Whose depression deteriorates during acute phase antidepressant treatment?

•Clinical predictors of worsening depression during antidepressant treatment were explored by using our previous multi-center randomized practical trial for patients with major depression.•Total of 6.0% or less showed any deterioration of depression, and younger age at onset, of first episode of major depressive disorder, current older age, and larger increase in PHQ-9 score between week 0 and week 3 were significant predictors of worsening depression.•A small proportion of patients may experience deterioration of depression during acute phase antidepressant treatment and age at onset at first depressive episode, current age, and early negative response to antidepressants may be useful predictors of subsequent worsening of depression.