Research has demonstrated that depressed patients with psychotic features show poorer outcomes when treated with pharmacotherapy alone compared with those without psychotic features. However, research has not investigated whether this differential response also applies to combined treatment that includes pharmacotherapy and psychotherapy. In the current study, data were pooled from two clinical trials in which patients diagnosed with major depressive disorder with or without psychotic features were treated with combined treatment. Although similar in severity at pretreatment, results indicated that patients with psychotic depression showed a poorer response in terms of depression severity at postoutpatient treatment and at 6-month follow-up compared with those with nonpsychotic depression. Following treatment, patients with psychotic depression were over four times as likely to exhibit high levels of depression and suicidal ideation. Current state-of-the-art combined treatments have poorer efficacy in depressed patients with psychotic symptoms, and adapted treatment approaches are needed.