Psychotic depression is the most severe form of depression and patients that suffer from it respond poorly to antidepressants alone. Two treatments are effective: combined use of antidepressant and antipsychotic drugs, and electroconvulsive therapy.

However, combining some of the newer antidepressants (especially selective serotonin re-uptake inhibitors) with antipsychotics can raise the concentrations of both the drugs, so monitoring is required.

Electroconvulsive therapy is exclusively done inside hospitals, causing most patients to remain as inpatients while it lasts. It is effective only for the depressed patients who either are deluded or have marked psychomotor retardation. For the patients it consists of a general anaesthetic twice a week for two or three weeks and they experience a mild confusion for an hour or so after each session.