What's the next step in therapy when the antidepressants and psychotherapy doesn't work at all?

Differing drugs: There are several different classes of antidepressents. If those fail, your doctor may decide to augment your therapy with another medication. Electroconvulsive therapy may be an option as well.

Alternatives: Adjusting the antidepressant dose, switching to another antidepressant in same group, augmenting the antidepressant with another medicine, or using other techniques such as deep brain stimulation or ect, are all options. Discuss with your doctor.

Second opinion: Treatment resistant depression is a common problem. In major depressions, the cause is generally biologic, and biologic treatments are the mainstay of care. The person may have low thyroid, another medical illness, bipolar disorder, a gastrointestinal disorder preventing absorption, taking antacids, and so on. Transcutaneous magnetic therapy, vagal nerve stimulation, and ECT are all safe.