in PHQ-9 scores between week 0 and week 3.The time of the primary endpoint might not have been sufficiently long. The present study did not include a placebo arm, and potentially relevant predictors might not have been comprehensively investigated.A small proportion of patients may experience deterioration of depression during acute phase antidepressant treatment. Age at onset at first depressive episode, current age, and early negative response to antidepressants may be useful predictors of subsequent worsening of depression.
