A long-term study of remoxipride in chronic schizophrenic patients.

The purpose of this study was to assess the tolerability and efficacy of 150-600 mg remoxipride (predominantly a DA2 receptor antagonist) in an open long-term (1 year) multicentre trial in chronic schizophrenic patients. The mean duration of illness before entering the study was 21 years and the pre-study neuroleptic dosage in chlorpromazine equivalents was 930 mg/day. The clinical efficacy was measured with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale. The adverse events were recorded by a 26-item Adverse Symptom Checklist and by the Abnormal Involuntary Movements Scale. Forty-five patients were included in the study. The mean daily dose of remoxipride during the last week of treatment was 378 mg. Eighty percent (36 patients) withdrew prematurely (< 1 year). The main reasons for withdrawal were: ineffectiveness (n = 15), treatment refusal (n = 12) and adverse events (n = 8). The most frequently reported adverse events were insomnia (n = 20) and tiredness (n = 7), whereas only a few (n = 6) extrapyramidal symptoms were reported. There was no relationship between remoxipride plasma concentration and clinical efficacy nor was any relationship found between the ratio of pretrial chlorpromazine equivalent to last remoxipride dose and the therapeutic effect. Remoxipride alone seemed to have an insufficient neuroleptic efficacy in these chronic and treatment-resistant schizophrenic patients but was well tolerated.

Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia.

Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect. This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia (TD) and less rebound aggravation after withdrawal than pure D2 antagonists. In this study the effect of zuclopenthixol (mixed D1/D2 antagonist) and haloperidol (D2 antagonist) was evaluated in chronic psychotic patients with TD. Fifteen patients completed a randomized crossover study with blind evaluation of TD and parkinsonism. The test medications, haloperidol and zuclopenthixol, caused a significant suppression of TD and a significant increase of parkinsonism. No significant differences between haloperidol and zuclopenthixol were observed. No TD aggravation was seen. The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD.

Remoxipride and haloperidol in schizophrenia: a double-blind multicentre study.

Ninety-two patients with schizophrenia were included in a double-blind multicentre parallel-group trial comparing remoxipride and haloperidol. The mean daily dose during the last week of treatment was 316 mg (range, 150-600 mg) in the remoxipride group and 8.7 mg (range, 5-20 mg) in the haloperidol group. The study period was six weeks with at least one day of washout. Both Clinical Global Impression (CGI) rating, and Brief Psychiatric Rating Scale (BPRS) total scores declined at the end of the trial compared with pretreatment values in both groups. No significant differences were found between the remoxipride and haloperidol groups with regard to the treatment outcome. Treatment-emergent extrapyramidal symptoms were statistically more frequent and more severe during haloperidol than during remoxipride treatment. Haloperidol-treated patients reported also significantly more concentration difficulties. Severe extrapyramidal side effects in the haloperidol group and clinical ineffectiveness in the remoxipride group were the most frequent reasons for premature discontinuation of treatment.