A double-blind multicentre study comparing remoxipride, two and three times daily, with haloperidol in schizophrenia
1
Laux G , Klieser E, Schroder H G, et al. A double-blind multicentre study comparing remoxipride, two and three times daily, with haloperidol. Acta Psychiatr Scand 1990; 82 (Supp1.358): 125-129.
G.Laux', E.flieser*, H.G.Sc,roder3, V.Dittmann B.Unterweger , H.Schuvrt$ P.Konig7, H.V$Schony*, J.Bunse and H.Beckmann
Abstract: A double-blind multicentre study comparing the efficacy and safety of remoxipride in relation to haloperidol was conducted in 160 inpatients with schizophrenic illness diagnosed according to DSM-111. The study period was 4 weeks. The mean daily dose of remoxipride (whether given twice or three times daily) during the last week of treatment was 395 mg; the corresponding dose of haloperidol was 17 mg per day. No significant difference in therapeutic efficacy was found; Brief Psychiatric Rating Scale (BPRS) median total scores dropped from 41 to 20 (remoxipride twice daily, n=51), 43 to 20 (remoxipride three times daily, n=44) 40 to 19 (haloperidol three times daily, n=48) at last valid rating. According to Clinical Global Impression (CGI) 68% in the remoxipride twice daily, 58% in the three times daily and 60% in the haloperidol group were very much or much improved. Treatment-emergent extrapyramidal checklist symptoms (hypokinesia, rigidity and tremor) were statistically significantly more frequent and more severe during haloperidol than during remoxipride treatment despite a statistically significantly higher concurrent use of anticholinergic drugs in the haloperidol group. Haloperidol treated patients reported more tiredness and drowsiness than remoxipride treated patients. Also, haloperidol treated patients had a significantly higher frequency of extrapyramidal symptoms on 8 out of 10 items of the Simpson and Angus scale.
'Department of Psychiatry, University of Wurzburg, 'Department of Psychiatry, University of Dusseldorf, 3Psychiatric State Hospital Warstein, 4Departmentof Psychiatry, University of Lubeck, FRG, 'Department of Psychiatry, University of Innsbruck, 'Psychiatric State Hospital Hall, Austria, 'Psychiatric State Hospital Rankweil, FRG, BPsychiatricState Hospital Linz, Austria, 'Department of Psychiatry, University of Gelsenkirchen, FRG
Remoxipride is a novel substituted benzamide derivative with selective dopamine D2 receptor blocking properties. It has a preferential action on the mesolimbic dopamine system compared to the nigrostriatal system in both behavioural and receptor-binding studies in animals (1). This suggests that therapeutically effective doses in schizophrenia may be less likely than classical neuroleptics to produce extrapyramidal symptoms.The evaluation of the open phase I1 trials, which included more than 200 schizophrenic patients, concluded that remoxipride, in a dose range of 75-600 mg/day, had a potential antipsychotic effect comparable with that of standard neuroleptics (2-6). These studies also indicated that remoxipride had a low incidence of extrapyramidal side effects. On the basis of these results, a study was set up to compare remoxipride 150-600 mg/day with a standard drug, haloperidol 7.5- 30 mg/day, in a double-blind, controlled trial in floridly ill schizophrenic or schizophreniform patients. The study was also designed to compare the effects of twice daily and three times daily dosages of remoxipride.
Key words: remoxipride - haloperidol - acute schizophrenia Gerd Laux, M.D. , Psychiatric Clinic of the University of Wurzburg, Fuchsleinstrasse15, D-8700 Wurzburg, FRG
Patients and methods This study was organized as a 9-hospital multicentre trial between October 1985 and February 1987.Patients entered the study if they fulfilled the following criteria: age 18-65 years; clinical diagnosis of schizophrenia; acute phase; diagnosis of schizophrenia or schizophrenifonn disorder according to DSM-III(7); at least moderately ill on the Clinical Global Impression (CGI) scale (8) and a minimum score of 18 on the Brief Psychiatric Rating Scale (BPRS) (9) at the baseline assessment immediately before active treatment. Exclusion criteria were the presence of any other primary psychiatric diagnosis; significant concurrent somatic disease; alcoholism or other drug dependence; neuroleptic-induced extrapyramidalsymptoms; and lactation, pregnancy or the possibility of pregnancy during the study. The study was approved by the ethical committee of each hospital, and written informed consent was obtained from the patients. Psychiatrists from p a ticipating hospitals met regularly before and during the study for video-rater training to ensure inter-rater agreement on the assessment of patients.
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Laux et al. Table 1. Demographic and clinical characteristics of patients Treatment group Rernoxipride Rernoxipride Haloperidol Total twice three times three times (n=lM) daily (n=55) daily (n=53) daily (n=52) Age (years) 36.0 35.3 36.1 35.8 Mean Range 18-63 20-57 19-63 18-63 Sex Male@) 31 (56.4%) 23 (43.40/) 21 (40.4%) 75 (46.9?/0) Female (n) 24 (43.6°/0) 30 (56.6Oh) 31 (59.6°/0) 85 (53.1%) Duration of illness (years) Mean 8.4 8.7 9.8 9.0 Range 4-31
1
Laux G , Klieser E, Schroder H G, et al. A double-blind multicentre study comparing remoxipride, two and three times daily, with haloperidol. Acta Psychiatr Scand 1990; 82 (Supp1.358): 125-129.
