Can typical and atypical antipsychotics show differential effectiveness in treating paranoia and hallucinations in schizophrenia?

A dopamine excess is thought to be involved in positive psychotic symptoms in schizophrenia. All current antipsychotics show a degree of dopamine receptor antagonism. Little is known about the differential effectiveness of different antipsychotics in treating specific sets of symptoms. We report the case of a 35-year-old man with schizophrenia who presented with prominent hallucinatory symptoms (Positive and Negative Syndrome Scale [PANSS] P1=5, P3=5, P6=5) resistant to high doses of a dopamine, serotonin receptor antagonist, olanzapine. Switching from olanzapine to zuclopenthixol, a dopamine D2 receptor antagonist, led to a complete shift of his symptomatology: his hallucinations abated, however, he presented as very highly paranoid (PANSS P1=6, P3=2, P6=7). On a combination of both antipsychotics, his symptoms subsided (PANSS P1=3, P3=2, P6=2). We discuss the potential for differential effectiveness of different antipsychotic medications in treating hallucinations and paranoia. We argue that future studies could address this question by stratifying patients based on symptoms.