Delusional depression is characterised by the presence of symptoms such as hallucinations (typically auditory) and delusions either mood congruent and incongruent. Most commonly the content of delusions is consistent with the depressive themes: guilt, unworthlessness, poverty, death. Hallucinations, when present, are not elaborate and may involve voices that berate the patient for shortcomings or sins. Mood incongruent psychotic symptoms include persecutory delusions, delusions of thought insertion or thought broadcasting. Several pharmacological studies have demonstrated a differential response pattern in delusional depression and in nondelusional depression. Delusional depressives in fact, have a much lower response rate to tricyclic antidepressant treatment alone (20-25%) than nondelusional depressives (70-80%). The combination treatment with tricyclic and neuroleptic drugs leads to a dramatic improvement in the response rate in these patients (68-95%). The drugs most widely used are, for tricyclics, amitryptiline (150-215 mg/day) and desipramine (150-200 mg/day), and for neuroleptics, perphenazine (30-50 mg/day), but good results have also been reported with haloperidol (8-20 mg/day). The better results obtained with the tricyclic-neuroleptic association seem to be related to 3 factors: an increased tricyclic plasma level due to a competitive hynibition in the hepatic hydroxilation processes caused by neuroleptic agents: a dopaminergic blockade and an increased serotonergic and noradrenergic activity. Treatment with neuroleptics alone improves the symptomatology only in 19-50% of the patients. If the patient does not show a good response to the combination of tricyclics and neuroleptics, lithium augmentation (600-1200 mg/day) notably ameliorates the rates of clinical response (80-90% of cases). The treatment of delusional depressive patients with amoxapine leads to positive results in 70-80% of cases. Very good results have also been noted with bupropione (300-750 mg/day) after only a week of therapy. A complete symptomatological remission has been observed with 1-Dopa (1000 mg/day). The relatively low number of delusional depressive patients treated with SSRI to date does not allow to draw any consistent and definite conclusion on their real efficacy in this severe form of depression. For the continuation treatment it is recommended to continue the tricyclic-neuroleptic treatment for at least 6 months, at the lowest neuroleptic dosage which allows a long lasting clinical remission. Once the clinical remission is complete, the neuroleptic agent can be gradually tapered in some months, unless the patient had previous recurrence with the tricyclic agent alone. To the patients who show a symptomatological re-exacerbation during neuroleptic tapering, must be given again the combination treatment. In these cases it is important to assess more often and carefully the patient because of the increased risk of tardive diskinesia. Inconsistent results have been reported regarding the role of lithium in preventing relapses and recurrences: some authors suggest a prophylactic treatment with lithium and/o tricyclics in monotherapy to avoid the risks linked to a long-lasting neuroleptic treatment; others authors have documented a higher risk of relapse with lithium and/o tricyclics in monotherapy than with the tricyclic-neuroleptic combination treatment.