Paranoid schizophrenia with long-term course is a challenge for the clinical and therapeutic research, particularly because chronic course is difficult to identify due to the high rate of mortality in this category of patients. The therapeutic stability on an
antipsychotic molecule (
haloperidol) is indeed an exception, since the current trend in the case of unfavorable course is based on therapeutic versatility and
polypharmacy.
Haloperidol is the first-generation
antipsychotic that is referred in the therapeutic guidelines as the "golden standard" regarding its efficacy on positive symptoms. The research in fundamental and molecular psychopharmacology has shown the aggressivity of this molecule on the secondary and tertiary signaling chains, including mitochondrial alterations. On male patients with
paranoid schizophrenia (positive symptoms) and a chronic course of more than 35 years who received exclusively
haloperidol, our study demonstrated an negative outcome with the loss of social functioning, persistence of positive symptoms, chronic extrapyramidal symptoms and
mild cognitive impairment. The neuroimaging evaluations have shown
atrophy in the temporal poles, posterior ventriculomegaly, cerebellar
atrophy and calcification on choroid plexus and pineal gland. The difference between the histological changes induced by
haloperidol on animal model and the ones on the patients in our study is located in the frontal cortex, thus suggesting the presence of two neurobiological models of
schizophrenia in men: fronto-striatal and temporal-limbic-striatal. The persistence of extrapyramidal symptoms during the treatment with
haloperidol may be considered as a
clinical marker of the risk for negative outcome and a potential indication for the therapeutic switch.