G.Laux', E.flieser*, H.G.Sc,roder3, V.Dittmann B.Unterweger , H.Schuvrt$ P.Konig7, H.V$Schony*, J.Bunse and H.Beckmann
Abstract: A double-blind multicentre study comparing the efficacy and safety of remoxipride in relation to haloperidol was conducted in 160 inpatients with schizophrenic illness diagnosed according to DSM-111. The study period was 4 weeks. The mean daily dose of remoxipride (whether given twice or three times daily) during the last week of treatment was 395 mg; the corresponding dose of haloperidol was 17 mg per day. No significant difference in therapeutic efficacy was found; Brief Psychiatric Rating Scale (BPRS) median total scores dropped from 41 to 20 (remoxipride twice daily, n=51), 43 to 20 (remoxipride three times daily, n=44) 40 to 19 (haloperidol three times daily, n=48) at last valid rating. According to Clinical Global Impression (CGI) 68% in the remoxipride twice daily, 58% in the three times daily and 60% in the haloperidol group were very much or much improved. Treatment-emergent extrapyramidal checklist symptoms (hypokinesia, rigidity and tremor) were statistically significantly more frequent and more severe during haloperidol than during remoxipride treatment despite a statistically significantly higher concurrent use of anticholinergic drugs in the haloperidol group. Haloperidol treated patients reported more tiredness and drowsiness than remoxipride treated patients. Also, haloperidol treated patients had a significantly higher frequency of extrapyramidal symptoms on 8 out of 10 items of the Simpson and Angus scale.
'Department of Psychiatry, University of Wurzburg, 'Department of Psychiatry, University of Dusseldorf, 3Psychiatric State Hospital Warstein, 4Departmentof Psychiatry, University of Lubeck, FRG, 'Department of Psychiatry, University of Innsbruck, 'Psychiatric State Hospital Hall, Austria, 'Psychiatric State Hospital Rankweil, FRG, BPsychiatricState Hospital Linz, Austria, 'Department of Psychiatry, University of Gelsenkirchen, FRG
Remoxipride is a novel substituted benzamide derivative with selective dopamine D2 receptor blocking properties. It has a preferential action on the mesolimbic dopamine system compared to the nigrostriatal system in both behavioural and receptor-binding studies in animals (1). This suggests that therapeutically effective doses in schizophrenia may be less likely than classical neuroleptics to produce extrapyramidal symptoms.The evaluation of the open phase I1 trials, which included more than 200 schizophrenic patients, concluded that remoxipride, in a dose range of 75-600 mg/day, had a potential antipsychotic effect comparable with that of standard neuroleptics (2-6). These studies also indicated that remoxipride had a low incidence of extrapyramidal side effects. On the basis of these results, a study was set up to compare remoxipride 150-600 mg/day with a standard drug, haloperidol 7.5- 30 mg/day, in a double-blind, controlled trial in floridly ill schizophrenic or schizophreniform patients. The study was also designed to compare the effects of twice daily and three times daily dosages of remoxipride.
Key words: remoxipride - haloperidol - acute schizophrenia Gerd Laux, M.D. , Psychiatric Clinic of the University of Wurzburg, Fuchsleinstrasse15, D-8700 Wurzburg, FRG
Patients and methods This study was organized as a 9-hospital multicentre trial between October 1985 and February 1987.Patients entered the study if they fulfilled the following criteria: age 18-65 years; clinical diagnosis of schizophrenia; acute phase; diagnosis of schizophrenia or schizophrenifonn disorder according to DSM-III(7); at least moderately ill on the Clinical Global Impression (CGI) scale (8) and a minimum score of 18 on the Brief Psychiatric Rating Scale (BPRS) (9) at the baseline assessment immediately before active treatment. Exclusion criteria were the presence of any other primary psychiatric diagnosis; significant concurrent somatic disease; alcoholism or other drug dependence; neuroleptic-induced extrapyramidalsymptoms; and lactation, pregnancy or the possibility of pregnancy during the study. The study was approved by the ethical committee of each hospital, and written informed consent was obtained from the patients. Psychiatrists from p a ticipating hospitals met regularly before and during the study for video-rater training to ensure inter-rater agreement on the assessment of patients.
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Laux et al. Table 1. Demographic and clinical characteristics of patients Treatment group Rernoxipride Rernoxipride Haloperidol Total twice three times three times (n=lM) daily (n=55) daily (n=53) daily (n=52) Age (years) 36.0 35.3 36.1 35.8 Mean Range 18-63 20-57 19-63 18-63 Sex Male@) 31 (56.4%) 23 (43.40/) 21 (40.4%) 75 (46.9?/0) Female (n) 24 (43.6°/0) 30 (56.6Oh) 31 (59.6°/0) 85 (53.1%) Duration of illness (years) Mean 8.4 8.7 9.8 9.0 Range 4-31
