Abstract
This new version of the psychotic depression algorithm has been developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. The most effective treatment modality for inpatients with severe psychotic depression is electroconvulsive therapy. The first-line psychopharmacological treatment is a combination of an antidepressant (either a tricyclic or a selective serotonin reuptake inhibitor) and an antipsychotic. If one of these combinations has failed, consider switching to the other. If both combinations have failed, the next psychopharmacological option would be to augment the combination with lithium. Another option, though with limited evidence, is monotherapy with clozapine. If there is a good reason to avoid combination therapy with an antipsychotic, then a trial of monotherapy with a TCA or an SSRI can be supported. If that fails, adding an antipsychotic or ECT should be considered.