Case Reports in Medicine hallucinations, both of which were noted for the ﬁrst time in the patient’s medical history. A year before hospitalisation in question, the patient had suﬀered a cerebral stroke and was therefore following a prescribed treatment of anticoagulants and statins. She was also aﬀected by mild vascular hypertension which, in turn, was being treated with ACE inhibitors. The results of the patient’s neurological clinical exam showed a mild strength deﬁcit at upper and lower left limbs, resulting from the cerebral stroke. The patient’s cerebral TC scan was negative, as were her routine blood tests. The patient’s HAM-D score was 28, with higher scores related to anxiety/somatisation, cognitive disorders and sleep disorders items. This particular episode for which the patient was admit- ted was treated as a new psychotic major depressive episode; however, we considered the possibility that the prescribed high dosage of sertraline may have induced the patient’s psychotic symptoms (although rare, psychotic symptoms through SSRI therapy have been documented) [15, 16]. During the ﬁrst seven days of hospitalisation we reduced, and then interrupted, the patient’s intake of sertraline and trazodone. These were substituted with venlafaxine (225 mg per day) and olanzapine (5 mg per day) together with alprazolam (2 mg per day) and ﬂurazepam (30 mg per day), with which the patient was already being treated. Due to the fact that the patient had previously suﬀered a cerebral stroke the patient provided us with her informed consent in order to allow us to administer olanzapine. The patient showed a prompt remission of symptoms and was subsequently discharged after 18 days. The patient’s HAM-D score at discharge was 8, showing a reduction of over 75% in all areas. At the patient’s one-month follow-up assessment a good clinical balance was being maintained and there were no signs of side eﬀects caused by the drugs administered. As a precaution, the dosage of olanzapine was gradually reduced and ﬁnally suspended two-months after discharge, whereas the treatment with venlafaxine continues to the present day. 2. Discussion These three case reports seem to demonstrate the positive eﬀects of a venlafaxine and olanzapine combination in the treatment of psychotic major depression. What is of particular relevance is the promptness of clinical response; two of the patients in our case studies being discharged in just over a fortnight and the third patient responding to the combination after one-month. This promptness is particularly interesting, when taking into consideration the symptoms of psychotic major depres- sion which include greater severity, greater incapacitation and prolonged periods of illness when compared to nonpsy- chotic major depression. The eﬃcacy of remission was similar in all three cases: both with the patients suﬀering recurrent depression, who had previously undergone several other treatments in their medical history, as with the patient suﬀering her ﬁrst episode. 3 Furthermore all cases presented showed a good response to medium-low dosage (from 150 mg to 225 mg per day of venlafaxine and 5 mg to 10 mg per day of olanzapine). This might also explain the almost complete absence of side eﬀects. In particular the medium-low dosage of venlafaxine administered to the two patients (A and C) aﬀected by hypertension had no inﬂuence on their respective parameters (an increase in blood pressure being a dose-related eﬀect of venlafaxine). Bearing in mind the study carried out by Zanardi et al. [17], which considers venlafaxine 300 mg per day an eﬀective treatment for psychotic depression, we suggest that a combination with olanzapine may result in a useful option for those patients suﬀering psychotic major depression and hypertension. With regard to the duration of treatment, it is not yet clear how long the antidepressant and antipsychotic association should last [3]. The fact that the patient described in Case A relapsed after an episode of nonadherence to therapy, two years after her initial discharge seems to indicate, in accordance with recent literature [18], the need for long-term treatment where antipsychotic and antidepressant combinations are prescribed, including cases in which the patient is suﬀering their ﬁrst episode of psychotic major depression. On the other hand in case C the precautionary suspen- sion of olanzapine has not led to any clinical relapse though the venlafaxine dosage has not been modiﬁed (it has now been seven months since the patient’s discharge). In this case we maintain the belief that sertraline may have caused the onset of the patient’s psychotic symptoms. Overall the association of venlafaxine and olanzapine in psychotic major depression has demonstrated eﬃcacy, at least as much as the most investigated combination, between ﬂuoxetine and olanzapine. The data still need to be conﬁrmed through clinical trials; however, there are diﬃculties in carrying out such studies given that patients are often admitted when they are in a crit- ical condition and, as such, unable to provide an adequate, informed consent (e.g., patients who are in a catatonic state or who are aﬀected by delusions of persecution). The resulting mechanism from this combination of venlafaxine and olanzapine remains, as yet, unclear. It could be related to the speciﬁc mechanisms of olanzapine and venlafaxine, and their pharmacodynamic interaction. Olan- zapine is an antagonist and binds to serotonin (5HT2A/2C) and dopamine (D1–4) receptors, and thus may combine AD and AP eﬀects in a single compound. Furthermore, olanzapine could increase the eﬀect of serotonin antagonism in venlafaxine, likewise in ﬂuoxetine. However venlafaxine, unlike ﬂuoxetine, has a dual mechanism of action including a noradrenergic property, which may explain its more rapid and eﬀective results in psychotic major depression patients. Conﬂict of Interests The authors declare that they have no Conﬂict of Interests.