Discontinuation of citalopram and initiation of a different antidepressant such as bupropion is the most appropriate next step in the management of this patient. About 40% of patients with depression do not respond to antidepressant monotherapy. However, patients who do not respond to full-dose antidepressant monotherapy for 6 weeks may respond to switching to a different antidepressant drug, either from the same or a different class, or the addition of a second antidepressant drug.

Available evidence is not convincing regarding the efficacy of liothyronine in combination with, or augmenting, selective serotonin reuptake inhibitor treatment of depression.

Patients who do not respond to full-dose antidepressant monotherapy for 6 weeks may respond to the addition of an antipsychotic drug. The FDA has approved the following combinations of antidepressant and antipsychotic drugs for the treatment of depression: aripiprazole or quetiapine extended-release added to any antidepressant, and olanzapine added to fluoxetine. However, olanzapine monotherapy is not an appropriate treatment for this patient.

Electroconvulsive therapy may be appropriate for patients with depression refractory to multiple antidepressant drugs (or intolerance of such drugs), with or without psychotherapy, and patients with severe life-threatening depression (for example, suicidal ideation and catatonia).

Most patients with depression are treated with either antidepressant drugs or psychotherapy; a minority receive combined therapy. However, in a recent meta-analysis, pharmacotherapy combined with psychotherapy was more effective than pharmacotherapy alone in the treatment of depression. In addition to switching to a different antidepressant or adding a second antidepressant or an antipsychotic agent, clinicians should consider psychotherapy for depressed patients who do not respond to antidepressant drug monotherapy.