The presence of delusions or hallucinations in major depressive disord
er indicates a severe form of that disorder. Compared with patients wi
th nonpsychotic depression, those with psychotic depression have depre
ssive symptoms that are individually more. severe. They also are more
likely to have hypothalamic-pituitary adrenal axis hyperactivity and i
ncreased ventricular-to-brain ratios. The short- and long-term outcome
s for such patients are poor. Findings that this prognostic disadvanta
ge may be permanent and that psychotic features recur at high rates in
subsequent episodes indicate that these symptoms in major depressive
disorder have a lifelong significance. Although monotherapy with antid
epressants may be effective, recovery is more rapid when antidepressan
ts are combined with antipsychotics. Electroconvulsive therapy is part
icularly effective for psychotic depression. The importance of combina
tion therapy for prophylaxis is unknown.