A controlled dose‐ranging study of remoxipride and haloperidol in schizophrenia ‐ a Canadian multicentre trial

Abstract

The efficacy and side‐effect profile for three dose ranges of remoxipride were compared with haloperidol in 242 schizophrenic inpatients in 13 centres. All patients were in a productive phase of schizophrenia according to DSM‐III criteria. Relative efficacy of low dose (30–90 mg daily) vs middle dose (120–240 mg daily) vs high dose (300–600 mg daily) was compared with the standard dose of haloperidol (15–45 mg daily), as were the side effects. It was concluded that the therapeutic efficacy of remoxipride was comparable to that of haloperidol for acute episodes of schizophrenia; that the low dose range was significantly less effective than the higher ranges; that there was a clear advantage of remoxipride over haloperidol with respect to incidence and severity of extrapyramidal symptoms. The general I safety profile of remoxipride as assessed from clinical chemistry, haematology, and cardiovascular variables suggests that remoxipride in the dose ranges studied can be used safely for the treatment of schizophrenic patients.

Influence of the dosing interval on prolactin release after remoxipride.

“…It is a selective D2-dopamine receptor antagonist [3]. Controlled clinical trials have shown that remoxipride has a good antipsychotic effect, with a significantly lower frequency of extrapyramidal symptoms compared with haloperidol [4,5]. The effect of remoxipride on plasma prolactin elevation is short-lasting [6,7].…”

Remoxipride: pharmacokinetics and effect on plasma prolactin.

“…It is a dopamine D2-receptor antagonist having virtually no affinity for muscarinic, adrenergic, histaminergic, serotoninergic or -y-aminobutyric acid (GABA) receptors (Ogren et al, 1984). Controlled clinical trials have shown that remoxipride has an antipsychotic effect, with a significantly lower frequency of extrapyramidal symptoms than haloperidol (Lapierre et al, 1990;Lewander et al, 1990).…”

Measuring Receptor Occupancy with PET

“…Variability of the response can therefore not be attributed to failure of the neuroleptic drug to reach its target. Moreover, much less time is required for occupation of the DA2 receptor (hours) than for expression of the antipsychotic effect (several days or weeks) [43,50]. These data suggest that occupancy of dopamine DA2 receptors is a necessary prerequisite, but by itself not sufficient for expression of the antipsychotic effect.…”