Patients who remain unresponsive to two different antipsychotics should be given clozapine. However, some of the schizophrenic patients had presented an unsatisfactory benefit under clozapine monotherapy or clozapine cannot be used because of toxicity or patient refusal. Finding an efficient therapy represents a tough challenge in this situation, other drugs or drug combinations can be tried.

To choose a therapeutic scheme that improves acute psychotic symptoms and has a good tolerability. Olanzapine has antagonist activity at dopamine, serotonin, muscarinic, ⍺1-adrenergic and histamine receptors. Zuclopenthixol has high affinity for both dopamine D₁ and D₂ receptors, high affinity for ⍺1-adrenergic and 5-HT₂ receptors, a weaker histamine H₁ receptor blocking activity, and even lower affinity for muscarinic cholinergic and ⍺₂-adrenergic receptors.

2 schizophrenic females patients, hospitalized for an active phase episode. Both patient had perssistent hallucinations during the course of their illness despite the antipsychotic treatment and the good compliance. In the past they followed multiple therapeutic schemes. Antipsychotic medication was adjusted following the clinical outcome. Instruments: PANSS, CGI, weight, glycemia, lipide profile, blood pressure, heart rate, full blood count, hepatic enzymes, EKG, adverse events and relapse (follow-up 6 months).

Olanzapine and zuclopenthixol combined therapy led to psychotic symptoms remission.

In this case olanzapine and zuclopenthixol may represent an option for treatment of refractory schizophrenia. No new side effects have been observed or any unfavorable drug interactions. These results have maintained untill the end of the follow-up period.